Efficacy of ranolazine in preventing atrial fibrillation following cardiac surgery: Results from a meta-analysis

Abstract

Background: Atrial fibrillation (AF) is a common complication after cardiac surgery. Ranolazine is a Food and Drug Administration approved anti-ischemic drug, which also has anti-arrhythmic properties. Recent studies have demonstrated the benefit of ranolazine in preventing post-operative AF (POAF) in patients undergoing cardiac surgery. Hence, we performed a meta-analysis of published studies comparing ranolazine plus standard therapy versus standard therapy for POAF prevention in patients undergoing cardiac surgery.

Methods: We performed a comprehensive search of Medline, Google Scholar, PubMed, abstracts from annual scientific sessions, and Cochrane library database for studies that assessed the effectiveness of ranolazine plus standard therapy by comparing it with standard therapy alone in preventing POAF in patients undergoing cardiac surgery. From all the studies, data on POAF events among groups were collected, and the random-effects (DerSimonian and Laird) method was used for meta-analysis.

Results: Four studies with 663 patients were included in the final analysis, with 300 and 363 patients in the ranolazine plus standard therapy and standard therapy groups, respectively. The types of cardiac surgeries were coronary artery bypass grafting (CABG), valve surgery or combination of CABG, and valve surgeries. After pooled analysis, ranolazine plus standard therapy was associated with a significant reduction in POAF events compared to standard therapy alone (risk ratio=0.44 [0.25, 0.78], p-value=0.005). There was no difference in adverse events between the two therapies. However, in one study, more patients in the ranolazine group had transient symptomatic hypotension after the surgery.

Conclusions: Ranolazine may prove beneficial in POAF prevention following cardiac surgeries. Although the pooled treatment effect is quite impressive with a reduction of more than 50% of risk of developing POAF, small number of studies and variation in ranolazine dose regimen in each study make our results inconclusive, but worthy of further investigation. That is why this result has to be interpreted as only hypothesis generating, rather than conclusion drawing.

Keywords: Atrial fibrillation; Cardiac surgery; Metaanalysis; Post-operative atrial fibrillation; Ranolazine.

Fig. 1

Selection process of studies included in the systematic review. (AF=atrial fibrillation) Search criteria: ("ranolazine"[MeSH Terms] OR "ranolazine"[All Fields]) AND ("atrial fibrillation"[MeSH Terms] OR ("atrial"[All Fields] AND "fibrillation"[All Fields]) OR "atrial fibrillation"[All Fields]).

Fig. 2

Forest plot showing the risk ratio (RR) of atrial fibrillation associated with ranolazine use in each study and the overall RR. Square boxes denote RR; horizontal lines represent 95% confidence interval (random effects model was used to calculate pooled estimate).

Fig. 3

Funnel plot of the standard error by logarithm risk ratio. There is no presence of publication bias on visual estimation [Also, there was no evidence of publication bias by Egger׳s test (p-value=0.31) or Begg and Mazumdar׳s rank correlation test (p-value=0.50).]