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

详细信息    查看全文

• 作者：Harvey White ; Claes Held ; Ralph Stewart ; David Watson ; Robert Harrington ; Andrzej Budaj ; Ph. Gabriel Steg ; Christopher P. Cannon ; Susan Krug-Gourley ; Janet Wittes ; Trupti Trivedi ; Elizabeth Tarka ; Lar
• 刊名：American Heart Journal
• 出版年：2010
• 出版时间：October 2010
• 年：2010
• 卷：160
• 期：4
• 页码：655-661.e2
• 全文大小：341 K

文摘

Background

Elevated plasma levels of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) 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-PLA₂ with darapladib added to the standard of care confers clinical benefit to patients with CHD.