Homocysteine levels and treatment effect in the PROspective Study of Pravastatin in the Elderly at Risk

J Am Geriatr Soc. 2014 Feb;62(2):213-21. doi: 10.1111/jgs.12660. Epub 2014 Jan 21.

Abstract

Objectives: To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.

Design: A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.

Setting: Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).

Participants: Individuals (n = 3,522, aged 70-82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.

Intervention: Pravastatin (40 mg) versus placebo.

Measurements: Fatal and nonfatal CHD and mortality.

Results: In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2-2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = -1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7-10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11-10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3-36.6) for high homocysteine and 64.5 (95% CI = 21.4-∞) for low homocysteine.

Conclusion: In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.

Keywords: cardiovascular risk; homocysteine; older persons; prevention; statins.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Coronary Disease / mortality
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Homocysteine / blood*
  • Homocysteine / drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Netherlands / epidemiology
  • Pravastatin / administration & dosage
  • Pravastatin / therapeutic use*
  • Prospective Studies
  • Scotland / epidemiology
  • Survival Rate / trends
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Homocysteine
  • Pravastatin