Medication use may be associated with increased risk of mortality.
New research suggests that the use of beta-blockers may be associated with an increased mortality risk in patients with diabetes, particularly among those who have coronary heart disease (CHD).
A prospective cohort study was done to assess the relationship between use of β-blockers and all-cause mortality in patients with and without diabetes, using data from the U.S. National Health and Nutrition Examination Survey 1999-2010. The study participants were followed-up from the survey participation date until December 31, 2011 and used a Cox proportional hazards model for all-cause mortality analysis. The multivariate-adjusted hazard ratios (HRs) of the participants taking β-blockers were compared with those of the participants not taking β-blockers.
Beta-adrenergic receptor blockers have been shown to improve survival in patients following myocardial infarction (MI), and in those with congestive heart failure (CHF) because of left ventricular systolic dysfunction.
The study population was comprised of 2,840 participants with diabetes (of whom 697 were taking beta-blockers) and 14,684 without diabetes, including 1,584 who were taking beta-blockers. Both CHD and CHF were more prevalent in those taking, versus not taking, beta-blockers (P < .001).
Among those with diabetes, all-cause death event rates per 1,000 person-years were 40.6 for those taking beta-blockers versus 17.1 for those not taking them. Among participants without diabetes, those rates were 13.8 and 5.9, respectively. In multivariate analysis, the adjusted hazard ratio (HR) for all-cause mortality among those with diabetes for those taking, versus not taking, beta-blockers was 1.49 (P =.01).
Similar results were found for those taking β1-selective beta-blockers (adjusted HR, 1.60; P =.007) and those taking specific beta-blockers (bisoprolol, metoprolol, and carvedilol) compared with those not taking beta-blockers (adjusted HR, 1.55; P =.01).
Among participants without diabetes, the adjusted HR didn’t differ significantly between those taking and not taking beta-blockers (0.99; P = .96). In addition, all-cause mortality was significantly higher among those with diabetes and CHD who were taking beta-blockers versus those who weren’t (adjusted HR, 1.64; P =.02), whereas the risk was significantly lower with beta-blockers among those who had CHD but didn’t have diabetes (adjusted HR, 0.68; P =.02).
Dr. Tetsuro Tsujimoto, lead researcher, added that, “Beta-blockers have never been found to improve survival in all other patients with stable CHD in the absence of MI or CHF without systolic dysfunction. Moreover, the efficacy of beta-blockers in diabetic patients with CHD/CHF remains unknown.” Tsujimoto and colleagues conclude, “Use of beta-blockers may be associated with an increased risk of mortality for patients with diabetes and among the subset who have CHD.”
Franz Meserli, MD, and Thomas Suter, MD, of the Department of Cardiology and Clinical Research, University Hospital Bern, Switzerland, and Sripal Bangalore, MD, Leon H Charney Division of Cardiology New York University School of Medicine, wrote that, under the umbrella of cardioprotection, solid evidence gathered in these post-MI trials has been uncritically extrapolated to other indications, such as hypertension, diabetes, chronic kidney disease, and even cerebrovascular disease. Despite the lack of evidence, the marketing of beta-blockers for such comprehensive cardioprotection proved to be exceedingly successful, and many of these ill-documented beta-blocker indications have persisted in the minds of healthcare providers up to today.
The study authors pointed out that much of the data in support of beta-blocker benefit come from studies carried out decades ago, prior to the era of reperfusion and current pharmacologic therapies, such as new oral anticoagulants, lipid-lowering agents, and renin-angiotensin system blockers.
“If nothing else, these powerful drugs have significantly reduced the overall risk in post-MI patients and, as a consequence, made it more difficult to document the possible benefits of beta-blockers,” they added.
And in people with diabetes in particular, increased hypoglycemia and weight associated with beta-blockers may contribute to adverse outcomes, along with the possibility that the agents increase central blood pressure, which would be expected to be more pronounced in people with stiffer arteries, as is the case for many with diabetes.
- β-blockers are associated with a significantly increased risk of CV events in patients with or without CHD/HF and those receiving standard therapy.
- Increased risk of CV events associated with β-blockers may outweigh their protective effect on the heart and vasculature during hypoglycemia.
- The indication for β-blockers in T2DM may need reconsideration, but randomized controlled trials are needed.
The findings, from prospective cohort data from the US National Health and Nutrition Examination Survey 1999–2010, were published in the April issue of Mayo Clinic Proceedings by Tetsuro Tsujimoto, MD, PhD, of the Department of Diabetes, Endocrinology, and Metabolism, Center Hospital, Tokyo, Japan, and colleagues.