Combined Use of PDE5 Inhibitors and Nitrates in the Treatment of Pulmonary Arterial Hypertension in Patients With Heart Failure

Abstract

Background Phosphodiesterase-5 (PDE5) inhibitors, which induce relaxation of smooth muscle with some selectivity for the pulmonary vasculature, are used in the treatment of pulmonary hypertension. In some patients, the use of PDE5 inhibitors does not result in the desired magnitude of pulmonary vasodilation. The use of additional vasodilators to further reduce pulmonary vascular resistance is often accompanied by unacceptable reductions in systemic arterial pressure. Methods and Results In 3 patients with heart failure, pulmonary hypertension and low systemic arterial pressures treated with sildenafil, systemic nitrates were added to reduce pulmonary hypertension further. Hemodynamic measurements were made before and after addition of nitrates. Addition of systemic nitrates to sildenafil led to a reduction in mean pulmonary arterial pressure of 11 mm Hg, from 37 mm Hg to 26 mm Hg ( P = .06), whereas mean systemic arterial pressure decreased by only 4 mm Hg, from 77 mm Hg to 73 mm Hg ( P = .53). The ratio of pulmonary vascular resistance to systemic vascular resistance was reduced by 45% ( P = .1). Treatment with sildenafil and nitrates was continued for two to eight months, with no episodes of marked systemic hypotension, syncope, or lightheadedness. Conclusions These results suggest that addition of systemic nitrates to sildenafil results in a potentiation of vasodilation that is relatively selective for the pulmonary vasculature, and that this combination may be safe and effective in the treatment of pulmonary hypertension in patients with low systemic arterial pressures.