A comparison of two long-acting vasoselective calcium antagonists in pulmonary hypertension secondary to COPD

STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and may predict mortality in this disorder. We have compared the pulmonary vasodilator effects, dose-response characteristics, and tolerability of two calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10 patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH.

Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg), increasing weekly for 3 weeks, in a randomized investigator-blinded crossover manner with a 1-week wash-out period between the two treatments.

Doppler measurements of pulmonary hemodynamics were made on the seventh day of treatment at each drug dose. Lung function, arterial blood gases, and adverse events were also monitored weekly.

A dose-dependent decline of pulmonary artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a significant decrease in PAP compared with baseline (20% amlodipine, 17% felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that were similar for both drugs, but did not reach statistical significance compared with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance and increase in oxygen delivery with amlodipine and felodipine ER. Lung function and blood gas values were stable throughout. Side effects (headache and ankle edema) were less frequent during amlodipine treatment (p<0.05).

Both amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg, are effective pulmonary vasodilators in COPD patients with PH. Their dose-response characteristics are similar, but amlodipine treatment was associated with fewer side effects.