Statins May Have Protective Effect on Chemotherapy-Induced Cardiotoxicity

Among women with early stage breast cancer treated with anthracycline- and trastuzumab-based chemotherapy, statin exposure seems to lower the risk of hospitalization for heart failure, according to a new population-based retrospective cohort study.

Despite the cardiac risk associated with chemotherapy, “the effectiveness of these medications—anthracycline and trastuzumab—for breast cancer treatment means we cannot forgo their use, which necessitates that we protect the heart,” explained David Bobrowski, BHSc (University of Toronto, Canada), in an online press conference this week when presenting his results. “Limited evidence suggests that statins may protect against cardiotoxicity after chemotherapy with anthracycline and trastuzumab, but this data is from small, single-center studies primarily and they focused on declines in heart function, specifically left ventricular ejection fraction for the most part.”

Bobrowski et al’s findings provide support for prospective clinical trials “to determine if pretreatment with statins is actually an effective intervention to prevent cardiotoxicity secondary to anthracycline and trastuzumab,” he added.

The study was originally selected for presentation at the American College of Cardiology 2020 Scientific Session, which has since converted to a virtual meeting due to the continuing threat of COVID-19. The meeting is going ahead virtually with a truncated program later this month.

Martha Gulati, MD (University of Arizona, Phoenix), who moderated the web briefing, said the study results are “very interesting given that use of statins is a big part of what we do for cardiovascular risk assessment.” The findings support the development of a prospective trial to understand the mechanism behind how statins reduce heart failure hospitalizations. “Also knowing why these patients were treated with a statin might make a difference as well,” she said. “We're projecting we're improving heart failure with reduced ejection fraction here given what we know of those drugs, but how it's preserved by statins is still unclear.”

Bobrowski and colleagues used administrative data to look at the effects of statins in women aged ≥ 66 years without a history of heart failure who were diagnosed with early stage breast cancer between 2007 and 2017 in Ontario, Canada. Statin use was defined as dispensed prescriptions in the year before chemotherapy.

The researchers matched 723 pairs of anthracycline-treated women (median age 69 years) and 399 pairs of trastuzumab-treated women (median age 71 years). The risk of hospitalization for heart failure was lower with statin exposure both in the anthracycline (P = 0.01) and trastuzumab cohorts (P = 0.02).

Heart Failure Hospitalization Risk

To TCTMD, Bobrowski said it’s too early to begin proactively treating breast cancer patients with statins. “We can only comment on the association, and we cannot go as far as saying there's a cause and effect relationship,” he said. “The results are suggestive, but it could be explained by potential other causes like patients who are getting statins are more health aware or had maybe better doctors and that was the cause of their lower risk of heart failure. We won't know this for sure without a randomized controlled trial.”

We can only comment on the association, and we cannot go as far as saying there's a cause and effect relationship. David Bobrowski

It is notable that the study found a protective effect of statins after both anthracycline and trastuzumab treatment, as most studies so far have only looked at the former, Bobrowski said. This suggests that “the protective effect with statins from trastuzumab cardiotoxicity is not because we're preventing heart failure from anthracyclines in particular, and we didn't necessarily do subanalyses looking at other particular risk factors like whether having diabetes or having other cardiovascular risk factors is more or less protective, but that is something we could definitely look into for future study,” he observed.

Unfortunately, he added, the data set used meant they were unable to “account for some important variables like left ventricular ejection fraction. That is one of the limits, and that is why we're advocating for a prospective clinical trial to be able to have that data.”

Gulati, too, pointed out several unknowns. “It's important to note that especially anthracycline damage to the left ventricle can occur both early but also late, and the question always is: Do you need to be on the statin short-term? Long-term? Why are you on the statin? Or do you just give it to everyone who's getting this therapy?” she said. “[This] is why we really do need prospective trials to help us determine whether this is for everyone.”