Can we use calcium antagonist better in antihypertensive therapy? Circadian consideration.
On the basis of theoretical reasoning, it has been thought that calcium antagonists should be better than other classes of antihypertensive agents. However in several large scale clinical trials, the benefits have been smaller than expected. Meta-analysis has indicated that dihydropyridine calcium antagonists failed to reduce cardiac mortality and morbidity. The reason for this is probably multifactorial. Reflex activation of the sympathetic nervous system (SNS) secondary to the reduction of blood pressure by calcium antagonists may play a very important role. It has been documented that the cardiovascular system has circadian rhythm and that most of the cardiovascular events in the general population happen in the morning, when the SNS is at its most active. Thus intrinsic activation of SNS set by circadian rhythm and extrinsic activation secondary to direct vasodilatation induced by calcium antagonists may overlap, which could increase cardiovascular risks and therefore result in poor clinical outcome. Antihypertensive therapy with calcium antagonists could be improved if it were possible to avoid the reflex activation and inhibit the intrinsic activation of SNS. A new chronotherapy is suggested, of which the basic principle is: to choose two classes of drugs with different mechanisms of action and use them at different periods of time during the day. By appropriate choice of the drugs and their acting time, not only the adverse effects, but also the risk during the vulnerable period could be reduced. Clinical research is needed to test this hypothesis.
Zhang
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W
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002940:Circadian Rhythm; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology
D002121:Calcium Channel Blockers