Beta blockers, renin-angiotensin inhibitors suppress anthracycline-induced cardiotoxicity

Beta blockers (BB) and renin-angiotensin inhibitors (RAI) effectively protect against anthracycline-induced cardiotoxicity among cancer patients, preserving left ventricular ejection fraction (LVEF) and cutting cardiac events, according to a new study presented at the recently concluded 2019 Congress of the Asian Pacific Society of Cardiology (APSC).

The present meta-analysis was carried out “[t]o determine the efficacy of BBs and RAIs in preventing anthracycline-induced cardiotoxicity,” said researchers, adding that the efficacy of these agents against cardiac mortality and heart failure was also an area of interest.

The initial database search yielded 121 studies for potential inclusion. After excluding reviews, ongoing trials, those that were insufficiently relevant, studies on nonhuman systems, meta-analyses, articles that concomitantly used other chemotherapeutic agents and those with short follow-ups, six randomized controlled trials emerged eligible for analysis.

The resulting cumulative sample included 511 cancer patients treated with anthracycline. Among the presenting malignancies were leukaemia, Hodgkin’s and non-Hodgkin’s lymphoma, multiple myeloma, and breast cancer. Enalepril, telmisartan and candesartan were the RAIs given, while carvedilol, metoprolol and nebivolol were the BBs of interest. [APSC 2019, poster 30]

Pooled analysis of all studies included showed that treatment with either BBs or RAIs resulted in a significantly more preserved LVEF relative to placebo (mean difference, 4.27, 95 percent CI, 1.88–6.65; Z, 3.51; p=0.0005). However, there was significant heterogeneity of evidence (p<0.00001).

When the analysis was stratified, researchers found that the primary finding was driven by the significant beneficial effect RAIs exerted on LVEF (mean difference, 1.72, 0.64–2.80, Z, 3.12; p=0.002). BBs, despite showing a strong magnitude of impact, failed to demonstrate statistical significance for LVEF preservation (mean difference, 5.24, –1.92 to 12.41, Z, 1.43; p=0.15).

Two studies were included in the pooled analysis of the effect of RAIs and BBs on cardiac events. This yielded a significant reduction in the associated risk (risk ratio, 0.27, 0.09–0.77, Z, 2.44; p=0.01). No significant heterogeneity in evidence was documented (p=0.74).

In the present study, researchers accessed the repositories of Medline, Clinical Key, Science Direct, Scopus and Cochrane Database for randomized controlled trials that investigated the efficacy of BBs or RAIs vs placebo as prophylaxis against anthracycline-induced cardiotoxicity. Only those that enrolled adult participants without histories of heart failure were eligible for inclusion.

In the selected studies, epirubicin and doxorubicin were the anthracyclines of choice, with follow-up durations ranging from 6–36 months.

“Initiation of BB and/or RAI has been shown to preserve LVEF and reduce cardiac events among cancer patients receiving anthracyclines,” said researchers. However, the significant heterogeneity of sources emphasizes the need for further, more well-designed studies.