Survival benefit of secondary prevention medical therapy in takotsubo cardiomyopathy: a Bayesian network meta-analysis

Abstract

Aims: Takotsubo cardiomyopathy (TTC) is a form of transient left ventricular systolic dysfunction without evidence of complicated coronary artery disease. Efficacy of medical therapy in secondary prevention of all-cause mortality is not well established. We performed a systematic review and network meta-analysis to compare survival benefit of secondary prevention medical therapy in patients with TTC.

Methods and results: PubMed, Embase, and Cochrane were searched up to 6 January 2024. Eligible studies included multivariable-adjusted or propensity-matched studies of patients receiving medical therapy with beta-blockers, angiotensin-converting enzyme inhibitors (ACE) or angiotensin receptor blockers (ARBs), aspirin, and statins after an index presentation with TTC. The primary outcome was all-cause mortality at any time point. Secondary outcome was TTC recurrence. Random-effect hierarchical Bayesian meta-analysis was performed. We identified 13 observational studies. Takotsubo cardiomyopathy mortality was reported in 435 (4.7%) out of 9237 patients, across a median follow-up of 2.18 years. Mean age was 69.7 ± 12.5 years, and 7906 patients (90.7%) were females. Beta-blockers were associated with a statistically significant reduction in mortality compared to control [hazard ratio (HR) 0.65, 95% confidence interval (CI) (0.55-0.77)]. ACE inhibitors/ARBs showed a nonsignificant trend towards mortality reduction [HR 0.76, 95% CI (0.54-1.07)]. Statins [HR 0.96, 95% CI (0.77-1.19)] and aspirin [HR 0.87, 95% CI (0.55-1.38)] showed no significant mortality benefit. Bayesian probability ranks favoured beta-blockers as the most effective treatment for TTC mortality prevention.

Conclusion: This review highlights the modest efficacy of secondary prevention medications in the management of TTC, as ACE or ARBs, beta-blockers, aspirin, and statins failed to demonstrate comparative mortality benefit. Randomized controlled trials are needed to confirm efficacy of pharmacotherapy in this vulnerable patient cohort.

Keywords: Acute coronary syndrome; Heart failure; Pharmacotherapy; Takotsubo cardiomyopathy.

Graphical Abstract

Figure 1

Study assessment and inclusion flowchart.

Figure 2

Forest plot comparing treatment arms [ACE/ARB, beta-blocker (BB), aspirin, statin] with hazard ratio (HR, 95% confidence intervals) for all-cause mortality.

Figure 3

Network diagram comparing survival benefit of medical therapy in takotsubo cardiomyopathy. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB), aspirin, statins, beta-blockers, and control (no pharmacotherapy) are represented as nodes. The size of each node reflects the number of patients who received that treatment across the included studies. Lines between nodes represent direct comparisons between two treatments, with the width proportional to the number of contributing studies. Arrows indicate the direction of comparison, pointing from the reference treatment to the comparator. Hazard ratios (HRs) and 95% confidence intervals (CIs) are displayed on the arrows and reflect the relative hazard of mortality for the comparator compared to the reference treatment. For example, the arrow from ACE/ARB to beta-blockers displays an HR of 0.86 [95% CI (0.48–1.51)], indicating that, in the studies that directly compared these two treatments, patients who received beta-blockers had a numerically lower—but not statistically significant—hazard of mortality compared to those who received ACE/ARB therapy. An HR < 1.0 favours the comparator (in this case, beta-blockers), while an HR > 1.0 would favour the reference treatment. The absence of a connecting line between two nodes indicates that no direct comparison was available in the included studies.