Doxorubicin and subsequent risk of cardiovascular diseases among survivors of diffuse large B-cell lymphoma in Hong Kong

Abstract

Evidence regarding the dose-related impact of doxorubicin on subsequent cardiovascular diseases (CVDs) in Asian patients with diffuse large B-cell lymphoma (DLBCL) without preexisting CVDs is lacking. From a territory-wide electronic database in Hong Kong, we identified adults who were diagnosed with DLBCL and treated with chemotherapy between 2000 and 2018. We evaluated the patients for incident CVDs (including ischemic heart disease, heart failure, and cardiomyopathy). We evaluated the cause-specific cumulative incidence (csCI) of CVD with levels of doxorubicin exposure by using flexible parametric competing risk analysis and adjusting for demographics, comorbidities, therapeutic exposure, cardiovascular risk factors, and lifestyle factors. Controls were age- and sex-matched to DLBCL patients. We analyzed 2600 patients and 13 000 controls. The adjusted cause-specific hazard ratio (HR) for CVD in patients treated with >500 mg doxorubicin compared with non-doxorubicin regimens was 2.65 (95% confidence interval [CI], 1.23-5.74; P = .013). The 5-, 10-, and 15-year csCIs were 8.2%, 11.3%, and 12.8% in patients vs 3.1%, 4.4%, and 5.2% in controls, respectively. Hypertension (HR, 6.20; 95% CI, 0.79-48.44; P = .082) and use of aspirin/angiotensin-converting enzyme inhibitor/beta-blocker at baseline (HR, 2.13-4.63; P < .001 to .002) might confer a higher risk of subsequent CVDs. In this Hong Kong population-based study, doxorubicin exposure (absolute dose >500 mg), together with hypertension or baseline use of medication for cardiovascular risk factors, was found to be associated with an increase in csCIs of CVDs. Tailoring therapeutic strategies to underlying CVD risk factors and risk-adapted monitoring and follow-up of susceptible DLBCL patients are advisable.