Management of Heart Failure in Special Populations
HF in Women
Clinical Characteristics and Prognosis. HF is common in women, and among the elderly the prevalence of HF is greater in women than in men.29 A growing body of evidence has demonstrated significant differences in the clinical characteristics and prognosis of HF in women and men. Early results from the Framingham Heart Study pointed to a difference in prognosis between men and women with HF, with men having worse survival than women.30-32 Subsequent findings from some HF databases have confirmed this observation in both a broad population of patients with HF and those at a very advanced stage.31,33-35 These studies have suggested that women's survival advantage is etiology-dependent, with better outcomes noted when the primary cause is non-ischemic. Hypertension and diabetes carry with them significantly greater risk of subsequent HF in women compared to men.36 For women with coronary artery disease but no symptoms of HF, diabetes confers particular risk for the subsequent development of HF.37 Diabetes and coronary disease are also associated with excess mortality in women with HF and systolic dysfunction compared to men.38
Sex and Cardiovascular Pathophysiology. A number of experimental studies point to fundamental, sex-related differences in the nature and extent of myocardial hypertrophy and adaptation, which might account for the survival advantage for females.39,40 Early studies of spontaneously hypertensive rats suggested that the adverse influence of hypertrophy on cardiac function was greater in male than in female rats.41 A number of animal studies suggest sex-related differences in myocardial remodeling in response to a pressure load and after MI.41-46
Treatment Response. Recognition of the pathophysiologic and clinical differences between men and women with HF has raised concern that treatment response might differ as well. Results of individual controlled clinical trials, even of standard therapeutic agents for HF from systolic dysfunction, generally are inconclusive, because of the small number of women enrolled. Data from pooled analyses are equally sparse. Recommendations are made in the context of this limited database.
Recommendation
Beta blocker therapy is recommended for women with HF from:
- symptomatic LV systolic dysfunction (Strength of Evidence = B)
- asymptomatic LV systolic dysfunction (Strength of Evidence = C)
Background
Women are underrepresented in HF clinical trials, as they are in clinical studies of other cardiovascular diseases.47 However, a review of the experience of women in several of the large-scale prospective mortality trials of beta blockade in patients with symptomatic LV dysfunction does suggest that women and men benefit to a similar degree.48 Similarly, a pooling of the mortality results from several other large trials showed strong evidence of a similar beneficial effect in women and men.48,49 Given the absence of contrary data, the most prudent course is to recommend the routine use of beta blockade for HF in both women and men.
Recommendation
ACE inhibitor therapy is recommended as standard therapy in all women with symptomatic or asymptomatic LV systolic dysfunction. (Strength of Evidence = B)
Background
As with beta blockers, the available data on ACE inhibition suggest comparable effects in women and men with HF. A meta-analysis of large-scale HF and post-MI randomized trials demonstrated evidence of a mortality benefit of ACE inhibition in women. A more convincing effect was seen on the composite end point of death, reinfarction, or admission for HF. Comparable findings related to sex were also noted in the meta-analysis of mostly small-scale, short-term studies of ACE inhibition, which found similar favorable point estimates for reduction in mortality and for mortality plus hospitalization in women.25,50
Recommendation
ARBs are recommended for administration to symptomatic and asymptomatic women with an LVEF <=40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insufficiency. (Strength of Evidence = A)
Background
Investigators in both the Valsartan Heart Failure Trial (Val-Heft) and the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) trials have analyzed the benefits of valsartan and candesartan, respectively, in women with HF and systolic dysfunction. In Val-HeFT significant reductions in both morbidity and mortality and HF hospitalizations were reported for women and were the same as benefits reported in men.51 In CHARM there was a significant reduction in all-cause mortality and HF hospitalization that was the same as in men.38 Subgroup analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT) study also showed no difference in the effects of ARB vs. ACE inhibitor in men and women status post MI complicated by HF, LV dysfunction or both.52 Thus the recommendations for ARBs in women have a level of evidence similar to those for men. Cough due to ACE inhibitors is more than twice as common in women compared to men and thus substitution of ARBs for ACE inhibitors is also likely to be more common in women compared to men.53