(1)
University of Ottawa The Ottawa Hospital, Ottawa, ON, Canada
Are ARBs as Effective as ACE Inhibitor Therapy for Heart Failure?
The carefully run RCTs CHARM (2003), Val-HeFT (2001), and TRANSCEND (2008) did not show a decrease in total mortality in heart failure (HF) subjects (see Chaps. 4 and 12). This surprising finding was observed in patients intolerant to ACE inhibitor administration. It is abundantly clear that ARBs are not as effective as ACE inhibitor therapy for HF, hypertension, or stroke. The salutary effects of ARBs are probably less than that observed with digoxin, yet these agents are used widely and excessively. In Val-HeFT valsartan when combined with a beta-blocker caused significantly more cardiac events. A total of 5,010 patients with HF class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily.
The incidence of the combined end point was a modest 13.2 % lower with valsartan than with placebo), predominantly because of a lower number of patients hospitalized for heart failure: 455 (18.2 %) in the placebo group and 346 (13.8 %) in the valsartan group.
“Overall mortality was not reduced by valsartan administration” (Cohn and Tognoni 2001); see results for digoxin.
Unfortunately, less than 36 % of subjects received a beta-blocker and ~68 % received digoxin.
“The post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concern about the potential safety of this specific combination” (Cohn and Tognoni 2001).
Often in patients with HF, a beta-blocker is needed as proven therapy. Thus an ACE inhibitor must be used, not an ARB; telmisartan also failed in HF trials.
Caution: valsartan should not be combined with a beta-blocker.
In VALIANT 2003: a clinical trial of valsartan, captopril, or both in MI complicated by HF, left ventricular dysfunction, or both, during a median follow-up of 24.7 months, total mortality was not reduced by valsartan: 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group. There was no placebo group.
Caution: valsartan therapy does not decrease mortality and is not advisable in HF patients because in this large number of patients, a beta-blocker is a needed therapy.
Management of Heart Failure Preserved Ejection Fraction
Heart failure preserved ejection fraction (HFPEF) is not uncommon in elderly women. Atrial fibrillation is common in the elderly, and ventricular rates even when not very rapid (120–140) may precipitate HFPEF. Is it preferable to adopt the term HFPEF rather than diastolic HF? Not all patients with HFPEF show definite diagnostic diastolic abnormalities. Controversies abound, however, among the experts.
Mauer et al. (2004 stated that HF with normal ejection fraction is preferred over the term diastolic heart failure (DHF) mainly because:
Doppler-derived diastolic parameters do not provide specific information on intrinsic passive diastolic properties; thus, diastolic dysfunction cannot be diagnosed reliably by Doppler echocardiography.
Delayed relaxation and/or stiffened passive properties may not be the unifying pathophysiologic mechanisms in all patients who present with HF and normal EF.
Nonetheless, abnormal diastolic function is a common cause of HFPEF if atrial fibrillation as a cause is excluded.
Oh et al. (2006) criticized Mauer and colleagues and emphasized that diastolic HF is easily diagnosed by echocardiography in a patient with a preserved left ventricular (LV) EF with evidence of abnormal relaxation, decreased compliance, increased filling pressure, and normal LV dimensions. However, Oh et al. describe the situation that exists in most sophisticated diagnostic laboratories with highly trained echocardiographers and clinicians and that does not represent the real world of medicine.
The diagnosis of probable diastolic HF can be made by using the criteria of Vasan and Levy (2000).
Differential diagnosis and mimics include:
1.
Incorrect diagnosis or incorrect measurement of EF. The echocardiographic assessment of EF is fraught with errors but remains a useful guide to diagnosis and management of systolic HF.
2.
Valvular disease.
3.
Pericardial constriction and left atrial myxoma are rare and do not genuinely represent HFPEF; in this setting there is simply restriction to ventricular filling.
4.
Severe hypertension can cause both systolic HF and HFPEF.
5.
Myocardial ischemia more commonly causes systolic HF but can cause a combination of both types of HF and rarely pure HFPEF.
Age and the diseases listed appear to cause changes in cross-linking of intercellular connective tissue. The heart fills less and empties less, and the percentage ejected may be relatively normal, but the stroke output and cardiac index are decreased; thus, the renin-angiotensin-aldosterone system (RAAS) is stimulated. Systolic dysfunction impairs the ability of the left ventricle to relax and fill at low pressure. Thus, systolic dysfunction is a principal cause of diastolic dysfunction.
Treatment
Importantly, the treatment of HFPEF is treatment of the cause. With systolic HF, medications help considerably to improve outcomes versus HFPEF, in which medications are unproved except for symptomatic improvement enhanced by judicious diuretic therapy.
The judicious use of diuretics is recommended to relieve symptoms.< div class='tao-gold-member'>Only gold members can continue reading. Log In or Register to continue
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