Pulmonary Hypertension: Treatment

My patient is an 82-year-old woman with a history of coronary artery bypass grafting (CABG), chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and mild intermittent angina on exertion, which is relieved by sublingual nitroglycerin. She is now taking sildenafil for the pulmonary hypertension; this agent has dramatically increased her pulmonary exertional tolerance. Because sublingual nitroglycerin is contraindicated in patients who are receiving sildenafil, I would appreciate any suggestions for an alternative antianginal medication.

---- Markus S. Kryger, MD Forsyth, Mo

Long-term use of sildenafil improves exercise capacity and pulmonary hemodynamics in patients with severe pulmonary artery hypertension.¹ In a randomized, placebo-controlled, double-blind study of 278 patients with pulmonary artery hypertension, those treated with sildenafil had a significantly greater increase in exercise tolerance time than did those who received placebo.² In addition, the patients who received sildenafil had significantly greater decreases in mean pulmonary artery pressure and pulmonary artery resistance-together with greater increases in both cardiac output and mixed venous oxygen saturation-than did those who received placebo.³

Sildenafil has produced a dramatic improvement in your patient's pulmonary exertional tolerance; thus, this medication should be continued. The dosage I would recommend is 20 mg tid.

Your patient also has a history of CABG and has used sublingual nitroglycerin occasionally to relieve mild intermittent angina pectoris precipitated by exertion. The American College of Cardiology/American Heart Association guidelines state that 6 pharmacological half-lives, or 24 hours, must pass between the ingestion of sildenafil and the administration of nitrates for ischemic heart disease.⁴

However, this patient does not need to use nitrates and can be treated with a different antianginal medication that can prevent her mild exertional angina pectoris. Consider a ß-blocker such as metoprolol instead of nitroglycerin.

Although ß-blockers are contraindicated in those with bronchospasm, the vast majority of patients with COPD do not have bronchospasm.⁵ Among antianginal agents, ß-blockers are the most effective at reducing both the frequency and severity of anginal attacks, increasing exercise tolerance, and reducing myocardial ischemia.⁵ In the Cooperative Cardiovascular Project, which involved 201,752 Medicare patients who had sustained a myocardial infarction, the use of ß-blockers in those patients who had COPD reduced 2-year mortality by 40% (from 27.8% in patients with COPD who did not receive ß-blockers to 16.8% in those who did).⁶

If your patient cannot tolerate a ß-blocker, consider a calcium channel blocker.⁵ Finally, if she cannot tolerate ß-blockers or calcium channel blockers, prescribe ranolazine to prevent anginal episodes.⁵

---- Wilbert S. Aronow, MD Clinical Professor of Medicine Divisions of Cardiology, Geriatrics, and Pulmonary/Critical Care Medicine New York Medical College Valhalla, NY

References:

REFERENCES:

1.

Ghofrani HA, Rose F, Schermuly RT, et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension.

J Am Coll Cardiol

. 2003;42:158-164.

2.

Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension.

N Engl J Med

. 2005;353:2148-2157.

3.

Rubin L, Burgess G, Parpia T, et al. Hemodynamic effects of sildenafil citrate in patients with pulmonary arterial hypertension (PAH).

Am J Hypertens

. 2005; 18:93A.

4.

Cheitlin MD, Hutter AM Jr, Brindis RG, et al. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association.

J Am Coll Cardiol

. 1999;33:273-282.

5.

Aronow WS, Frishman WH. Angina in the elderly. In Aronow WS, Fleg JL, Rich MW, eds.

Cardiovascular Disease in the Elderly.

4th ed. New York: Informa Healthcare. In press.

6.

Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction.

N Engl J Med

. 1998;339:489-497.