As Drs. Ghali and Hershman point out, Psaty and colleagues attempted to avoid an indication bias. No matter how carefully a retrospective case control-study is done, however, an indication bias can never be ruled out: In retrospect it is impossible to second guess the reason a specific cardiovascular drug was prescribed for a given patient. In another report from the same patient cohort [1], the authors freely admit that "as expected those with cardiovascular disease were more likely to be taking calcium channel blockers and ß blockers. ..." Because all patients had hypertension (which, by definition, is a cardiovascular disease), it was impossible to exclude persons with known cardiovascular disease.

It is by no means unexpected that patients receiving ß-blockers had better outcomes than did those receiving calcium antagonists. Given that most of these short-acting calcium antagonists were not approved for treating hypertension and that they were prescribed at an inappropriate dosing schedule (that is, once a day or twice a day as Dr. Psaty recently conceded [2]), the outcome is not surprising. Nifedipine capsules given once or twice a day will, at best, decrease arterial pressure for a few hours only and, at worst, lead to hypotension, sympathetic stimulation, reflexive tachycardia, and possibly myocardial ischemia [3]. Such a regimen deviates from accepted standards of medical practice, and it should be no surprise when the outcome also deviates from these standards.

Finally, I am not certain about the take-home message of Psaty and colleagues' study to strictly follow the Joint National Committee guidelines. Recent case–control studies [4, 5] have shown an increased risk for sudden death with ß-blockers and diuretics compared with other therapies for hypertension. Interestingly, news media coverage of these reports was minimal compared with that elicited by the calcium antagonists. These data notwithstanding, diuretics are the only drug class for which a reduction in mortality has been unequivocally shown in patients with hypertension. Such data are lacking for all others (such as ß-blockers, -blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers). Why single out calcium antagonists? Perhaps we should be more concerned about the ink that is currently wasted on misleading case–control studies, meta-analyses, and other "bouillabaisse" and about the underlying reasons for the excessive media coverage than about the safety of the long-acting calcium antagonists.