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CARDIOPROTECTIVE EFFECT OF SECOND-GENERATION CALCIUM CHANNEL BLOCKERS

Executive Summary

CARDIOPROTECTIVE EFFECT OF SECOND-GENERATION CALCIUM CHANNEL BLOCKERS is suggested by experimental evidence to date and merits further study, Norman Kaplan, MD, University of Southwestern Medical Center, concluded in an article published in the Aug. 11 edition of the Journal of the American Medical Association. "Current data suggest a more specific pharmacologic action that is more focused on vascular smooth muscle," Kaplan said. "This more specific vasodilatory action may result in fewer side effects (than with first generation calcium channel blockers) and expand the indications for these agents." Nicardipine (Syntex' Cardene) and nimodipine (Miles' Nimotop) are the only second-generation products to have reached the U.S. market. The latter is approved exclusively for treatment of subarachnoid hemorrhage. Other second-generation calcium entry blockers in development are Pfizer's amlodipine, Merck's felodipine (Splendil), isradipine (to be co-promoted by Glaxo and Sandoz as DynaCirc), and two Miles agents, nitrendipine (Baypress, to be co-promoted by Roche), and nisoldipine. Kaplan pointed out that none of the first-generation calcium channel blockers has been shown to be cardioprotective either during or after myocardial infarction. First-generation calcium channel blockers include diltiazem (Marion's Cardizem), nifedipine (Pfizer's Procardia) and verapamil (Searle's Calan and Knoll's Isoptin). "There are no data regarding the effect of calcium-entry blockers on the primary prevention of coronary artery disease in patients with hypertension," Kaplan said. A study published in the New England Journal of Medicine last year reported conflicting results on the use of Cardizem in preventing second heart attacks ("The Pink Sheet" Aug. 22, 1988, p. 2). Verapamil was the first calcium channel blocker to be approved for mild-to-moderate hypertension. The others were initially indicated for angina, with labeling subsequently broadened to include hypertension. Calling calcium entry blockers "important drugs" for treating hypertension, Kaplan predicted that the agents increasingly will be used for that indication. "Beyond their as-yet unproved potential to protect the brain, heart and kidneys in special ways beyond the effects of other antihypertensive agents, [the products] are attractive choices for the treatment of many subsets of patients with hypertension," the article states. These include patients with existing conditions -- such as diabetes, asthma, gout and peripheral vascular disease -- that preclude other antihypertensive drug therapies. "On the other hand, patients with various other diseases may receive additional benefits" from calcium channel blockers prescribed for hypertension, Kaplan continued. "These include patients with coronary artery disease, migraine, cerebrovascular disease and esophageal spasm."
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