| Trial | control | p<0.05 | harm | NS |
|---|
| Marmorstein, 1962 | estrogen vs placebo | | | |
| Stamler, 1963 | estrogen vs placebo | | | |
| VA Neurology Section (estrogen), 1966 | estrogen vs placebo | | | |
| CDP estrogen 5, 1975 | estrogen vs placebo | | | |
| CDP estrogen 2.5, 1975 | estrogen vs placebo | | | |
| VA drugs (Estrogen or thyroxine), 1968 | estrogen or thyroxine vs placebo | all cause deaths 0.39 [0.25; 0.62] coronary deaths 0.33 [0.15; 0.76] non cardiovascular death 0.43 [0.24; 0.77] | | |
| ERA (estrogen alone ), 2000 | estrogen vs placebo | | | all cause death 1.40 [0.50; 3.89] Coronary events (CHD) 0.90 [0.59; 1.35] Cv death 1.40 [0.32; 6.10] non fatal MI 0.90 [0.31; 2.59] stroke 0.88 [0.28; 2.78] CV events 0.98 [0.51; 1.88] venous thromboembolism 5.25 [0.62; 44.16] |
| WAVE, 2002 | combined estrogen and progestogen vs placebo | | | all cause death 1.78 [0.76; 4.14] Cv death 1.35 [0.48; 3.83] non fatal MI 2.28 [0.71; 7.30] stroke 1.76 [0.96; 3.22] CV events 0.92 [0.67; 1.28] venous thromboembolism 1.01 [0.26; 4.00] |
| WELL-HART (estrogen alone), 2003 | estrogen vs placebo | | | all cause death 0.50 [0.09; 2.65] CV events 1.00 [0.54; 1.85] |
| Schulman (NHLBI) (estrogen alone), 2002 | estrogen vs placebo | | | |
| EAGAR, 2006 | combined estrogen and progestogen vs placebo | | CV events 1.55 [1.02; 2.36] | all cause death 0.54 [0.10; 2.78] |
| HERS, 1998 | combined estrogen and progestogen vs placebo | | venous thromboembolism 26.29 [15.18; 45.51] | all cause death 1.06 [0.84; 1.34] Coronary events (CHD) 0.98 [0.80; 1.19] Cv death 1.19 [0.85; 1.67] non fatal MI 0.91 [0.72; 1.15] stroke 1.11 [0.85; 1.44] CV events 0.99 [0.90; 1.10] PE 2.76 [0.88; 8.63] |
| EPAT, 2001 | estrogen vs placebo | | | all cause death 0.00 [0.00; NaN] Cv death 0.00 [0.00; NaN] non fatal MI 1.00 [0.06; 15.79] stroke ∞ [NaN; ∞] CV events 1.50 [0.26; 8.80] |
| EVTET, 2000 | combined estrogen and progestogen vs placebo | | | venous thromboembolism 7.77 [1.00; 60.53] PE 2.92 [0.31; 27.35] |
| Hall, 1998 | combined estrogen and progestogen vs placebo | | | all cause death 0.00 [0.00; NaN] Cv death ∞ [NaN; ∞] stroke ∞ [NaN; ∞] CV events 0.75 [0.24; 2.36] |
| ESPRIT, 2002 | estrogen vs placebo | | | all cause death 0.81 [0.51; 1.27] Coronary events (CHD) 1.00 [0.72; 1.39] Cv death 0.69 [0.40; 1.18] non fatal MI 1.30 [0.83; 2.04] stroke 1.64 [0.60; 4.47] venous thromboembolism 1.96 [0.18; 21.60] PE 0.98 [0.20; 4.84] |
| WEST, 2001 | estrogen vs placebo | | | all cause death 1.14 [0.77; 1.67] Cv death 0.82 [0.37; 1.81] non fatal MI 1.13 [0.53; 2.41] stroke 1.09 [0.79; 1.51] CV events 0.79 [0.62; 1.00] venous thromboembolism 0.73 [0.16; 3.23] PE 0.97 [0.14; 6.85] |
| WHI, 2002 | combined estrogen and progestogen vs placebo | | Coronary events (CHD) 1.28 [1.01; 1.62] non fatal MI 1.32 [1.02; 1.71] stroke 1.42 [1.08; 1.87] CV events 1.19 [1.05; 1.36] venous thromboembolism 2.15 [1.61; 2.86] PE 2.15 [1.41; 3.28] | all cause death 1.01 [0.84; 1.21] Cv death 1.21 [0.72; 2.02] |
| WHISP, 2006 | combined estrogen and progestogen vs placebo | | | all cause death 0.00 [NaN; NaN] Cv death 0.00 [NaN; NaN] non fatal MI 0.00 [NaN; NaN] stroke 0.00 [NaN; NaN] CV events 0.00 [NaN; NaN] venous thromboembolism 0.00 [NaN; NaN] |
| WISDOM, 2007 | combined estrogen and progestogen vs placebo | | venous thromboembolism 7.31 [2.19; 24.39] PE 4.98 [1.09; 22.72] | all cause death 1.59 [0.52; 4.87] Coronary events (CHD) ∞ [NaN; ∞] Cv death NaN [NaN; NaN] non fatal MI ∞ [NaN; ∞] stroke 0.73 [0.37; 1.46] CV events ∞ [NaN; ∞] |
| ERA (estrogen plus medroxyprogesterone), 2000 | combined estrogen and progestogen vs placebo | | | all cause death 0.50 [0.13; 1.97] Cv death 0.67 [0.11; 3.95] non fatal MI 0.87 [0.30; 2.49] stroke 1.01 [0.34; 3.03] CV events 1.68 [0.41; 6.86] venous thromboembolism 2.02 [0.19; 21.93] |
