Sanjit Jolly writes that data suggest that impaired microvascular perfusion after primary percutaneous coronary intervention (PCI) is strongly associated with subsequent mortality.1 Manual thrombectomy aims to reduce distal embolisation and improve microvascular perfusion during primary PCI.
The TAPAS (Thrombus aspiration during primary percutaneous coronary intervention) trial, a single-centre trial (n=1,071), showed that manual thrombectomy improved primary outcome of impaired microvascular perfusion (myocardial blush grade 0 or 1).2 Also, long-term follow up at one year showed a reduction in mortality with thrombectomy—which led to guideline changes recommending routine thrombectomy during primary PCI.3
However, the TASTE (Thrombus aspiration in myocardial infarction) trial (n=7,244) did not show a mortality benefit with thrombectomy. It was performed as a follow up to the TAPAS trial, and it was the first time a randomisation was paired to the SCAAR (Swedish coronary angiography and angioplasty register) registry (in Sweden).4
In the study, patients with ST-segment elevation myocardial infarction (STEMI) undergoing urgent PCI within 24 hours were randomised to receive thrombectomy plus PCI or to receive PCI alone. The trial showed no difference in primary outcome of all-cause mortality at 30 days (2.8% vs 3.0%; HR 0.94, 95% CI [0.72-1.22]).5 There were non-significant trends toward reduction of rehospitalisation for myocardial infarction (HR 0.61, 95% CI [0.34-1.07]) and stent thrombosis (HR 0.57, 95% CI [0.20-1.02]) with thrombectomy.
When interpreting the TASTE trial, it is critical to look at statistical assumptions. The trial was initially powered for a 30% relative risk reduction (RRR) and needed 456 events to achieve 80% power. However, due to much lower than expected mortality, only 213 out of the required 456 events occurred—suggesting caution is needed before excluding a clinically important treatment effect.5 The issue of study power is highlighted by looking at prior landmark trials: 25 years ago, ISIS 2 (second international study of infarct survival) required 17,000 patients to show that aspirin (23% RRR) and streptokinase (25% RRR) reduced mortality compared with placebo.6
An additional limitation of TASTE relates to the interpretation of the secondary outcomes, such as recurrent myocardial infarction or heart failure. We should be cautious about looking at these events because they are not adjudicated and may be under-reported in a registry. Long-term follow up of TASTE will be important; however, thrombectomy is an upfront intervention without ongoing treatment so longer term follow up may not increase study power.
TOTAL—a trial of routine aspiration thrombectomy with PCI vs. PCI alone in patients with STEMI undergoing primary PCI (n=10,700)—is an ongoing traditional randomised trial.7 The primary outcome is the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock or class IV heart failure up to 180 days. It is powered for a 20% RRR in primary outcome and is expected to report in spring of 2015. The TOTAL trial will provide important further data on manual thrombectomy during primary PCI and will help complete the story of manual thrombectomy during primary PCI.
1. Stone et al. J Am Coll Cardiol 2002; 39: 591–97
2. Svilaas et al. N Engl J Med 2008; 358: 557–567
3. Vlaar et al. Lancet. 2008; 371: 1915–20
4. Frobert et al. International journal of cardiology 2010.145: 572–73
5. Frobert et al. N Engl J Med 2013; 369: 1587–97
6. Isis-2. Isis-2 (second international study of infarct survival) collaborative group. Lancet 1988; 2: 349–60
7. Jolly et al. American heart journal. 2014;167: 315-321 e311
Sanjit Jolly, Hamilton Health Sciences, McMaster University, Hamilton, Canada