High-Dose Beta-Blockers More Effective in Chronic Heart Failure, Diabetes

Patients with chronic heart failure and diabetes may have a greater reduction in mortality with higher beta blocker doses than those without diabetes, according to a prospective cohort study published in Diabetes Care.¹

Researchers identified 1797 patients with chronic heart failure secondary to left ventricular systolic dysfunction; 503 of these patients also had diabetes.¹ Although angiotensin converting enzyme inhibitors (ACEIs) and beta blockers have previously demonstrated a reduction in mortality in patients with chronic heart failure,^2-4 no recent study has compared this effect in patients with and without diabetes. Therefore, patients in the current study were divided into groups according to whether they had diabetes and prescribed doses of beta blockers (no beta blocker or bisoprolol equivalent doses of <2.5 mg/day [low dose], 2.5-7.4 mg/day [medium dose], and 7.5 mg/day [high dose]) and ACEIs (no ACEI or ramipril equivalent doses of <2.5 mg/day [low dose], 2.5-7.4 mg/day [medium dose], and 7.5 mg/day [high dose]).¹

After a mean follow-up of 4 years, increasing beta blocker doses were associated with lower all-cause mortality in patients with and without diabetes (8.9% vs 3.5% per mg/day, respectively), and the magnitude of this association was significantly greater in patients with diabetes (P =.027).¹ Similarly, higher doses of ACEIs led to lower mortality in patients with and without diabetes (5.9% vs 5.1% per mg/day, respectively), but the difference between these groups was not significant (P =.76).

More than one-third of patients with chronic heart failure associated with left ventricular systolic dysfunction also suffer from diabetes,^5,6 which increases mortality.^7-9 This study demonstrated that higher beta blocker doses are associated with lower mortality, particularly in patients with diabetes who have severely impaired left ventricular function.¹ The researchers concluded that “[t]hese data should provide reassurance to patients and health care providers and encourage careful but determined uptitration of β-blockers in this high-risk group of patients.”

References

1. Witte KK, Drozd M, Walker AMN, et al. Mortality reduction associated with β-adrenoceptor inhibition in chronic heart failure is greater in patients with diabetes [published online October 5, 2017]. Diabetes Care. doi: 10.2337/dc17-1406
2. Yusuf S, Pitt B, Davis CE, Hood WB, Cohn JN, for the SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293-302.
3. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001-2007.
4. Mann DL, Bristow MR. Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation. 2005;111(21):2837-2849.
5. Standl E, Schnell O, McGuire DK. Heart failure considerations of antihyperglycemic medications for type 2 diabetes. Circ Res. 2016;118(11):1830-1843.
6. Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus – mechanisms, management and clinical considerations. Circulation. 2016;133(24):2459-2502.
7. Dauriz M, Targher G, Laroche C, et al; for the ESC-HFA Heart Failure Long-Term Registry. Association between diabetes and 1-year adverse clinical outcomes in a multinational cohort of ambulatory patients with chronic heart failure: results from the ESC-HFA Heart Failure Long-Term Registry. Diabetes Care. 2017;40(5):671-678.
8. MacDonald MR, Petrie MC, Varyani F, et al; for the CHARM Investigators. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J. 2008;29(11):1377-1385.
9. Cubbon RM, Adams B, Rajwani A, et al. Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology. Diab Vasc Dis Res. 2013;10(4):330-336.