ANTIHYPERTENSIVE DRUGS LARGE-SCALE COMPARATIVE TRIALS
ANTIHYPERTENSIVE DRUGS LARGE-SCALE COMPARATIVE TRIALS comparing their risk/benefit ratios on cardiovascular morbidity and mortality is recommended by the National Heart, Lung and Blood Institute's Task Force on Research in Hypertension. In a preliminary report just released, the task force concluded that there is little information on the relative benefits and risks of specific forms of antihypertensive therapy, and that drugs may have different effects on the cardiovascular disease associated with hypertension. For example, the report says "some of the newer agents, such as angiotensin-converting enzyme inhibitors and calcium channel blockers, do not cause unfavorable changes in potassium, magnesium, uric acid, lipids, or insulin, and the use of these agents has therefore been considered theoretically attractive." "Moreover," the report states, "the beneficial effects of beta blockers in patients with ischemic heart disease and the lack of such benefits following the use of some calcium channel blockers constitute additional evidence suggesting that the effects of all antihypertensive agents may not be uniform and that their relative benefits should be evaluated. Further," the report continues, "because of the strong correlation between left ventricular hypertrophy and sudden cardiac death in hypertensive populations, drugs that cause regression of left ventricular hypertrophy are considered attractive." Also, the report states that removal of excess angiotensin II might have favorable vascular consequences, compared to the elevation of angiotensin II by diuretics. However, the report asserts that despite the "theoretical attractions" of these alternatives to diuretics, "there is no definitive evidence that they are even as beneficial as diuretic drugs in reducing mortality." The "importance of serious, but infrequent, adverse effects associated with the newer agents requires an assessment of the risk/benefit ratio in various grades of hypertension." The task force's preliminary report was presented at a May 20 meeting of NHLBI's advisory council. The report includes dozens of recommendations for future research in three categories -- basic, clinical and population-based. NHLBI Director Claude Lenfant, MD, called the report a "blueprint of what needs to be done in hypertension." Subsequent to determining the optimal drug intervention through a large-scale morbidity and mortality study, the report says researchers should assume as a priority the study of the benefits and risks of specific forms of antihypertensive therapies in patients with mild hypertension and on the optimal level to which blood pressure should be lowered. The report also recommends that an attempt be made to identify surrogate endpoints that might predict both beneficial and adverse cardiovascular outcomes. The task force recommends further research to improve the detection of left ventricular hypertrophy (LVH) and to understand the hemodynamic factors, cellular mechanisms, and changes in myocardial and vascular structure and function that contribute to LVH and related cardiovascular complications. Similarly, the report recommends further research to understand abnormalities in the function of the kidney that lead to hypertension. High priority is also given to research on the effects of race and gender on the causes and treatment of hypertension, in addition to other individual risk factors and population determinants, such as age, obesity, insulin activity, emotional stress, diet, or the role of pregnancy. The report expresses concern over the lack of funding for research training programs and the declining number of qualified researchers interested in hypertensive research. It warns that "strong evidence now indicates that the present and future availability of [qualified researchers] is in jeopardy and will severely limit further advances in hypertension research and the clinical application of basic science discoveries." In regard to funding, the report notes that "[a]lthough some funding is available from pharmaceutical companies for drug testing, research in this area is not directed at elucidating basic pathophysiological mechanisms or testing hypotheses." The task force recommends the development of and increased funding for specific hypertensive research and training programs. Specifically, the report says consideration should be given to development of new programs for centers of excellence directed at multidisciplinary research and training in hypertension. The task force also called for the implementation of a grant proposal review mechanism to ensure that investigational proposals are reviewed by individuals with expertise in clinical research. The development of new animal models of hypertension is also recommended.
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