Prospective ARNI vs ACE Inhibitor Trial to DetermIne Superiority in Reducing Heart Failure Events After MI (PARADISE-MI)

• ClinicalTrials.gov Identifier: NCT02924727
• Recruitment Status: Completed
• First Posted: October 5, 2016
• Results First Posted: June 22, 2023
• Last Update Posted: June 22, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Myocardial Infarction
• Interventions: Drug: LCZ696 (sacubitril/valsartan); Drug: Ramipril; Drug: Placebo of LCZ696; Drug: Placebo of ramipril; Drug: Valsartan; Drug: Placebo of valsartan
• Enrollment: 5669

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 5669 patients were randomized in a 1:1 ratio to the sacubitril/valsartan treatment group and the ramipril treatment group at 493 sites in 41 countries. A total of 8 patients were mis-randomized, 4 from each treatment group. One of the mis-randomized patients of the ramipril group died. The Full analysis set (FAS) was comprised of 5661 patients.

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Period Title: Overall Study
Started [1]	2834	2835
Full Analysis Set (FAS) [2]	2830	2831
Safety Set (SAF) [3]	2820	2816
Completed	2605	2576
Not Completed	229	259
Reason Not Completed
Withdrawal by Subject	2	4
Lost to Follow-up	2	5
Death	221	247
Mis-randomized (one mis-randomized patient in the Ramipril group also died)	4	3
[1] All randomized patients (RAN); [2] All patients in the RAN population who were not mis-randomized patients (who were not qualified for randomization and who did not take study drug, but were inadvertently randomized into the study).; [3] All randomized patients who received at least one dose of study drug.

Baseline Characteristics

Arm/Group Title		LCZ696 (Sacubitril/Valsartan)	Ramipril	Total
Arm/Group Description		Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.	Total of all reporting groups
Overall Number of Baseline Participants		2830	2831	5661
Baseline Analysis Population Description		The Full Analysis Set (FAS) consisted of 5661 patients and consisted of patients in the Randomized population who were not mis-randomized patients. Out of the 5669 patients randomized, a total of 8 patients were mis-randomized, 4 from each treatment group. Following the intent-to-treat (ITT) principle, patients in the FAS were analyzed according to the treatment they were assigned to at randomization.
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	2830 participants	2831 participants	5661 participants
<65 years		1386 49.0%	1451 51.3%	2837 50.1%
≥65 years		1444 51.0%	1380 48.7%	2824 49.9%
<75 years		2286 80.8%	2324 82.1%	4610 81.4%
≥75 years		544 19.2%	507 17.9%	1051 18.6%
		[1] Measure Description: Participants in age categories can be counted more than once in the appropriate category.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2830 participants	2831 participants	5661 participants
	Female	663 23.4%	700 24.7%	1363 24.1%
	Male	2167 76.6%	2131 75.3%	4298 75.9%
Race/Ethnicity, Customized [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	2830 participants	2831 participants	5661 participants
Caucasian		2125	2138	4263
Black		35	40	75
Asian		475	478	953
Native American		45	45	90
Pacific Islander		0	4	4
Unknown		22	21	43
Other		128	105	233
		[1] Measure Description: Race/Ethnicity

Outcome Measures

1. Primary Outcome

Title	Number of Participants With First CEC (Clinical Endpoint Committee) Confirmed Primary Composite Endpoint
Description	A confirmed composite endpoint includes cardiovascular (CV) death, heart failure (HF) hospitalization, or outpatient heart failure
Time Frame	From randomization to first occurrence (up to approximately 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Count of Participants
Primary Composite	338	373
Cardiovascular (CV) Death	168	191
First Heart Failure (HF) Hospitalization	170	195
First Outpatient Heart Failure (HF)	39	57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	Primary Composite
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1659
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9012
	Confidence Interval	(2-Sided) 95%; 0.7778 to 1.0441
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	CV Death
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2031
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8740
	Confidence Interval	(2-Sided) 95%; 0.7104 to 1.0754
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	First HF Hospitalization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1679
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8653
	Confidence Interval	(2-Sided) 95%; 0.7044 to 1.0629
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	First Outpatient HF
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0667
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.6831
	Confidence Interval	(2-Sided) 95%; 0.4546 to 1.0266
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants With a Confirmed Composite of CV Death or HF Hospitalization
Description	A confirmed composite endpoint for this outcome measure includes cardiovascular death or heart failure hospitalization.
Time Frame	Time from randomization to first occurrence (up to approximately 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Participants
	308	335

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	CV death or HF hospitalization
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2507
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9133
	Confidence Interval	(2-Sided) 95%; 0.7824 to 1.0662
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Participants With a Confirmed Composite of HF Hospitalization or Outpatient HF
Description	A confirmed composite endpoint includes first occurrence of heart failure hospitalization or outpatient heart failure
Time Frame	Time from randomization to first occurrence (approximately up to 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Participants
	201	237

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	HF hospitalization or Outpatient HF
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0732
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8422
	Confidence Interval	(2-Sided) 95%; 0.6979 to 1.0163
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Participants With a Confirmed Composite of CV Death, Non-fatal Spontaneous Myocardial Infarction or Non-fatal Stroke
Description	A confirmed composite endpoint for this outcome measure includes cardiovascular death, non-fatal spontaneous myocardial infarction or non-fatal stroke
Time Frame	Time from randomization to first occurrence (approximately up to 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Participants
	315	349

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	CV death, Non-fatal spontaneous MI or Non-fatal stroke
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1785
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.9007
	Confidence Interval	(2-Sided) 95%; 0.7734 to 1.0489
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Total Number of Confirmed Composite Endpoints
Description	A confirmed composite endpoint includes cardiovascular death, heart failure hospitalization, non-fatal spontaneous MI hospitalization, and non-fatal stroke hospitalization
Time Frame	Time from randomization to end of study (approximately up to 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Events
	416	455

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	Total Number of Confirmed Composite Endpoints
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0452
	Comments	[Not Specified]
	Method	Negative Binomial regression model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.8361
	Confidence Interval	(2-Sided) 95%; 0.7018 to 0.9961
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	All-cause Mortality for Full Analysis Set (FAS)
Description	All-cause mortality defined as deaths related to Cardiovascular (CV) and non-CV events for patients in the Full Analysis Set up to a cut-off date of 31-Dec-2020.
Time Frame	Time from randomization to death (approximately up to 43 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed	2830	2831
Measure Type: Number; Unit of Measure: Participants
	213	242

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LCZ696 (Sacubitril/Valsartan), Ramipril
	Comments	All-Cause Death
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1556
	Comments	[Not Specified]
	Method	Cox's Proportional Hazard Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.8751
	Confidence Interval	(2-Sided) 95%; 0.7279 to 1.0520
	Estimation Comments	[Not Specified]

