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NHLBI Statement on Use of Rosiglitazone in Two NHLBI-Funded Clinical Trials

For Immediate Release:
June 15, 2007

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health supports two clinical trials testing approaches that use rosiglitazone to reduce cardiovascular disease in people with diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.  Rosiglitazone (Avandia) is a drug used to treat type 2 diabetes.  Neither ACCORD nor BARI 2D is specifically testing the effect of rosiglitazone.  Rather, each trial tests a question of treatment strategy, not any specific drug.

Recently published studies on the effect of rosiglitazone on cardiovascular disease and death1,2 prompted the Institute to ask the ACCORD and BARI 2D Data and Safety Monitoring Boards (DSMBs) to conduct a thorough review of the safety of participants enrolled in each trial, including study interim data, and to consider the implications of the recent reports for the conduct of the trials.

The DSMBs of both ACCORD and BARI 2D found no evidence to require discontinuing the use of rosiglitazone in the trials or to revise the study protocols.  Because ACCORD is testing a strategy of intensive blood sugar lowering using multiple medications, the ACCORD DSMB additionally recommended that participants who wish to discontinue taking rosiglitazone should have the option of using alternate medications after discussion with their study physician.  The NHLBI has thoroughly reviewed the recent findings and accepts the recommendations of both DSMBs.

NHLBI-appointed DSMBs serve as independent advisory groups.  They review the safety of study participants on an ongoing basis. DSMB members have extensive expertise in patient care, clinical trials, study participant safety, statistics, and medical ethics.  The DSMBs of the ACCORD and BARI 2D studies also include physicians with specific expertise in diabetes. 

One of the recent published reports reviewed by the DSMBs, an analysis that combined data from 42 clinical trials, concluded that rosiglitazone may be associated with an increased risk of heart attack.  The report also found a trend (not statistically significant) for increased cardiovascular deaths from rosiglitazone.  The other report reviewed by the DSMBs was from a clinical trial called RECORD, which was conducted by the drug's manufacturer.  RECORD reported no significant increase in cardiovascular deaths or death from any cause, and no significant increase in heart attack rates, but did report an increased risk of heart failure from rosiglitazone.

ACCORD is a multicenter clinical trial designed to compare intensive versus standard control of blood sugar, blood pressure, and blood lipids in reducing the rate of major cardiovascular disease events in adults with type 2 diabetes.  Rosiglitazone is one of many medications used in ACCORD to achieve blood sugar control. The primary outcome of the trial is a composite of deaths from cardiovascular causes, non-fatal heart attack, and non-fatal stroke. The trial is also evaluating total deaths, health-related quality of life, and cost-effectiveness. ACCORD has enrolled 10,251 adult patients in 77 clinical sites in the United States and Canada.

The BARI 2D trial is testing two approaches to controlling blood sugar in 2,368 patients with type 2 diabetes and known coronary artery disease.  The approaches are to (1) provide insulin or insulin-stimulating medication such as a sulfonylurea, or (2) provide medication that sensitizes the body to the available insulin (such as rosiglitazone).  At the same time, BARI 2D is testing whether a treatment regimen that includes initial elective treatment with angioplasty or bypass surgery is better than a regimen that initially relies only on medical management.

1Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356:2457-71

2Home, PD, Pocock, S, et al.  Rosiglitazone evaluated for cardiovascular outcomes – an interim analysis.  N Engl J Med 2007; 10.1056/NEJMoa073394 at on June 5, 2007.