#Timi trials trial#
8 The current phase 3 trial evaluated the efficacy and safety of darapladib on a background of optimal medical therapy in patients recently hospitalized with acute coronary syndrome (ACS). 7 In the STABILITY trial (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy), darapladib did not significantly reduce the primary end point of cardiovascular death, myocardial infarction (MI), or stroke in patients with stable CHD (hazard ratio, 0.94 P = .20) however, darapladib nominally reduced the occurrence of secondary end points including major coronary events (HR, 0.90 P = .045) and total coronary events (HR, 0.91 P = .02). 6 In phase 2 testing, darapladib did not modify total coronary atheroma volume when compared with placebo on a background of statin therapy, but it appeared to prevent necrotic core expansion as assessed by intravascular ultrasound virtual histology. 4ĭarapladib is a selective Lp-PLA 2 inhibitor that reduces Lp-PLA 2 activity in plasma 5 and in atherosclerotic plaques. 3 Further, in 2 case-control studies, natural deficiency of Lp-PLA 2 activity due to carriage of the V279F null allele in the Lp-PLA 2 gene was associated with a lower risk of developing coronary heart disease (CHD). 2 Lp-PLA 2 has been shown to be highly concentrated in unstable and ruptured atherosclerotic plaques.
1 A number of epidemiologic studies have shown that higher circulating levels of Lp-PLA 2 activity or mass are associated with an increased risk of coronary events in primary and stable secondary prevention cohorts. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) has been hypothesized to play a causal role in the development of atherosclerosis and to contribute to plaque instability through pathways related to inflammation.
#Timi trials registration#
Trial Registration Identifier: NCT01000727 Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5% vs 2.5%) and also more likely to report diarrhea (10.6% vs 5.6%).Ĭonclusions and Relevance In patients who experienced an ACS event, direct inhibition of Lp-PLA 2 with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events.
There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group P = .40). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0% vs 15.0% at 3 years HR, 0.99 P = .78). Results During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3% vs 15.6% at 3 years hazard ratio, 1.00 P = .93). Kaplan-Meier event rates are reported at 3 years. Main Outcomes and Measures The primary end point (major coronary events) was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization for myocardial ischemia. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. Interventions Patients were randomized to either once-daily darapladib (160 mg) or placebo on a background of guideline-recommended therapy. Objective To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event.ĭesign, Setting, and Participants SOLID-TIMI 52 was a multinational, double-blind, placebo-controlled trial that randomized 13 026 participants within 30 days of hospitalization with an ACS (non–ST-elevation or ST-elevation myocardial infarction ) at 868 sites in 36 countries. Darapladib is an oral, selective inhibitor of the Lp-PLA 2 enzyme. Importance Lipoprotein-associated phospholipase A 2 (Lp-PLA 2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience.Challenges in Clinical Electrocardiography.
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