7. Post-Hoc Outcome

Title	All Collected Deaths
Description	Pre-treatment deaths were collected from randomization to the day before first dose of study medication, for a maximum duration of 5 days. On-treatment and post-treatment safety follow-up deaths were collected from first dose of study medication to 30 days after the last dose of study medication. All deaths refer to the sum of pre-treatment, on-treatment and post-treatment safety follow-up deaths.
Time Frame	Pre-treatment: Up to 5 days before Day 1. On-treatment and post-treatment safety follow up: up to 4 years

Outcome Measure Data

Analysis Population Description

All subjects to whom study treatment was assigned by randomization, regardless of whether or not treatment was administered

Arm/Group Title		LCZ696 (Sacubitril/Valsartan)	Ramipril
Arm/Group Description:		Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
Overall Number of Participants Analyzed		2834	2835
Measure Type: Number; Unit of Measure: Participants
pre-treatment deaths	Number Analyzed	2834 participants	2835 participants
		1	3
On-treatment deaths and extended safety follow-up	Number Analyzed	2820 participants	2816 participants
		220	244
All deaths	Number Analyzed	2834 participants	2835 participants
		221	247

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of approximately 4 years. All-Cause Mortality was collected from randomization until the end of study treatment plus 30 days post-treatment, up to a maximum duration of approximately 4 years.
Adverse Event Reporting Description	Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. All-Cause Mortality is using the Randomized Set, including patients who were not treated.
Arm/Group Title	LCZ696 Pre-treatment	Ramipril Pre-treatment	LCZ696	Ramipril
Arm/Group Description	Only for pre-treatment deaths that are not included in the safety set.	Only pre-treatment deaths that are not included in the safety set	Following randomization, patients received LCZ696 in titrated doses from level 1 up to level 3 (50, 100 and 200 mg twice daily). Patients were required to take a total of two pills, (one tablet from the LCZ696 pack and one capsule from Ramipril matching placebo pack) twice a day for the duration of the study. Patients randomized to LCZ who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization, received a valsartan bridge for one day. These patients received two doses of valsartan for 1 day in a blinded manner prior to beginning double-blind LCZ696 treatment.	Following randomization, patients received Ramipril in titrated doses from level 1 up to level 3 (1.25, 2.5 and 5 mg twice daily). Patients were required to take a total of two pills, (one capsule from the Ramipril pack and one tablet from LCZ696 matching placebo pack) twice a day for the duration of the study. Patients randomized to Ramipril who were previously treated with ACE inhibitors, receiving the last dose of that agent during the last 36 hours prior to randomization immediately started on double-blind ramipril; however, to maintain double blind/double dummy of the valsartan bridge, these patients received two doses of matching valsartan placebo for 1 day in a blinded manner prior to beginning double-blind LCZ696 placebo.
All-Cause Mortality
	LCZ696 Pre-treatment	Ramipril Pre-treatment	LCZ696	Ramipril
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/2834 (0.04%)	3/2835 (0.11%)	220/2820 (7.80%)	244/2816 (8.66%)
Serious Adverse Events
	LCZ696 Pre-treatment	Ramipril Pre-treatment	LCZ696	Ramipril
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0	1146/2820 (40.64%)	1126/2816 (39.99%)
Blood and lymphatic system disorders
Anaemia † 1	0/0	0/0	30/2820 (1.06%)	23/2816 (0.82%)
Anaemia macrocytic † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Anaemia vitamin B12 deficiency † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Blood loss anaemia † 1	0/0	0/0	3/2820 (0.11%)	1/2816 (0.04%)
Eosinophilia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Febrile neutropenia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Hypochromic anaemia † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Hypocoagulable state † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Immune thrombocytopenia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Iron deficiency anaemia † 1	0/0	0/0	7/2820 (0.25%)	4/2816 (0.14%)
Leukocytosis † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Leukopenia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Lymphadenopathy † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Microcytic anaemia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Normocytic anaemia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pancytopenia † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Splenic haemorrhage † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cardiac disorders
Acute coronary syndrome † 1	0/0	0/0	11/2820 (0.39%)	13/2816 (0.46%)
Acute left ventricular failure † 1	0/0	0/0	9/2820 (0.32%)	6/2816 (0.21%)
Acute myocardial infarction † 1	0/0	0/0	92/2820 (3.26%)	95/2816 (3.37%)
Adams-Stokes syndrome † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Angina pectoris † 1	0/0	0/0	59/2820 (2.09%)	84/2816 (2.98%)
Angina unstable † 1	0/0	0/0	65/2820 (2.30%)	76/2816 (2.70%)
Anginal equivalent † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Aortic valve disease † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Aortic valve incompetence † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Aortic valve stenosis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Arrhythmia † 1	0/0	0/0	9/2820 (0.32%)	3/2816 (0.11%)
Arteriosclerosis coronary artery † 1	0/0	0/0	2/2820 (0.07%)	5/2816 (0.18%)
Atrial fibrillation † 1	0/0	0/0	30/2820 (1.06%)	22/2816 (0.78%)
Atrial flutter † 1	0/0	0/0	6/2820 (0.21%)	7/2816 (0.25%)
Atrial tachycardia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Atrioventricular block † 1	0/0	0/0	5/2820 (0.18%)	1/2816 (0.04%)
Atrioventricular block complete † 1	0/0	0/0	2/2820 (0.07%)	4/2816 (0.14%)
Atrioventricular block second degree † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Bradycardia † 1	0/0	0/0	6/2820 (0.21%)	4/2816 (0.14%)
Cardiac aneurysm † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Cardiac arrest † 1	0/0	0/0	24/2820 (0.85%)	31/2816 (1.10%)
Cardiac asthma † 1	0/0	0/0	2/2820 (0.07%)	3/2816 (0.11%)
Cardiac discomfort † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cardiac disorder † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Cardiac failure † 1	0/0	0/0	149/2820 (5.28%)	183/2816 (6.50%)
Cardiac failure acute † 1	0/0	0/0	28/2820 (0.99%)	22/2816 (0.78%)
Cardiac failure chronic † 1	0/0	0/0	12/2820 (0.43%)	8/2816 (0.28%)
Cardiac failure congestive † 1	0/0	0/0	27/2820 (0.96%)	37/2816 (1.31%)
Cardiac perforation † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Cardiac tamponade † 1	0/0	0/0	0/2820 (0.00%)	6/2816 (0.21%)
Cardiac ventricular thrombosis † 1	0/0	0/0	4/2820 (0.14%)	8/2816 (0.28%)
Cardio-respiratory arrest † 1	0/0	0/0	7/2820 (0.25%)	1/2816 (0.04%)
Cardiogenic shock † 1	0/0	0/0	17/2820 (0.60%)	12/2816 (0.43%)
Cardiomyopathy † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cardiopulmonary failure † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Cardiovascular disorder † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Cardiovascular insufficiency † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Chronic left ventricular failure † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Congestive cardiomyopathy † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Coronary artery disease † 1	0/0	0/0	23/2820 (0.82%)	30/2816 (1.07%)
Coronary artery insufficiency † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Coronary artery occlusion † 1	0/0	0/0	3/2820 (0.11%)	6/2816 (0.21%)
Coronary artery perforation † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Coronary artery stenosis † 1	0/0	0/0	1/2820 (0.04%)	4/2816 (0.14%)
Dressler's syndrome † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Endocarditis noninfective † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Intracardiac thrombus † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Ischaemic cardiomyopathy † 1	0/0	0/0	6/2820 (0.21%)	10/2816 (0.36%)
Left ventricular dysfunction † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Left ventricular failure † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Microvascular coronary artery disease † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Mitral valve incompetence † 1	0/0	0/0	5/2820 (0.18%)	4/2816 (0.14%)
Myocardial fibrosis † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Myocardial infarction † 1	0/0	0/0	51/2820 (1.81%)	44/2816 (1.56%)
Myocardial ischaemia † 1	0/0	0/0	9/2820 (0.32%)	9/2816 (0.32%)
Palpitations † 1	0/0	0/0	4/2820 (0.14%)	1/2816 (0.04%)
Papillary muscle disorder † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Paroxysmal atrioventricular block † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pericardial effusion † 1	0/0	0/0	2/2820 (0.07%)	6/2816 (0.21%)
Pericardial haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pericarditis † 1	0/0	0/0	6/2820 (0.21%)	8/2816 (0.28%)
Pulseless electrical activity † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Sinus bradycardia † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Sinus node dysfunction † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Supraventricular tachycardia † 1	0/0	0/0	2/2820 (0.07%)	3/2816 (0.11%)
Tachycardia † 1	0/0	0/0	3/2820 (0.11%)	1/2816 (0.04%)
Ventricle rupture † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Ventricular arrhythmia † 1	0/0	0/0	2/2820 (0.07%)	5/2816 (0.18%)
Ventricular dysfunction † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Ventricular extrasystoles † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Ventricular fibrillation † 1	0/0	0/0	12/2820 (0.43%)	11/2816 (0.39%)
Ventricular remodelling † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Ventricular tachyarrhythmia † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Ventricular tachycardia † 1	0/0	0/0	19/2820 (0.67%)	23/2816 (0.82%)
Congenital, familial and genetic disorders
Ventricular septal defect † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Ear and labyrinth disorders
Vertigo † 1	0/0	0/0	4/2820 (0.14%)	5/2816 (0.18%)
Vertigo positional † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Vestibular disorder † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Endocrine disorders
Adrenal mass † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Hyperthyroidism † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Eye disorders