| WELL-HART (estrogen-progestin), 2003 | combined estrogen and progestogen vs placebo | | | all cause death 0.77 [0.18; 3.32] CV events 1.16 [0.64; 2.09] |
| Schulman (NHLBI) (estrogen-progestogen), 2002 | combined estrogen and progestogen vs placebo | | | |
| Trial | Treatments | Patients | Method |
|---|
| Marmorstein, 1962 | estrogen (n=285) vs. placebo (n=147) | | Parallel groups Sample size: 285/147 Primary endpoint: FU duration: 5.0 y |
| Stamler, 1963 | estrogen (n=156) vs. placebo (n=119) | | Parallel groups Sample size: 156/119 Primary endpoint: FU duration: 5.0 years |
| VA Neurology Section (estrogen), 1966 | estrogen (n=295) vs. placebo (n=287) | | Parallel groups Sample size: 295/287 Primary endpoint: FU duration: 1.4 years |
| CDP estrogen 5, 1975 | estrogen 5.0 mg daily (n=1119) vs. placebo (n=2788) | | Parallel groups Sample size: 1119/2788 Primary endpoint: FU duration: 1.5 years |
| CDP estrogen 2.5, 1975 | estrogen 2.5 mg daily (n=1101) vs. placebo (n=2789) | | Parallel groups Sample size: 1101/2789 Primary endpoint: FU duration: 4.7 years |
| VA drugs (Estrogen or thyroxine), 1968 | estrogen or thyroxine (n=427) vs. placebo (n=143) | | Parallel groups Sample size: 427/143 Primary endpoint: FU duration: 3.2 years |
| ERA (estrogen alone ), 2000 | estrogen alone (0.625 mg of conjugated estrogen per day) (n=100) vs. placebo (n=105) 3 arms: 0.625 mg of conjugated estrogen per day,
0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone
acetate per day, or placebo | Postmenopausal women with established coronary atherosclerosis | double-blind Parallel groups Sample size: 100/105 Primary endpoint: mean minimal coronary-artery diameter FU duration: 3.6y |
| WAVE, 2002 | 0.625 mg/d of conjugated equine estrogen (plus 2.5 mg/d of medroxyprogesterone acetate for women who had not had a hysterectomy) (n=210) vs. placebo (n=213) factorial design of hormone replacement therapy and antioxidant vitamins | Postmenopausal women, up to age 86, with angiographically documented coronary artery disease of at least 15 percent, but no more than 75 percent occlusion | double blind Factorial plan Sample size: 210/213 Primary endpoint: change in minimum lumen diameter from baseline FU duration: 2.8 y |
| WELL-HART (estrogen alone), 2003 | micronized 17beta-estradiol alone (n=76) vs. placebo (n=76) 3 arms: usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group) | Postmenopausal women with angiographically-documented coronary disease | double blind Parallel groups Sample size: 76/76 Primary endpoint: percent stenosis FU duration: 3.3 y |
| Schulman (NHLBI) (estrogen alone), 2002 | intravenous followed by oral
conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen
plus medroxyprogesterone for 21 days (n=100) vs. placebo (n=99) 3 arms: intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days and placebo | Postmenopausal women with unstable angina | double blind Parallel groups Sample size: 100/99 Primary endpoint: number of ischemic episodes FU duration: 6 months |
| EAGAR, 2006 | estradiol +/-medroxyprogesterone (n=44) vs. placebo (n=51) | Postmenopausal women who had undergone coronary artery bypass graft | double blind Parallel groups Sample size: 44/51 Primary endpoint: angiographic study FU duration: 33 months |
| HERS, 1998 | Premarin .625 mg daily plus medroxyprogesterone 2.5 mg daily (n=1380) vs. placebo (n=1383) | women with coronary disease, younger than 80 years, and postmenopausal with an intact uterus | double-blind Cross over Sample size: 1380/1383 Primary endpoint: CHD events FU duration: 4.1 y |
