Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (DAPA-HF)

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ClinicalTrials.gov Identifier: NCT03036124

Recruitment Status : Completed

First Posted : January 30, 2017

Results First Posted : September 1, 2020

Last Update Posted : September 1, 2020

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
Interventions	Drug: Dapagliflozin Drug: Placebo
Enrollment	4744

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Dapa 10mg	Placebo
Arm/Group Description	Dapagliflozin 10 mg, given once dai...	Placebo tablet to match dapaglifloz...
Arm/Group Description	Dapagliflozin 10 mg, given once daily per oral use.	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Period Title: Overall Study
Started	2373	2371
Completed	2368	2365
Not Completed	5	6
Reason Not Completed
Lost to Follow-up	0	2
Withdrawal by Subject	5	4

Baseline Characteristics

Arm/Group Title		Dapa 10mg	Placebo	Total
Arm/Group Description		Dapagliflozin 10 mg, given once dai...	Placebo tablet to match dapaglifloz...	Total of all reporting groups
Arm/Group Description		Dapagliflozin 10 mg, given once daily per oral use.	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.	Total of all reporting groups
Overall Number of Baseline Participants		2373	2371	4744
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	2373 participants	2371 participants	4744 participants
		66.2 (11.0)	66.5 (10.8)	66.3 (10.9)
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	<=50	208 8.8%	188 7.9%	396 8.3%
	>50	2165 91.2%	2183 92.1%	4348 91.7%
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	<=65	1032 43.5%	998 42.1%	2030 42.8%
	>65	1341 56.5%	1373 57.9%	2714 57.2%
Age, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	<=65	1032 43.5%	998 42.1%	2030 42.8%
	66 - 75	825 34.8%	886 37.4%	1711 36.1%
	>75	516 21.7%	487 20.5%	1003 21.1%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	Female	564 23.8%	545 23.0%	1109 23.4%
	Male	1809 76.2%	1826 77.0%	3635 76.6%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	Hispanic or Latino	381 16.1%	387 16.3%	768 16.2%
	Not Hispanic or Latino	1992 83.9%	1984 83.7%	3976 83.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	White	1662 70.0%	1671 70.5%	3333 70.3%
	Black or African American	122 5.1%	104 4.4%	226 4.8%
	Asian	552 23.3%	564 23.8%	1116 23.5%
	Native Hawaiian or other Pacific Islander	0 0.0%	2 0.1%	2 0.0%
	American Indian or Alaska Native	3 0.1%	1 0.0%	4 0.1%
	Other	34 1.4%	29 1.2%	63 1.3%
Main etiology of HF Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	Ischaemic	1316 55.5%	1358 57.3%	2674 56.4%
	Non-Ischaemic	857 36.1%	830 35.0%	1687 35.6%
	Unknown	200 8.4%	183 7.7%	383 8.1%
Prior HF hospitalization Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	Yes	1124 47.4%	1127 47.5%	2251 47.4%
NYHA class at enrollment ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	II	1606 67.7%	1597 67.4%	3203 67.5%
	III	747 31.5%	751 31.7%	1498 31.6%
	IV	20 0.8%	23 1.0%	43 0.9%
		[1] Measure Description: New York Heart Association (NYHA) Functional Classification places patients in one of four categories based on how much they are limited during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath and/or angina. A higher class means a worse functional condition.
Type 2 diabetes at baseline Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	2373 participants	2371 participants	4744 participants
	Yes	1075 45.3%	1064 44.9%	2139 45.1%
	No	1298 54.7%	1307 55.1%	2605 54.9%
LVEF Mean (Standard Deviation) Unit of measure: Percentage of blood leaving the heart
	Number Analyzed	2373 participants	2371 participants	4744 participants
		31.2 (6.7)	30.9 (6.9)	31.1 (6.8)

Outcome Measures

1.Primary Outcome


Title	Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure or Urgent Visit Due to Heart Failure.
Description	Primary efficacy
Description	Primary efficacy
Time Frame	Up to 27.8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Measure Type: Count of Participants Unit of Measure: Participants
	386 16.3%	502 21.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Stratified by Type 2 Diabetes status at randomization and including the history of hospitalizations due to Heart failure as a factor.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	95% 0.65 to 0.85
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Subjects Included in the Composite Endpoint of CV Death or Hospitalization Due to Heart Failure.
Description	Secondary
Description	Secondary
Time Frame	Up to 27.8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Measure Type: Count of Participants Unit of Measure: Participants
	382 16.1%	495 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Stratified by Type 2 Diabetes status at randomization and including the history of hospitalizations due to Heart failure as a factor.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	95% 0.65 to 0.85
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Events Included in the Composite Endpoint of Recurrent Hospitalizations Due to Heart Failure and CV Death.
Description	Secondary
Description	Secondary
Time Frame	Up to 27.8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Measure Type: Number Unit of Measure: events
	567	742

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	LWYY proportional rates model
	Comments	Stratified by Type 2 Diabetes status at randomization and including the history of hospitalizations due to Heart failure as a factor.

Method of Estimation	Estimation Parameter	Rate Ratio (RR)
	Estimated Value	0.75
	Confidence Interval	95% 0.65 to 0.88
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change From Baseline in the KCCQ Total Symptom Score
Description	KCCQ is a 23-item, self-administered instrument that quantifies physic...
Description	KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ total symptom score incorporates the symptom domains into a single score. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Time Frame	Baseline and 8 months or death before 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Mean (Standard Deviation) Unit of Measure: Scores on a scale
	6.1 (18.6)	3.3 (19.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	The p-value is obtained from a rank ANCOVA adjusted for baseline KCCQ score and stratified by T2DM status at randomization.
	Method	Win Ratio
	Comments	Stratified by Type 2 Diabetes status at randomization and including baseline score as a covariate.

Method of Estimation	Estimation Parameter	Win Ratio (WR)
	Estimated Value	1.18
	Confidence Interval	95% 1.11 to 1.26
	Estimation Comments	The composite of change from baseline in total symptom score at 8 months, or death before 8 months.

5.Secondary Outcome


Title	Subjects Included in the Composite Endpoint of ≥50% Sustained Decline in eGFR, ESRD or Renal Death.
Description	Secondary
Description	Secondary
Time Frame	Up to 27.8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Measure Type: Count of Participants Unit of Measure: Participants
	28 1.2%	39 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.1681
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Stratified by Type 2 Diabetes status at randomization and including baseline eGFR as a covariate.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	95% 0.44 to 1.16
	Estimation Comments	[Not Specified]

6.Secondary Outcome


Title	Subjects Included in the Endpoint of All-cause Mortality.
Description	Secondary
Description	Secondary
Time Frame	Up to 27.8 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dapa 10 mg	Placebo
Arm/Group Description:	Dapagliflozin 10 mg tablets adminis...	Placebo tablet to match dapaglifloz...
Arm/Group Description:	Dapagliflozin 10 mg tablets administered orally once daily	Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
Overall Number of Participants Analyzed	2373	2371
Measure Type: Count of Participants Unit of Measure: Participants
	276 11.6%	329 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0217
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	Stratified by Type 2 Diabetes status at randomization.

