UK-based study compares drug classes over 4-year period.
Diabetes is known to increase the risk of death in individuals who have chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF). More than one-third of CHF patients will develop diabetes. In CHF, two of the most common classes of drugs used to reduce mortality risk are beta-blockers and ACE inhibitors. There is a concern that beta-blockers may not be safe for CHF patients with diabetes because they can potentially elevate blood glucose and mask signs and symptoms of hypoglycemia. Past studies have evaluated this relationship. However, there have been no current studies that analyze how beta-blockers and ACE inhibitors compare in relation to mortality in CHF patients with and without diabetes.
The following prospective cohort study included 1,797 patients with CHF and reduced LVEF with and without diabetes. The study aimed to determine how beta-blockers and ACE inhibitors affect mortality on this population over a 4-year period. Patients were recruited from four U.K. hospitals only if they were seeing cardiology specialists. They also had to meet the study criteria, which included occurrence of CHF signs and symptoms for 3 months or longer, 18 years of age or older, and LVEF of 45% or less. Medical history, and medication and dosing history, along with chronic disease history was obtained upon enrollment. Severity of CHF signs and symptoms were determined through use of the New York Heart Association (NYHA) Functional Classification.
Among the 1,797 participants, 508 or 28% had diabetes. Out of the 508 participants with diabetes, only 6 or 1.2% had type 1 diabetes. Patients with diabetes were found to be on higher doses of both beta-blockers and ACE inhibitors, but their heart rates were similar to those without diabetes. It was also found that 1,523 or 84.8% of patients were taking beta-blockers, the most frequent being bisoprolol. Patients with and without diabetes were split up into groups consisting of those taking low, medium, or high bisoprolol equivalent doses (mg/day) and those not taking any beta-blockers. Patients with and without diabetes were also split up into groups consisting of those taking low, medium, or high ramipril equivalent doses (mg/day) and those not taking ACE inhibitors or ARBS. Cox regression analysis was utilized to determine the association between beta-blocker and ACE inhibitor doses and mortality in patients with and without diabetes.
It was determined that there was 3.5% mortality reduction for every mg/day increase of bisoprolol dose in patients without diabetes (95% Cl 0.7 to 6.3). The mortality reduction in these patients was much lower when compared to patients with diabetes who experienced an 8.9% mortality reduction for every mg/day increase of bisoprolol dose (95% Cl 5 to 12.6). It was also found that there was a 5.1% mortality reduction for every mg/day increase of ramipril dose in patients without diabetes (95% Cl 2.6 to 7.6). These results were similar when compared to patients with diabetes who had a 5.9% mortality reduction for every mg/day increase in ramipril.
Overall, the study suggests that mortality is reduced in CHF patients with and without diabetes as doses of beta-blockers are increased. However, the mortality reduction was significantly more pronounced in patients with diabetes. Increasing ACE inhibitor doses also resulted in mortality reduction in CHF patients, but mortality reduction was similar in those with and without diabetes. Although the study did provide important results, limitations should be considered. Results are not generalizable to patients with CHF and preserved ejection fraction because they were excluded from the study. The study also failed to provide cause and effect of how beta-blockers reduce mortality in this patient population. Also, past exposure to beta-blockers and ACE inhibitors was not considered.
- In CHF patients with and without diabetes, mortality is reduced with higher beta-blocker doses.
- There is a greater mortality reduction with beta-blocker use in CHF patients with diabetes.
- There are similar mortality reductions in CHF patients with and without diabetes taking higher ACE inhibitor doses.
Witte KK, Drozd M, Walker AM, et al. Mortality Reduction Associated With β-Adrenoceptor Inhibition in Chronic Heart Failure Is Greater in Patients With Diabetes. Diabetes Care. 2017; 40(11): 1-7.
Graciela Nieto, Pharm. D. Candidate 2018, LECOM School of Pharmacy