Table 1 Characteristics of the RCTs included in the meta-analysis
Trial name, year publication | Population | Setting | Intervention | Control | Follow up (in months) | Male (%) | Mean / median age (years) | Mean BMI (kg/m2) | Mean cholesterol (mg/dL) | Mean LDL (mg/dL) | Mean HDL (mg/dL) | Mean triglyceride (mg/dL) | Non-smoker (%) | Hypertension (%) | Heart failure (%) | Diabetes mellitus (%) | Ischaemic / coronary artery disease (%) | Chronic kidney disease (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
4C (2016) [16] | Patients with IHD after coronary stent implantation | 39 centres in Japan | Candesartan | Standard care without ARB | 36 | 73 | 69 | 24 | NR | 111 | 49 | 140 | 83 | 73 | 8 | 35 | 100 | NR |
ACTIVE I (2011) [17] | Patients with atrial fibrillation | 600 centres worldwide | Irbesartan | Placebo | 54 | 61 | 70 | 29 | NR | NR | NR | NR | 50 | 88 | 32 | 20 | NR | NR |
CARP (2011) [18] | Patients that received a coronary stent | 5 centres in Hiroshima, Japan | Valsartan | Non-ARB therapy | 48 | 79 | 65 | 24 | NR | NR | NR | NR | 50 | 75 | NR | 43 | 100 | 30 |
CASE-J (2008) [19] | Patients with high-risk hypertension | 527 physicians from Japan | Candesartan | Amlodipine | 41 | 55 | 64 | 25 | NR | NR | NR | NR | 79 | 100 | 0 | 43 | 43 | 24 |
CHARM-Added (2003) [20] | Patients with CHF and LVEF< 40 | 618 centres in 26 countries | Candesartan | Placebo | 41 | 79 | 64 | 28 | NR | NR | NR | NR | 83 | 48 | 100 | 30 | 68 | NR |
CHARM-Alternative (2003) [7] | Patients with symptomatic CHF and LVEF< 40% | 618 centres in 26 countries | Candesartan | Placebo | 34 | 68 | 67 | 28 | NR | NR | NR | NR | 86 | 50 | 100 | 27 | 62 | NR |
CHARM-Preserved (2003) [21] | Patients with HF and LVEF> 40 | 618 centres in 26 countries | Candesartan | Placebo | 37 | 60 | 67 | 29 | NR | NR | NR | NR | 87 | 64 | 100 | 28 | 56 | NR |
Cice et al. (2010) [22] | Patients with CHF and in haemodialysis | 30 clinics in Italy | Telmisartan | Placebo | 36 | 90 | 63 | NR | NR | NR | NR | NR | 61 | NR | 100 | 29 | 57 | 100 |
DETAIL (2004) [23] | Patients with diabetes mellitus and nephropathy | 39 centres in northern Europe | Telmisartan | Enalapril | 60 | 73 | 61 | 31 | 223 | 137 | 48 | 207 | 37 | 100 | 0 | 100 | NR | 100 |
DIRECT-Prevent 1 (2008) [15] | Patients with type 1 diabetes a no retinopathy | 309 centres worldwide | Candesartan | Placebo | 56 | 56 | 30 | 24 | 184 | NR | 66 | NR | 74 | NR | NR | 100 | NR | 0 |
DIRECT-Protect 1 (2008) [15] | Patients with type 1 diabetes and retinopathy | 309 centres worldwide | Candesartan | Placebo | 56 | 57 | 32 | 25 | 186 | NR | 66 | NR | 74 | NR | NR | 100 | NR | 0 |
DIRECT-Protect 2 (2008) [24] | Patients with type 2 diabetes and retinopathy | 309 centres worldwide | Candesartan | Placebo | 56 | 50 | 57 | 29 | 205 | NR | NR | NR | 73 | 62 | NR | 100 | 5 | 0 |
E-COST (2005) [25] | Patients with hypertension | Centres in Saitama, Japan | Candesartan | Non-ARB therapy | 37 | 48 | NR | NR | NR | NR | NR | NR | NR | 100 | 0 | 0 | 0 | NR |
E-COST-R (2005) [26] | Patients with hypertension and mild renal impairment | Centres in Saitama, Japan | Candesartan | Non-ARB therapy | 37 | 59 | 67 | NR | 181 | NR | NR | NR | NR | 100 | 0 | 0 | 6 | 100 |
