Circadian variations and chronotherapeutic implications for cardiovascular management: a focus on COER verapamil

The circadian variation in biologic functions (chronobiology) may play a large role in the pathogenesis and exacerbation of many different diseases. Traditional treatment regimens for medical conditions associated with circadian variation often do not account for fluctuations in disease activity. A novel type of treatment approach, known as chronotherapy, is being evaluated in the treatment of many different disorders, including cardiovascular disease. Chronotherapeutic regimens are designed to provide pharmacologic intervention at the most appropriate time point in accordance with circadian rhythms, and may offer benefits over traditional regimens. This can be accomplished through appropriate dose scheduling (e.g., scheduling higher doses during greater disease activity and lower doses during low disease activity) or through unique drug-delivery systems. One chronotherapeutic formulation that uses a unique drug-delivery system, controlled-onset extended-release (COER) verapamil, aligns peak plasma drug levels with times when blood pressure, heart rate, and myocardial oxygen demand are at their highest levels. The efficacy and safety of COER verapamil have been evaluated in several clinical trials in patients with hypertension and angina. The purpose of this article is to review the concepts of chronobiology and chronotherapy and to review results of key efficacy and safety trials of COER verapamil.