Cardioprotective drugs and heart failure/cardiomyopathy incidence in chemotherapy-treated cancer survivors of breast cancer and non-Hodgkin lymphoma: a retrospective cohort study in England.

Abstract

Aims: Evidence for the use of beta-blockers, angiotensin II receptor blockers (ARB), or angiotensin-converting enzyme inhibitors (ACEi) to mitigate chemotherapy-induced cardiotoxicity is inconclusive. The objectives are to investigate associations between prescription of ARBs, ACEis, and/or beta-blockers in the year following cancer diagnosis and subsequent risk of heart failure/cardiomyopathy (HF/CM) in chemotherapy-treated breast cancer and non-Hodgkin lymphoma (NHL) survivors.

Methods and results: This cohort study used linked English electronic healthcare records from 9875 adult (≥18 years) breast cancer and NHL survivors who received chemotherapy. Cox regression was used to estimate the association between primary care-prescribed beta-blocker, ARB, and ACEi use in the year following cancer diagnosis, and subsequent HF/CM incidence, adjusting for potential confounders. Likelihood ratio tests were used to assess effect modification. The mean follow-up duration was 4.9 years (maximum 21.4). After adjusting for age, the risk of HF/CM was higher in the exposed group [hazard ratio (HR): 1.69, 95% confidence interval (CI): 1.34-2.14], but further adjustment for gender, comorbidities, and other medications reduced the association to close to null (HR: 1.07, 95% CI: 0.68-1.69). There was no evidence that the association differed by cancer site, age, radiotherapy, prior cardiovascular disease, or years since cancer diagnosis.

Conclusion: We found no evidence that general practitioner prescribed beta-blocker, ARB, or ACEi use was associated with a reduced incidence of HF/CM in this population of chemotherapy-treated breast cancer and NHL survivors. This might be because the drug dosage and timing were not optimized to prevent chemotherapy-related cardiac damage; residual confounding by indication may also have obscured any treatment benefit.