Arteriosclerotic retinopathy † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Blindness unilateral † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cataract † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Diplopia † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Eye oedema † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Eye swelling † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Glaucoma † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Intraocular haematoma † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Iridocyclitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Keratitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Open angle glaucoma † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Optic ischaemic neuropathy † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Periorbital oedema † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Retinal detachment † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Rhegmatogenous retinal detachment † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Visual impairment † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Vitreous haemorrhage † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Abdominal hernia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Abdominal hernia obstructive † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Abdominal mass † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Abdominal pain † 1	0/0	0/0	8/2820 (0.28%)	5/2816 (0.18%)
Abdominal pain upper † 1	0/0	0/0	7/2820 (0.25%)	5/2816 (0.18%)
Acute abdomen † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Ascites † 1	0/0	0/0	1/2820 (0.04%)	4/2816 (0.14%)
Colitis † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Colitis ischaemic † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Constipation † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Crohn's disease † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Dental cyst † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Diarrhoea † 1	0/0	0/0	4/2820 (0.14%)	8/2816 (0.28%)
Diarrhoea haemorrhagic † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Diverticular perforation † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Diverticulum intestinal † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Diverticulum intestinal haemorrhagic † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Duodenal ulcer † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Duodenal ulcer haemorrhage † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Dyspepsia † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Dysphagia † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Enteritis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Enterocolitis † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Faeces discoloured † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Food poisoning † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Gastric haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Gastric ulcer † 1	0/0	0/0	1/2820 (0.04%)	5/2816 (0.18%)
Gastric ulcer haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Gastritis † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Gastritis erosive † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Gastritis haemorrhagic † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Gastrointestinal disorder † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Gastrointestinal haemorrhage † 1	0/0	0/0	15/2820 (0.53%)	12/2816 (0.43%)
Gastrooesophageal reflux disease † 1	0/0	0/0	4/2820 (0.14%)	2/2816 (0.07%)
Haematemesis † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Haematochezia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Haemorrhoidal haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Haemorrhoids † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Haemorrhoids thrombosed † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Ileus † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Ileus paralytic † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Impaired gastric emptying † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Inguinal hernia † 1	0/0	0/0	5/2820 (0.18%)	2/2816 (0.07%)
Intestinal haemorrhage † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Intestinal ischaemia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Intestinal obstruction † 1	0/0	0/0	0/2820 (0.00%)	3/2816 (0.11%)
Intestinal pseudo-obstruction † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Large intestinal obstruction † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Large intestine perforation † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Large intestine polyp † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Lip swelling † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Lower gastrointestinal haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Malabsorption † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Mechanical ileus † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Melaena † 1	0/0	0/0	7/2820 (0.25%)	1/2816 (0.04%)
Mesenteric arterial occlusion † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Mouth swelling † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Nausea † 1	0/0	0/0	5/2820 (0.18%)	1/2816 (0.04%)
Oesophageal achalasia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Pancreatitis † 1	0/0	0/0	0/2820 (0.00%)	3/2816 (0.11%)
Pancreatitis acute † 1	0/0	0/0	2/2820 (0.07%)	5/2816 (0.18%)
Peptic ulcer † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Peritoneal adhesions † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Rectal haemorrhage † 1	0/0	0/0	3/2820 (0.11%)	6/2816 (0.21%)
Rectal polyp † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Retroperitoneal haemorrhage † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Small intestinal obstruction † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Umbilical hernia † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Upper gastrointestinal haemorrhage † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Volvulus † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Vomiting † 1	0/0	0/0	5/2820 (0.18%)	5/2816 (0.18%)
General disorders
Adverse event † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Asthenia † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Cardiac death † 1	0/0	0/0	5/2820 (0.18%)	4/2816 (0.14%)
Chest discomfort † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Chest pain † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Complication associated with device † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Death † 1	0/0	0/0	27/2820 (0.96%)	31/2816 (1.10%)
Disease progression † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Drowning † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Exercise tolerance decreased † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Fatigue † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
General physical health deterioration † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Generalised oedema † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Hypothermia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Impaired healing † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Malaise † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Multiple organ dysfunction syndrome † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Necrosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Non-cardiac chest pain † 1	0/0	0/0	54/2820 (1.91%)	66/2816 (2.34%)
Oedema peripheral † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Polyp † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Pyrexia † 1	0/0	0/0	7/2820 (0.25%)	3/2816 (0.11%)
Sudden cardiac death † 1	0/0	0/0	10/2820 (0.35%)	14/2816 (0.50%)
Sudden death † 1	0/0	0/0	9/2820 (0.32%)	8/2816 (0.28%)
Surgical failure † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Ulcer haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Unevaluable event † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Vascular stent stenosis † 1	0/0	0/0	5/2820 (0.18%)	5/2816 (0.18%)
Vascular stent thrombosis † 1	0/0	0/0	7/2820 (0.25%)	7/2816 (0.25%)
Hepatobiliary disorders
Acute hepatic failure † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Autoimmune hepatitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Bile duct stenosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Bile duct stone † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Biliary colic † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Biliary cyst † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Biliary dilatation † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Biliary dyspepsia † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cholangitis acute † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Cholecystitis † 1	0/0	0/0	4/2820 (0.14%)	9/2816 (0.32%)
Cholecystitis acute † 1	0/0	0/0	9/2820 (0.32%)	6/2816 (0.21%)
Cholelithiasis † 1	0/0	0/0	4/2820 (0.14%)	1/2816 (0.04%)
Drug-induced liver injury † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Hepatic cirrhosis † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Hepatic failure † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Hepatic mass † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Hepatic pain † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Hepatitis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Hepatitis acute † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Ischaemic hepatitis † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Jaundice cholestatic † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Immune system disorders
Anaphylactic shock † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Contrast media allergy † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Drug hypersensitivity † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Infections and infestations
Abscess † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Abscess jaw † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Abscess limb † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Abscess oral † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Anal abscess † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Appendicitis † 1	0/0	0/0	3/2820 (0.11%)	3/2816 (0.11%)
Bacteraemia † 1	0/0	0/0	3/2820 (0.11%)	1/2816 (0.04%)
Bacterial abdominal infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Bacterial infection † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Bacterial sepsis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Biliary sepsis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Bone abscess † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Bronchitis † 1	0/0	0/0	3/2820 (0.11%)	6/2816 (0.21%)
COVID-19 † 1	0/0	0/0	13/2820 (0.46%)	16/2816 (0.57%)
COVID-19 pneumonia † 1	0/0	0/0	6/2820 (0.21%)	8/2816 (0.28%)
Carbuncle † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Cellulitis † 1	0/0	0/0	11/2820 (0.39%)	5/2816 (0.18%)
