Efficacy of antihypertensive drugs given once a day: the calcium antagonists revisited

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Abstract

Background

A large number of antihypertensive drugs have been approved for administration once or twice a day, but no standardized evidence is required to demonstrate that the reduction in blood pressure is sustained over 24 h.

Aim

To test the validity of claims of a long duration of action for second-generation calcium antagonists.

Method

Literature search.

Flaws in reported studies

Most studies relied on ambulatory blood pressure monitoring. However, several reports were difficult to interpret because (1) the study was not blinded or random; (2) the statistical analysis was inappropriate for the study design; (3) analyses were confined to the means of 24-h, daytime and night-time blood pressure; (4) there was no baseline adjustment or formal statistical testing; (5) patients were subdivided into responders and non-responders after treatment; (6) there was no specified time frame linking drug intake to the observed antihypertensive effects.

Claims not substantiated

The authors of the articles reviewed concluded that amlodipine, nitrendipine and modified (slow-release) formulations of diltiazem, isradipine, nifedipine and verapamil reduced both conventional (clinic) and the 24-h blood pressure levels. In some studies separate results were presented for the daytime (awake) and night-time (sleeping) periods; some investigated the reduction in blood pressure at the end of the dose interval; and some compared the diurnal blood pressure profiles with different drug treatments. However, these reports gave discrepant results, suggesting that at least under certain study conditions the effect of nitrendipine and of slow-release diltiazem, isradipine and nifedipine did not give full 24-h cover with a single daily dose.

Conclusions

We conclude that the interpretation of studies on long-acting antihypertensive agents using ambulatory blood pressure monitoring would be easier if the same standards were applied as required in clinical studies using conventional blood pressure measurements.

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