Table 1

Characteristics of included studies

Trial name, yearPatient cohortNo of patientsMean age (years)Men (%)Follow-up (weeks)RAS blocker monotherapyRAS blocker combinationRisk of biasData available
ACE inhibitor/ARB combination v RAS blocker monotherapy:
 AMAZE14 2004Essential hypertension109654588LisinoprilLisinopril+candesartanHighSafety
 Azizi et al15 2000Mild to moderate hypertension177NR646Enalapril or losartanEnalapril+losartanHighSafety
 CALM16 2001Diabetes, hypertension and microalbuminuria197606524Lisinopril or candesartanLisinopril+candesartanHighSafety
 CALM II17 2005Hypertension and diabetes75557552LisinoprilLisinopril+candesartanHighSafety
 CHARM Added18 2003Heart failure and ejection fraction ≤40%25486479178Any ACE inhibitorACE inhibitor+candesartanLowEfficacy and safety
 Cice et al19 2010Haemodialysis, heart failure with ejection fraction ≤40%3326354156Any ACE inhibitorACE inhibitor+telmisartanLowEfficacy and safety
 IMPROVE20 2007High risk cardiovascular disease and microalbuminuria405666120RamiprilRamipril+irbesartanHighSafety
 Kanno et al21 2006Hypertension and chronic kidney disease906040156Any ACE inhibitorACE inhibitor+candesartanLowSafety
 Kum et al22 2008Chronic systolic heart failure with ejection fraction <50%50667252Any ACE inhibitorACE inhibitor+irbesartanHighEfficacy and safety
 Mehdi et al23 2009Diabetes, hypertension, and albuminuria81504848LisinoprilLisinopril+losartanHighSafety
 Ogawa et al24 2007Hypertension and diabetic nephropathy164624896Temocapril, candesartanTemocapril+candesartanHighSafety
 ONTARGET25 2008High risk cardiovascular disease25 6206773243Ramipril or telmisartanRamipril+telmisartanLowEfficacy and safety
 RESOLVD26 1999Heart failure with ejection fraction <40%768648343Enalapril or candesartanEnalapril+candesartanLowSafety
 Ruilope et al27 2000Hypertension, chronic kidney disease with or without proteinuria10857704ValsartanBenazepril+valsartanHighSafety
 Titan et al28 2011Diabetic nephropathy56586316EnalaprilEnalapril+losartanHighSafety
 Tonkon et al29 2000Chronic heart failure109647612Any ACE inhibitorACE inhibitor+irbesartanHighSafety
 VALERIA30 2008Hypertension and microalbuminuria133596930Lisinopril or valsartanLisinopril+valsartanLowSafety
 Val-HeFT31 2001NYHA class II-IV heart failure50106380100Any ACE inhibitorACE inhibitor+valsartanLowEfficacy and safety
 V-HeFT32 1999Symptomatic NYHA class II-IV heart failure83641004Any ACE inhibitorACE inhibitor+valsartanHighSafety
 VALIANT33 2003Acute myocardial infarction complicated by heart failure14 7036569107Captopril or valsartanCaptopril+valsartanLowEfficacy and safety
 White et al34 2007Symptomatic heart failure with ejection fraction ≤40%80629026Any ACE inhibitorACE inhibitor+candesartanHighSafety
 Yasamura et al35 2004Mild to moderate chronic heart failure106658026Any ACE inhibitorACE inhibitor+ARBHighSafety
ACE inhibitor/aliskiren combination v RAS blocker monotherapy:
 ALOFT36 2008Hypertension and NYHA class II-IV heart failure302677812Any ACE inhibitorACE inhibitor+aliskirenLowSafety
 ASPIRE37 2011Post-myocardial infarction with systolic dysfunction820608236Any ACE inhibitorACE inhibitor+aliskirenLowSafety
 Uresin et al38 2007Diabetes mellitus and hypertension83759598Ramipril or aliskirenRamipril+aliskirenLowSafety
ARB/aliskiren combination v RAS blocker monotherapy:
 ALLAY39 2009Hypertension and left ventricular hypertrophy460597636Losartan or aliskirenLosartan+aliskirenLowSafety
 AVANTE GARDE40 2010Acute coronary syndrome without heart failure, raised natriuretic peptide110163688Valsartan or aliskirenValsartan+aliskirenLowSafety
 AVOID41 2008Hypertension and diabetic nephropathy599627124LosartanLosartan+aliskirenLowSafety
 Drummond et al42 2011Diabetes mellitus and hypertension363575412ValsartanValsartan+aliskirenLowSafety
 Oparil et al43 2007Hypertension179752618Valsartan or aliskiren,Valsartan+aliskirenLowSafety
 Pool et al44 2007Mild to moderate hypertension112356568Valsartan or aliskirenValsartan+aliskirenLowSafety
 VANTAGE45 2010Stage 2 hypertension45157518ValsartanValsartan+aliskirenHighSafety
ACE inhibitor or ARB/aliskiren combination v RAS blocker monotherapy:
 ALTITUDE46 2012Diabetic nephropathy85616568139AliskirenACE inhibitor or ARB+aliskirenLowEfficacy and safety

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