Cholangitis infective † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Clostridium difficile infection † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Coronavirus infection † 1	0/0	0/0	4/2820 (0.14%)	3/2816 (0.11%)
Cystitis † 1	0/0	0/0	7/2820 (0.25%)	2/2816 (0.07%)
Device related infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Diabetic foot infection † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Diabetic gangrene † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Diarrhoea infectious † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Diverticulitis † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Empyema † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Endocarditis † 1	0/0	0/0	3/2820 (0.11%)	0/2816 (0.00%)
Endocarditis staphylococcal † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Endometritis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Epididymitis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Erysipelas † 1	0/0	0/0	6/2820 (0.21%)	5/2816 (0.18%)
Escherichia bacteraemia † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Escherichia sepsis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Escherichia urinary tract infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Fournier's gangrene † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Gangrene † 1	0/0	0/0	3/2820 (0.11%)	5/2816 (0.18%)
Gas gangrene † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Gastroenteritis † 1	0/0	0/0	11/2820 (0.39%)	7/2816 (0.25%)
Gastroenteritis viral † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Gastrointestinal infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Genital herpes † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Haematoma infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Helicobacter duodenal ulcer † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Implant site infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Incision site abscess † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Infected dermal cyst † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Infected skin ulcer † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Infection † 1	0/0	0/0	4/2820 (0.14%)	3/2816 (0.11%)
Infective exacerbation of chronic obstructive airways disease † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Influenza † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Joint abscess † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Labyrinthitis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Liver abscess † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Localised infection † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Lower respiratory tract infection † 1	0/0	0/0	4/2820 (0.14%)	2/2816 (0.07%)
Lung abscess † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Meningitis bacterial † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Necrotising fasciitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Neutropenic sepsis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Oral candidiasis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Orchitis † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Osteomyelitis † 1	0/0	0/0	4/2820 (0.14%)	1/2816 (0.04%)
Osteomyelitis acute † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Otitis externa † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Otitis media † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Parotitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Peritonitis † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Pharyngeal abscess † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Pharyngotonsillitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pneumonia † 1	0/0	0/0	61/2820 (2.16%)	73/2816 (2.59%)
Pneumonia bacterial † 1	0/0	0/0	3/2820 (0.11%)	0/2816 (0.00%)
Pneumonia mycoplasmal † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pneumonia pneumococcal † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pneumonia staphylococcal † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Pneumonia viral † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Post procedural sepsis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Postoperative wound infection † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Pulmonary tuberculosis † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Pyelonephritis † 1	0/0	0/0	3/2820 (0.11%)	2/2816 (0.07%)
Pyelonephritis acute † 1	0/0	0/0	3/2820 (0.11%)	1/2816 (0.04%)
Pyelonephritis chronic † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Respiratory tract infection † 1	0/0	0/0	3/2820 (0.11%)	6/2816 (0.21%)
Respiratory tract infection viral † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Rhinovirus infection † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Scrotal abscess † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Sepsis † 1	0/0	0/0	19/2820 (0.67%)	13/2816 (0.46%)
Septic shock † 1	0/0	0/0	9/2820 (0.32%)	8/2816 (0.28%)
Skin infection † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Staphylococcal bacteraemia † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Staphylococcal sepsis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Suspected COVID-19 † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Tooth abscess † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Upper respiratory tract infection † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Urinary tract infection † 1	0/0	0/0	28/2820 (0.99%)	16/2816 (0.57%)
Urosepsis † 1	0/0	0/0	6/2820 (0.21%)	2/2816 (0.07%)
Vestibular neuronitis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Viral labyrinthitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Viral sepsis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Wound abscess † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Wound infection † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Wound infection bacterial † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Injury, poisoning and procedural complications
Accidental exposure to product † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Acetabulum fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Anaemia postoperative † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Anastomotic leak † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Ankle fracture † 1	/0	/0	3/2820 (0.11%)	2/2816 (0.07%)
Arterial bypass occlusion † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Arterial injury † 1	/0	/0	3/2820 (0.11%)	1/2816 (0.04%)
Cardiac function disturbance postoperative † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Cardiac procedure complication † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cardiac valve rupture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Cervical vertebral fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Chest injury † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Clavicle fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Concussion † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Contusion † 1	/0	/0	4/2820 (0.14%)	5/2816 (0.18%)
Coronary artery restenosis † 1	/0	/0	0/2820 (0.00%)	3/2816 (0.11%)
Coronary bypass thrombosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Coronary vascular graft occlusion † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Craniocerebral injury † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Electric shock † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Fall † 1	/0	/0	5/2820 (0.18%)	7/2816 (0.25%)
Femoral neck fracture † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Femur fracture † 1	/0	/0	4/2820 (0.14%)	4/2816 (0.14%)
Fibula fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Foot fracture † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Foreign body in gastrointestinal tract † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Fracture displacement † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hand fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Head injury † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Hip fracture † 1	/0	/0	2/2820 (0.07%)	3/2816 (0.11%)
Humerus fracture † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Incisional hernia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Intentional overdose † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Jaw fracture † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Joint dislocation † 1	/0	/0	0/2820 (0.00%)	3/2816 (0.11%)
Limb injury † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Lower limb fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lumbar vertebral fracture † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Muscle injury † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Muscle rupture † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Overdose † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Periorbital haemorrhage † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Periprocedural myocardial infarction † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Pneumothorax traumatic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Poisoning † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Post intensive care syndrome † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Post procedural complication † 1	/0	/0	1/2820 (0.04%)	3/2816 (0.11%)
Post procedural discharge † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Post procedural fistula † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Post procedural haematuria † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Post procedural haemorrhage † 1	/0	/0	4/2820 (0.14%)	2/2816 (0.07%)
Post procedural myocardial infarction † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Post procedural urine leak † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Prevertebral soft tissue swelling of cervical space † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Procedural complication † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Procedural haemorrhage † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pulmonary contusion † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Radius fracture † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Rib fracture † 1	/0	/0	1/2820 (0.04%)	3/2816 (0.11%)
Road traffic accident † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Skin abrasion † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Skin laceration † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Spinal compression fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Splenic rupture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Sternal fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Stomal hernia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Subcutaneous haematoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Subdural haematoma † 1	/0	/0	1/2820 (0.04%)	4/2816 (0.14%)
