Statins associated with reduced heart dysfunction from anthracyclines

The STOP-CA trial results suggest that statins may be cardioprotective in patients receiving chemotherapy with anthracyclines for lymphoma. The participants in this phase 2, multicentre, randomised trial were significantly less likely to experience heart dysfunction after taking atorvastatin for 1 year.

Each year, over 1 million cancer patients worldwide are treated with anthracyclines such as doxorubicin, epirubicin, and idarubicin. Prof. Tomas Neilan (Massachusetts General Hospital, MA, USA) pointed out that these agents have been known to be cardiotoxic [1]. Patients treated with anthracyclines have a 10 to 15-fold increased risk of heart failure. Prof. Neilan explained the choice to include lymphoma patients in STOP-CA (NCT02943590) by the high survival rate, which renders the impact of late toxicities of added importance.

The study enrolled 300 patients with lymphoma scheduled to receive treatment with an anthracycline at a median dose of 300 mg/m². The median age was 52 years, and 47% were women. The participants were randomised to atorvastatin 40 mg daily or a matching placebo, starting before their first dose of anthracyclines and continuing for 1 year. The study's primary endpoint was the proportion of participants with a decline in left ventricular ejection fraction (LVEF) of ≥10% to a final value of <55% after 1 year.

The study was completed by 286 patients (95%). Adherence to atorvastatin was documented in >90%. At baseline, the LVEF was 63% across the cohort; after 1 year it was 58%. The LVEF decreased by 4.1% in the atorvastatin group and by 5.4% in the placebo group. The primary endpoint occurred in 9% of the atorvastatin group and 22% of the placebo group (P=0.002). The odds of a ≥10% decline in LVEF to <55% after anthracyclines was almost 3 times higher in the placebo group: OR 2.9 (95% CI 1.4–6.4). A decline in LVEF of ≥5% to <55% was observed in 13% of the atorvastatin group and 29% of the placebo group (P=0.001).

Atorvastatin 40 mg was safe with no effect on heart rate, blood pressure, or blood parameters (other than lipids), and no serious study-related side effects. There were 11 cases of heart failure, with no difference between groups (P=0.77). Prof. Neilan noted that it is unclear whether the 12-month beneficial effect of atorvastatin would have been noted had the LVEF been checked at a later time point. Future confirmatory and mechanistic studies may help to clarify the role of statins in this population.

1. Neilan T, et al. Statins to prevent the cardiotoxicity from anthracyclines: The STOP-CA trial. Session 402-10, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.

 

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Posted on 7 June 2023