Statins counter heart risks in breast cancer radiotherapy

For patients with breast cancer undergoing adjuvant radiotherapy, statin therapy appears to confer cardioprotective effects, mitigating the risk of major adverse cardiovascular event (MACE), according to a retrospective study.

In the propensity-score matched (PSM) cohort, the incidence of MACE was significantly lower among statin users at 33.61 percent vs 20.28 percent among nonusers (p<0.0001). This trend was observed uniformly across all specific MACE components, including acute coronary syndrome/ischaemic heart disease (10.83 percent vs 21.67 percent), cerebrovascular accidents (8.89 percent vs 2.22 percent), heart failure (5.56 percent vs 10.28 percent), and cardiovascular death (1.39 percent vs 4.72 percent; p<0.05 for all). [J Am Heart Assoc 2024;doi:10.1161/JAHA.124.036411]

Statin use was associated with a 66-percent reduction in the risk of MACE (adjusted hazard ratio [aHR], 0.34, 95 percent confidence interval [CI], 0.25–0.44; p<0.0001). All classes of statins demonstrated a MACE risk-lowering benefit, with aHRs of 0.23 (95 percent CI, 0.13–0.41) with hydrophilic statins and 0.38 (95 percent CI, 0.28–0.52) with lipophilic statins. According to their efficacy, statins were ranked as follows: rosuvastatin, pravastatin, simvastatin, lovastatin, atorvastatin, and fluvastatin.

A clear dose-response relationship was observed between statin use and the risk of MACE, with higher cumulative defined daily doses and daily intensity doses yielding greater cardioprotection. The 5‐year cumulative incidence of MACE was 12.24 percent among statins users, which was significantly lower than the 31.70 percent recorded among nonusers (p<0.0001).

The present data suggest that “statins may serve as an adjunctive therapy to reduce radiation‐induced cardiotoxicity, improving long‐term cardiovascular outcomes in patients with breast cancer undergoing radiotherapy,” the investigators said.

Multifaceted action

“The potential of statins to mitigate radiotherapy‐induced cardiotoxicity arises from their pleiotropic effects, surpassing their conventional role in lipid metabolism,” the investigators noted.

“Experimental evidence suggests that statins harbour antioxidant, anti‐inflammatory, and antifibrotic properties, all implicated in cardiac radiopathology. Moreover, statin therapy has been shown to augment DNA double‐strand break repair and suppress apoptosis pathways in normal cardiopulmonary cell types, mechanisms directly relevant to radiotherapy‐induced cardiotoxicity,” they pointed out. [Cell Death Dis 2017;8:e2978]

In murine models subjected to whole‐heart irradiation, statin exposure attenuated radiation tissue damage and functional impairment—a protective effect attributed to the modulation of the Rho/ROCK (Rho‐associated protein kinase) pathway, which is a critical mediator of cardiopulmonary radiation toxicity. [Curr Drug Targets 2010;11:1395-1404; Pharmacol Res Perspect 2015;3:e00145; Physiol Res 2016;65(Suppl 1):S129-S137; J Clin Invest 2001;108:1429-1437]

“Although the precise mechanisms underlying the radioprotective effects of statins on other key pathways involved in radiotherapy‐induced cardiotoxicity, such as the renin‐angiotensin system and growth factor signalling, necessitate further elucidation, the multifaceted actions of statins render them promising candidates for alleviating radiotherapy‐induced cardiotoxicity. Our clinical investigation outcomes, aligned with preclinical studies, provide valuable insights into the potential of statins in mitigating radiotherapy‐induced cardiotoxicity, paving the way for future research in this critical domain,” the investigators said.

The PSM cohort comprised 720 patients (median age 55 years, mean BMI 23.8 kg/m²) with early‐stage breast cancer undergoing breast‐conserving surgery and adjuvant radiotherapy with (n=360) or without (n=360) statin therapy. The distribution of covariates, including comorbidities and use of other medications, among others, was similar between the two groups. The median follow‐up duration was 5.02 years.