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.