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TOTAL: Manual thrombectomy with PCI does not improve outcomes, increases short-term stroke rate
SAN DIEGO — Manual thrombectomy with primary PCI did not benefit patients with STEMI and was associated with an increased rate of stroke at 30 days, according to findings from the TOTAL trial.
Previously, the small TAPAS study suggested manual thrombectomy may improve outcomes by reducing distal embolization and improving microvascular perfusion, but the TASTE trial did not show a difference in all-cause mortality at 30 days or 1 year between patients who had manual thrombectomy followed by PCI and those who had PCI alone, Sanjit S. Jolly, MD, MSc, associate professor of medicine and interventional cardiologist at McMaster University, Hamilton, Ontario, Canada, said during a press conference at the American College of Cardiology Scientific Sessions.
Sanjit S. Jolly
Jolly and colleagues randomly assigned 10,732 patients with STEMI undergoing primary PCI to routine upfront manual thrombectomy in conjunction with PCI, or PCI alone. Approximately 7% of patients from the PCI-alone group required manual thrombectomy after PCI alone failed, he said.
The primary outcome was a composite of CV death, recurrent MI, cardiogenic shock or NYHA class IV HF within 180 days. The key safety outcome was stroke at 30 days.
The primary outcome occurred in 6.9% of the thrombectomy group vs. 7% in the PCI-only group (HR = 0.99; 95% CI, 0.85-1.15).
The researchers also reported no differences between the groups in CV death (thrombectomy group, 3.1%; PCI-only group, 3.5%; HR = 0.9; 95% CI, 0.73-1.12) or the primary outcome plus stent thrombosis and target vessel revascularization (9.9% vs. 9.8%, respectively; HR = 1; 95% CI, 0.89-1.14).
However, Jolly said, stroke within 30 days occurred in 0.7% of those in the thrombectomy group vs. 0.3% of those in the PCI-only group (HR = 2.06; 95% CI, 1.13-3.75).
“The stroke findings were unexpected and require confirmation in other studies,” Jolly said. “Detailed analyses are ongoing to understand the etiology of these strokes.”
A lesson from the study is that benefits seen in small studies may not turn out to be true in larger ones, Jolly said.
“As an interventional cardiologist who believed that early trial, and in fact followed the guidelines of using thrombectomy routinely, the TOTAL and TASTE trials have now shown us the truth, and we need these [larger] trials to determine what the true effect of interventions are in order to move the field forward and help patients,” he said. – by Erik Swain
References:
Jolly SS, et al. Late-Breaking Clinical Trials V: TCT@ACC-i2 Interventional Cardiology. Presented at: American College of Cardiology Scientific Sessions; March 14-16, 2015; San Diego.
Jolly SS, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1415098.
Disclosure: The study was funded by Medtronic, the Canadian Network and Centre for Trials Internationally (CANNeCTIN) and the Canadian Institutes of Health Research. Jolly reports receiving grant support from the Canadian Institutes of Health Research, CANNeCTIN and Medtronic, and receiving personal fees from AstraZeneca and St. Jude Medical.
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The TOTAL trial will remind clinicians to be more conservative regarding the performance of thrombectomy. I don’t think that the performance of thrombectomy is exclusively ruled out, though, based on the trial findings. It might be ambitious for us to think that simply evacuating thrombus out of a coronary artery is in and of itself going to provide a mortality reduction. If it did, that would be highly welcome and we would appreciate that. That said, there are other aspects of performing thrombectomy that facilitate the procedure and reduce periprocedural complications.
After the results of the two predicate trials, TAPAS and TASTE, many clinicians still continued, as evidenced by large databases from the ACC, to perform thrombectomy. However, now there is a potential suggestion of a safety hazard. In a very large trial of more than 10,000 patients, we have the opportunity for statistical significance for low-frequency events, which is a good thing. However, the stroke event rates early on are 0.7% and 0.3%. Yet in the TASTE trial, the event rate was 0.5% in both arms. We’re simply straddling around that event rate. If we can in further analyses truly translate the procedure of thrombectomy to a higher stroke rate, then I think performing thrombectomy at all needs to be revisited, given that there would be a potential safety issue. Any reduction in stroke is clinically meaningful.
On the other hand, there is an opportunity to investigate the potential differences in stroke and nonstroke patients. In further analyses, I think we will learn that there are many other comorbidities in the individuals who experience stroke, and if that seems to account for the differences rather than thrombectomy per se, then that would be an important consideration.
The final issue is that in an as-treated analysis, the stroke rate was not significantly different in the early phase. That also needs to be considered.
The lesson from this is that we can’t advocate thrombectomy as a routine procedure in every patient with STEMI, nor is that being performed today in clinical practice. In selected instances, in terms of bailout and when there is persistence of thrombus or no reflow in the coronary artery, there still may be clinical utility for thrombectomy.
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Previously, the thought had been that there might be a reduction in ischemic events with manual aspiration thrombectomy. Meta-analyses of smaller trials that had been done in years past on this topic actually showed a reduction in all-cause mortality with manual thrombus aspiration and individually a number of the trials showed reductions in stent thrombosis and improvement in a variety of surrogate endpoints.
However, TASTE, a large, registry-based, randomized clinical trial, did not find any benefit in the primary endpoint for manual aspiration thrombectomy. The TOTAL trial was meant to be the tie-breaker, to definitely figure out whether manual aspiration thrombectomy reduces ischemic events, and as it turns out, the trial found no hint of benefit and indeed found a statistically significant increase in the rate of stroke in the patients randomized to manual thrombus aspiration (although the stroke finding does need further detailed analysis). Those, of course, are not data that would be supportive of routine thrombus aspiration during STEMI, and for that reason I am going to change my practice. I think this shows that sometimes meta-analyses of small studies can be misleading. Alternatively, maybe times have changed since those studies were done, and now with low-profile, second-generation drug-eluting stents and quicker door-to-balloon times, perhaps the potential benefit of aspiration isn't as great as it used to be.
Also, this trial doesn't rule out the possibility that patients with large thrombus burden may still benefit from manual aspiration thrombectomy. So I wouldn't go so far as to say it should never be done, but certainly on the basis of this trial and TASTE, it shouldn't be part of routine primary PCI.
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The TOTAL trial was a very important study. It has clearly demonstrated, following on the heels of the TASTE trial, that there are no clinical benefits to routine use of aspiration thrombectomy in acute MI, and that in fact there may even be harm, in terms of an increased risk for stroke. While it’s possible that the risk for stroke is a spurious finding, I think physicians need to stop the routine use of a practice that has no benefit and possibly might have harm.
TOTAL does not end the use of thrombus aspiration. There are likely some patients who would benefit from it, but the trick is to find the patient in whom the benefits outweigh the potential risks. More data from these studies are necessary to try to tease that out.