darapladib and Angina--Unstable

Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.. Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.. In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).. The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.

Topics: Angina, Unstable; Benzaldehydes; Coronary Disease; Endpoint Determination; Heart Failure; Hospitalization; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Myocardial Infarction; Oximes; Percutaneous Coronary Intervention; Phospholipase A2 Inhibitors; Placebos; Stroke

High-potency statins reduce cardiovascular events after acute coronary syndromes but remain underused in clinical practice. We examined predictors of nonuse of high-potency statins after acute coronary syndromes.. The Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial enrolled patients after an acute coronary syndrome in 36 countries between 2009 and 2011. Statin use was strongly encouraged throughout the trial, and statin potency was at the discretion of the treating physician. A high-potency statin was defined as ≥40 mg atorvastatin, ≥20 mg rosuvastatin, or 80 mg simvastatin daily. Predictors of nonuse of high-potency statins were examined using logistic regression. Of the patients included (n=12 446), 11 850 (95.2%) were treated with a statin at baseline after acute coronary syndrome (median 14 days), but only 5212 (41.9%) were on a high-potency statin. Selected patient factors associated with nonuse of high-potency statins included age ≥75 years (odds ratio 1.39, 95% CI 1.24-1.56), female sex (odds ratio 1.11, 95% CI 1.02-1.22), renal dysfunction (odds ratio 1.17, 95% CI 1.03-1.32), and heart failure during hospital admission (odds ratio 1.43, 95% CI 1.27-1.62). At 3 months after baseline, only 49% of patients had low-density lipoprotein cholesterol <70 mg/dL. Among the 5490 patients (59%) who were not on a high-potency statin at 3 months, lower low-density lipoprotein cholesterol was a predictor of nonuse of a high-potency statin after a median of 2.3 years (odds ratio 1.15 for 10 mg/dL decrease, 95% CI 1.11-1.19).. Despite the widespread use of statins after acute coronary syndromes, most patients are not treated with high-potency statins early and late after the event, including patients at the highest risk of recurrent cardiovascular events.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01000727.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angina, Unstable; Atorvastatin; Benzaldehydes; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Oximes; Phospholipase A2 Inhibitors; Practice Patterns, Physicians'; Randomized Controlled Trials as Topic; Renal Insufficiency; Rosuvastatin Calcium; Secondary Prevention; Sex Factors; Simvastatin