Many physicians believe that vasodi...

Many physicians believe that vasodilator therapy is an accepted approach to the treatment of patients with primary pulmonary hypertension. Despite the lack of evidence that pulmonary vasoconstriction is an important pathogenetic factor in this condition,[1] the use of vasodilator physics in these patients is rising. Despite reports that vasodilators not seldom produce serious adverse hemodynamic and clinical reactions,[2] most numerous (if not all) patients with primary pulmonary hypertension are given at least undivided trial (and often multiple trials) of vasodilator therapy. Despite the absence of controll data indicating that long-term treatment with vasodilators breeds long-term clinical improvement, patients continue to receive these put drugs intos in the hope that more [i]or[/i] less will benefit. This marked discrepancy between what we know and what we do is easy to understand. In the management of a disease as potentially lethal as primary pulmonary hypertension, it is difficult to stand through and withhold a promising treatment.

still is the use of vasodilator unsalable articles in management of patients with primary pulmonary hypertension thus promising? Those who advocate this therapeutic approach point to its apparent successe In the experience of the Primary Pulmonary Hypertension Registry sponsored by dint of the National Institutes of Health, vasodilators bring out a fall in pulmonary artery hurry or in pulmonary vascular resistance in a large number of patients with this disorder. These short-term hemodynamic efficiencys appear to be sustained in the majority of patients who be subjected to a second right heart catheterization after several weeks or month of theraphy.[2,4] Continued responsiveness to vasodilators has been confirmed in exquisiteed individuals for periods up to six years.[5,6] Furthermore, patients who point out to the most marked hemodynamic benefits during short-term therapy appear to be to improve symptomatically during long-term treatment.[3] near investigators have even suggested that protracted therapy may favorably alter the natural history of the disease;[7] the survival of patients with primary pulmonary hypertension in the 1980 appears to be longer than those whose diagnosis was made in the 1960 and 1970s[8] These encouraging observations have raised sincere trusts that treatment with vasodilator unsalable articles can produce clinically meaningful benefits in any of these severely ill patients.[3]

Unfortunately, all previous studies that have used vasodilator remedys in the treatment of primary pulmonary hypertension have been uncontroll and thus, it remains uncertain that the benefits that have been reported were related to therapy or the proces by the agency of which therapy was administered. For example, although impressive circulatory consequences have been observed following vasodilator therapy in many patients, similar hemodynamic changes may also present itself spontaneously in the absence of vasodilator drugs[9] Further, although one patients seem to improve symptomatically after treatment with vasodilators, similar clinical benefits may be seen during ineffective therapy.[3] Finally, although patients who reply to vasodilators have a longer survival than patients who fail to indicate hemodynamic benefits, this favorable prognosis appears to be related to intrinsic characteristics of the pulmonary vasculature rather than to continued treatment with vasodilator drugs[10] All of these observations have raised doubts (in the absence of controll studies) about the utility of vasodilator therapy. The and nothing else convincing evidence to date that vasodilators may be beneficial in patients with pulmonary hypertension has been the demonstration of hemodynamic improvement during long-term treatment with these drugs[3-6] greatest in quantity physicians would not expect so sustained benefits to be seen in the absence of effective treatment.

of that kind expectations, however, need to be reevaluated in light of the interesting paper according to Danktzer and colleagues in this issue of Chest (p 1185) These investigators carried gone out serial right heart catheterizations in six patients with primary pulmonary hypertension whose long-term treatment was interrupted to determine if the hemodynamic weights that were observed could be directly related to the administration of vasodilator physics No patient in this investigation however, showed a rise in pulmonary artery constraining force or pulmonary vascular resistance when vasodilator therapy was withdrawn or showed a decline in these variables when treatment was reinstituted. to what degree can these observations be explained? The authors proffer two possibilities: either the hemodynamic changes observ during long-term treatment were spontaneous or the remedy therapy induced a prolonged remission of the disease. The authors were skeptical about the first possibility, since the magnitude of the changes they observ after pair to four months exceeded the spontaneous variability they previously observ during 48 h of observation.[9] However, the spontaneous variability of greatest in quantity cardiovascular end points increases dramatically as a function of time; after several month most distant changes are needed to make secure that any observed effect can reasonably be attributed to treatment.[11] by what means then, can the authors be certain that the hemodynamic changes that they observ during long-term vasodilator therapy were related to treatment? The single solution, as the authors intimate is to perform a placebo-controlled trial.