ng major coronary events by 34% (60 vs 91 women with one or more event). The randomization was stratified by angina alone (21% of each treatment group) or a previous MI. Because there were only 57 deaths among the patients with angina alone at baseline, the effect of simvastatin on mortality in this subgroup could not be adequately assessed. However, trends in reduced coronary mortality, major coronary events and revascularization procedures were consistent between this group and the total study cohort. Additionally, simvastatin resulted in similar decreases in relative risk for total mortality, CHD mortality, and major coronary events in elderly patients (≥65 years), compared with younger patients.
The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on simvastatin 40 mg and 10,267 on placebo), including 5963 patients with diabetes mellitus (2978 on simvastatin and 2985 on placebo). Patients were allocated to treatment using a covariate adaptive method which took into account the distribution of 10 important baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients had a mean age of 64 years (range 40-80 years), were 97% Caucasian and were at high risk of developing a major coronary event because of existing CHD (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males ≥65 years (6%). At baseline, 3421 patients (17%) had LDL-C levels below 100 mg/dL, of whom 953 (5%) had LDL-C levels below 80 mg/dL; 7068 patients (34%) had levels between 100 and 130 mg/dL; and 10,047 patients (49%) had levels greater than 130 mg/dL.
The HPS results showed that simvastatin 40 mg/day significantly reduced: total and CHD mortality; non-fatal MI, stroke, and revascularization procedures (coronary and non-coronary) (see Table 16).
Table 16: Summary of Heart Protection Study Results Endpoint Simvastatin
(N=10,269)
n (%)* Placebo
(N=10,267)
n (%)* Risk Reduction
(%) (95% CI) p-Value
*
n = number of patients with indicated event
Primary
Mortality 1328 (12.9) 1507 (14.7) 13 (6-19) p=0.0003
CHD mortality 587 (5.7) 707 (6.9) 18 (8-26) p=0.0005
Secondary
Non-fatal MI 357 (3.5) 574 (5.6) 38 (30-46) p<0.0001
Stroke 444 (4.3) 585 (5.7) 25 (15-34) p<0.0001
Tertiary
Coronary revascularization 513 (5) 725 (7.1) 30 (22-38) p<0.0001
Peripheral and other non-coronary revascularization 450 (4.4) 532 (5.2) 16 (5-26) p=0.006
Two composite endpoints were defined in order to have sufficient events to assess relative risk reductions across a range of baseline characteristics (see Figure 3). A composite of major coronary events (MCE) was comprised of CHD mortality and non-fatal MI (analyzed by time-to-first event; 898 patients treated with simvastatin had events and 1212 patients on placebo had events). A composite of major vascular events (MVE) was comprised of MCE, stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures (analyzed by time-to-first event; 2033 patients treated with simvastatin had events and 2585 patients on placebo had events