ELITE (1997) [27] | Patients with CHF and LVEF< 40% | 125 centres in the USA, Europe, and South America | Losartan | Captopril | 13 | 67 | 74 | NR | NR | NR | NR | NR | 88 | 57 | 100 | 25 | 50 | 7 |
ELITE II (2000) [28] | Patients with CHF and LVEF< 40% | 289 centres in 46 countries | Losartan | Captopril | 23 | 69 | 71 | NR | NR | NR | NR | NR | NR | 49 | 100 | 24 | 79 | NR |
GISSI-AF (2009) [29] | Patients with history of atrial fibrillation | 100 centres in Italy | Valsartan | Placebo | 12 | 62 | 68 | 28 | NR | NR | NR | NR | 81 | 85 | 8 | 15 | 12 | 3 |
HIJ-CREATE (2009) [30] | Patients with coronary artery disease and hypertension | 14 centres in Japan | Candesartan | Non-ARB therapy | 50 | 80 | 66 | 25 | 193 | NR | 45 | 128 | 64 | 100 | 21 | 38 | 100 | NR |
HOPE-3 (2016) [31] | Patients with intermediate cardiovascular risk | 228 centres in 21 countries | Candesartan + hydrochlorothiazide | Placebo | 67 | 54 | 66 | 27 | 201 | 128 | 45 | 128 | 72 | 38 | 0 | 5.8 | 0 | 0 |
IDNT (2003) [32] | Patients with diabetes mellitus and nephropathy | Centres in the North America, Europe, Latin America, South East Asia, and Oceania | Irbesartan | Amlodipine or placeboa | 31 | 64 | 59 | 31 | NR | NR | NR | NR | NR | 100 | 0 | 100 | 28 | 100 |
I-PRESERVE (2008) [33] | Patients with CHF and LVEF > 45% | Centres in 25 countries | Irbesartan | Placebo | 50 | 40 | 72 | 30 | NR | NR | NR | NR | NR | 89 | 100 | 28 | 0 | 0 |
IRMA-2 (2001) [34] | Patients with hypertension, diabetes mellitus, and micro-albuminuria | 96 centres worldwide | Irbesartanb | Placebo | 24 | 69 | 58 | 30 | 224 | 140 | 44 | 180 | 81 | 100 | NR | 100 | 6 | 0 |
J-RHYTHM II (2011) [35] | Patients with hypertension and atrial fibrillation | 48 centres in Japan | Candesartan | Amlodipine | 12 | 69 | 66 | NR | NR | NR | NR | NR | NR | 100 | 3 | 9 | 1 | NR |
Kondo et al. (2003) [36] | Patients with history of coronary intervention | Ogaki Municipal Hospital in Japan | Standard care + Candesartan | Standard care without candesartan | 24 | 76 | 65 | 24 | 187 | 114 | 49 | 126 | 76 | 44 | 2 | 25 | 100 | NR |
KYOTO HEART (2009) [37] | Patients with uncontrolled hypertension | 31 centres from Kyoto, Japan | Valsartan | Non-ARB therapy | 39 | 57 | 66 | 39 | NR | 122 | 55 | 149 | 78 | 100 | 7 | 27 | 23 | NR |
LIFE (2002) [38] | Patients with hypertension and left ventricular hypertrophy | 830 centres from the USA, the UK, and Scandinavia | Losartan | Atenolol | 58 | 46 | 67 | 28 | 232 | NR | 58 | NR | 84 | 100 | 0 | 13 | 16 | NR |
MOSES (2005) [39] | High-risk hypertensive patients | Centres in Germany and Austria | Eprosartan | Nitredipine | 45 | 54 | 68 | 28 | NR | NR | NR | NR | NR | 100 | 26 | 37 | 26 | 5.4 |
NAVIGATOR (2010) [40] | Patients with impaired glucose tolerance | 806 centres in 40 countries | Valsartan | Placebo | 60 | 49 | 64 | 31 | 210 | 127 | 50 | 151 | 89 | 78 | NR | 49 | 12 | 11 |
OCTOPUS (2013) [41] | Patients with hypertension and in haemodialysis | 66 dialysis centres in Okinawa, Japan | Olmesartan | Non-ARB therapy | 60 | 62 | 60 | 24 | 155 | NR | NR | 155 | 65 | 100 | NR | 32 | 7 | 100 |
