A reply.

We read with interest the editorial by Staessen et al., which discusses very objectively the position of calcium antagonists in the treatment of hypertension. As scientists who are familiar with calcium antagonists both in daily practice and pre-clinical experiments, we have had difficulty in accepting negative clinical trial results on the use of calcium antagonists in hypertension. We use calcium antagonists both in acute hypertensive crisis as well as in long-term treatment, especially in the elderly with multiple metabolic diseases, and feel that these drugs are safe and effective, although at the moment they cannot be considered as first-line drugs. One disadvantage of most calcium antagonists are the pharmacokinetics. The first pass effect is generally variable and therefore variable plasma concentrations, as well as comparable short half-lives, may yield diurnal changes of pharmacodynamic effects. Due to the circadian course of cardiovascular events, the question arises: do calcium antagonists protect against the critical rise of blood pressure, including high concentrations of catecholamines, in the morning hours, when most cardiovascular events occur? Could this, at least partially, be responsible for the negative results in clinical trials with calcium channel blockers? Vasodilation alone may be insufficient, but from the theoretical point of view, beta-receptor blockade should be the ideal co-medication in order to reduce the double product. We ask whether it may be an advantage to administer calcium antagonists twice daily and add a once daily dose of a beta-blocker agent in the late evening hours, to protect the heart against beta-stimulation in the morning. The concept of sympathetic arousal during the morning hours also gives an additional possible explanation as to why diabetic patients have a better outcome when treated with calcium antagonists alone, as heart rate is much more rigid in those patients due to autonomic impairment and may therefore react less to sympathetic influence. H. J. KOCH C. RASCHKA Psychiatric Clinic,