In many patients with primary pulmonary hypertension the downhill course is progressive despite treatment, and therapy must be palliative. The use of anticoagulants has been considered of doubtful value, provided chronic pulmonary embolic phenomena can be excluded. However, in a retrospective natural history study of 120 patients, postmortem examinations in 56 patients showed organized thrombus in small arteries (embolic or in situ) to be present in over 50 percent of patients; the only apparent clinical difference between these patients and those with plexiform arteriopathy was a somewhat older average age. Anticoagulation within 12 months of diagnosis was an independent predictor of improved survival rate, and anticoagulant therapy was recommended for all patients. The diagnosis of chronic thrombotic obstruction of major pulmonary arteries is important because surgical thromboendarterectomy in such patients has been successful in a number of patients.

Right-sided heart failure should be treated with a cardiotonic and diuretic regimen. Since there is no hypercapnia in these patients, the hypoxia which may accompany heart failure can be treated safely with oxygen therapy.

Recent reports have indicated that in some patients pharmacologic therapy can produce clinical and hemodynamic improvement. Although long-term observations concerning prolongation of life are not available, several categories of drugs have been found useful in small groups of patients: (1) direct vascular smooth-muscle relaxants (nitroprusside, diazoxide, nitroglycerine, and hydralazine); (2) beta agonists (sublingual isoproterenol, oral terbutaline); (3) alpha-adrenergic blocking agents (phentolamine and phenoxybenzamine); (4) calcium antagonists (nifedipine and verapamil); and (5) angiotensin converting enzyme inhibitors. Immunosuppressive agents and prostaglandin antagonists (indomethacin) have rarely been used. Prostacyclin (PGI2) has been employed successfully intravenously as a test of vascular reactivity and for short-term therapy.

In some patients, favorable hemodynamic effects from orally administered drugs such as diazoxide or hydralazine have been sustained for many months, with clinical improvement manifested by relief of severe dyspnea and reduction in the number of syncopal episodes. Hydralazine and nifedipine are currently used most commonly. The calcium channel blocker nifedipine has been reported to lower pulmonary artery pressure and pulmonary vascular resistance and to increase cardiac output, as well as to improve exercise tolerance in some patients. Although few long-term studies are available, limited data suggest that the lowered pulmonary vascular resistance may be maintained over many months in some patients. Initial studies suggest that the angiotensin-converting enzyme inhibitor captopril may be effective in a few patients, but it appears to have its main effect on the systemic circulation to lower arterial pressure and increase cardiac output, with a less prominent action on the pulmonary circulation. Prior to instituting long-term therapy with such drugs, measurement of the acute responses of the pulmonary artery pressure, pulmonary vascular resistance, cardiac output, and arterial pressure is usually indicated in order to assess efficacy and to detect unfavorable effects. In some patients hemodynamic deterioration has been reported following the use of vasodilators.

Heart and lung transplantation has now been successful in a number of patients, with survival for several years. Although early mortality was relatively high (about 30 percent), the functional status of survivors has been good, and such treatment represents a possible approach in selected patients if suitable donors can be found.