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Statins reduced heart failure risk during anthracycline chemotherapy
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Continual statin use lowers the risk for heart failure in patients with breast cancer who undergo anthracycline chemotherapy, according to the results of an observational study.
Comprehensive management of treatments such as surgery, radiation and chemotherapy have resulted in prolonged cancer-related survival for patients with breast cancer. Still, treatment-related cardiotoxicity is a major concern for this patient population.
Cumulative dosing of anthracycline is associated with cardiomyopathy, which often is irreversible and potentially deadly. Statins are believed to ease cardiotoxicity without compromising treatment effects, according to background information provided by researchers.
In this study, Sinziana Seicean, MD, PhD, MPH, adjunct assistant professor in the department of epidemiology and biostatistics for the Heart and Vascular Institute at Cleveland Clinic, and colleagues investigated whether uninterrupted statin use protected against cardiotoxicity in patients with newly diagnosed breast cancer who were undergoing anthracycline chemotherapy.
Seicean and colleagues retrospectively identified and analyzed 628 women aged at least 18 years with newly diagnosed with breast cancer (mean age, 51.5 years). All patients were treated with anthracycline between January 2005 and December 2010.
Hospitalization due to heart failure served as the primary outcome.
After mean follow-up of 2.55 years, Seicean and colleagues compared outcomes in patients who received uninterrupted statin therapy with those of patients who did not take statins.
Sixty-seven patients (10.7%) received uninterrupted statin therapy through the follow-up period. Statin users were older and more likely to have a cardiac risk. Thirty-nine percent of the statin users were on angiotensin-converting enzyme inhibitors, and 45% were on beta-blockers.
Seicean and colleagues matched the statin users with 134 controls who did not receive continual statin therapy.
Regression analysis showed a significantly lower risk for heart failure (HR= 0.3; 95% CI, 0.1-0.9) among patients who received uninterrupted statin therapy.
Researchers also reported a significantly higher combined incidence of heart failure and cancer-related mortality among patients in the statin group (four of 67; 6%) compared with the control group (23 of 134; 17.2%).
Study results showed cardiotoxicity factors at the time of cancer diagnosis (HR=5.0; 95% CI, 2.2-11.1), baseline ejection fraction <55% (HR=2.7; 95% CI, 1.2-6.3) and trastuzumab (Herceptin, Genentech) use (HR=3.0; 95% CI, 1.3-7.2) were significant predictors of heart failure for this patient population.
“In this study of relatively young women with breast cancer treated with anthracyclines, we found that uninterrupted statin therapy initiated before and concurrent with chemotherapy reduced the risk for incident heart failure,” Seicean and colleagues wrote. “Lower risk persisted after adjustment for many of the known risk factors.”
Prospective trials are needed to verify the association, they added.
“In addition, it may be beneficial to expand our understanding of the effects of statins on cardiac tissue and on cancer cells,” the researchers wrote.
In an accompanying editorial, Daniel J. Lenihan, MD, professor of medicine in the division of cardiovascular medicine at Vanderbilt University Medical Center, said the data in the study illustrated a valuable principle.
“Chemotherapy, especially potentially cardiotoxic chemotherapy such as that based on anthracycline and trastuzumab, is a major cardiovascular stressor and all reasonable efforts to enhance cardiovascular reserve should be undertaken,” Lenihan wrote said.
It has become clear that statins improve cancer outcomes, Lenihan added.
“In a manner similar to athletes training to become ‘fit for battle’ and perform at their peak, statins appear to be a necessary component for patients with cancer to ready themselves for their cancer war,” he wrote.
Disclosure: Seicean receives funding through the Agency for Healthcare Research and Quality Pre-Doctoral Training Fellowship. Lenihan reports no relevant financial disclosures.
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Debasish “Debu” Tripathy, MD
This is an interesting but rather small case-control study showing that statin use is associated with a lower incidence of cardiomyopathy following anthracycline therapy. The high rate of heart failure in the overall cohort is much higher than reported in prospective trials and therefore clouds the interpretation. While we would clearly want to understand if statins, angiotensin-converting enzyme inhibitors and beta blockers can reduce cardiac effects of certain cancer drugs, the only way to determine this is through a prospective controlled trial.
Such a trial would need to be large given the low projected event rate. In the absence of pharmaceutical companies funding such a trial (which is unlikely), the questions remaining are whether the cooperative groups, insurance companies or some other entity has the appetite to perform this necessary study and, if so, which drugs should be tested.
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