Statins may have a role in reducing mortality in patients with heart failure and preserved ejection fraction (HFpEF), a meta-analysis suggested.
In pooled results of observational studies, statin use was associated with a 40% reduction in the risk of dying through up to 10 years of follow-up (RR 0.60, 95% CI 0.49-0.74), according to Xiao-Hong Huang, MD, PhD, of Fu Wai Hospital in Beijing, and colleagues.
The reduction was significant both for studies that followed patients for less than 5 years (RR 0.34, 95% CI 0.15-0.77) and for those that followed patients for longer (RR 0.64, 95% CI 0.47-0.89), the researchers reported online in the American Journal of Cardiology.
They acknowledged, however, that randomized trials are needed to confirm the results.
John Erwin III, MD, vice chair of the department of internal medicine at Scott & White Heart and Vascular Institute in Temple, Texas, agreed.
"This meta-analysis is encouraging as to the possible therapeutic benefit of statins in HFpEF, but it does beg for randomized controlled studies with pre-defined endpoints in this population before we can have some degree of assurance as to cause and effect," he wrote in an email to MedPage Today.
But, he added, "I certainly would maintain a low threshold towards treating cholesterol per our guidelines in those patients with HFpEF and elevated cholesterol levels."
No treatments have been shown to alter the clinical course of patients with HFpEF, Erwin noted, and clinicians have focused on dealing with traditional cardiovascular risk factors.
As for using statins, the most recent American College of Cardiology/American Heart Association guidance for the management of heart failure states that they "should not be prescribed primarily for the treatment of heart failure to improve clinical outcomes."
That recommendation is based on randomized data showing that despite beneficial effects on cardiac function and the symptoms of heart failure, statins have not improved mortality in patients with heart failure in recent trials, including CORONA and GISSI-HF.
But the vast majority of patients in those trials had heart failure with reduced ejection fraction, and the results might not apply to those with HFpEF, in whom no treatments have been shown to improve clinical outcomes.
To examine the potential utility of statins in patients with HFpEF, Huang and colleagues performed a meta-analysis of 11 observational studies with a total of 17,985 participants. The length of follow-up in the studies ranged from 1 to 10 years. Most of the studies (six), were conducted in North America, with four coming from Europe and one from Asia.
The association between statin use and reduced mortality was significant among the studies that accounted for major confounders, including age, sex, lipids, hypertension, diabetes, and coronary artery disease (RR 0.63, 95% CI 0.51-0.77), but fell just short of significance among the studies that did not (RR 0.49, 95% CI 0.24-1.01).
The researchers speculated that these findings in patients with HFpEF might differ from those in the recent clinical trials of patients primarily with reduced ejection fraction because of differences in pathophysiology.
Hearts that experience heart failure with reduced ejection fraction "undergo progressive expansion of the ventricle, coupled with cardiomyocyte elongation and extracellular matrix remodeling that produces eccentric left ventricular (LV) remodeling," they wrote. "Conversely, in HFpEF, hearts undergo hypertrophy with a marked increase in fibrosis leading to concentric LV remodeling."
In addition, patients with HFpEF are generally older and have higher rates of diabetes, hypertension, and coronary artery disease -- all conditions in which statins have proven beneficial.
Aside from addressing those comorbidities, statins also might help patients with HFpEF through positive effects on left ventricular hypertrophy, interstitial fibrosis, left ventricular relaxation and diastolic function, and left ventricular remodeling seen in previous animal and human studies, according to the researchers.
They acknowledged, however, that their analysis was limited by the lack of information on compliance with statin therapy and statin dose or type, and by a high level of heterogeneity between the included studies.
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