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 todarapladib 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.
RCT Entities:
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.
Authors: Harald Grallert; Josée Dupuis; Joshua C Bis; Abbas Dehghan; Maja Barbalic; Jens Baumert; Chen Lu; Nicholas L Smith; André G Uitterlinden; Robert Roberts; Natalie Khuseyinova; Renate B Schnabel; Kenneth M Rice; Fernando Rivadeneira; Ron C Hoogeveen; João Daniel Fontes; Christa Meisinger; John F Keaney; Rozenn Lemaitre; Yurii S Aulchenko; Ramachandran S Vasan; Stephen Ellis; Stanley L Hazen; Cornelia M van Duijn; Jeanenne J Nelson; Winfried März; Heribert Schunkert; Ruth M McPherson; Heide A Stirnadel-Farrant; Bruce M Psaty; Christian Gieger; David Siscovick; Albert Hofman; Thomas Illig; Mary Cushman; Jennifer F Yamamoto; Jerome I Rotter; Martin G Larson; Alexandre F R Stewart; Eric Boerwinkle; Jacqueline C M Witteman; Russell P Tracy; Wolfgang Koenig; Emelia J Benjamin; Christie M Ballantyne Journal: Eur Heart J Date: 2011-10-14 Impact factor: 29.983
Authors: V A Tyurin; K Balasubramanian; D Winnica; Y Y Tyurina; A S Vikulina; R R He; A A Kapralov; C H Macphee; V E Kagan Journal: Cell Death Differ Date: 2014-01-24 Impact factor: 15.828