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	95% 0.71 to 0.97
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Up to 28.3 months.
Adverse Event Reporting Description	For analysis of Adverse Events Safety analysis set is used. Safety analysis set : Consisted of all randomized patients who received at least one dose of study drug.

Arm/Group Title	Dapa 10mg		Placebo
Arm/Group Description	Dapagliflozin 10 mg, given once dai...		Placebo tablet to match dapaglifloz...
Arm/Group Description	Dapagliflozin 10 mg, given once daily per oral use.		Placebo tablet to match dapagliflozin 10 mg, given once daily per oral use.
All-Cause Mortality
	Dapa 10mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	286/2368 (12.08%)		333/2368 (14.06%)
Serious Adverse Events Serious Adverse Events
	Dapa 10mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	895/2368 (37.80%)		994/2368 (41.98%)
Blood and lymphatic system disorders
Anaemia ^† 1	3/2368 (0.13%)	4	11/2368 (0.46%)	13
Blood loss anaemia ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Coagulopathy ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Febrile neutropenia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Iron deficiency anaemia ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Leukopenia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Splenic infarction ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	5/2368 (0.21%)	6	3/2368 (0.13%)	3
Acute left ventricular failure ^† 1	2/2368 (0.08%)	2	5/2368 (0.21%)	5
Acute myocardial infarction ^† 1	37/2368 (1.56%)	37	38/2368 (1.60%)	40
Angina pectoris ^† 1	12/2368 (0.51%)	12	12/2368 (0.51%)	12
Angina unstable ^† 1	21/2368 (0.89%)	24	30/2368 (1.27%)	31
Aortic valve incompetence ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Aortic valve stenosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Arrhythmia ^† 1	2/2368 (0.08%)	2	8/2368 (0.34%)	8
Arteriosclerosis coronary artery ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Atrial fibrillation ^† 1	26/2368 (1.10%)	27	39/2368 (1.65%)	43
Atrial flutter ^† 1	8/2368 (0.34%)	9	3/2368 (0.13%)	3
Atrial tachycardia ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Atrial thrombosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Atrioventricular block complete ^† 1	3/2368 (0.13%)	3	4/2368 (0.17%)	4
Atrioventricular block second degree ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Bradyarrhythmia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Bradycardia ^† 1	2/2368 (0.08%)	2	7/2368 (0.30%)	7
Bundle branch block left ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac aneurysm ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac arrest ^† 1	9/2368 (0.38%)	9	10/2368 (0.42%)	10
Cardiac disorder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac failure ^† 1	262/2368 (11.06%)	380	351/2368 (14.82%)	523
Cardiac failure acute ^† 1	42/2368 (1.77%)	58	59/2368 (2.49%)	75
Cardiac failure chronic ^† 1	27/2368 (1.14%)	32	33/2368 (1.39%)	46
Cardiac failure congestive ^† 1	65/2368 (2.74%)	102	70/2368 (2.96%)	106
Cardiac tamponade ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac valve disease ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cardio-respiratory arrest ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Cardiogenic shock ^† 1	9/2368 (0.38%)	10	15/2368 (0.63%)	16
Cardiomyopathy ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Cardiopulmonary failure ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Cardiorenal syndrome ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Cardiovascular insufficiency ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Chronic left ventricular failure ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Congestive cardiomyopathy ^† 1	2/2368 (0.08%)	2	4/2368 (0.17%)	4
Coronary artery disease ^† 1	9/2368 (0.38%)	10	8/2368 (0.34%)	8
Coronary artery insufficiency ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Coronary artery stenosis ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Extrasystoles ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Frederick's syndrome ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ischaemic cardiomyopathy ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Left ventricular dysfunction ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Left ventricular failure ^† 1	2/2368 (0.08%)	2	4/2368 (0.17%)	5
Low cardiac output syndrome ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Mitral valve incompetence ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Myocardial fibrosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Myocardial infarction ^† 1	16/2368 (0.68%)	16	17/2368 (0.72%)	17
Myocardial ischaemia ^† 1	3/2368 (0.13%)	3	4/2368 (0.17%)	4
Palpitations ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Pericardial effusion ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Pericarditis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Prosthetic cardiac valve thrombosis ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Pulseless electrical activity ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Right ventricular failure ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Sinus node dysfunction ^† 1	3/2368 (0.13%)	3	1/2368 (0.04%)	1
Sinus tachycardia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Supraventricular tachycardia ^† 1	3/2368 (0.13%)	3	3/2368 (0.13%)	3
Tachyarrhythmia ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Tachycardia ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Torsade de pointes ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Tricuspid valve incompetence ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ventricular arrhythmia ^† 1	6/2368 (0.25%)	6	7/2368 (0.30%)	8
Ventricular extrasystoles ^† 1	4/2368 (0.17%)	4	1/2368 (0.04%)	1
Ventricular fibrillation ^† 1	11/2368 (0.46%)	11	6/2368 (0.25%)	7
Ventricular tachyarrhythmia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ventricular tachycardia ^† 1	34/2368 (1.44%)	41	54/2368 (2.28%)	65
Ear and labyrinth disorders
Vertigo ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Vertigo positional ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Vestibular disorder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Endocrine disorders
Hyperthyroidism ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Hypothyroidism ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Eye disorders
Angle closure glaucoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cataract ^† 1	4/2368 (0.17%)	4	8/2368 (0.34%)	8
Diabetic retinopathy ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Glaucoma ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Optic ischaemic neuropathy ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Retinal artery occlusion ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Retinal detachment ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Strabismus ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vision blurred ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vitreous haemorrhage ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Gastrointestinal disorders
Abdominal adhesions ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Abdominal distension ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Abdominal pain ^† 1	4/2368 (0.17%)	4	3/2368 (0.13%)	4
Abdominal wall haematoma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Ascites ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Chronic gastritis ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Constipation ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Diarrhoea ^† 1	4/2368 (0.17%)	4	4/2368 (0.17%)	4
Diverticulum intestinal ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Diverticulum intestinal haemorrhagic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Duodenal ulcer haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Duodenal ulcer perforation ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Duodenitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Dyspepsia ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Enteritis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastric haemorrhage ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Gastric ulcer ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Gastric ulcer haemorrhage ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Gastritis ^† 1	2/2368 (0.08%)	2	5/2368 (0.21%)	5
Gastritis erosive ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Gastritis haemorrhagic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Gastrointestinal angiectasia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastrointestinal angiodysplasia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Gastrointestinal disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastrointestinal haemorrhage ^† 1	4/2368 (0.17%)	5	7/2368 (0.30%)	7
Gastrointestinal obstruction ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastrointestinal polyp haemorrhage ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Gastrointestinal ulcer ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastrooesophageal reflux disease ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Haematemesis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Haematochezia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Haemorrhoidal haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Ileus ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Ileus paralytic ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Inguinal hernia ^† 1	9/2368 (0.38%)	9	5/2368 (0.21%)	5
Intestinal haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Intestinal ischaemia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Intestinal obstruction ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Intestinal perforation ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Large intestine polyp ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Lower gastrointestinal haemorrhage ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Megacolon ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Melaena ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Mesenteric artery thrombosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Nausea ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Obstructive pancreatitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Oesophageal ulcer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pancreatic disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pancreatic mass ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pancreatitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pancreatitis acute ^† 1	6/2368 (0.25%)	6	4/2368 (0.17%)	4
Pancreatitis chronic ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Rectal polyp ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Retroperitoneal haemorrhage ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Small intestinal obstruction ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Thrombosis mesenteric vessel ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Umbilical hernia ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Vomiting ^† 1	1/2368 (0.04%)	1	4/2368 (0.17%)	4
General disorders