ONTARGET (2008) [42] | Patients with coronary, peripheral, cerebrovascular disease or diabetes with end-organ damage | 733 centres in 40 countries | Telmisartan | Ramipril or ramipril + telmisartanc | 56 | 77 | 66 | 28 | 190 | 112 | 50 | 151 | 36 | 69 | 0 | 37 | 75 | NR |
OPTIMAAL (2002) [43] | Patients with acute myocardial infarction and heart failure | 329 centres in 7 European countries | Losartan | Captopril | 35 | 69 | 67 | 27 | 212 | 130 | 45 | 168 | NR | 36 | 6 | 17 | 100 | NR |
ORIENT (2011) [44] | Patients with diabetes mellitus with proteinuria | Centres in Japan and Hong Kong | Olmesartan | Placebo | 38 | 69 | 59 | 25 | 208 | NR | NR | NR | 75 | 100 | 4 | 100 | 5 | 100 |
PRoFESS (2008) [45] | Patients with a recent ischaemic stroke | 695 centres in 35 countries | Telmisartan | Placebo | 30 | 64 | 66 | 27 | NR | NR | NR | NR | 43 | 74 | 3 | 28 | NR | NR |
RENAAL (2001) [46] | Patients with diabetes and nephropathy | 250 centres in 28 countries | Losartan | Placebo | 41 | 63 | 60 | 30 | 228 | 142 | 45 | 219 | 82 | 93 | 0 | 100 | 11 | 100 |
ROAD (2007) [47] | Patients with proteinuria and chronic renal insufficiency | Nanfang Hospital Renal Division in China | Losartan | Benazepril | 44 | 63 | 50 | 23 | 97 | NR | NR | 177 | NR | 63 | 0 | 0 | 0 | 100 |
SCAST (2011) [48] | Patients with acute stroke | 146 centres in Europe | Candesartan | Placebo | 6 | 58 | 71 | NR | NR | NR | NR | NR | NR | 70 | NR | 16 | NR | NR |
SCOPE (2003) [49] | Patients with mild to moderate elevated blood pressure | 527 centres in Europe | Candesartan | Placebo | 45 | 36 | 76 | 27 | 239 | NR | NR | NR | 91 | 52 | NR | 12 | 4 | NR |
SUPPORT (2015) [50] | Patients with hypertension and CHF | 17 centres in Tohoku, Japan | Olmesartan | Non-ARB therapy | 53 | 75 | 66 | 25 | NR | 108 | NR | NR | NR | 100 | 100 | 50 | 47 | 0 |
Suzuki et al. (2008) [51] | Patients with kidney failure treated with haemodialysis | 5 dialysis centres in Saitama, Japan | Losartan, candesartan, or valsartan | Non-ARB therapy | 36 | 59 | 60 | 21 | 157 | NR | NR | NR | 78 | 93 | 16 | 52 | 2 | 100 |
Takahashi et al. (2006) [52] | Patients with kidney failure treated with haemodialysis | Enshu General Hospital in Japan | Candesartan | Nothing | 19 | 58 | 61 | 20 | NR | NR | NR | NR | NR | 81 | 0 | 33 | 0 | 100 |
TRANSCEND (2008) [53] | Patients with coronary, peripheral, cerebrovascular disease or diabetes with end-organ damage, and intolerant to ACE inhibitors | 630 centres in 40 countries | Telmisartan | Placebo | 56 | 57 | 67 | 28 | 197 | 117 | 49 | 158 | 47 | 76 | 0 | 36 | 74 | NR |
T-VENTURE (2009) [54] | Patients with acute myocardial infarction | 4 centres in Japan | Valsartan | ACE inhibitor therapy | 6 | 83 | 63 | NR | NR | NR | NR | NR | 40 | 57 | 0 | 34 | 100 | NR |
Val-HeFT (2001) [55] | Patients with heart failure | 302 centres in 16 countries | Valsartan | Placebo | 23 | 80 | 63 | NR | NR | NR | NR | NR | NR | NR | 100 | 25 | 57 | NR |
VALIANT (2003) [56] | Patients with recent myocardial infarction and LVEF < 35% | 931 centres in 24 countries | Valsartan | Captoprild | 25 | 78 | 65 | 27 | NR | NR | NR | NR | NR | 56 | 15 | 23 | 100 | NR |
VALUE (2004) [6] | Patients with hypertension and high risk of cardiac event | Centres in 31 countries | Valsartan | Amlodipine | 50 | 58 | 67 | 29 | NR | NR | NR | NR | NR | 93 | 6 | NR | 45 | NR |