Subdural haemorrhage † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Thermal burn † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Thoracic vertebral fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Toxicity to various agents † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Traumatic intracranial haemorrhage † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Upper limb fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Vascular pseudoaneurysm † 1	/0	/0	3/2820 (0.11%)	3/2816 (0.11%)
Vasoplegia syndrome † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Wound dehiscence † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Wrist fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Investigations
Angiocardiogram † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Anticoagulation drug level above therapeutic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Biopsy bladder † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Biopsy prostate † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Blood creatinine increased † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Blood glucose fluctuation † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Blood glucose increased † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Blood sodium decreased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Cardiac output decreased † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cardiac ventriculogram † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Coagulation test abnormal † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Ejection fraction † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Ejection fraction abnormal † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Ejection fraction decreased † 1	/0	/0	6/2820 (0.21%)	12/2816 (0.43%)
Electrocardiogram QT prolonged † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Glycosylated haemoglobin increased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Haemoglobin decreased † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Heart rate decreased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hepatic enzyme increased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Influenza B virus test positive † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
International normalised ratio increased † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Liver function test abnormal † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Liver function test increased † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Neutrophil count decreased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Occult blood positive † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Renal function test abnormal † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
SARS-CoV-2 test positive † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Scan myocardial perfusion abnormal † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Stress echocardiogram † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Transaminases increased † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Troponin increased † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Weight decreased † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Weight increased † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Metabolism and nutrition disorders
Acidosis hyperchloraemic † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Cachexia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Decreased appetite † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Dehydration † 1	/0	/0	9/2820 (0.32%)	10/2816 (0.36%)
Diabetes mellitus † 1	/0	/0	2/2820 (0.07%)	3/2816 (0.11%)
Diabetes mellitus inadequate control † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Diabetic ketoacidosis † 1	/0	/0	3/2820 (0.11%)	2/2816 (0.07%)
Diabetic metabolic decompensation † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Electrolyte imbalance † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Euglycaemic diabetic ketoacidosis † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Fluid overload † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Food intolerance † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Gout † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Hypercalcaemia † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Hyperglycaemia † 1	/0	/0	6/2820 (0.21%)	4/2816 (0.14%)
Hyperkalaemia † 1	/0	/0	15/2820 (0.53%)	4/2816 (0.14%)
Hypertriglyceridaemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hypervolaemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hypoglycaemia † 1	/0	/0	7/2820 (0.25%)	10/2816 (0.36%)
Hypokalaemia † 1	/0	/0	5/2820 (0.18%)	3/2816 (0.11%)
Hyponatraemia † 1	/0	/0	3/2820 (0.11%)	4/2816 (0.14%)
Hypophosphataemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hypovolaemia † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Ketoacidosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lactic acidosis † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Malnutrition † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Metabolic acidosis † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Obesity † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Pseudohyponatraemia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Type 2 diabetes mellitus † 1	/0	/0	0/2820 (0.00%)	4/2816 (0.14%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	/0	/0	4/2820 (0.14%)	0/2816 (0.00%)
Arthritis † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Arthritis reactive † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Back disorder † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Back pain † 1	/0	/0	2/2820 (0.07%)	3/2816 (0.11%)
Bursitis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Chondrocalcinosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Costochondritis † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Deformity thorax † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Enthesopathy † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Fistula discharge † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Gouty arthritis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Haemarthrosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Intervertebral disc degeneration † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Intervertebral disc disorder † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Intervertebral disc protrusion † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lumbar spinal stenosis † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Mobility decreased † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Muscular weakness † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Musculoskeletal chest pain † 1	/0	/0	5/2820 (0.18%)	5/2816 (0.18%)
Musculoskeletal pain † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Myalgia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Osteitis † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Osteoarthritis † 1	/0	/0	3/2820 (0.11%)	6/2816 (0.21%)
Osteochondrosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Osteoporotic fracture † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pain in extremity † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pathological fracture † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Periostosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Polyarthritis † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Polymyalgia rheumatica † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Pseudarthrosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Rhabdomyolysis † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Spinal osteoarthritis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Adenocarcinoma of colon † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Adenocarcinoma pancreas † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Anaplastic meningioma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
B-cell lymphoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
B-cell small lymphocytic lymphoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
B-cell unclassifiable lymphoma low grade † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Basal cell carcinoma † 1	/0	/0	4/2820 (0.14%)	3/2816 (0.11%)
Benign duodenal neoplasm † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Bladder cancer † 1	/0	/0	4/2820 (0.14%)	0/2816 (0.00%)
Bladder neoplasm † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Bladder transitional cell carcinoma † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Bowen's disease † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Breast cancer † 1	/0	/0	3/2820 (0.11%)	1/2816 (0.04%)
Breast cancer stage II † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Bronchial carcinoma † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Cholangiocarcinoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Chronic lymphocytic leukaemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Chronic myeloid leukaemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Clear cell renal cell carcinoma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Colon cancer † 1	/0	/0	1/2820 (0.04%)	5/2816 (0.18%)
Colon neoplasm † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Colorectal adenocarcinoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Colorectal cancer † 1	/0	/0	3/2820 (0.11%)	1/2816 (0.04%)
Endometrial cancer † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Gallbladder adenosquamous carcinoma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Gallbladder cancer † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Gastric cancer † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Gastric neoplasm † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Gastrointestinal carcinoma † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Gastrointestinal neoplasm † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Glioblastoma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Haemangioma of liver † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hepatic cancer † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Hepatocellular carcinoma † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Hypopharyngeal cancer † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Infected neoplasm † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Keratoacanthoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Laryngeal cancer † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Laryngeal squamous cell carcinoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Lip squamous cell carcinoma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lung adenocarcinoma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lung cancer metastatic † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Lung neoplasm † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Lung neoplasm malignant † 1	/0	/0	2/2820 (0.07%)	5/2816 (0.18%)