Asthenia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cardiac death ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Chest discomfort ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Chest pain ^† 1	4/2368 (0.17%)	4	5/2368 (0.21%)	5
Complication associated with device ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Death ^† 1	48/2368 (2.03%)	48	48/2368 (2.03%)	48
General physical health deterioration ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Implant site haemorrhage ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Malaise ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Medical device site inflammation ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Multiple organ dysfunction syndrome ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Necrosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Non-cardiac chest pain ^† 1	6/2368 (0.25%)	6	16/2368 (0.68%)	19
Pyrexia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Sudden cardiac death ^† 1	18/2368 (0.76%)	18	27/2368 (1.14%)	27
Sudden death ^† 1	19/2368 (0.80%)	19	10/2368 (0.42%)	10
Ulcer haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vascular stent occlusion ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Vascular stent stenosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vascular stent thrombosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Hepatobiliary disorders
Bile duct obstruction ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Bile duct stenosis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Bile duct stone ^† 1	1/2368 (0.04%)	1	4/2368 (0.17%)	4
Biliary dilatation ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cholangitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Cholangitis acute ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	2
Cholecystitis ^† 1	3/2368 (0.13%)	3	5/2368 (0.21%)	5
Cholecystitis acute ^† 1	6/2368 (0.25%)	6	8/2368 (0.34%)	8
Cholecystitis chronic ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Cholelithiasis ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Cryptogenic cirrhosis ^† 1	1/2368 (0.04%)	3	0/2368 (0.00%)	0
Drug-induced liver injury ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gallbladder enlargement ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hepatic cirrhosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hepatic failure ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hepatitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hepatitis acute ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ischaemic hepatitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Jaundice ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Jaundice cholestatic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Immune system disorders
Heart transplant rejection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Infections and infestations
Abdominal abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Abdominal wall abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Abscess limb ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Acute sinusitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Anal abscess ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Appendicitis ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Bacteraemia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Bacterial sepsis ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Biliary sepsis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Bronchitis ^† 1	12/2368 (0.51%)	13	6/2368 (0.25%)	6
Bursitis infective ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cardiac infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cellulitis ^† 1	9/2368 (0.38%)	11	10/2368 (0.42%)	12
Cellulitis gangrenous ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cervicitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Clostridial infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Clostridium difficile colitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Clostridium difficile infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cystitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Dengue fever ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Device related infection ^† 1	3/2368 (0.13%)	3	3/2368 (0.13%)	3
Diabetic foot infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Diabetic gangrene ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Disseminated tuberculosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Diverticulitis ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Endocarditis ^† 1	1/2368 (0.04%)	1	4/2368 (0.17%)	4
Endocarditis bacterial ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Endotoxic shock ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Enteritis infectious ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Enterococcal bacteraemia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Epididymitis ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Erysipelas ^† 1	1/2368 (0.04%)	2	4/2368 (0.17%)	4
Fournier's gangrene ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Furuncle ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gangrene ^† 1	2/2368 (0.08%)	5	6/2368 (0.25%)	7
Gastroenteritis ^† 1	3/2368 (0.13%)	3	6/2368 (0.25%)	6
Gastroenteritis rotavirus ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastrointestinal infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Gastrointestinal viral infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hiv infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Herpes zoster ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Herpes zoster oticus ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Implant site infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Infected dermal cyst ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Infected skin ulcer ^† 1	1/2368 (0.04%)	2	1/2368 (0.04%)	1
Infection ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Infectious pleural effusion ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Influenza ^† 1	2/2368 (0.08%)	2	3/2368 (0.13%)	3
Intestinal sepsis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Liver abscess ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Localised infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Lower respiratory tract infection ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Lung infection ^† 1	4/2368 (0.17%)	7	4/2368 (0.17%)	4
Lyme disease ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Mediastinal abscess ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Medical device site infection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Meningitis tuberculous ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Metapneumovirus infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Nasopharyngitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Oral candidiasis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Oropharyngeal candidiasis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Osteomyelitis ^† 1	7/2368 (0.30%)	9	1/2368 (0.04%)	1
Otitis media ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Otitis media acute ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Perichondritis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Periodontitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Peritonitis ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Peritonsillar abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pneumonia ^† 1	76/2368 (3.21%)	83	82/2368 (3.46%)	87
Pneumonia bacterial ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Postoperative abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Postoperative wound infection ^† 1	3/2368 (0.13%)	3	1/2368 (0.04%)	1
Pulmonary sepsis ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Pulmonary tuberculosis ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Pyelocystitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pyelonephritis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Pyelonephritis acute ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Rectal abscess ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal abscess ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Renal cyst infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Respiratory syncytial virus infection ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Respiratory tract infection ^† 1	3/2368 (0.13%)	3	5/2368 (0.21%)	5
Rickettsiosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Sepsis ^† 1	13/2368 (0.55%)	13	14/2368 (0.59%)	14
Septic shock ^† 1	8/2368 (0.34%)	9	8/2368 (0.34%)	9
Sinusitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Skin infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Staphylococcal infection ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Subdiaphragmatic abscess ^† 1	1/2368 (0.04%)	2	1/2368 (0.04%)	1
Systemic candida ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Tracheobronchitis ^† 1	3/2368 (0.13%)	3	0/2368 (0.00%)	0
Tuberculosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Upper respiratory tract infection ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Urinary tract infection ^† 1	11/2368 (0.46%)	13	17/2368 (0.72%)	17
Urinary tract infection staphylococcal ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Urosepsis ^† 1	4/2368 (0.17%)	4	7/2368 (0.30%)	7
Wound infection ^† 1	5/2368 (0.21%)	5	0/2368 (0.00%)	0
Injury, poisoning and procedural complications
Abdominal wound dehiscence ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Accidental overdose ^† 1	3/2368 (0.13%)	3	2/2368 (0.08%)	2
Acetabulum fracture ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Alcohol poisoning ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ankle fracture ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Bone contusion ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Brain contusion ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Brain herniation ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cardiac valve rupture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Compression fracture ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Craniocerebral injury ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Fall ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Femoral neck fracture ^† 1	3/2368 (0.13%)	3	2/2368 (0.08%)	2
Femur fracture ^† 1	4/2368 (0.17%)	4	3/2368 (0.13%)	3
Fibula fracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Foot fracture ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Head injury ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Hip fracture ^† 1	7/2368 (0.30%)	7	2/2368 (0.08%)	2
Humerus fracture ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Joint dislocation ^† 1	1/2368 (0.04%)	3	1/2368 (0.04%)	1
Limb injury ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Lower limb fracture ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Lumbar vertebral fracture ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Multiple fractures ^† 1	3/2368 (0.13%)	3	2/2368 (0.08%)	2
Overdose ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Patella fracture ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pelvic fracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Poisoning ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Post procedural haematoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Post procedural haematuria ^† 1	1/2368 (0.04%)	3	0/2368 (0.00%)	0
