CURE trial

CURE trial
Name	CURE trial
Full name	Clopidogrel in Unstable angina to prevent Recurrent Events
Type	Randomized controlled trial
Started	1999
Completed	2001
Primary outcome	Composite of cardiovascular death, nonfatal myocardial infarction, or stroke

CURE trial The CURE trial was a landmark randomized controlled trial evaluating the addition of clopidogrel to aspirin for patients with acute coronary syndromes without ST-segment elevation. The study influenced guidelines from organizations such as American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence, and affected practice in hospitals like Mayo Clinic, Cleveland Clinic, and Massachusetts General Hospital.

Background

The trial arose amid debates following earlier studies like ISIS-2, GUSTO, and CLAP regarding antiplatelet strategies after presentations such as unstable angina and non–ST-elevation myocardial infarction. Key investigators and steering committees included clinicians affiliated with institutions such as Harvard Medical School, Johns Hopkins Hospital, and University of Oxford, and the sponsor interactions involved pharmaceutical companies like Sanofi and Bristol-Myers Squibb. Regulatory and guideline contexts included discussion at bodies such as Food and Drug Administration, European Medicines Agency, and professional meetings like the American College of Cardiology Annual Scientific Session.

Trial Design

CURE was an international, randomized, double-blind, placebo-controlled trial modeled on factorial designs used in trials such as PARIS and CURE-NSTEMI substudies. Randomization procedures referenced standards from CONSORT and data monitoring used independent committees similar to those in ISIS and GUSTO. Endpoints mirrored composite outcomes used in FRISC-II and TACTICS-TIMI 18 and employed adjudication frameworks used in TIMI studies and registries such as GRACE.

Participants and Setting

The trial enrolled patients presenting with acute coronary syndromes across sites in regions including United States, United Kingdom, Canada, Australia, Japan, and France, with participating centers including Royal Brompton Hospital, St Thomas' Hospital, and large tertiary centers such as Beth Israel Deaconess Medical Center. Eligibility criteria referenced prior cohorts from FRISC-II and definitions from consensus statements by World Health Organization panels and committees at European Society of Cardiology. The demographic and clinical characterization paralleled registries like Get With The Guidelines and trials such as TIMI 11B.

Interventions and Outcomes

Participants received either clopidogrel plus aspirin or placebo plus aspirin, with dosing strategies informed by pharmacology studies from groups at University of California, San Francisco, Karolinska Institutet, and University of Maastricht. Primary outcome was a composite including cardiovascular death, nonfatal myocardial infarction, and stroke, similar to endpoints in CHARISMA and TRITON-TIMI 38. Secondary outcomes included urgent revascularization and refractory ischemia as captured in prior trials like RITA-3 and SYNTAX analyses. Statistical methods used hazard ratios and Kaplan–Meier curves analogous to those in PROVE IT-TIMI 22.

Results

The trial demonstrated a reduction in the primary composite outcome with clopidogrel plus aspirin compared with aspirin alone, echoing findings from antiplatelet research including CREDO and influencing interpretation alongside trials such as TRITON-TIMI 38. Subgroup analyses referenced populations characterized in PLATO and observational cohorts like CRUSADE. Outcomes were presented at major meetings including the American Heart Association Scientific Sessions and published in journals similar to The New England Journal of Medicine and The Lancet.

Safety and Adverse Events

Clopidogrel was associated with increased bleeding risk, a finding consistent with safety signals seen in studies such as TRITON-TIMI 38 and surveillance programs coordinated with agencies like Food and Drug Administration and European Medicines Agency. Bleeding classifications used frameworks from TIMI and GUSTO, and peri-procedural bleeding issues were discussed in relation to practices at centers like Cleveland Clinic and recommendations from Society for Cardiovascular Angiography and Interventions.

Impact and Legacy

The trial led to guideline changes by organizations including European Society of Cardiology, American College of Cardiology, and National Institute for Health and Care Excellence recommending dual antiplatelet therapy in selected presentations, and it informed subsequent trials such as CHARISMA, CREDO, and PLATO. Its findings influenced practice in cardiology departments at institutions like Mount Sinai Hospital, Stanford Health Care, and University College Hospital, and shaped regulatory labeling by Food and Drug Administration and post-marketing research coordinated by academic centers including Duke University Hospital and Vanderbilt University Medical Center.

Category:Clinical trials