Statin Exposure and Risk of Heart Failure After Anthracycline‐ or Trastuzumab‐Based Chemotherapy for Early Breast Cancer: A Propensity Score‒Matched Cohort Study

Abstract

Background Statins are hypothesized to reduce the risk of cardiotoxicity associated with anthracyclines and trastuzumab. Our aim was to study the association of statin exposure with hospitalization or emergency department visits (hospital presentations) for heart failure (HF) after anthracycline‐ and/or trastuzumab‐containing chemotherapy for early breast cancer. Methods and Results Using linked administrative databases, we conducted a retrospective cohort study of women aged ≥66 years without prior HF who received anthracyclines or trastuzumab for newly diagnosed early breast cancer in Ontario between 2007 to 2017. Statin‐exposed and unexposed women were matched 1:1 using propensity scores. Trastuzumab‐treated women were also matched on anthracycline exposure. We matched 666 statin‐discordant pairs of anthracycline‐treated women and 390 pairs of trastuzumab‐treated women (median age, 69 and 71 years, respectively). The 5‐year cumulative incidence of HF hospital presentations after anthracyclines was 1.2% (95% CI, 0.5%–2.6%) in statin‐exposed women and 2.9% (95% CI, 1.7%–4.6%) in unexposed women ( P value, 0.01). The cause‐specific hazard ratio associated with statins in the anthracycline cohort was 0.45 (95% CI, 0.24–0.85; P value, 0.01). After trastuzumab, the 5‐year cumulative incidence of HF hospital presentations was 2.7% (95% CI, 1.2%–5.2%) in statin‐exposed women and 3.7% (95% CI, 2.0%–6.2%) in unexposed women ( P value 0.09). The cause‐specific hazard ratio associated with statins in the trastuzumab cohort was 0.46 (95% CI, 0.20–1.07; P value, 0.07). Conclusions Statin‐exposed women had a lower risk of HF hospital presentations after early breast cancer chemotherapy involving anthracyclines, with non‐significant trends towards lower risk following trastuzumab. These findings support the development of randomized controlled trials of statins for prevention of cardiotoxicity.

Statins: a repurposed drug to fight cancer

“…In a propensity score-matched cohort study, statin-exposed women had a lower risk of heart failure (HF)-related hospital presentations after anthracycline chemotherapy for early breast cancer, with non-significant trends toward lower risk following treatment with trastuzumab. These findings support the ability of statins to prevent the cardiotoxicity of chemotherapy [ 314 ]. In addition, a fraction of patients undergoing androgen deprivation therapy for advanced prostate cancer will develop recurrent castrate-resistant prostate cancer in bone.…”

Caveolin-1 temporal modulation enhances trastuzumab and trastuzumab-drug conjugate efficacy in heterogeneous gastric cancer

“…Based on the medical records, statin users included here initiated statins before or while on trastuzumab therapy and presumably tolerated these cholesterol-depleting agents well. Other studies also suggest that statins prevent heart failure in patients receiving trastuzumab [60]. Therefore, these results indicate that the combination approach may hold a clinically acceptable safety profile and may achieve reasonable tumors selectivity when used in a controlled manner.…”

Statin Use Can Attenuate the Decline in Left Ventricular Ejection Fraction and the Incidence of Cardiomyopathy in Cardiotoxic Chemotherapy Recipients: A Systematic Review and Meta-Analysis

“…A total of seven studies with 3042 subjects (1382 subjects received the concurrent statin) were included in our meta-analysis [17][18][19][20][21][22][23]. The main characteristics of the included studies are described in Table 1.…”

“…The mean pre-and post-chemotherapy LVEF information was provided in the studies by Nabati et al [21], Acar et al [18], Calvillo-Argüelles et al [19], and Chotenimitkhun et al [20]. In regards to the incidence of cardiomyopathy, the study by Calvillo-Argüelles et al [19] and Abdel-Qadir et al [17] provided the value of OR and its corresponding 95% CI. In the studies by Acar et al [18], Seicean et al [22], and Tase et al [23], the raw data for the number of subjects with CIC in the control and the statin groups are provided, and calculations were manually performed to obtain the OR and its corresponding 95% CI.…”

“…Some individual studies have suggested that statins may also play an important role in decreasing the risk of CIC [17][18][19][20][21][22][23]. To the best of our knowledge, there is no meta-analysis that studied the overall pooled cardioprotective effect of statins against CIC.…”