Post procedural haemorrhage ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Postoperative wound complication ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Rib fracture ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	2
Road traffic accident ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Skin injury ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Skull fracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Skull fractured base ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Spinal compression fracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Spinal fracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Splenic injury ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Subdural haematoma ^† 1	4/2368 (0.17%)	4	4/2368 (0.17%)	4
Subdural haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Tendon injury ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Thermal burn ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Thoracic vertebral fracture ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Toxicity to various agents ^† 1	1/2368 (0.04%)	4	0/2368 (0.00%)	0
Traumatic haematoma ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Traumatic intracranial haemorrhage ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Upper limb fracture ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Wrist fracture ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Investigations
Blood creatinine increased ^† 1	4/2368 (0.17%)	4	3/2368 (0.13%)	3
Blood glucose increased ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Blood pressure increased ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Ejection fraction decreased ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Glomerular filtration rate decreased ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
International normalised ratio increased ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pulmonary arterial pressure increased ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Transaminases increased ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Troponin increased ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Metabolism and nutrition disorders
Cachexia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Decreased appetite ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Dehydration ^† 1	10/2368 (0.42%)	10	8/2368 (0.34%)	8
Diabetes mellitus ^† 1	5/2368 (0.21%)	6	4/2368 (0.17%)	4
Diabetes mellitus inadequate control ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Diabetic ketoacidosis ^† 1	2/2368 (0.08%)	3	1/2368 (0.04%)	1
Diabetic ketosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Diabetic metabolic decompensation ^† 1	6/2368 (0.25%)	6	2/2368 (0.08%)	2
Fluid overload ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Fluid retention ^† 1	1/2368 (0.04%)	3	0/2368 (0.00%)	0
Gout ^† 1	2/2368 (0.08%)	2	4/2368 (0.17%)	4
Hyperglycaemia ^† 1	3/2368 (0.13%)	3	5/2368 (0.21%)	5
Hyperglycaemic hyperosmolar nonketotic syndrome ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Hyperkalaemia ^† 1	2/2368 (0.08%)	2	5/2368 (0.21%)	5
Hypoglycaemia ^† 1	1/2368 (0.04%)	1	4/2368 (0.17%)	4
Hypokalaemia ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Hypomagnesaemia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Hyponatraemia ^† 1	4/2368 (0.17%)	4	1/2368 (0.04%)	1
Hypovolaemia ^† 1	3/2368 (0.13%)	3	2/2368 (0.08%)	2
Ketoacidosis ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Lactic acidosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Steroid diabetes ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Type 2 diabetes mellitus ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Musculoskeletal and connective tissue disorders
Arthritis ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Arthritis reactive ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Back pain ^† 1	2/2368 (0.08%)	2	5/2368 (0.21%)	6
Chondrocalcinosis pyrophosphate ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Dupuytren's contracture ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Gouty arthritis ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Intervertebral disc degeneration ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Intervertebral disc protrusion ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	3
Joint effusion ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Lumbar spinal stenosis ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Muscle spasms ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Muscular weakness ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Musculoskeletal chest pain ^† 1	2/2368 (0.08%)	2	4/2368 (0.17%)	4
Musculoskeletal pain ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Myalgia ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	3
Osteoarthritis ^† 1	5/2368 (0.21%)	6	7/2368 (0.30%)	7
Osteonecrosis of jaw ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Pain in extremity ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pleural mass ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Polymyalgia rheumatica ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pseudarthrosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Spinal pain ^† 1	2/2368 (0.08%)	3	1/2368 (0.04%)	1
Spinal stenosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Spondyloarthropathy ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Spondylolisthesis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Abdominal neoplasm ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Acute myeloid leukaemia ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Adenocarcinoma of colon ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Basal cell carcinoma ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Benign breast neoplasm ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Benign neoplasm of bladder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Benign uterine neoplasm ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Bladder cancer ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Bladder neoplasm ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Bladder transitional cell carcinoma ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Breast cancer ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Breast cancer female ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Breast cancer recurrent ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Brenner tumour ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cervix carcinoma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cholangiocarcinoma ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Chronic lymphocytic leukaemia ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Chronic myeloid leukaemia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Colon cancer ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Colon cancer metastatic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Colon neoplasm ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Colorectal adenocarcinoma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Colorectal cancer metastatic ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Ductal adenocarcinoma of pancreas ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Gastric cancer ^† 1	3/2368 (0.13%)	3	0/2368 (0.00%)	0
Gastrointestinal cancer metastatic ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Glioblastoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Glioblastoma multiforme ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Hepatocellular carcinoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Large intestine benign neoplasm ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Laryngeal cancer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Leukaemia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Leukaemia recurrent ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Lung adenocarcinoma ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Lung cancer metastatic ^† 1	3/2368 (0.13%)	3	0/2368 (0.00%)	0
Lung neoplasm malignant ^† 1	6/2368 (0.25%)	6	4/2368 (0.17%)	4
Malignant melanoma ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Malignant neoplasm of unknown primary site ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Meningioma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Metastases to central nervous system ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Metastases to liver ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Metastatic carcinoma of the bladder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Metastatic malignant melanoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Myelodysplastic syndrome ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Myelofibrosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Nasal cavity cancer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Non-small cell lung cancer ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Oesophageal carcinoma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Ovarian cancer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pancreatic carcinoma ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Pancreatic neoplasm ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Papillary renal cell carcinoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pituitary tumour benign ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Plasma cell myeloma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pleomorphic adenoma ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Polycythaemia vera ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Prostate cancer ^† 1	6/2368 (0.25%)	6	1/2368 (0.04%)	1
Rectal cancer ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Renal cancer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal neoplasm ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Squamous cell carcinoma ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Squamous cell carcinoma of lung ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Squamous cell carcinoma of the tongue ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Tonsil cancer ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Transitional cell carcinoma ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Nervous system disorders
Brain injury ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Brain oedema ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Brain stem infarction ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Carotid artery stenosis ^† 1	3/2368 (0.13%)	3	2/2368 (0.08%)	2
Cerebellar stroke ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cerebral haematoma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Cerebral haemorrhage ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Cerebral infarction ^† 1	8/2368 (0.34%)	9	11/2368 (0.46%)	12
Cerebral ischaemia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Cerebral thrombosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Cerebrovascular accident ^† 1	7/2368 (0.30%)	7	5/2368 (0.21%)	5
