Packer, M. (2018). “Does a Target Dose or a Target Heart Rate Matter to Outcomes When Prescribing beta-Blockers to Patients With Chronic Heart Failure?” Circ Cardiovasc Qual Outcomes 11(4): e004605.
Full text of this article.
For better or worse, many cardiovascular disorders are treated based on changes in a biomarker. Antihypertensive drugs are titrated to achieve specific decreases in blood pressure, and the doses of lipid-lowering drugs are often adjusted based on serum cholesterol. Investigators have proposed measuring natriuretic peptides and C-reactive protein to titrate drugs for heart failure and for high-risk coronary artery disease, respectively. Use of a biomarker often represents an effort to practice personalized medicine; theoretically, a drug is given only to people who need it and only in a dose that achieves what is perceived to be a worthwhile change. Yet, biomarkers present us with challenges. When observed in populations, even small differences in a biomarker—for example, 1- to 2-mm Hg difference in blood pressure—are clinically important; yet, when treating individuals, few physicians are inclined to increase the dose of an antihypertensive drug with the primary intent of achieving such a small additional decrease in blood pressure. The oldest biomarker in cardiovascular medicine is resting heart rate. Physicians have been monitoring the rapidity and quality of the pulse for several thousand years, and great emphasis has been placed on changes in heart rate as an indicator of impending improvement or deterioration. Many patients suffer when their heart rates are too fast or too slow. Yet, even in the absence of a tachyarrhythmia or bradyarrhythmia, physicians dutifully record the resting heart rate during normal sinus rhythm at nearly every patient encounter. The resting heart rate has recently gained attention as a biomarker in the management of patients with chronic heart failure. Heart rate (measured at rest and during sinus rhythm) has prognostic importance in patients with left ventricular systolic dysfunction, and changes in heart rate are predictive of outcomes. The If current antagonist ivabradine was specifically developed to modulate heart rate during sinus rhythm. When prescribed to patients with heart failure, the resting heart rate is not only used to identify those who might benefit from the drug but it is also typically used to titrate the appropriate dose of the agent. When administered to patients who are already receiving a β-blocker and who continue to demonstrate elevated heart rates, the decreases in sinus rate achieved by ivabradine are accompanied by a reduction in the combined risk of cardiovascular death and hospitalization for heart failure. (Excerpt from text, p. 1; no abstract available.)