y 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). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p<0.0001). Treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetic patients showed risk reductions for MCE and MVE (27% and 22%, respectively; p<0.0001) due to simvastatin treatment regardless of baseline A1C levels or obesity with the greatest effects seen for diabetic patients without CHD.
Figure 3 The Effects of Treatment with Simvastatin on Major Vascular Events and Major Coronary Events in HPS
N = number of patients in each subgroup. The inverted triangles are point estimates of the relative risk, with their 95% confidence intervals represented as a line. The area of a triangle is proportional to the number of pati |