| EPAT, 2001 | micronized 17beta-estradiol (1 mg/d) (n=111) vs. placebo (n=111) | postmenopausal women 45 years of age or older without preexisting cardiovascular disease and with low-density lipoprotein cholesterol levels of 3.37 mmol/L or greater (>/=130 mg/dL) | double-blind Parallel groups Sample size: 111/111 Primary endpoint: intima-media thickness FU duration: 2 y |
| EVTET, 2000 | 2 mg estradiol plus 1 mg norethisterone acetate, 1 tablet daily (n=71) vs. placebo (n=69) | postmenopausal women younger than 70 years who had suffered previous DVT or PE | double-blind Parallel groups Sample size: 71/69 Primary endpoint: recurrent deep venous thrombosis or pulmonary embolism FU duration: 24 months |
| Hall, 1998 | transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally (n=40) vs. placebo (n=20) | postmenopausal women with coronary
artery disease aged 44–75 years | double-blind Parallel groups Sample size: 40/20 Primary endpoint: not defined FU duration: 1 y |
| ESPRIT, 2002 | oestradiol valerate 2 mg daily (n=513) vs. placebo (n=504) | postmenopausal women, age 50-69 years who had survived a first myocardial infarction | double-blind Parallel groups Sample size: 513/504 Primary endpoint: reinfarction or cardiac death, and all-cause mortality FU duration: 24 months |
| WEST, 2001 | estrogen therapy (1 mg of estradiol-17beta per day) (n=337) vs. placebo (n=327) | postmenopausal women who had recently had an ischemic stroke or transient ischemic attack | double-blind Parallel groups Sample size: 337/327 Primary endpoint: stroke or death FU duration: 2.8 y |
| WHI, 2002 | conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n=8506) vs. placebo (n=8102) | postmenopausal women aged 50-79 years with an intact uterus at baseline | double-blind Factorial plan Sample size: 8506/8102 Primary endpoint: coronary heart disease FU duration: 5.2 y |
| WHISP, 2006 | oral oestradiol-17beta 1 mg plus norethisterone acetate 0.5 mg daily (n=49) vs. placebo (n=51) | post-menopausal women >55 years were enrolled between 2 and 28 days after an acute coronary syndrome | double-blind Parallel groups Sample size: 49/51 Primary endpoint: not defined FU duration: 1 y |
| WISDOM, 2007 | combined estrogen and progestogen (n=2196) vs. placebo (n=2189) | postmenopausal women aged 50-69 | double-blind Parallel groups Sample size: 2196/2189 Primary endpoint: major cardiovascular disease, osteoporotic fractures, breast cancer and dementia FU duration: 11.9 months |
| ERA (estrogen plus medroxyprogesterone), 2000 | estrogen plus medroxyprogesterone acetate ( 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day)
(n=104) vs. placebo
(n=105) 3 arms: 0.625 mg of conjugated estrogen per day,
0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone
acetate per day, or placebo
| Postmenopausal women with established coronary atherosclerosis
| double-blind Parallel groups Sample size: 104/105 Primary endpoint: mean minimal coronary-artery diameter FU duration: 3.6y
|
| WELL-HART (estrogen-progestin), 2003 | 17 beta-estradiol plus sequentially administered
medroxyprogesterone acetate (n=74) vs. placebo
(n=76) 3 arms: usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group)
| Postmenopausal women with angiographically-documented coronary disease
| double blind Sample size: 74/76 Primary endpoint: percent stenosis FU duration: 3.3 y
|
| Schulman (NHLBI) (estrogen-progestogen), 2002 | intravenous estrogen followed by oral conjugated estrogen
plus medroxyprogesterone for 21 days
(n=94) vs. placebo
(n=99) 3 arms: intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days and placebo
| Postmenopausal women with unstable angina
| double blind Parallel groups Sample size: 94/99 Primary endpoint: number of ischemic episodes FU duration: 6 months
|
