"The observational nature of this study means we cannot conclude that there is a cause-and-effect relationship," Dr. Husam Abdel-Qadir of Women's College Hospital and University Health Network, in Toronto, Canada, cautioned in an email to Reuters Health.
However, it is "plausible that statins may ameliorate anthracycline- and trastuzumab-induced heart damage by decreasing reactive oxygen species production and promoting cardiac muscle cell survival," he said.
As reported in the Journal of the American Heart Association, using administrative databases in Ontario, the researchers examined the association of statin use with the risk of heart failure among older women with early stage breast cancer treated with anthracyclines or trastuzumab between 2007 and 2017. Statin-exposed and unexposed women were matched 1:1 using propensity scores.
In the 666 statin-discordant pairs of women treated with anthracyclines, the five-year cumulative incidence of heart failure was 1.2% in statin-exposed women versus 2.9% in unexposed women.
Among anthracycline-treated women, those taking a statin were 55% less likely to be treated at the hospital for heart failure than their peers not on statin therapy (hazard ratio, 0.45; P=0.01).
In the 390 statin-discordant pairs of women treated with trastuzumab, the five-year cumulative incidence of heart failure was 2.7% in statin-exposed women versus 3.7% in statin-unexposed women.
Among trastuzumab-treated women, those taking statins were 54% less likely to be treated at the hospital for heart failure, a trend that did not reach statistical significance (hazard ratio, 0.46; P=0.07).
"Our study revealed that the risk of hospitalizations or emergency department visits where heart failure was the most responsible diagnosis was significantly lower among women who were taking a statin when starting anthracyclines. We also saw a tendency towards lower risk in women who were on statins when they started trastuzumab, but this was not statistically significant," Dr. Abdel-Qadir told Reuters Health.
"This study," he cautioned, "does not allow us to go as far as to say that a statin should be started in the absence of other indications (outside a clinical trial). Our study thus provides motivation for a randomized controlled trial."
"We do not think practice should change, but there is more importance that women starting chemotherapy who already have indications for a statin should be taking it at the time they start chemotherapy," Dr. Abdel-Qadir said. "For women who do not have an indication for a statin, they should ask if they can join one of the clinical trials studying the benefit of statins in protecting against cardiotoxicity."
Dr. Charles L. Shapiro, director of Translational Breast Cancer Research at Tisch Cancer Institute at Mount Sinai, in New York, said several points are worth mentioning.
"The use of anthracyclines is likely to diminish in this age group, and in general, because of the development of effective non-anthracycline-containing regimens," he told Reuters Health by email.
"The second point is that heart failure from anthracyclines is very different than trastuzumab," said Dr. Shapiro, who was not involved in the study. "Anthracyclines cause myocardial cells to die and the damage is permanent, although often can be improved by cardiac medications, whereas trastuzumab causes 'heart dysfunction' with over 50% of patients recovering their heart function and going on to be treated with trastuzumab again. This may explain the lack of significance of statins in women treated with trastuzumab."
The study was funded by the Ted Rogers Centre for Heart Research and the Canadian Cardiovascular Society.
SOURCE: https://bit.ly/2JN3R4m Journal of the American Heart Association, online January 6, 2021.
By Megan Brooks
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