From the Guidelines
Valsartan has demonstrated mortality benefit in heart failure, while atenolol has not. Valsartan, an angiotensin II receptor blocker (ARB), reduces mortality in patients with heart failure by blocking the harmful effects of the renin-angiotensin-aldosterone system, which contributes to cardiac remodeling and progression of heart failure. The Val-HeFT and VALIANT trials showed significant reductions in heart failure hospitalizations and mortality with valsartan 1. In contrast, atenolol, a beta-blocker, has not shown the same level of mortality benefit in heart failure patients. While beta-blockers as a class (particularly carvedilol, metoprolol succinate, and bisoprolol) have proven mortality benefits in heart failure, atenolol specifically lacks robust evidence for mortality reduction in this population. For heart failure patients requiring beta-blockade, carvedilol, metoprolol succinate, or bisoprolol would be preferred over atenolol based on stronger evidence for mortality benefit.
The most recent guidelines from the American College of Cardiology/American Heart Association (2022) support the use of ARBs, such as valsartan, in patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality 1. Additionally, the guidelines recommend the use of ACE inhibitors or ARBs in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients with HFrEF 1.
Key points to consider:
- Valsartan has demonstrated mortality benefit in heart failure patients
- Atenolol lacks robust evidence for mortality reduction in heart failure patients
- Beta-blockers, such as carvedilol, metoprolol succinate, and bisoprolol, have proven mortality benefits in heart failure
- ARBs, such as valsartan, are recommended in patients with HFrEF to reduce morbidity and mortality
- ACE inhibitors or ARBs should be used in conjunction with evidence-based beta blockers and aldosterone antagonists in selected patients with HFrEF.
From the FDA Drug Label
The Valsartan Heart Failure Trial (Val-HeFT) was a multinational, double-blind study in which 5,010 patients with NYHA class II (62%) to IV (2%) heart failure and LVEF less than 40%, on baseline therapy chosen by their physicians, were randomized to placebo or valsartan (titrated from 40 mg twice daily to the highest tolerated dose or 160 mg twice daily) and followed for a mean of about 2 years. Although the overall morbidity result favored valsartan, this result was largely driven by the 7% of patients not receiving an ACE inhibitor, as shown in the following table. Without ACE Inhibitor Placebo (N=181) Valsartan (N=185) Events (%) 77 (42.5%) 46 (24.9%) Hazard ratio (95% CI) 0. 51 (0.35,0.73) p-value 0.0002 Secondary end points in the subgroup not receiving ACE inhibitors were as follows Placebo (N=181) Valsartan (N=185) Hazard Ratio (95% CI) Components of HF morbidity All-cause mortality 49 (27.1%) 32 (17.3%) 0.59 (0.37,0.91)
Mortality benefit in HF: Valsartan has a mortality benefit in heart failure patients not receiving an ACE inhibitor.
- Hazard Ratio: 0.59 (0.37,0.91) for all-cause mortality.
- Comparison to Atenolol: There is no direct comparison to Atenolol in the provided text. 2
From the Research
Mortality Benefit in Heart Failure
- Valsartan has been shown to reduce the risk of mortality and morbidity in patients with heart failure who are not receiving ACE inhibitors 3, 4.
- In the Valsartan Heart Failure Trial (Val-HeFT), valsartan reduced the risk of the combined endpoint of mortality and morbidity by 13.2% compared with placebo 3.
- However, there was no significant difference in overall mortality between the valsartan and placebo groups in the Val-HeFT trial 3.
- A subgroup analysis of the Val-HeFT trial found that valsartan reduced all-cause mortality and the composite of all-cause mortality and morbidity in patients not receiving ACE inhibitors 4.
- Compared to ACE inhibitors or angiotensin receptor blockers, sacubitril/valsartan reduced heart failure hospitalizations, cardiovascular mortality, and all-cause mortality in patients with heart failure 5.
- However, sacubitril/valsartan was not superior to equivalent doses of ACE inhibitors or angiotensin receptor blockers in reducing mortality and worsening heart failure 6.
- In elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction, mortality and morbidity remained high despite therapy with captopril and/or valsartan 7.