Table 1

Characteristics of included studies

Trial name, year	Patient cohort	No of patients	Mean age (years)	Men (%)	Follow-up (weeks)	RAS blocker monotherapy	RAS blocker combination	Risk of bias	Data available
ACE inhibitor/ARB combination v RAS blocker monotherapy:
AMAZE¹⁴2004	Essential hypertension	1096	54	58	8	Lisinopril	Lisinopril+candesartan	High	Safety
Azizi et al¹⁵ 2000	Mild to moderate hypertension	177	NR	64	6	Enalapril or losartan	Enalapril+losartan	High	Safety
CALM¹⁶2001	Diabetes, hypertension and microalbuminuria	197	60	65	24	Lisinopril or candesartan	Lisinopril+candesartan	High	Safety
CALM II¹⁷2005	Hypertension and diabetes	75	55	75	52	Lisinopril	Lisinopril+candesartan	High	Safety
CHARM Added¹⁸2003	Heart failure and ejection fraction ≤40%	2548	64	79	178	Any ACE inhibitor	ACE inhibitor+candesartan	Low	Efficacy and safety
Cice et al¹⁹2010	Haemodialysis, heart failure with ejection fraction ≤40%	332	63	54	156	Any ACE inhibitor	ACE inhibitor+telmisartan	Low	Efficacy and safety
IMPROVE²⁰ 2007	High risk cardiovascular disease and microalbuminuria	405	66	61	20	Ramipril	Ramipril+irbesartan	High	Safety
Kanno et al²¹2006	Hypertension and chronic kidney disease	90	60	40	156	Any ACE inhibitor	ACE inhibitor+candesartan	Low	Safety
Kum et al²² 2008	Chronic systolic heart failure with ejection fraction <50%	50	66	72	52	Any ACE inhibitor	ACE inhibitor+irbesartan	High	Efficacy and safety
Mehdi et al²³2009	Diabetes, hypertension, and albuminuria	81	50	48	48	Lisinopril	Lisinopril+losartan	High	Safety
Ogawa et al²⁴ 2007	Hypertension and diabetic nephropathy	164	62	48	96	Temocapril, candesartan	Temocapril+candesartan	High	Safety
ONTARGET²⁵2008	High risk cardiovascular disease	25 620	67	73	243	Ramipril or telmisartan	Ramipril+telmisartan	Low	Efficacy and safety
RESOLVD²⁶1999	Heart failure with ejection fraction <40%	768	64	83	43	Enalapril or candesartan	Enalapril+candesartan	Low	Safety
Ruilope et al²⁷2000	Hypertension, chronic kidney disease with or without proteinuria	108	57	70	4	Valsartan	Benazepril+valsartan	High	Safety
Titan et al²⁸2011	Diabetic nephropathy	56	58	63	16	Enalapril	Enalapril+losartan	High	Safety
Tonkon et al²⁹2000	Chronic heart failure	109	64	76	12	Any ACE inhibitor	ACE inhibitor+irbesartan	High	Safety
VALERIA³⁰2008	Hypertension and microalbuminuria	133	59	69	30	Lisinopril or valsartan	Lisinopril+valsartan	Low	Safety
Val-HeFT³¹2001	NYHA class II-IV heart failure	5010	63	80	100	Any ACE inhibitor	ACE inhibitor+valsartan	Low	Efficacy and safety
V-HeFT³²1999	Symptomatic NYHA class II-IV heart failure	83	64	100	4	Any ACE inhibitor	ACE inhibitor+valsartan	High	Safety
VALIANT³³2003	Acute myocardial infarction complicated by heart failure	14 703	65	69	107	Captopril or valsartan	Captopril+valsartan	Low	Efficacy and safety
White et al³⁴2007	Symptomatic heart failure with ejection fraction ≤40%	80	62	90	26	Any ACE inhibitor	ACE inhibitor+candesartan	High	Safety
Yasamura et al³⁵ 2004	Mild to moderate chronic heart failure	106	65	80	26	Any ACE inhibitor	ACE inhibitor+ARB	High	Safety
ACE inhibitor/aliskiren combination v RAS blocker monotherapy:
ALOFT³⁶2008	Hypertension and NYHA class II-IV heart failure	302	67	78	12	Any ACE inhibitor	ACE inhibitor+aliskiren	Low	Safety
ASPIRE³⁷2011	Post-myocardial infarction with systolic dysfunction	820	60	82	36	Any ACE inhibitor	ACE inhibitor+aliskiren	Low	Safety
Uresin et al³⁸2007	Diabetes mellitus and hypertension	837	59	59	8	Ramipril or aliskiren	Ramipril+aliskiren	Low	Safety
ARB/aliskiren combination v RAS blocker monotherapy:
ALLAY³⁹2009	Hypertension and left ventricular hypertrophy	460	59	76	36	Losartan or aliskiren	Losartan+aliskiren	Low	Safety
AVANTE GARDE⁴⁰2010	Acute coronary syndrome without heart failure, raised natriuretic peptide	1101	63	68	8	Valsartan or aliskiren	Valsartan+aliskiren	Low	Safety
AVOID⁴¹2008	Hypertension and diabetic nephropathy	599	62	71	24	Losartan	Losartan+aliskiren	Low	Safety
Drummond et al⁴² 2011	Diabetes mellitus and hypertension	363	57	54	12	Valsartan	Valsartan+aliskiren	Low	Safety
Oparil et al⁴³2007	Hypertension	1797	52	61	8	Valsartan or aliskiren,	Valsartan+aliskiren	Low	Safety
Pool et al⁴⁴2007	Mild to moderate hypertension	1123	56	56	8	Valsartan or aliskiren	Valsartan+aliskiren	Low	Safety
VANTAGE⁴⁵2010	Stage 2 hypertension	451	57	51	8	Valsartan	Valsartan+aliskiren	High	Safety
ACE inhibitor or ARB/aliskiren combination v RAS blocker monotherapy:
ALTITUDE⁴⁶ 2012	Diabetic nephropathy	8561	65	68	139	Aliskiren	ACE inhibitor or ARB+aliskiren	Low	Efficacy and safety

ACE=angiotensin converting enzyme; ARB=angiotensin receptor blocker; RAS=renin-angiotensin system; NR=not recorded; NYHA=New York Heart Association.