Diabetic ketoacidotic hyperglycaemic coma ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Dizziness ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Embolic stroke ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Epilepsy ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Facial paralysis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Generalised tonic-clonic seizure ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Haemorrhage intracranial ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Haemorrhagic stroke ^† 1	3/2368 (0.13%)	3	1/2368 (0.04%)	1
Haemorrhagic transformation stroke ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Headache ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Iiird nerve paresis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ischaemic cerebral infarction ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ischaemic stroke ^† 1	24/2368 (1.01%)	26	26/2368 (1.10%)	28
Loss of consciousness ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Nervous system disorder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Neuralgia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Parkinson's disease ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	2
Peroneal nerve palsy ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Post herpetic neuralgia ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Presyncope ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Sciatica ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Subarachnoid haemorrhage ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Syncope ^† 1	7/2368 (0.30%)	7	13/2368 (0.55%)	14
Transient ischaemic attack ^† 1	13/2368 (0.55%)	13	7/2368 (0.30%)	7
Vascular dementia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vascular encephalopathy ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Vertebral artery occlusion ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vertebral artery stenosis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Vertebrobasilar insufficiency ^† 1	1/2368 (0.04%)	2	0/2368 (0.00%)	0
Product Issues
Device dislocation ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Device failure ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Device inappropriate shock delivery ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Device lead issue ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Device malfunction ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Lead dislodgement ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Psychiatric disorders
Alcohol withdrawal syndrome ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Anxiety disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Bipolar i disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Completed suicide ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Confusional state ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Delirium ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Depression ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Mental status changes ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Suicide attempt ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	23/2368 (0.97%)	25	46/2368 (1.94%)	49
Anuria ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Bladder neck obstruction ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	3
Chronic kidney disease ^† 1	4/2368 (0.17%)	4	8/2368 (0.34%)	10
Cystitis noninfective ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
End stage renal disease ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Haematuria ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Hydronephrosis ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Nephrolithiasis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Nephropathy ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Nephropathy toxic ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Postrenal failure ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Prerenal failure ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal artery stenosis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Renal colic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal cyst ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Renal disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Renal failure ^† 1	8/2368 (0.34%)	8	8/2368 (0.34%)	9
Renal impairment ^† 1	7/2368 (0.30%)	7	13/2368 (0.55%)	14
Renal injury ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ureterolithiasis ^† 1	3/2368 (0.13%)	3	0/2368 (0.00%)	0
Urethral stenosis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Urinary retention ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Reproductive system and breast disorders
Acquired hydrocele ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Adenomyosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Balanoposthitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Benign prostatic hyperplasia ^† 1	5/2368 (0.21%)	5	2/2368 (0.08%)	2
Endometrial hyperplasia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Metrorrhagia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Orchitis noninfective ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Ovarian cyst ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema ^† 1	1/2368 (0.04%)	1	4/2368 (0.17%)	5
Acute respiratory failure ^† 1	7/2368 (0.30%)	9	14/2368 (0.59%)	16
Aspiration ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Asthma ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Bronchiectasis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Chronic obstructive pulmonary disease ^† 1	14/2368 (0.59%)	16	22/2368 (0.93%)	34
Chronic respiratory failure ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Dyspnoea ^† 1	4/2368 (0.17%)	4	6/2368 (0.25%)	6
Eosinophilic pneumonia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Epistaxis ^† 1	2/2368 (0.08%)	2	3/2368 (0.13%)	3
Haemoptysis ^† 1	2/2368 (0.08%)	2	0/2368 (0.00%)	0
Hypoxia ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Interstitial lung disease ^† 1	0/2368 (0.00%)	0	3/2368 (0.13%)	3
Lung cyst ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pharyngeal lesion ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pleural effusion ^† 1	2/2368 (0.08%)	2	3/2368 (0.13%)	3
Pleurisy ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Pleuritic pain ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pneumomediastinum ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pneumonia aspiration ^† 1	3/2368 (0.13%)	3	4/2368 (0.17%)	4
Pneumonitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pneumothorax ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Pneumothorax spontaneous ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pulmonary alveolar haemorrhage ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pulmonary congestion ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Pulmonary embolism ^† 1	7/2368 (0.30%)	7	14/2368 (0.59%)	14
Pulmonary hypertension ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Pulmonary mass ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pulmonary oedema ^† 1	3/2368 (0.13%)	4	5/2368 (0.21%)	5
Pulmonary toxicity ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Pulmonary vasculitis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Respiratory failure ^† 1	3/2368 (0.13%)	3	7/2368 (0.30%)	7
Skin and subcutaneous tissue disorders
Blister ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Decubitus ulcer ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Dermatitis allergic ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Diabetic foot ^† 1	2/2368 (0.08%)	3	2/2368 (0.08%)	2
Drug eruption ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Eczema ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Petechiae ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Psoriasis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Rash ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Skin haemorrhage ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Skin necrosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Skin ulcer ^† 1	2/2368 (0.08%)	2	1/2368 (0.04%)	1
Urticaria ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Vascular disorders
Accelerated hypertension ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Angiodysplasia ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Aortic aneurysm ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Aortic aneurysm rupture ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Aortic dissection ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Aortic stenosis ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Circulatory collapse ^† 1	1/2368 (0.04%)	1	3/2368 (0.13%)	3
Deep vein thrombosis ^† 1	3/2368 (0.13%)	3	6/2368 (0.25%)	7
Diabetic vascular disorder ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Dry gangrene ^† 1	1/2368 (0.04%)	2	0/2368 (0.00%)	0
Embolism arterial ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Essential hypertension ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Extremity necrosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Haematocoele ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Haematoma ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Hypertension ^† 1	2/2368 (0.08%)	2	2/2368 (0.08%)	2
Hypertensive crisis ^† 1	3/2368 (0.13%)	3	3/2368 (0.13%)	3
Hypertensive emergency ^† 1	0/2368 (0.00%)	0	2/2368 (0.08%)	2
Hypertensive urgency ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Hypotension ^† 1	7/2368 (0.30%)	9	11/2368 (0.46%)	12
Hypovolaemic shock ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Iliac artery occlusion ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Orthostatic hypotension ^† 1	2/2368 (0.08%)	2	5/2368 (0.21%)	6
Peripheral arterial occlusive disease ^† 1	11/2368 (0.46%)	11	10/2368 (0.42%)	11
Peripheral artery occlusion ^† 1	1/2368 (0.04%)	1	2/2368 (0.08%)	2
Peripheral artery stenosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Peripheral embolism ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Peripheral ischaemia ^† 1	9/2368 (0.38%)	11	5/2368 (0.21%)	8
Peripheral vascular disorder ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Shock ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Thrombophlebitis ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Thrombophlebitis superficial ^† 1	0/2368 (0.00%)	0	1/2368 (0.04%)	1
Thrombosis ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
Vasculitis ^† 1	1/2368 (0.04%)	1	1/2368 (0.04%)	1
Venous thrombosis limb ^† 1	1/2368 (0.04%)	1	0/2368 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Dapa 10mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	299/2368 (12.63%)		325/2368 (13.72%)
Cardiac disorders
Atrial fibrillation ^† 1	58/2368 (2.45%)	63	52/2368 (2.20%)	55
Cardiac failure ^† 1	76/2368 (3.21%)	90	130/2368 (5.49%)	154
Infections and infestations
Nasopharyngitis ^† 1	63/2368 (2.66%)	84	76/2368 (3.21%)	100
Renal and urinary disorders
Renal impairment ^† 1	63/2368 (2.66%)	67	56/2368 (2.36%)	60
Vascular disorders
Hypotension ^† 1	88/2368 (3.72%)	98	73/2368 (3.08%)	81
1 Term from vocabulary, MedDRA 22.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	AstraZeneca Clinical Study Information Center
Organization:	AstraZeneca
Phone:	+1-877-240-9479
EMail:	information.center@astrazeneca.com

