When Clinical Trials Fail to Address Treatment Gaps: The Failure of Niacin-Laropiprant to Reduce Cardiovascular Events

Abstract

Introduction: The Heart Protection Study-2-THRIVE trial (official title: A Randomized Trial of the Long-term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant) was designed to investigate the effect raising HDL cholesterol (HDL-C) with extended release niacin (ERN) 2 g plus laropiprant (LRPT) 40mg daily versus placebo on the time to the first major vascular event (composite of nonfatal myocardial infarction [MI], coronary heart disease [CHD] death, stroke, or arterial revascularization) in patients with a history of occlusive arterial disease (MI, ischemic stroke or transient ischemic attack, peripheral arterial disease, or diabetes with other CHD) who were receiving simvastatin 40 mg daily as background therapy. Methods: Prior to randomization, the trial incorporated a runin phase in which 42,424 participants received open-label treatment with simvastatin 40 mg daily to achieve a total cholesterol level<135 mg/dL (3.5 mmol/L) or simvastatin 40 mg/ezetimibe 10 mg daily when this goal was not achieved. In the second part of the run-in phase, the remaining 38,369 participants received ERN/LRPT 1 g/40 mg nightly for 4 weeks followed by ERN/LRPT 2 g/40 mg nightly for an additional 3 to 6 weeks. At the end of the run-in phase, participants were randomized into the trial if they were able to tolerate the study medications and their adherence to ERN/LRPT and simvastatin or simvastatin/ezetimibe was 90 % or higher. A total of 25,673 participants were randomized to receive ERN/LRPT or placebo, and were followed for a median of 3.9 years.