High-dose calcium channel-blocking therapy for primary pulmonary hypertension: Evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy

In an attempt to produce substantial reductions in pulmonary arterial pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension, a new treatment strategy using high doses of calcium channel-blocking drugs was developed. Thirteen patients were given an initial test dose of 60 mg diltiazem or 20 mg nifedipine followed by consecutive hourly doses until a 50% fall in pulmonary vascular resistance and 33% fall in pulmonary arterial pressure was achieved or untoward side effects developed. The initial drug challenges failed to produce significant reductions in mean pulmonary arterial pressure or pulmonary vascular resistance. In eight of 13 patients, continued hourly doses produced a reduction in mean pulmonary arterial pressure of 48% (61 to 35 mm Hg, p < .01) and a reduction in pulmonary vascular resistance of 60% (15 to 6 units, p < .01). These patients were discharged on high-dose (up to 720 mg/day diltiazem or 240 mg/day nifedipine) calcium channel-blocking drugs as long-term therapy. Five patients have returned for restudy after 1 year. In four of five the reductions in pulmonary arterial pressure and pulmonary vascular resistance were sustained and were associated with regression of right ventricular hypertrophy as assessed by electrocardiography and echocardiography. One patient who reduced her dose to a conventional level had a return of her pulmonary arterial pressure and pulmonary vascular resistance toward previous levels. We conclude that substantial reductions in pulmonary arterial pressure and pulmonary vascular resistance that are associated with regression of right ventricular hypertrophy are possible in some patients with primary pulmonary hypertension by use of calcium channel-blocking drugs. High doses of these drugs were required to produce marked hemodynamic responses in patients who exhibited marginal responses to conventional doses. In patients able to tolerate the high-dose therapy sustained reductions in pulmonary arterial pressure and pulmonary vascular resistance appear to last for a period of at least 1 year.