Stroke in the TOTAL Trial: Thrombectomy vs PCI Alone in STEMI
Stroke in the TOTAL Trial: Thrombectomy vs PCI Alone in STEMI
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.
Primary percutaneous coronary intervention (PCI) is the optimal method of achieving reperfusion in patients with ST segment elevation myocardial infarction (STEMI). However, one of the major limitations of primary PCI is distal embolization of thrombus after balloon inflation or stent deployment. Routine manual thrombectomy was considered to be a simple way of removing thrombus with the potential to reduce distal embolization during primary PCI.
A randomized trial of moderate size showed an apparent large benefit of routine manual thrombectomy, prompting a guideline recommendation for manual thrombectomy leading to incorporation into clinical practice. However, the confidence limits of the trial was wide and a significantly larger trial did not confirm a benefit.
On the other hand, meta-analyses of thrombectomy have suggested the possibility that stroke may be increased but these were cautiously interpreted given small numbers of events.
We conducted the Trial of Routine Aspiration Thrombectomy with PCI vs. PCI alone in patients with STEMI (TOTAL, N = 10 732) which showed no difference in cardiovascular (CV) death, recurrent myocardial infarction, cardiogenic shock, or class IV heart failure within 180 days but a significant increase in stroke. In this report, we set out to analyse in detail the occurrence of stroke in an attempt to understand the nature of this important finding as this may have important implications for the use of thrombectomy or other devices in similar circumstances.
Abstract and Introduction
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.
Introduction
Primary percutaneous coronary intervention (PCI) is the optimal method of achieving reperfusion in patients with ST segment elevation myocardial infarction (STEMI). However, one of the major limitations of primary PCI is distal embolization of thrombus after balloon inflation or stent deployment. Routine manual thrombectomy was considered to be a simple way of removing thrombus with the potential to reduce distal embolization during primary PCI.
A randomized trial of moderate size showed an apparent large benefit of routine manual thrombectomy, prompting a guideline recommendation for manual thrombectomy leading to incorporation into clinical practice. However, the confidence limits of the trial was wide and a significantly larger trial did not confirm a benefit.
On the other hand, meta-analyses of thrombectomy have suggested the possibility that stroke may be increased but these were cautiously interpreted given small numbers of events.
We conducted the Trial of Routine Aspiration Thrombectomy with PCI vs. PCI alone in patients with STEMI (TOTAL, N = 10 732) which showed no difference in cardiovascular (CV) death, recurrent myocardial infarction, cardiogenic shock, or class IV heart failure within 180 days but a significant increase in stroke. In this report, we set out to analyse in detail the occurrence of stroke in an attempt to understand the nature of this important finding as this may have important implications for the use of thrombectomy or other devices in similar circumstances.
