Stroke in the TOTAL trial: a randomized trial of routine thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction

Eur Heart J. 2015 Sep 14;36(35):2364-72. doi: 10.1093/eurheartj/ehv296. Epub 2015 Jun 29.

Abstract

Aims: TOTAL (N = 10 732), a randomized trial of routine manual thrombectomy vs. percutaneous coronary intervention alone in ST elevation myocardial infarction, showed no difference in the primary efficacy outcome but a significant increase in stroke. We sought to understand these findings.

Methods and results: A detailed analysis of stroke timing, stroke severity, and stroke subtype was performed. Strokes were adjudicated by neurologists blinded to treatment assignment. Stroke within 30 days, the primary safety outcome, was increased [33 (0.7%) vs. 16 (0.3%), hazard ratio (HR) 2.06; 95% confidence interval (CI) 1.13-3.75]. The difference in stroke was apparent within 48 h [15 (0.3%) vs. 5 (0.1%), HR 3.00; 95% CI 1.09-8.25]. There was an increase in strokes within 180 days with minor or no disability (Rankin 0-2) [18 (0.4%) vs. 13 (0.3%) HR 1.38; 95% CI 0.68-2.82] and in strokes with major disability or fatal (Rankin 3-6) [35 (0.7%) vs. 13 (0.3%), HR 2.69; 95% CI 1.42-5.08]. Most of the absolute difference was due to an increase in ischaemic strokes within 180 days [37 (0.7%) vs. 21 (0.4%), HR 1.71; 95% CI 1.03-3.00], but there was also an increase in haemorrhagic strokes [10 (0.2%) vs. 2 (0.04%), HR 4.98; 95% CI 1.09-22.7]. Patients that had a stroke had a mortality of 30.8% within 180 days vs. 3.4% without a stroke (P < 0.001). A meta-analysis of randomized trials (N = 21 173) showed an increase in risk of stroke (odds ratio 1.59; 95% CI 1.11-2.27) but a trend towards reduction in mortality odds ratio (odds ratio 0.87; 95% CI 0.76-1.00).

Conclusion: Thrombectomy was associated with a significant increase in stroke. Based on these findings, future trials must carefully collect stroke to determine safety in addition to efficacy.

Trial registration: ClinicalTrials.gov NCT01149044.

Keywords: Meta-analysis; Randomized trial; STEMI; Stroke; Thrombectomy.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Myocardial Infarction / mortality
  • Myocardial Infarction / surgery*
  • Percutaneous Coronary Intervention / methods*
  • Percutaneous Coronary Intervention / mortality
  • Postoperative Complications / etiology*
  • Stroke / etiology*
  • Stroke / mortality
  • Thrombectomy / methods*
  • Thrombectomy / mortality
  • Treatment Outcome

Associated data

  • ClinicalTrials.gov/NCT01149044