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

Docherty KF, Anand IS, Chiang CE, Chopra VK, Desai AS, Kitakaze M, Verma S, Vinh PN, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, Langkilde AM, Jhund PS, McMurray JJV. Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. JACC Asia. 2022 Mar 29;2(2):139-153. doi: 10.1016/j.jacasi.2022.02.004. eCollection 2022 Apr.

Desai AS, Jhund PS, Claggett BL, Vaduganathan M, Miao ZM, Kondo T, Barkoudah E, Brahimi A, Connolly E, Finn P, Lang NN, Mc Causland FR, McGrath M, Petrie MC, McMurray JJV, Solomon SD. Effect of Dapagliflozin on Cause-Specific Mortality in Patients With Heart Failure Across the Spectrum of Ejection Fraction: A Participant-Level Pooled Analysis of DAPA-HF and DELIVER. JAMA Cardiol. 2022 Dec 1;7(12):1227-1234. doi: 10.1001/jamacardio.2022.3736.

Adamson C, Cowan LM, de Boer RA, Diez M, Drozdz J, Dukat A, Inzucchi SE, Kober L, Kosiborod MN, Ljungman CEA, Martinez FA, Ponikowski P, Sabatine MS, Lindholm D, Bengtsson O, Boulton DW, Greasley PJ, Langkilde AM, Sjostrand M, Solomon SD, McMurray JJV, Jhund PS. Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF. Eur J Heart Fail. 2022 Oct;24(10):1856-1868. doi: 10.1002/ejhf.2649. Epub 2022 Aug 22.

Docherty KF, Welsh P, Verma S, De Boer RA, O'Meara E, Bengtsson O, Kober L, Kosiborod MN, Hammarstedt A, Langkilde AM, Lindholm D, Little DJ, Sjostrand M, Martinez FA, Ponikowski P, Sabatine MS, Morrow DA, Schou M, Solomon SD, Sattar N, Jhund PS, McMurray JJV; DAPA-HF Investigators and Committees. Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF. Circulation. 2022 Sep 27;146(13):980-994. doi: 10.1161/CIRCULATIONAHA.122.060511. Epub 2022 Aug 16.

Butt JH, Dewan P, DeFilippis EM, Biering-Sorensen T, Docherty KF, Jhund PS, Kosiborod MN, Martinez FA, Bengtsson O, Johansen ND, Langkilde AM, Sjostrand M, Vaduganathan M, Solomon SD, Sabatine MS, Kober L, Fiuzat M, McMurray JJV. Effects of Dapagliflozin According to the Heart Failure Collaboratory Medical Therapy Score: Insights From DAPA-HF. JACC Heart Fail. 2022 Aug;10(8):543-555. doi: 10.1016/j.jchf.2022.03.009. Epub 2022 Jun 8.

Yeoh SE, Docherty KF, Jhund PS, Petrie MC, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Boulton DW, Greasley PJ, Langkilde AM, Sjostrand M, Solomon SD, McMurray JJV. Relationship of Dapagliflozin With Serum Sodium: Findings From the DAPA-HF Trial. JACC Heart Fail. 2022 May;10(5):306-318. doi: 10.1016/j.jchf.2022.01.019. Epub 2022 Apr 6.

Butt JH, Dewan P, Merkely B, Belohlavek J, Drozdz J, Kitakaze M, Inzucchi SE, Kosiborod MN, Martinez FA, Tereshchenko S, Ponikowski P, Bengtsson O, Lindholm D, Langkilde AM, Schou M, Sjostrand M, Solomon SD, Sabatine MS, Chiang CE, Docherty KF, Jhund PS, Kober L, McMurray JJV. Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction : A Post Hoc Analysis of the DAPA-HF Trial. Ann Intern Med. 2022 Jun;175(6):820-830. doi: 10.7326/M21-4776. Epub 2022 Apr 26.

Adamson C, Docherty KF, Heerspink HJL, de Boer RA, Damman K, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Petrie MC, Ponikowski P, Sabatine MS, Schou M, Solomon SD, Verma S, Bengtsson O, Langkilde AM, Sjostrand M, Vaduganathan M, Jhund PS, McMurray JJV. Initial Decline (Dip) in Estimated Glomerular Filtration Rate After Initiation of Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: Insights From DAPA-HF. Circulation. 2022 Aug 9;146(6):438-449. doi: 10.1161/CIRCULATIONAHA.121.058910. Epub 2022 Apr 20.

Docherty KF, Simpson J, Jhund PS, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Sjostrand M, Lindholm D, Langkilde AM, Solomon SD, McMurray JJV; DAPA-HF Investigators and Committees. Effect of Dapagliflozin, Compared With Placebo, According to Baseline Risk in DAPA-HF. JACC Heart Fail. 2022 Feb;10(2):104-118. doi: 10.1016/j.jchf.2021.09.002. Epub 2022 Jan 12.

Docherty KF, Ogunniyi MO, Anand IS, Desai AS, Diez M, Howlett JG, Nicolau JC, O'Meara E, Verma S, Inzucchi SE, Kober L, Kosiborod MN, Lindholm D, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, Langkilde AM, Jhund PS, McMurray JJV. Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction. JACC Heart Fail. 2022 Jan;10(1):52-64. doi: 10.1016/j.jchf.2021.08.006. Epub 2021 Nov 10.

Ryden L, Ferrannini G. Is the impact of add on heart failure therapy influenced by background therapy? Lancet Diabetes Endocrinol. 2022 Jan;10(1):3-5. doi: 10.1016/S2213-8587(21)00311-9. Epub 2021 Nov 30. No abstract available.

