Cardioprotective effects of medical therapy for cancer therapy-related cardiac dysfunction: a systematic review and meta-analysis
TL;DR
It is hypothesized that severity of established CTRCD in this subgroup might be too advanced for significant LVEF improvements, and statins hold promise in the prevention of anthracycline- and/or anti-HER2-mediated CTRCD, whereas no beneficial effect was observed in patients with combination regimens.
Abstract
- Cancer therapy-related cardiac dysfunction (CTRCD) limits optimal cancer therapy regimens. Although heart failure guideline-recommended medical therapy (GRMT) has been proposed as a cardioprotective strategy, robust evidence from randomized controlled trials (RCTs) remains insufficient due to limited study availability and heterogeneous outcomes. We conducted a comprehensive systematic review and meta-analysis to investigate the cardioprotective potential of GRMT in patients receiving cancer therapy. - EMBASE and PubMed were systematically searched for RCTs evaluating GRMT for the prevention of CTRCD in cancer patients treated with any established anti-cancer drug cocktail. Two independent reviewers performed study selection, data extraction, and risk-of-bias assessment using the Cochrane risk-of-bias 2 (RoB 2) tool. GRMT classes included RAAS inhibitors, beta-blockers, mineralocorticoid antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Statins were additionally considered. Studies were stratified by cancer treatment: 1) anthracycline-based, 2) anti-HER2-based, and 3) combined anthracycline/anti-HER2 regimens. Primary outcome was a change in left ventricular ejection fraction (LVEF) in patients treated with versus without GRMT. Random-effect meta-analyses were conducted using STATA and presented as weighted mean differences (WMD). Anthracycline-mediated CTRCD data were visualized in the attached forest plots (figure 1). - 36 RCTs comprising 3968 patients were included. RAAS-inhibition significantly improved LVEF in anthracycline-mediated (group 1: WMD 3.64; [95% Confidence Interval 0.21 – 7.08]), and anti-HER2-mediated CTRCD (group 2: 4.15 [2.49-5.81]), but not in anthracycline/anti-HER2 regimens (group 3: 0.08 [-1.19-1.36]). Beta-blockers demonstrated a similar pattern (group 1: 1.05 [0.04-2.06]; group 2: 4.01 [2.07-5.96]; group 3: 0.67 [-0.68-2.01]). Statins were associated with a LVEF preservation in group 1 (2.54 [1.51-3.56]), however no claim could be made for group 2, as evidence was limited to a single study. MRAs and combined RAAS-inhibitors/beta-blockers therapies showed protective effects in group 1, although robust conclusions were limited due to sparse numbers of RCTs. No RCT data were available on SGLT2i. - RAAS inhibitors and beta-blockers significantly improved LVEF in patients exhibiting anthracycline- or anti-HER2-mediated CTRCD, whereas no beneficial effect was observed in patients with combination regimens. We hypothesize that severity of established CTRCD in this subgroup might be too advanced for significant LVEF improvements. Moreover, statins hold promise in the prevention of anthracycline- and/or anti-HER2-mediated CTRCD. Other GRMT classes, i.e. MRAs and SGLT2i, remain underrepresented in RCTs, despite their potential cardioprotective properties. These findings emphasize the need for future trials focusing on modern HF therapies in oncology patients.GRMT in anthracycline-mediated CTRCD