Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease

Am Heart J. 2010 Oct;160(4):655-61. doi: 10.1016/j.ahj.2010.07.006.

Abstract

Background: Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with increased risk of cardiovascular (CV) events. Direct inhibition of this proinflammatory enzyme with darapladib may benefit CV patients when given as an adjunct to standard of care, including lipid-lowering and antiplatelet therapies.

Methods: STABILITY is a randomized, placebo-controlled, double-blind, international, multicenter, event-driven trial. The study has randomized 15,828 patients with chronic coronary heart disease (CHD) receiving standard of care to darapladib enteric-coated (EC) tablets, 160 mg or placebo.

Results: The primary end point is the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary end points will include major coronary events, total coronary events, individual components of MACE, and all-cause mortality. Prespecified substudies include 24-hour ambulatory blood pressure monitoring, albuminuria progression, changes in cognitive function, and pharmacokinetic and biomarker analyses. Health economic outcomes and characterization of baseline lifestyle risk factors also will be assessed. The study will continue until 1,500 primary end points have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be 2.75 years.

Conclusions: STABILITY will assess whether direct inhibition of Lp-PLA(2) with darapladib added to the standard of care confers clinical benefit to patients with CHD.

Publication types

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

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / antagonists & inhibitors
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase / blood
  • Administration, Oral
  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / physiopathology
  • Benzaldehydes / administration & dosage*
  • Benzaldehydes / pharmacokinetics
  • Biomarkers / blood
  • Blood Pressure Monitoring, Ambulatory
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Coronary Disease / physiopathology
  • Double-Blind Method
  • Electrocardiography / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Oximes / administration & dosage*
  • Oximes / pharmacokinetics
  • Tablets, Enteric-Coated
  • Treatment Outcome

Substances

  • Benzaldehydes
  • Biomarkers
  • Oximes
  • Tablets, Enteric-Coated
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • darapladib