Butt JH, Adamson C, Docherty KF, de Boer RA, Petrie MC, Inzucchi SE, Kosiborod MN, Maria Langkilde A, Lindholm D, Martinez FA, Bengtsson O, Schou M, O'Meara E, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, Jhund PS, McMurray JJV, Kober L. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to N-Terminal Pro-B-Type Natriuretic Peptide: Insights From the DAPA-HF Trial. Circ Heart Fail. 2021 Dec;14(12):e008837. doi: 10.1161/CIRCHEARTFAILURE.121.008837. Epub 2021 Nov 22.

Berg DD, Docherty KF, Sattar N, Jarolim P, Welsh P, Jhund PS, Anand IS, Chopra V, de Boer RA, Kosiborod MN, Nicolau JC, O'Meara E, Schou M, Hammarstedt A, Langkilde AM, Lindholm D, Sjostrand M, McMurray JJV, Sabatine MS, Morrow DA. Serial Assessment of High-Sensitivity Cardiac Troponin and the Effect of Dapagliflozin in Patients With Heart Failure With Reduced Ejection Fraction: An Analysis of the DAPA-HF Trial. Circulation. 2022 Jan 18;145(3):158-169. doi: 10.1161/CIRCULATIONAHA.121.057852. Epub 2021 Nov 8.

Curtain JP, Docherty KF, Jhund PS, Petrie MC, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjostrand M, Solomon SD, McMurray JJV. Effect of dapagliflozin on ventricular arrhythmias, resuscitated cardiac arrest, or sudden death in DAPA-HF. Eur Heart J. 2021 Sep 21;42(36):3727-3738. doi: 10.1093/eurheartj/ehab560.

Docherty KF, Jhund PS, Claggett B, Ferreira JP, Bengtsson O, Inzucchi SE, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, McMurray JJV; DAPA-HF Investigators and Committees. Extrapolating Long-term Event-Free and Overall Survival With Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis of a Phase 3 Randomized Clinical Trial. JAMA Cardiol. 2021 Nov 1;6(11):1298-1305. doi: 10.1001/jamacardio.2021.2632.

Adamson C, Jhund PS, Docherty KF, Belohlavek J, Chiang CE, Diez M, Drozdz J, Dukat A, Howlett J, Ljungman CEA, Petrie MC, Schou M, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Bengtsson O, Langkilde AM, Lindholm D, Sjostrand M, McMurray JJV. Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index. Eur J Heart Fail. 2021 Oct;23(10):1662-1672. doi: 10.1002/ejhf.2308. Epub 2021 Jul 29.

Jhund PS, Ponikowski P, Docherty KF, Gasparyan SB, Bohm M, Chiang CE, Desai AS, Howlett J, Kitakaze M, Petrie MC, Verma S, Bengtsson O, Langkilde AM, Sjostrand M, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Sabatine MS, Solomon SD, McMurray JJV. Dapagliflozin and Recurrent Heart Failure Hospitalizations in Heart Failure With Reduced Ejection Fraction: An Analysis of DAPA-HF. Circulation. 2021 May 18;143(20):1962-1972. doi: 10.1161/CIRCULATIONAHA.121.053659. Epub 2021 Apr 9.

Butt JH, Docherty KF, Petrie MC, Schou M, Kosiborod MN, O'Meara E, Katova T, Ljungman CEA, Diez M, Ogunniyi MO, Langkilde AM, Sjostrand M, Lindholm D, Bengtsson O, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Jhund PS, McMurray JJV, Kober L. Efficacy and Safety of Dapagliflozin in Men and Women With Heart Failure With Reduced Ejection Fraction: A Prespecified Analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure Trial. JAMA Cardiol. 2021 Jun 1;6(6):678-689. doi: 10.1001/jamacardio.2021.0379.

Berg DD, Jhund PS, Docherty KF, Murphy SA, Verma S, Inzucchi SE, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Bengtsson O, Ponikowski P, Sjostrand M, Solomon SD, McMurray JJV, Sabatine MS. Time to Clinical Benefit of Dapagliflozin and Significance of Prior Heart Failure Hospitalization in Patients With Heart Failure With Reduced Ejection Fraction. JAMA Cardiol. 2021 May 1;6(5):499-507. doi: 10.1001/jamacardio.2020.7585.

Shen L, Kristensen SL, Bengtsson O, Bohm M, de Boer RA, Docherty KF, Inzucchi SE, Katova T, Kober L, Kosiborod MN, Langkilde AM, Lindholm D, Martinez MFA, O'Meara E, Nicolau JC, Petrie MC, Ponikowski P, Sabatine MS, Schou M, Sjostrand M, Solomon SD, Jhund PS, McMurray JJV. Dapagliflozin in HFrEF Patients Treated With Mineralocorticoid Receptor Antagonists: An Analysis of DAPA-HF. JACC Heart Fail. 2021 Apr;9(4):254-264. doi: 10.1016/j.jchf.2020.11.009. Epub 2021 Feb 3.

Dewan P, Docherty KF, Bengtsson O, de Boer RA, Desai AS, Drozdz J, Hawkins NM, Inzucchi SE, Kitakaze M, Kober L, Kosiborod MN, Langkilde AM, Lindholm D, Martinez FA, Merkely B, Petrie MC, Ponikowski P, Sabatine MS, Schou M, Sjostrand M, Solomon SD, Verma S, Jhund PS, McMurray JJV. Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of DAPA-HF. Eur J Heart Fail. 2021 Apr;23(4):632-643. doi: 10.1002/ejhf.2083. Epub 2021 Jan 18.

Inzucchi SE, Docherty KF, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Verma S, Belohlavek J, Bohm M, Chiang CE, de Boer RA, Diez M, Dukat A, Ljungman CEA, Bengtsson O, Langkilde AM, Sjostrand M, Jhund PS, McMurray JJV; DAPA-HF Investigators and Committees. Dapagliflozin and the Incidence of Type 2 Diabetes in Patients With Heart Failure and Reduced Ejection Fraction: An Exploratory Analysis From DAPA-HF. Diabetes Care. 2021 Feb;44(2):586-594. doi: 10.2337/dc20-1675. Epub 2020 Dec 18.

Yeoh SE, Dewan P, Jhund PS, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Bengtsson O, Sjostrand M, Langkilde AM, McMurray JJV; DAPA-HF Investigators and Committees. Patient Characteristics, Clinical Outcomes, and Effect of Dapagliflozin in Relation to Duration of Heart Failure: Is It Ever Too Late to Start a New Therapy? Circ Heart Fail. 2020 Dec;13(12):e007879. doi: 10.1161/CIRCHEARTFAILURE.120.007879. Epub 2020 Nov 9.

Docherty KF, Jhund PS, Bengtsson O, DeMets DL, Inzucchi SE, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Sabatine MS, Sjostrand M, Solomon SD, McMurray JJV; DAPA-HF Investigators and Committees. Effect of Dapagliflozin in DAPA-HF According to Background Glucose-Lowering Therapy. Diabetes Care. 2020 Nov;43(11):2878-2881. doi: 10.2337/dc20-1402. Epub 2020 Sep 2.

