4S Trial

Summary:

The Scandinavian Simvastatin Survival Study (4S trial) randomized 4,444 patients with acute coronary syndromes to simvastatin vs. placebo. All-cause mortality, fatal coronary events and coronary revascularization procedures were reduced in the simvastatin group. This was regardless of baseline HDL or LDL cholesterol levels. It is not recommended that all acute coronary syndrome patients take life-long statin therapy regardless of their HDL or LDL levels.

Original Publications:

Lancet. 1994 Nov 19;344(8934):1383-9.

Lancet. 1995 May 20;345(8960):1274-5.

Arch Intern Med. 1996 Oct 14;156(18):2085-92.

Trial Details:

Purpose: Evaluate the effect of cholesterol lowering with simvastatin (20-40 mg daily) on mortality and morbidity in patients with heart disease.

Format: Multi-centered, double-blind, randomized controlled trial.

Treatment Group: Simvastatin

Control Group: Placebo 

Number of Patients: 4,444

Inclusion Criteria: Prior MI or clinical coronary disease (angina), total cholesterol 212-309 mg/dL

Exclusion Criteria: 

  • Women of childbearing age
  • Secondary hyperlipidemia
  • Unstable or Prinzmetal angina
  • Tendon xanthomata
  • Planned coronary artery bypass grafting or angioplasty
  • Recent myocardial infarction within 6 months
  • Antiarrhythmic drug therapy
  • Congestive heart failure (CHF)
  • Persistent atrial fibrillation
  • Cardiomegaly
  • Significant valvular heart disease
  • Prior stroke
  • Impaired hepatic function
  • Peripheral arterial disease with partial ileal bypass
  • History of drug or alcohol abuse
  • Poor mental function
  • Other serious disease
  • Current treatment with another investigational drug
  • Hypersensitivity to HMG-CoA reductase inhibitors

Follow-up: Averaged 5.4 years 

Primary Endpoint(s): All-cause mortality

Secondary Endpoint(s): MACE (Major Adverse Cardiac Events), coronary revascularization, event-free survival, coronary events, non-coronary cardiac events