Beta-blockers and renin-angiotensin system inhibitors for Takotsubo syndrome recurrence: A network meta-analysis

Introduction: Takotsubo syndrome (TTS) is an acute heart failure syndrome, featured by transient left ventricular systolic dysfunction. Recurrences of TTS are not infrequent and there is no standard preventive therapy. The aim of this study was to evaluate in a network meta-analysis if beta-blockers (BB) and ACE inhibitors/angiotensin receptor blockers (ACEi/ARBs), in combination or not, can effectively prevent TTS recurrences. Methods: We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for clinical studies published between January 2010 and September 2022. We considered all those studies including patients receiving medical therapy with BB, ACEi/ARBs. The primary outcome was TTS recurrence. Results: We identified 6 clinical studies encompassing a total of 3407 patients with TTS. At 40±10 months follow-up, TTS recurrence was reported in 160 (4.7%) out of 3407 patients. Mean age was 69.8±2 years and 394 patients (11.5%) out of 3407 were male. There were no differences in terms of TTS recurrence when comparing ACEi/ARBs versus control (OR 0.83; 95% CI 0.47 to 1.47, p=0.52); BB versus control (OR 1.01; 95% CI 0.63 to 1.61, p=0.96) and ACEi/ARBs versus BB (OR 0.88; 95% CI 0.51 to 1.53, p=0.65).Combination of BB and ACEi/ARBs was also not effective in reducing the risk of recurrence versus control (OR 0.91; 95% CI 0.58 to 1.43, p=0.68) vs ACEi/ARBs (OR 0.79; 95% CI 0.46 to 1.34, p=0.38)) and vs BB (OR 0.77; 95% CI 0.49 to 1.21, p=0.26). Conclusions: Our study did not find sufficient statistical evidence regarding combination therapy with BB and ACEi/ARBs in reduction of TTS recurrence.