(Circulation. 1995;92:1068-1073.)
© 1995 American Heart Association, Inc.
Articles |
Nifedipine and Mortality
Grave Defects in the Dossier
From the Medical Research Council, University of Cape Town, South Africa (L.H.O.), and the Ochsner Clinic, New Orleans, La (F.H.M.).
Correspondence to Professor L.H. Opie, Heart Research Unit of the Medical Research Council, University of Cape Town Medical School, Observatory, 7925, Cape Town, South Africa, or Franz H. Messerli, MD, Section of Hypertensive Diseases, Ochsner Clinic, 1514 Jefferson Hwy, New Orleans, LA 70121.
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Introduction |
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When an approved treatment is considered for an unapproved indication, the physician must evaluate the safety of the medication, its value in related conditions, and the individual patient. What is asked is that he make a prudent decision based upon full knowledge of the available evidence."1
Furberg and his colleagues2 entitle their article "Nifedipine: Dose-Related Increase in Mortality in Patients With Coronary Heart Disease." They provide a valuable service by making us think more carefully about the benefit/risk ratio of the calcium antagonists as a group. However, by touting calcium antagonists as being unsafe and possibly lethal, they also create a great deal of uncertainty and anxiety among physicians and patients. We feel that they overstate their case. The following is an attempt to show that (1) the allegations focus on short-acting nifedipine, so that even if correct, they cannot be applied to other calcium antagonists; (2) the accusation of a dose-related increase in mortality rests on a biased selection of data chosen for the meta-analysis; and (3) several of the mechanisms suggested for the proposed adverse effects are unlikely. Finally, we shall argue that pharmaceutical companies have been remiss in not obtaining outcome studies for short-acting nifedipine and for other calcium antagonists, especially in the case of ischemic heart disease.
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The Indicted Agent Is Short-Acting Nifedipine, and Evidence for Other Calcium Antagonists Is Scant |
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Several aspects of the Furberg paper suggest that calcium antagonists in general are accused; for example, the statement that "the literature reviews strongly suggest that the problem may go beyond short-acting nifedipine. Troubling and major adverse cardiovascular events have
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