Antithrombotic therapy in patients with takotsubo cardiomyopathy: is heparin associated with lower mortality? - a nationwide cohort analysis

Abstract Background Takotsubo cardiomyopathy is characterised by transient left ventricular ballooning, which can cause thrombus formation. The European Society of Cardiology expert consensus recommends antithrombotic therapy, specifically heparin, for high-risk patients1. Recently, a Swedish registry study reported that the use of heparin was associated with a reduction in 30-day mortality rates 2. However, this Swedish study did not account for the timing of anticoagulation therapy or other confounding variables. Purpose We aimed to describe the real-world use of antithrombotic therapy in patients with Takotsubo cardiomyopathy in Japan. We also analysed 30-day mortality and other clinical outcomes in patients who received heparin compared to those who did not receive any antithrombotic therapy while adjusting for the timing of treatment initiation and baseline covariates. Methods The study participants were enrolled from fiscal years 2012 to 2021 using a nationwide inpatient database covering nearly all acute hospitals in Japan. We subsequently applied a previously reported diagnostic algorithm with a positive predictive value of 1.00. This study was restricted to patients who underwent coronary angiography on the day of admission, excluding those with atrial fibrillation. The patients were categorised into four groups based on their anticoagulant treatment on Day 2: no antithrombotic therapy, heparin, direct oral anticoagulants, and warfarin. The primary outcome measured was 30-day mortality. The secondary outcomes included ischemic events (cerebral infarction, transient ischaemic attack, and arterial thrombosis), bleeding events (intracerebral haemorrhage and gastrointestinal bleeding), and blood transfusions. We compared the outcomes between the heparin and non-anticoagulant groups using inverse probability weighting based on propensity scores, with statistical significance set at p 0.05. Results Among the 9,815 patients, 3,718 (37.8%) received heparin, 288 (2.9%) received DOACs, 394 (4.0%) received warfarin, and 5,414 (55.2%) did not receive any anticoagulant. Patients in the heparin group exhibited more severe baseline conditions, including higher rates of vasopressor use, oxygen therapy, mechanical ventilation, and mechanical circulatory support. After adjusting for these baseline factors, the 30-day mortality was significantly lower in the heparin group (2.9%) than in the no antithrombotic therapy group (4.0%, p=0.008). However, the rates of ischaemic and bleeding events, as well as blood transfusion, were relatively similar between the two groups. Conclusion Takotsubo cardiomyopathy patients receiving heparin therapy had a lower 30-day mortality rate compared to those not receiving any antithrombotic therapy. The findings of this study, along with the previous research suggest that heparin may offer benefits beyond its anticoagulant effects.