"Valsartan in Heart Failure Patients Already Treated with ACE Inhibitors". The New England Journal of Medicine. 2001. 345:1667-1675. PubMed
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Contents
1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcomes 8.2 Secondary Outcomes 9 Criticisms 10 Funding 11 Further Reading
In patients with heart failure already treated with prescribed therapy including ACE inhibitors and beta-blockers, does the addition of valsartan improve mortality and morbidity?
Valsartan significantly reduced the combined endpoint of mortality and morbidity in heart failure patients when added to prescribed therapy, without affecting overall mortality. However, it had an adverse effect on mortality in the subgroup receiving valsartan in combination with both an ACE inhibitor and a beta-blocker.
Despite the use of angiotensin-converting–enzyme (ACE) inhibitors and beta-blockers, heart failure remains a major cause of hospitalization and mortality. Valsartan, an angiotensin-receptor blocker, was tested to see if it could further reduce morbidity and mortality in heart failure patients already on optimal therapy.
This study, known as the Valsartan Heart Failure Trial (Val-HeFT), showed that valsartan reduced the combined endpoint (cardiac arrest with resuscitation, hospitalization for heart failure, or IV inotropic or vasodilator therapy) by 13.2% compared to placebo, predominantly due to a lower number of hospitalizations for heart failure. However, overall mortality did not differ significantly between the valsartan and placebo groups.
A post hoc analysis raised safety concerns about the specific combination of valsartan, an ACE inhibitor, and a beta-blocker, showing an adverse effect on mortality and morbidity in this subgroup.
Current guidelines recommend ACE inhibitors and beta-blockers as standard therapy for heart failure due to their proven efficacy in reducing mortality, but they do not specifically address the combination of these with valsartan. The Val-HeFT findings suggest valsartan could have a role in heart failure management, except possibly in those already on both an ACE inhibitor and a beta-blocker.
- Randomized, placebo-controlled, double-blind, parallel-group trial - N=5,010 patients with heart failure of NYHA class II, III, or IV - Interventions: - Valsartan (n=2,511), initiated at 40 mg twice daily, up titrated to a target of 160 mg twice daily - Placebo (n=2,499) - Primary outcomes: Mortality and the combined endpoint of mortality and morbidity
Inclusion Criteria
- Aged ≥18 with heart failure for at least three months - NYHA class II, III, or IV - Clinically stable on fixed-dose heart failure medication regimen for at least two weeks - Left ventricular ejection fraction <40% - Left ventricular dilatation
Exclusion Criteria
- Contraindications to valsartan - Current use of angiotensin-receptor blockers
Baseline Characteristics
- Mean age: 61.8 years - 23% female - Approx. 93% on ACE inhibitors, 35% on beta-blockers at baseline
- Valsartan or placebo, with the dose progressively titrated to target based on blood pressure, absence of hypotension symptoms, and kidney function.
- Overall mortality similar in two groups - Combined endpoint of mortality and morbidity 13.2% lower with valsartan (P=0.009)
- Reduction in hospitalizations for heart failure with valsartan - Improvements in NYHA class, ejection fraction, signs and symptoms of heart failure, and quality of life (P<0.01)
- The unexpected post hoc finding of an increased risk of mortality in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concerns about the safety of this combination.
Supported by a grant from Novartis Pharma, Basel, Switzerland.
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