HYDRALAZINE AND NITRATES
A major advance in the pharmacological management of CHF has been the demonstration that afterload re-duction improved survival. The concept of afterload reduction was developed for the treatment of mitral re-gurgitation. It was noted that a decrease in systemic vas-cular resistance, as reflected in lower arterial blood pres-sure, resulted in an increase in the percentage of blood that flowed from the left ventricle to the aorta as op-posed to the left atrium (decreased regurgitant fraction). The decrease in backup of blood into the lungs provided considerable symptomatic relief from dyspnea, fatigue, and chest pain. It was reasoned that patients with CHF often also have mitral regurgitation and might similarly benefit from more forward (left ventricle to aorta), as opposed to backward (left ventricle to left atrium), blood flow. A VA Cooperative Study in which vasodila-tors were added to digitalis and furosemide was the first to demonstrate a significant improvement in survival in CHF. Patients were given either prazosin as an α- adrenoceptor blocking agent or the combination of the direct vasodilator hydralazine and a nitric oxide– mediated vasodilator, that is, one of the nitrates. There were fewer deaths among the patients on the combina-tion of hydralazine and nitrates. Patients taking prazosin did not benefit, probably because chronic therapy with prazosin results in tachyphylaxis. The mechanisms of ac-tion of prazosin, hydralazine, and organic nitrates are discussed in more detail elsewhere.