The Anglo-Scandinavian Cardiac Outcomes Trial lipid lowering arm: extended observations 2 years after trial closure

Eur Heart J. 2008 Feb;29(4):499-508. doi: 10.1093/eurheartj/ehm583. Epub 2008 Jan 5.

Abstract

Aims: To determine the cardiovascular benefits in those originally assigned atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial-2.2 years after closure of the lipid-lowering arm of the trial (ASCOT-LLA).

Methods and results: The Blood Pressure Lowering Arm of the ASCOT trial (ASCOT-BPLA) compared two different antihypertensive treatment strategies on cardiovascular outcomes. ASCOT-LLA was a double-blind placebo-controlled trial of atorvastatin in those enrolled into ASCOT-BPLA with total cholesterol concentrations at baseline of < or =6.5 mmol/L. A total of 19 342 hypertensive patients were enrolled in ASCOT-BPLA and 10 305 were further assigned either atorvastatin, 10 mg, or placebo. ASCOT-LLA was stopped prematurely after a median 3.3 years follow-up because of substantial cardiovascular benefits in those assigned atorvastatin. Trial physicians were invited to offer atorvastatin to all ASCOT-LLA patients until the end of ASCOT-BPLA. The primary outcome of ASCOT-LLA was combined fatal coronary heart disease (CHD) or non-fatal myocardial infarction. Secondary outcomes included all coronary events, all cardiovascular events and procedures, fatal and non-fatal stroke, cardiovascular mortality, all cause mortality, development of chronic stable angina, heart failure, and peripheral arterial disease. By the end of ASCOT-LLA, there was a 36% relative risk reduction in primary events (n = 254) in favour of atorvastatin [hazard ratio (HR) 0.64, 95% CI: 0.50-0.83, P = 0.0005]. At the end of ASCOT-BPLA, 2.2 years later, despite extensive crossovers from and to statin usage, the relative risk reduction in primary events (n = 412) among those originally assigned atorvastatin remained at 36% (HR 0.64, 95% CI: 0.53-0.78, P = 0.0001). For almost all other endpoints, risk reductions also remained essentially unchanged and in the case of all cause mortality, the risk reduction of 15% now achieved borderline statistical significance (P = 0.02).

Conclusion: Carry-over benefits from those originally assigned atorvastatin but no longer taking the drug may account for unchanged relative risk reductions in most cardiovascular endpoints observed 2 years after ASCOT-LLA closed.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Antihypertensive Agents / therapeutic use
  • Atorvastatin
  • Coronary Disease / mortality
  • Coronary Disease / prevention & control*
  • Epidemiologic Methods
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / prevention & control*
  • Hypertension / drug therapy
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control*
  • Pyrroles / therapeutic use*
  • Stroke / mortality
  • Stroke / prevention & control

Substances

  • Anticholesteremic Agents
  • Antihypertensive Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Atorvastatin