Lung squamous cell carcinoma metastatic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lymphangiosis carcinomatosa † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Malignant melanoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Malignant neoplasm of pleura † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Malignant peritoneal neoplasm † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Marginal zone lymphoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Meningioma † 1	/0	/0	0/2820 (0.00%)	3/2816 (0.11%)
Metastases to liver † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Metastases to lymph nodes † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Metastasis † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Metastatic malignant melanoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Metastatic neoplasm † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Monoclonal gammopathy † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Myeloproliferative neoplasm † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Myxoid liposarcoma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Neoplasm malignant † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Neoplasm progression † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Neuroendocrine carcinoma † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Non-small cell lung cancer † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Oesophageal carcinoma † 1	/0	/0	3/2820 (0.11%)	0/2816 (0.00%)
Oropharyngeal cancer † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pancreatic carcinoma † 1	/0	/0	3/2820 (0.11%)	0/2816 (0.00%)
Papillary cystadenoma lymphomatosum † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Pleural mesothelioma malignant † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Prostate cancer † 1	/0	/0	5/2820 (0.18%)	3/2816 (0.11%)
Prostate cancer metastatic † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Rectal adenocarcinoma † 1	/0	/0	3/2820 (0.11%)	1/2816 (0.04%)
Rectal cancer † 1	/0	/0	4/2820 (0.14%)	1/2816 (0.04%)
Rectal neoplasm † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Renal cancer metastatic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Squamous cell carcinoma † 1	/0	/0	1/2820 (0.04%)	3/2816 (0.11%)
Squamous cell carcinoma of skin † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Squamous cell carcinoma of the parotid gland † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Testicular neoplasm † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Transitional cell cancer of the renal pelvis and ureter † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Transitional cell carcinoma † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Tumour haemorrhage † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Vulval cancer † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Nervous system disorders
Arachnoid cyst † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Ataxia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Brain stem ischaemia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Carotid artery occlusion † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Carotid artery stenosis † 1	/0	/0	5/2820 (0.18%)	2/2816 (0.07%)
Cerebellar infarction † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cerebral haemorrhage † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Cerebral hypoperfusion † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cerebral infarction † 1	/0	/0	8/2820 (0.28%)	9/2816 (0.32%)
Cerebral ischaemia † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Cerebral venous sinus thrombosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cerebrovascular accident † 1	/0	/0	32/2820 (1.13%)	33/2816 (1.17%)
Cerebrovascular disorder † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cerebrovascular insufficiency † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cervical radiculopathy † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cervicobrachial syndrome † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Demyelinating polyneuropathy † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Disturbance in attention † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Dizziness † 1	/0	/0	7/2820 (0.25%)	3/2816 (0.11%)
Dizziness postural † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Dysarthria † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Embolic stroke † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Encephalopathy † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Epilepsy † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Facial paralysis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Generalised tonic-clonic seizure † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Haemorrhage intracranial † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Haemorrhagic stroke † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Haemorrhagic transformation stroke † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Headache † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Hemianopia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Hemiparesis † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Hypoaesthesia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Hypoglycaemic coma † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hypoxic-ischaemic encephalopathy † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Irregular sleep wake rhythm disorder † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Ischaemic stroke † 1	/0	/0	12/2820 (0.43%)	15/2816 (0.53%)
Lacunar infarction † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lacunar stroke † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Loss of consciousness † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Metabolic encephalopathy † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Migraine † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Moyamoya disease † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Neuropathy peripheral † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Paraesthesia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Partial seizures † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Polyneuropathy † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Post stroke seizure † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Presyncope † 1	/0	/0	9/2820 (0.32%)	4/2816 (0.14%)
Psychogenic seizure † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Radiculopathy † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Sciatica † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Seizure † 1	/0	/0	2/2820 (0.07%)	6/2816 (0.21%)
Spinal cord haemorrhage † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Status epilepticus † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Subarachnoid haemorrhage † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Subdural hygroma † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Syncope † 1	/0	/0	36/2820 (1.28%)	30/2816 (1.07%)
Transient ischaemic attack † 1	/0	/0	9/2820 (0.32%)	10/2816 (0.36%)
Vertebrobasilar insufficiency † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Pre-eclampsia † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Product Issues
Device breakage † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Device defective † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Device dislocation † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Device failure † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Device fastener issue † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Device malfunction † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Device occlusion † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Lead dislodgement † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Psychiatric disorders
Anxiety † 1	/0	/0	2/2820 (0.07%)	5/2816 (0.18%)
Completed suicide † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Confusional state † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Delirium † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Delusion † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Depression † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Depression suicidal † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Disorientation † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Hallucination † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Intentional self-injury † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Major depression † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Mental status changes † 1	/0	/0	2/2820 (0.07%)	2/2816 (0.07%)
Personality change due to a general medical condition † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Psychiatric decompensation † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Restlessness † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Suicidal ideation † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Renal and urinary disorders
Acute kidney injury † 1	/0	/0	37/2820 (1.31%)	30/2816 (1.07%)
Anuria † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Azotaemia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Bladder tamponade † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Calculus bladder † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Chronic kidney disease † 1	/0	/0	5/2820 (0.18%)	1/2816 (0.04%)
Dysuria † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
End stage renal disease † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Haematuria † 1	/0	/0	9/2820 (0.32%)	7/2816 (0.25%)
Haemorrhage urinary tract † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Hydronephrosis † 1	/0	/0	3/2820 (0.11%)	2/2816 (0.07%)
Nephrolithiasis † 1	/0	/0	1/2820 (0.04%)	3/2816 (0.11%)
Nephrotic syndrome † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Renal colic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Renal failure † 1	/0	/0	10/2820 (0.35%)	8/2816 (0.28%)
Renal haematoma † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Renal impairment † 1	/0	/0	14/2820 (0.50%)	6/2816 (0.21%)
Ureteric obstruction † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Ureteric stenosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Ureterolithiasis † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Urethral obstruction † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Urethral stenosis † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Urinary bladder polyp † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Urinary retention † 1	/0	/0	6/2820 (0.21%)	1/2816 (0.04%)
