Search

Importance: The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain., Objective: To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management., Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017., Interventions: Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication., Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days., Results: Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group., Conclusions and Relevance: Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management., Trial Registration: clinicaltrials.gov Identifier: NCT01448642.

Background: Early termination of clinical trials due to low recruitment represents an understudied challenge for clinical research. We aimed to describe characteristics of cardiovascular trials terminated because of low recruitment and identify the major predictors of such early termination., Methods: We reviewed all cardiovascular clinical trials (7,042 studies) registered in ClinicalTrials.gov from February 29, 2000, to January 17, 2013, and assessed information about trials that were completed and those that were terminated early. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment., Results: Our search strategy identified 6,279 cardiovascular clinical trials, of which 684 (10.9%) were terminated prematurely. Of these halted trials, the main reason for termination was lower than expected recruitment (278 trials; 53.6%). When comparing trials that terminated early because of low recruitment with those that were completed, we found that studies funded by the National Institutes of Health or other US federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital-funded (OR 1.52, 95% CI 1.10-2.10) and mixed-source-funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates., Conclusions: Low recruitment represents the main cause of early termination of cardiovascular clinical trials. Funding source, type of intervention, and study design are factors associated with early termination due to low recruitment and might be good targets for improving enrollment into cardiovascular clinical trials., (Copyright © 2014 Mosby, Inc. All rights reserved.)