Renin angiotensin system inhibitors and outcome in patients with takotsubo syndrome: A propensity score analysis of the GEIST registry

Background: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). Methods: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. Registration: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 Results: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71 ± 11 vs 69 ± 13 years, P =.01), with higher prevalence of hypertension (74% vs 53%, P <.01) and diabetes (19% v s15%, P =.01), higher admission left ventricular ejection fraction (LVEF) (41 ± 11% vs 39 ± 12%, P <.01) and lower rates of in-hospital complications (18.9% vs 29.6%, P <.01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95% CI 0.45-0.87, P <.01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank P =.001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank P =.168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in 2 subgroups: patients with admission LVEF ≤ 40% (HR 0.54 95% CI 0.38-0.78, P =.001; HR 0.59, 95% CI 0.37-0.95, P =.030) and diabetes (HR 0.41, 95% CI 0.23-0.73, P =.002; HR 0.41, 95% CI 0.21-0.82, P =.011). Conclusions: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤ 40% or diabetes.