Reproductive system and breast disorders
Benign prostatic hyperplasia † 1	/0	/0	4/2820 (0.14%)	1/2816 (0.04%)
Breast necrosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Breast pain † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Cervical polyp † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Female genital tract fistula † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Hysterocele † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Ovarian cyst † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Postmenopausal haemorrhage † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Prostatomegaly † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Scrotal oedema † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Uterine haemorrhage † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Uterine polyp † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Uterine prolapse † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema † 1	/0	/0	19/2820 (0.67%)	13/2816 (0.46%)
Acute respiratory failure † 1	/0	/0	7/2820 (0.25%)	5/2816 (0.18%)
Asphyxia † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Aspiration † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Asthma † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Atelectasis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Chronic obstructive pulmonary disease † 1	/0	/0	14/2820 (0.50%)	13/2816 (0.46%)
Cough † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Dyspnoea † 1	/0	/0	34/2820 (1.21%)	28/2816 (0.99%)
Dyspnoea at rest † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Dyspnoea exertional † 1	/0	/0	6/2820 (0.21%)	2/2816 (0.07%)
Dyspnoea paroxysmal nocturnal † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Epistaxis † 1	/0	/0	1/2820 (0.04%)	7/2816 (0.25%)
Haemoptysis † 1	/0	/0	1/2820 (0.04%)	4/2816 (0.14%)
Haemothorax † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Hydrothorax † 1	/0	/0	4/2820 (0.14%)	1/2816 (0.04%)
Hypoxia † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Interstitial lung disease † 1	/0	/0	0/2820 (0.00%)	3/2816 (0.11%)
Lung consolidation † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Lung disorder † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Orthopnoea † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Painful respiration † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pleural effusion † 1	/0	/0	4/2820 (0.14%)	6/2816 (0.21%)
Pneumonia aspiration † 1	/0	/0	1/2820 (0.04%)	2/2816 (0.07%)
Pneumonitis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pneumothorax † 1	/0	/0	2/2820 (0.07%)	1/2816 (0.04%)
Pulmonary alveolar haemorrhage † 1	/0	/0	0/2820 (0.00%)	2/2816 (0.07%)
Pulmonary artery thrombosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Pulmonary congestion † 1	/0	/0	0/2820 (0.00%)	3/2816 (0.11%)
Pulmonary embolism † 1	/0	/0	8/2820 (0.28%)	5/2816 (0.18%)
Pulmonary hypertension † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Pulmonary mass † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Pulmonary oedema † 1	/0	/0	12/2820 (0.43%)	13/2816 (0.46%)
Pulmonary pain † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Respiratory distress † 1	/0	/0	1/2820 (0.04%)	1/2816 (0.04%)
Respiratory failure † 1	/0	/0	11/2820 (0.39%)	11/2816 (0.39%)
Sleep apnoea syndrome † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Tracheal stenosis † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Skin and subcutaneous tissue disorders
Angioedema † 1	/0	/0	4/2820 (0.14%)	5/2816 (0.18%)
Decubitus ulcer † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Dermatitis allergic † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Diabetic foot † 1	/0	/0	6/2820 (0.21%)	3/2816 (0.11%)
Diabetic wound † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Eczema † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Hyperhidrosis † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Pruritus † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Rash † 1	/0	/0	2/2820 (0.07%)	0/2816 (0.00%)
Rash maculo-papular † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Skin ulcer † 1	/0	/0	3/2820 (0.11%)	0/2816 (0.00%)
Symmetrical drug-related intertriginous and flexural exanthema † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Urticaria † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Social circumstances
Alcoholic † 1	/0	/0	1/2820 (0.04%)	0/2816 (0.00%)
Immobile † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Imprisonment † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Surgical and medical procedures
Cardiac pacemaker insertion † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Transcatheter aortic valve implantation † 1	/0	/0	0/2820 (0.00%)	1/2816 (0.04%)
Vascular disorders
Aneurysm ruptured † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Angiodysplasia † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Aortic aneurysm † 1	0/0	0/0	2/2820 (0.07%)	0/2816 (0.00%)
Aortic dissection † 1	0/0	0/0	0/2820 (0.00%)	3/2816 (0.11%)
Aortic occlusion † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Aortic stenosis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Arterial haemorrhage † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Arterial occlusive disease † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Arterial stenosis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Arterial thrombosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Arteriosclerosis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Brachiocephalic arteriosclerosis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Circulatory collapse † 1	0/0	0/0	0/2820 (0.00%)	3/2816 (0.11%)
Deep vein thrombosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Distributive shock † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Embolism arterial † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Extremity necrosis † 1	0/0	0/0	4/2820 (0.14%)	1/2816 (0.04%)
Femoral artery aneurysm † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Haematoma † 1	0/0	0/0	1/2820 (0.04%)	7/2816 (0.25%)
Hypertension † 1	0/0	0/0	6/2820 (0.21%)	9/2816 (0.32%)
Hypertensive crisis † 1	0/0	0/0	4/2820 (0.14%)	3/2816 (0.11%)
Hypertensive emergency † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Hypertensive urgency † 1	0/0	0/0	2/2820 (0.07%)	2/2816 (0.07%)
Hypotension † 1	0/0	0/0	37/2820 (1.31%)	15/2816 (0.53%)
Hypovolaemic shock † 1	0/0	0/0	2/2820 (0.07%)	1/2816 (0.04%)
Iliac artery occlusion † 1	0/0	0/0	1/2820 (0.04%)	2/2816 (0.07%)
Iliac artery stenosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Intermittent claudication † 1	0/0	0/0	1/2820 (0.04%)	3/2816 (0.11%)
Ischaemic limb pain † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Jugular vein thrombosis † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Obstructive shock † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Orthostatic hypotension † 1	0/0	0/0	5/2820 (0.18%)	3/2816 (0.11%)
Peripheral arterial occlusive disease † 1	0/0	0/0	7/2820 (0.25%)	9/2816 (0.32%)
Peripheral artery aneurysm † 1	0/0	0/0	0/2820 (0.00%)	2/2816 (0.07%)
Peripheral artery occlusion † 1	0/0	0/0	3/2820 (0.11%)	0/2816 (0.00%)
Peripheral artery stenosis † 1	0/0	0/0	3/2820 (0.11%)	0/2816 (0.00%)
Peripheral artery thrombosis † 1	0/0	0/0	3/2820 (0.11%)	1/2816 (0.04%)
Peripheral ischaemia † 1	0/0	0/0	6/2820 (0.21%)	9/2816 (0.32%)
Peripheral vascular disorder † 1	0/0	0/0	4/2820 (0.14%)	1/2816 (0.04%)
Phlebitis † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Reperfusion injury † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Subclavian artery occlusion † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Thrombophlebitis † 1	0/0	0/0	1/2820 (0.04%)	1/2816 (0.04%)
Thrombophlebitis superficial † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
Venous aneurysm † 1	0/0	0/0	0/2820 (0.00%)	1/2816 (0.04%)
Venous haemorrhage † 1	0/0	0/0	1/2820 (0.04%)	0/2816 (0.00%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	LCZ696 Pre-treatment	Ramipril Pre-treatment	LCZ696	Ramipril
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0	1769/2820 (62.73%)	1770/2816 (62.86%)
Blood and lymphatic system disorders
Anaemia † 1	0/0	0/0	130/2820 (4.61%)	123/2816 (4.37%)
Cardiac disorders
Angina pectoris † 1	0/0	0/0	125/2820 (4.43%)	140/2816 (4.97%)
Atrial fibrillation † 1	0/0	0/0	85/2820 (3.01%)	87/2816 (3.09%)
Cardiac failure † 1	0/0	0/0	128/2820 (4.54%)	150/2816 (5.33%)
Gastrointestinal disorders
Abdominal pain upper † 1	0/0	0/0	42/2820 (1.49%)	57/2816 (2.02%)
Constipation † 1	0/0	0/0	70/2820 (2.48%)	99/2816 (3.52%)
Diarrhoea † 1	0/0	0/0	227/2820 (8.05%)	179/2816 (6.36%)
Nausea † 1	0/0	0/0	93/2820 (3.30%)	101/2816 (3.59%)
General disorders
Asthenia † 1	0/0	0/0	67/2820 (2.38%)	58/2816 (2.06%)
Fatigue † 1	0/0	0/0	125/2820 (4.43%)	136/2816 (4.83%)
Non-cardiac chest pain † 1	0/0	0/0	183/2820 (6.49%)	156/2816 (5.54%)
Oedema peripheral † 1	0/0	0/0	122/2820 (4.33%)	125/2816 (4.44%)
Infections and infestations
Nasopharyngitis † 1	0/0	0/0	107/2820 (3.79%)	72/2816 (2.56%)
Pneumonia † 1	0/0	0/0	58/2820 (2.06%)	66/2816 (2.34%)
Upper respiratory tract infection † 1	0/0	0/0	54/2820 (1.91%)	57/2816 (2.02%)
Urinary tract infection † 1	0/0	0/0	97/2820 (3.44%)	95/2816 (3.37%)
Investigations
Blood creatinine increased † 1	0/0	0/0	51/2820 (1.81%)	58/2816 (2.06%)
Metabolism and nutrition disorders
Hyperkalaemia † 1	0/0	0/0	256/2820 (9.08%)	249/2816 (8.84%)
Hypokalaemia † 1	0/0	0/0	76/2820 (2.70%)	56/2816 (1.99%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/0	0/0	114/2820 (4.04%)	103/2816 (3.66%)
Back pain † 1	0/0	0/0	72/2820 (2.55%)	103/2816 (3.66%)
Myalgia † 1	0/0	0/0	70/2820 (2.48%)	80/2816 (2.84%)
Pain in extremity † 1	0/0	0/0	88/2820 (3.12%)	95/2816 (3.37%)
Nervous system disorders
Dizziness † 1	0/0	0/0	280/2820 (9.93%)	241/2816 (8.56%)
Headache † 1	0/0	0/0	78/2820 (2.77%)	69/2816 (2.45%)
Syncope † 1	0/0	0/0	52/2820 (1.84%)	57/2816 (2.02%)
Psychiatric disorders
Insomnia † 1	0/0	0/0	53/2820 (1.88%)	74/2816 (2.63%)
Renal and urinary disorders
Renal failure † 1	0/0	0/0	58/2820 (2.06%)	50/2816 (1.78%)
Renal impairment † 1	0/0	0/0	124/2820 (4.40%)	129/2816 (4.58%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/0	0/0	239/2820 (8.48%)	359/2816 (12.75%)
Dyspnoea † 1	0/0	0/0	185/2820 (6.56%)	251/2816 (8.91%)
Dyspnoea exertional † 1	0/0	0/0	63/2820 (2.23%)	51/2816 (1.81%)
Epistaxis † 1	0/0	0/0	60/2820 (2.13%)	79/2816 (2.81%)
Skin and subcutaneous tissue disorders
Rash † 1	0/0	0/0	72/2820 (2.55%)	59/2816 (2.10%)
Vascular disorders
Hypertension † 1	0/0	0/0	96/2820 (3.40%)	143/2816 (5.08%)
Hypotension † 1	0/0	0/0	447/2820 (15.85%)	288/2816 (10.23%)
Orthostatic hypotension † 1	0/0	0/0	66/2820 (2.34%)	32/2816 (1.14%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

