Patients with non-Hodgkin lymphoma (NHL) that was treated with anthracycline-based chemotherapy have an increased risk of heart failure (HF), and the chances are even higher for patients with preexisting cardiovascular risk factors, according to research published in the Journal of Clinical Oncology.
"Even in the absence of overt cardiovascular disease, the presence of hypertension, diabetes, and high cholesterol contribute significantly to the ongoing risk of HF and should be taken seriously," lead author Talya Salz, PhD, of the Department of Epidemiology and Biostatistics at Memorial Sloan Kettering Cancer Center in New York, told ASH Clinical News.
In this large, population-based cohort study, the investigators identified patients diagnosed with aggressive NHL between 2000 and 2010 who were enrolled in Danish registry databases (n=2,508; median age = 62 years; range = 52-71 years), then compared their survival and HF risk with a sex- and age-matched control group from the general population (n=7,339; median age = 62 years; range = 52-71 years). Patients who had a diagnosis of HF or any other cancers were excluded from the study.
The researchers then assessed whether the presence of cardiovascular risk factors (hypertension, dyslipidemia, and diabetes) or cardiovascular disease prior to NHL diagnosis (including vascular disease [myocardial infarction, coronary artery disease, stable or unstable angina, cardiac arrest, carotid artery disease, and transient ischemic attacks] and intrinsic disease [pericardial disease, valvular disease, myocardial disease, and cardiomyopathy without clinical HF]) contributed to a higher risk of HF.
In the NHL cohort, other reasons for exclusion from the analysis included relapse (n=575), death (n=285), secondary primary malignancy (SPM; n=153), or emigration (n=10).
Compared with the control cohort, NHL survivors had a 42 percent increased risk of HF (hazard ratio [HR] = 1.42; 95% CI 1.07-1.88; p value not provided).
Prior to NHL diagnosis, 975 (39%) patients had one or more cardiovascular risk factors. The most common risk factor prior to NHL diagnosis was hypertension (n=703; 28%), followed by dyslipidemia (n=337; 13%) and diabetes (n=137; 6%).
Almost all survivors (92%) received an anthracycline, with a median prescribed cumulative dose of 300 mg/m2 (interquartile range = 200-350 mg/m2). Nine percent of patients received chest radiation, and 4 percent received an autologous hematopoietic cell transplantation.
NHL survivors were followed from nine months after diagnosis until December 2012, for a median of 2.5 years (range = 0-10.8 years). During follow-up, the researchers identified 115 patients with HF; at five years, 604 survivors remained at risk for HF.
"Although treatment of NHL confers substantial risk of HF, the presence of cardiovascular risk factors and intrinsic heart disease before lymphoma diagnosis dramatically heightens the risk of HF months to years after treatment completion," the authors reported.
In multivariate analyses, the investigators found that a higher number of cardiovascular risk factors were associated with increased risk of later HF, compared with no cardiovascular risk factors (HR=1.63 [95% CI 1.07-2.47] for 1 vs. 0 cardiovascular risk factors; HR=2.86 [95% CI 1.56-5.23] for 2 vs. 0 cardiovascular risk factors; p<0.01 for both).
Other factors associated with increased risk of HF included:
- older age at diagnosis: 1.07 (95% CI 1.05-1.09; p<0.01)
- male sex: 1.61 (95% CI 1.09-2.38; p=0.02)
- vascular disease before NHL diagnosis: 1.4 (95% CI 0.88-2.24; p=0.16)
- intrinsic heart disease before NHL diagnosis: 2.71 (95% CI 1.15-6.36; p=0.02)
Although higher cumulative anthracycline dose (per 100 mg/m2) was associated with increased HF risk (HR=1.45; 95% CI 1.14-1.85; p<0.01), receiving anthracycline appeared to be associated with a lower risk of HF (HR=0.49; 95% CI 0.19-1.30; p=0.15). "We also found evidence of confounding by indication," the authors wrote, "because the prescription of anthracyclines was associated with the number of preexisting cardiovascular risk factors (p<0.01), preexisting vascular disease (p<0.01), and preexisting intrinsic heart disease (p<0.01), such that survivors with these conditions less frequently received anthracyclines."
When the authors conducted a sensitivity analysis with follow-up beginning at 12 months after diagnosis (allowing for the possibility that NHL treatment may extend beyond 9 months), neither the magnitude nor significance of the treatment's effects on cardiovascular risk factors differed substantially.
"Because the risk of HF among NHL survivors begins early, it is important to be vigilant about cardiovascular health and employ preventive strategies early on for newly diagnosed patients," Dr. Salz said. "The balance of potential benefits and harms in the use of anthracyclines as part of curative therapy for aggressive NHL should be considered with upfront therapy."
The study is limited by the possibility of missing data on SPMs and HF and, the authors noted, by the possibility of confounding by indication and that "the Danish population is predominantly white, which limits the generalizability of our findings."
The authors report no financial conflicts.
- Salz T, Zabor EC, Brown PDN, et al. Preexisting cardiovascular risk and subsequent heart failure among non-Hodgkin lymphoma survivors. J Clin Oncol. 2017 September 18. [Epub ahead of print]