Bayesian Meta-Analysis of Tissue Angiotensin-Converting Enzyme Inhibitors for Reduction of Adverse Cardiovascular Events in Patients with Diabetes Mellitus and Preserved Left Ventricular Function

Abstract

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients with preserved ventricular function is uncertain. Tissue ACE inhibitors have been defined by increased lipophilicity and structural characteristics that result in greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE inhibitors in prevention of cardiovascular disease among patients with diabetes mellitus and preserved left ventricular function. Four trials were selected that evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta-analysis of sequential trials and sensitivity analysis of therapeutic response were subsequently computed. Bayesian meta-analysis determined reduced risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need for invasive coronary revascularization (PB=.995) when compared with placebo. Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease the probability that diabetic patients with preserved left ventricular function will experience myocardial infarctions and cardiovascular death and reduce overall mortality.