THE ROLE OF PHARMACOLOGICAL THERAPY IN CHRONIC HEART VALVE DISEASES



Jeffrey S. Borer, M.D., SUNY Downstate Medical Center, Brooklyn and New York, NY, USA

Valvular heart diseases (VHDs) are progressive. When they are “primary”, i.e., due to intrinsic abnormality of valve structure and not secondary to comorbid conditions (e.g., ischemia), they generally are characterized by long asymptomatic phases during which cardiac functional and hemodynamic debility progresses. Ultimately, these developments lead to symptoms, other morbidities and, finally, death. Treatment depends on VHD type and severity. However, when VHDs are hemodynamically/functionally severe and symptomatic, therapy generally requires mechanical intervention (replacement or repair). Asymptomatic patients, and those who lack objective descriptors that predict high imminent risk, are managed by close clinical observation and efforts to minimize associated cardiovascular risk factors until surgical indications develop. In this setting, drugs often are prescribed based on theoretical concerns or preclinical studies or small clinical studies involving “surrogate” rather than clinical endpoints. However, no rigorous evidence supports pharmacological therapy in most chronic situations. For Aortic Stenosis, multiple drugs (statins, ACE inhibitors, bisphosphonates, etc.) have been tested. Rigorous randomized controlled trials are available only with statins and these generally have shown no benefit. For Aortic Regurgitation, multiple direct and indirect vasodilators have been studied, generally for effect on surrogate, rather than clinical, outcomes; the only drug shown in randomized controlled trials to benefit outcome has been long-acting nifedipine, and that benefit seems to have been largely related to effect on the comorbidity of hypertension. For Mitral Stenosis, no drugs have been rigorously studied for clinical outcome. For Mitral Regurgitation, few studies are available and all have been neutral or negative (i.e., potentially harmful). Based on these findings, hemodynamically active drugs generally should be avoided in asymptomatic patients with primary valve disease.