Cardiovascular Clinical Trials in Patients With Diabetes Mellitus

Abstract

Diabetes mellitus is a well-established risk factor for virtually all cardiovascular outcomes, with clinical trials and observational studies demonstrating greater mortality, more myocardial infarctions, and more episodes of heart failure in diabetic than in nondiabetic individuals.1–6 Moreover, diabetes mellitus is often associated with other cardiovascular risk factors, including hypertension and hyperlipidemia. The increased risk for adverse cardiovascular outcomes has made diabetic patients a particularly relevant target group for therapies that reduce cardiovascular risk because diabetic patients appear to benefit as much as or more than nondiabetic patients from successful cardiovascular therapies.7–9 Clinical trials that have assessed strategies to reduce cardiovascular risk in diabetic populations have generally focused on treatment of factors that have been linked to higher risk of cardiovascular disease, such as blood pressure, lipid levels, or albuminuria. Trials of therapies for these risk factors in exclusively diabetic populations benefit from higher overall event rates, which translate to increased power in clinical trials, so that therapies can be tested in fewer patients at lower cost. Although this approach may come at the expense of a broad indication for a specific therapy, the increasing worldwide prevalence of diabetes mellitus somewhat mitigates this concern and makes trials exclusively in diabetic populations financially more palatable for sponsors. Another reason to test therapies exclusively in a specific patient population is the finding of differential benefit in that population. Such a differential benefit in diabetic patients was observed in a subgroup analysis of the original Bypass Angioplasty Revascularization Investigation (BARI) trial, which randomized patients with multivessel coronary disease to either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).10 Although BARI showed no difference between those randomized to PCI or those randomized to CABG, CABG appeared superior in the subgroup of diabetic patients. Whether this differential benefit was a result …