Response to: Correspondence on “Beta-blockers and renin-angiotensin system inhibitors for Takotsubo syndrome recurrence: a network meta-analysis” by John E Madias

[...]there are no data from randomised trials in Takotsubo syndrome (TTS); second, there is paucity of data on drug dose regimens at follow-up, and, third, patients receiving beta-blockers (BB) and/or renin–angiotensin system inhibitors (RASi) could have a more severe clinical phenotype. [...]given the relatively low long-term recurrence rates of TTS, about 4%,2 randomised trials would require a relatively large number of patients. [...]there is an urgent need for pharmacological trial testing heart failure medications in this context. [...]a persistent long-term heart failure phenotype can be found in patients with TTS.5 As a matter of fact, in a propensity score analysis RASi therapy was associated with improved survival at 1 year.6 BB could have some potential benefit mainly in patients who experienced cardiogenic shock or hypertension.7 8 Although in this meta-analysis there was no sufficient statistical evidence regarding combination therapy with BB and RASi in reducing TTS recurrence, there was a trend towards some potential benefit for this therapy. [...]our research group, in a meta-regression analysis, showed that there was a significant correlation between rates of prescription of RASi and rates of recurrence of TTS at follow-up.9 Additionally, another meta-regression analysis found a correlation between higher rates of combined prescription of BB and ACEi/ARBs and lower recurrence rates of TTS.10 These data strongly support the need for randomised trials assessing the efficacy of such medications in adequately powered populations.