Ehvidence
Favorable Efficacy (RCT)

Statins for secondary prevention

Statin therapy vs. Placebo · for Established cardiovascular disease · real-time analysis of 4 studies · updated 2026-05-29

In people who already have cardiovascular disease, statins reduce major cardiovascular events, coronary death, stroke, and all-cause mortality. The relative reductions are similar to primary prevention, but because baseline risk is much higher the absolute benefit is larger and the number-needed-to-treat far smaller.

Efficacy (RCT): Efficacy evidence on clinical outcomes. Effects are risk ratios with number-needed-to-treat where a baseline risk is available. Glossary →

Interpretation & tips

Same drug class as primary prevention, but higher baseline risk makes NNTs far smaller (~12–35 over five years vs dozens to hundreds). 4S (1994) first showed a statin cuts all-cause mortality. HPS enrolled a mixed high-risk population (~two-thirds prior CHD), not pure secondary prevention. The CTT meta-analyses report effects per 1.0 mmol/L LDL reduction—a different scale than the raw ratios here.

24% lower risk of major cardiovascular events
Pooled RR 0.76 (95% CI 0.72–0.80) across 4 studies, 38,153 patients (random-effects, I² 30%).
0.76
Pooled RR
0.72–0.80
95% CI
4
Studies
38,153
Patients
17
NNT

Forest plot—Major cardiovascular events

HPS 2002 0.79 [0.75–0.83] LIPID 1998 0.76 [0.68–0.85] CARE 1996 0.76 [0.64–0.91] 4S 1994 0.69 [0.62–0.77] Pooled (RE) 0.76 [0.72–0.80] 0.1 0.25 0.5 1 2 4 ← favors treatment favors control →

Study results—Major cardiovascular events

Study Design Dose / regimen Treatment Control RR [95% CI] Improvement NNT Weight
HPS 2002 note DB-RCT Simvastatin 40 mg 2033/10269 2585/10267 0.79 [0.75–0.83] 21% 19 49%
LIPID 1998 note DB-RCT Pravastatin 40 mg — — 0.76 [0.68–0.85] 24% 27 20%
CARE 1996 note DB-RCT Pravastatin 40 mg — — 0.76 [0.64–0.91] 24% 32 10%
4S 1994 note DB-RCT Simvastatin 20-40 mg 431/2221 622/2223 0.69 [0.62–0.77] 31% 12 21%

RR < 1 favors treatment for outcomes where lower is better. Rows in gray have a confidence interval crossing 1 (individually inconclusive). “~” marks effects reported as OR/HR and treated as RR-approximations. “excl” = excluded from pooling (e.g. reviews).

Notes & interpretation

  • HPS 2002—Major vascular events. Mixed high-risk population, not pure secondary prevention.
  • LIPID 1998—CHD death or nonfatal MI; RR from reported RRR 24% (95% CI 15-32%).
  • CARE 1996—CHD death or nonfatal MI; RR from reported RRR 24% (95% CI 9-36%).
  • 4S 1994—Major coronary events. The trial that first showed a statin reduces all-cause mortality.

Background

Secondary prevention treats people with established cardiovascular disease (prior MI, established CHD, prior stroke). Landmark placebo-controlled trials (4S, CARE, LIPID) and the high-risk Heart Protection Study established that statins cut recurrent events and death; the CTT meta-analyses confirmed benefit proportional to LDL reduction.

Topic methodology & caveats

Risk ratios from reported event counts (2×2) for 4S, CARE, and HPS; LIPID and several outcomes are entered as reported ratios with CIs derived from published relative-risk reductions. Some stroke figures are post hoc. CTT (per 1.0 mmol/L) is described, not pooled here.

Studies