β-blockers are among the current treatment options to lower heart rate, improve cardiac function, and reduce cardiovascular events in post-myocardial infarction patients and in heart failure patients.7-9 Heart rate reduction seems to be the principal mechanism of action of β-blockers and reversal of β-blocker induced reduction in heart rate has deleterious effects even on ventricular function.10

However, despite the availability of β-blockers and all advances in the field of cardiovascular medicine, CAD remains the leading cause of death.11 The presence of left ventricular dysfunction has a further dramatic negative influence on mortality.12 Furthermore, not all patients can take β-blockers due to their side effects,13-15 and resting heart rate may not be sufficiently controlled in all CAD patients on β-blockers.16 Epidemiological studies suggest that 50% of patients, despite receiving β-blockers, have a heart rate >70 bpm.4

References:

7. Kjekshus JK. Importance of heart rate in determining beta-blocker efficacy in acute and long-term acute myocardial infarction intervention trials. Am J Cardiol. 1986;57:43F-49F.
8. Freemantle N, Cleland J, Young P, et al. Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730-1737.
9. Lechat P, Hulot JS, Escolano S, et al. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001;103:1428-1433.
10. Thackray SD, Ghosh JM, Wright GA, et al. The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers. Am Heart J. 2006;152:713 e719-713.
11. Projections of Global Mortality and Burden of Disease from 2002 to 2030 PLoS Med 3(11): e442. doi:10.1371/journal.pmed.0030442
12. Burns RJ, Gibbons RJ, Yi Q, et al. The relationships of left ventricular ejection fraction, end-systolic volume index and infarct size to six-month mortality after hospital discharge following myocardial infarction treated by thrombolysis. J Am Coll Cardiol. 2002;39:30-36.
13. Gupta R, Tang WH, Young JB. Patterns of beta-blocker utilization in patients with chronic heart failure: experience from a specialized outpatient heart failure clinic. Am Heart J. 2004;147:79-83.
14. Butler J, Khadim G, Belue R, et al. Tolerability to beta-blocker therapy among heart failure patients in clinical practice. J Card Fail. 2003;9:203-209.
15. Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction. Eur Heart J. 2006;27:1153-1158.
16. Kolloch R, Legler UF, et al. Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST). Eur Heart J. 2008;29:1327-1334.