Jhund PS, Solomon SD, Docherty KF, Heerspink HJL, Anand IS, Bohm M, Chopra V, de Boer RA, Desai AS, Ge J, Kitakaze M, Merkley B, O'Meara E, Shou M, Tereshchenko S, Verma S, Vinh PN, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjostrand M, McMurray JJV. Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF. Circulation. 2021 Jan 26;143(4):298-309. doi: 10.1161/CIRCULATIONAHA.120.050391. Epub 2020 Oct 12.

Docherty KF, Jhund PS, Anand I, Bengtsson O, Bohm M, de Boer RA, DeMets DL, Desai AS, Drozdz J, Howlett J, Inzucchi SE, Johanson P, Katova T, Kober L, Kosiborod MN, Langkilde AM, Lindholm D, Martinez FA, Merkely B, Nicolau JC, O'Meara E, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, Tereshchenko S, Verma S, McMurray JJV. Effect of Dapagliflozin on Outpatient Worsening of Patients With Heart Failure and Reduced Ejection Fraction: A Prespecified Analysis of DAPA-HF. Circulation. 2020 Oct 27;142(17):1623-1632. doi: 10.1161/CIRCULATIONAHA.120.047480. Epub 2020 Sep 4.

Serenelli M, Bohm M, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, DeMets DL, Bengtsson O, Sjostrand M, Langkilde AM, Anand IS, Chiang CE, Chopra VK, de Boer RA, Diez M, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Verma S, Docherty KF, Jhund PS, McMurray JJV. Effect of dapagliflozin according to baseline systolic blood pressure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF). Eur Heart J. 2020 Sep 21;41(36):3402-3418. doi: 10.1093/eurheartj/ehaa496.

Jackson AM, Dewan P, Anand IS, Belohlavek J, Bengtsson O, de Boer RA, Bohm M, Boulton DW, Chopra VK, DeMets DL, Docherty KF, Dukat A, Greasley PJ, Howlett JG, Inzucchi SE, Katova T, Kober L, Kosiborod MN, Langkilde AM, Lindholm D, Ljungman CEA, Martinez FA, O'Meara E, Sabatine MS, Sjostrand M, Solomon SD, Tereshchenko S, Verma S, Jhund PS, McMurray JJV. Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. Circulation. 2020 Sep 15;142(11):1040-1054. doi: 10.1161/CIRCULATIONAHA.120.047077. Epub 2020 Jul 16. Erratum In: Circulation. 2020 Nov 17;142(20):e369.

Solomon SD, Jhund PS, Claggett BL, Dewan P, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Inzucchi SE, Desai AS, Bengtsson O, Lindholm D, Sjostrand M, Langkilde AM, McMurray JJV. Effect of Dapagliflozin in Patients With HFrEF Treated With Sacubitril/Valsartan: The DAPA-HF Trial. JACC Heart Fail. 2020 Oct;8(10):811-818. doi: 10.1016/j.jchf.2020.04.008. Epub 2020 Jul 8.

Dewan P, Solomon SD, Jhund PS, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, DeMets DL, Sabatine MS, Bengtsson O, Sjostrand M, Langkilde AM, Anand IS, Belohlavek J, Chopra VK, Dukat A, Kitakaze M, Merkely B, O'Meara E, Schou M, Vinh PN, McMurray JJV; DAPA-HF Investigators and Committees. Efficacy and safety of sodium-glucose co-transporter 2 inhibition according to left ventricular ejection fraction in DAPA-HF. Eur J Heart Fail. 2020 Jul;22(7):1247-1258. doi: 10.1002/ejhf.1867. Epub 2020 Jun 15.

Petrie MC, Verma S, Docherty KF, Inzucchi SE, Anand I, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett J, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Vinh PN, Schou M, Tereshchenko S, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD, Johanson P, Greasley PJ, Boulton D, Bengtsson O, Jhund PS, McMurray JJV. Effect of Dapagliflozin on Worsening Heart Failure and Cardiovascular Death in Patients With Heart Failure With and Without Diabetes. JAMA. 2020 Apr 14;323(14):1353-1368. doi: 10.1001/jama.2020.1906. Erratum In: JAMA. 2021 Apr 6;325(13):1335.

Kosiborod MN, Jhund PS, Docherty KF, Diez M, Petrie MC, Verma S, Nicolau JC, Merkely B, Kitakaze M, DeMets DL, Inzucchi SE, Kober L, Martinez FA, Ponikowski P, Sabatine MS, Solomon SD, Bengtsson O, Lindholm D, Niklasson A, Sjostrand M, Langkilde AM, McMurray JJV. Effects of Dapagliflozin on Symptoms, Function, and Quality of Life in Patients With Heart Failure and Reduced Ejection Fraction: Results From the DAPA-HF Trial. Circulation. 2020 Jan 14;141(2):90-99. doi: 10.1161/CIRCULATIONAHA.119.044138. Epub 2019 Nov 17.

Martinez FA, Serenelli M, Nicolau JC, Petrie MC, Chiang CE, Tereshchenko S, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Ponikowski P, Sabatine MS, DeMets DL, Dutkiewicz-Piasecka M, Bengtsson O, Sjostrand M, Langkilde AM, Jhund PS, McMurray JJV. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation. 2020 Jan 14;141(2):100-111. doi: 10.1161/CIRCULATIONAHA.119.044133. Epub 2019 Nov 17.

McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Belohlavek J, Bohm M, Chiang CE, Chopra VK, de Boer RA, Desai AS, Diez M, Drozdz J, Dukat A, Ge J, Howlett JG, Katova T, Kitakaze M, Ljungman CEA, Merkely B, Nicolau JC, O'Meara E, Petrie MC, Vinh PN, Schou M, Tereshchenko S, Verma S, Held C, DeMets DL, Docherty KF, Jhund PS, Bengtsson O, Sjostrand M, Langkilde AM; DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. doi: 10.1056/NEJMoa1911303. Epub 2019 Sep 19.

McMurray JJV, DeMets DL, Inzucchi SE, Kober L, Kosiborod MN, Langkilde AM, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, Sjostrand M, Solomon SD; DAPA-HF Committees and Investigators. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019 Nov;21(11):1402-1411. doi: 10.1002/ejhf.1548. Epub 2019 Jul 15.

Nassif ME, Kosiborod M. Effects of sodium glucose cotransporter type 2 inhibitors on heart failure. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:19-23. doi: 10.1111/dom.13678.

Layout table for additonal information

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT03036124
Other Study ID Numbers:	D1699C00001 2016-003897-41 ( EudraCT Number )
First Submitted:	January 26, 2017
First Posted:	January 30, 2017
Results First Submitted:	July 6, 2020
Results First Posted:	September 1, 2020
Last Update Posted:	September 1, 2020

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