In this study there were 25 patients who did not take study treatment after randomization, and thus were not included in the safety set.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mehran R, Steg PG, Pfeffer MA, Jering K, Claggett B, Lewis EF, Granger C, Kober L, Maggioni A, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Ducrocq G, Berwanger O, De Pasquale CG, Landmesser U, Petrie M, Leng DSK, van der Meer P, Lefkowitz M, Zhou Y, Braunwald E. The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial. Circulation. 2022 Dec 6;146(23):1749-1757. doi: 10.1161/CIRCULATIONAHA.122.060841. Epub 2022 Nov 2.

Shah AM, Claggett B, Prasad N, Li G, Volquez M, Jering K, Cikes M, Kovacs A, Mullens W, Nicolau JC, Kober L, van der Meer P, Jhund PS, Ibram G, Lefkowitz M, Zhou Y, Solomon SD, Pfeffer MA. Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy. Circulation. 2022 Oct 4;146(14):1067-1081. doi: 10.1161/CIRCULATIONAHA.122.059210. Epub 2022 Sep 9.

Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, Fernandez A, Filippatos G, Jering K, Landmesser U, Menon V, Merkely B, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Wang Y, Braunwald E. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial. Circulation. 2022 Jan 4;145(1):87-89. doi: 10.1161/CIRCULATIONAHA.121.057429. Epub 2021 Nov 19. No abstract available.

Pfeffer MA, Claggett B, Lewis EF, Granger CB, Kober L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, East C, Fernandez A, Jering K, Landmesser U, Mehran R, Merkely B, Vaghaiwalla Mody F, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Gong J, Braunwald E; PARADISE-MI Investigators and Committees. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. N Engl J Med. 2021 Nov 11;385(20):1845-1855. doi: 10.1056/NEJMoa2104508. Erratum In: N Engl J Med. 2021 Dec 30;385(27):2592.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT02924727
• Other Study ID Numbers: CLCZ696G2301; 2016-002154-20 ( EudraCT Number )
• First Submitted: October 4, 2016
• First Posted: October 5, 2016
• Results First Submitted: January 20, 2022
• Results First Posted: June 22, 2023
• Last Update Posted: June 22, 2023