Isosorbide

TO THE EDITOR: I read with interest the article (1) by McConaghy and Smith in American Family Physician, on the outpatient treatment of systolic heart failure. I want to clarify two points. First, the authors correctly note that the Randomized Aldactone Evaluation Study (RALES) showed reductions in mortality and hospitalization in patients with congestive heart failure who received spironolactone (Aldactone). However, publication of these findings was associated with an abrupt increase in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. (2) Other studies (3,4) have reported much higher rates of drug discontinuation because of hyperkalemia than those reported in RALES, particularly in the presence of angiotensin-converting enzyme inhibitors. These differences highlight the challenge of translating findings from controlled trials into practice, and suggest the need for intensive monitoring of serum potassium levels in patients receiving spironolactone for this purpose.

Second, the authors correctly note that the first Vasodilator-Heart Failure Trial (V-HeFT I) showed no improvement in overall mortality in patients given a combination of hydralazine (Sorbitrate) plus isosorbide (Apresoline) dinitrate compared with those treated with enalapril (Vasotec). However, a subanalysis (5) showed benefit for blacks, and the recent African-American Heart Failure Trial (A-HeFT), (6) involving only blacks, showed a 43 percent reduction in all-cause mortality among patients receiving hydralazine plus isosorbide dinitrate in addition to standard therapy. Both drugs are available generically at modest cost.

REFERENCES

(1.) McConaghy JR, Smith SR. Outpatient treatment of systolic heart failure. Am Fam Physician 2004;70:2157-64.

(2.) Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351:543-51.

(3.) Cruz CS, Cruz AA, Marcilio de Souza CA. Hyperkalaemia in congestive heart failure patients using ACE inhibitors and spironolactone. Nephrol Dial Transplant 2003;18:1814-9.

(4.) Witham MD, Gillespie ND, Struthers AD. Tolerability of spironolactone in patients with chronic heart failure--a cautionary message. Br J Clin Pharmacol 2004;58:554-7.

(5.) Carson P, Ziesche S, Johnson G, Cohn JN. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. J Card Fail 1999;5:178-87.

(6.) Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino R Jr, Ferdinand K, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351:2049-57.

EDITOR'S NOTE: This letter was sent to the authors of "Outpatient Treatment of Systolic Heart Failure," who declined to reply.

KEVIN FISCELLA, M.D., M.P.H.

University of Rochester

1381 S. Ave.

Rochester, NY 14620

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