The Effect of High-Doses of Calcium-Channel Blockers on Survival in Primary Pulmonary-Hypertension
Rich, S., Kaufmann, E., & Levy, P. (1992). The Effect of High-Doses of Calcium-Channel Blockers on Survival in Primary Pulmonary-Hypertension. New England Journal of Medicine, 327(2), 76-81.
Background. Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Vasodilator drugs have been used as a treatment, but their efficacy is uncertain. Methods. We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers. Patients who responded to treatment (defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge) were treated for up to five years. Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health (NIH) Registry on Primary Pulmonary Hypertension. Warfarin was given to 55 percent of the patients as concurrent therapy, on the basis of a lung scan showing nonuniformity of pulmonary blood flow (47 percent of patients who responded and 57 percent of those who did not respond). Results. Seventeen patients (26 percent) responded to treatment, as indicated by a 39 percent fall in pulmonary-artery pressure and a 53 percent fall in the pulmonary-vascular-resistance index (P<0.001). Nifedipine (mean [+/-SD] daily dose, 172+/-41 mg) was given to 13 patients, and diltiazem (mean daily dose, 720+/-208 mg) was given to 4 patients. After five years, 94 percent of the patients who responded (16 of 17) were alive, as compared with 55 percent of the patients who did not respond (26 of 47, P = 0.003). The survival of the patients who responded was also significantly better than that of the NIH registry cohort (P = 0.002) and patients from the NIH registry who were treated at the University of Illinois (P = 0.001). The use of warfarin was associated with improved survival (P = 0.025), particularly in the patients who did not respond. Conclusions. This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period