A Chronobiologic Approach to the Pharmacotherapy of Hypertension and Angina

OBJECTIVE: To review the chronobiology of hypertension and coronary artery disease and the application of chronotherapeutics to their treatment and prevention. DATA SOURCES: Clinical trials and review articles (English-language) on the topic of chronotherapy and cardiovascular disease were identified via a MEDLINE search from 1990 to March 2000, using the search terms chronotherapy, circadian rhythm, cardiovascular disease, hypertension, and angina. DATA EXTRACTION: Search and evaluation focused on published clinical trials and review articles of circadian variation associated with pharmacotherapy for cardiovascular disease. DATA SYNTHESIS: The existence of circadian rhythm in cardiovascular disease is well established. Heart rate and blood pressure peak during the morning hours and reach a nadir at bedtime. The incidence of myocardial infarction, stroke, sudden cardiac death, and myocardial ischemia also increases during the early-morning hours. Based on these relationships, researchers have begun to apply the science of chronotherapeutics, or timing of drug effect with biologic need, to improve cardiovascular outcomes. This includes administering traditional agents at specific times throughout the day and developing new agents--chronotherapeutic formulations with special release mechanisms--targeted at inducing the greatest effect during the morning surges. Chronotherapeutic agents are specifically designed to provide peak plasma concentrations during the early-morning hours, when effect appears most needed; lowest concentrations occur at night, when heart rate and blood pressure are lowest and, consequently, cardiovascular events are least likely to occur. CONCLUSIONS: Whether chronotherapy of cardiovascular disease offers an advantage in long-term outcomes over traditional therapy must be studied in clinical trials.