Mortality Reduction Associated With β-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes

Abstract

OBJECTIVEDiabetes increases mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction. Studies have questioned the safety of b-adrenoceptor blockers (b-blockers) in some patients with diabetes and reduced left ventricular ejection fraction. We examined whether b-blockers and ACE inhibitors (ACEIs) are associated with differential effects on mortality in CHF patients with and without diabetes. RESEARCH DESIGN AND METHODSWe conducted a prospective cohort study of 1,797 patients with CHF recruited between 2006 and 2014, with mean follow-up of 4 years. b-Blocker dose was expressed as the equivalent dose of bisoprolol (mg/day) and ACEI dose as the equivalent dose of ramipril (mg/day). Cox regression analysis was used to examine the interaction between diabetes and drug dose on all-cause mortality. RESULTSPatients with diabetes were prescribed larger doses of b-blockers and ACEIs than were patients without diabetes. Increasing b-blocker dose was associated with lower mortality in patients with diabetes (8.9% per mg/day; 95% CI 5-12.6) and without diabetes (3.5% per mg/day; 95% CI 0.7-6.3), although the effect was larger in people with diabetes (interaction P = 0.027). Increasing ACEI dose was associated with lower mortality in patients with diabetes (5.9% per mg/day; 95% CI 2.5-9.2) and without diabetes (5.1% per mg/day; 95% CI 2.6-7.6), with similar effect size in these groups (interaction P = 0.76). CONCLUSIONSIncreasing b-blocker dose is associated with a greater prognostic advantage in CHF patients with diabetes than in CHF patients without diabetes.Chronic heart failure (CHF) associated with left ventricular systolic dysfunction is a global health care problem affecting more than 26 million individuals (1,2). More than one-third of these people will also suffer from diabetes (3,4). A recent study of 1.9 million individuals demonstrated that CHF was second only to peripheral artery disease as a cardiovascular complication of type 2 diabetes (5). In addition to being an important risk factor for the development of CHF, diabetes also imparts a significant prognostic disadvantage to patients with established CHF (6-8). In a large prospective cohort study specifically designed to examine prognostic factors in CHF associated with

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