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MATRIX: In patients with ACS needing angiography, access site matters but anticoagulant might not
SAN DIEGO — In the MATRIX study of patients with ACS undergoing angiography and PCI, transradial access was associated with better outcomes compared with transfemoral access, but a comparison of bivalirudin with standard anticoagulation yielded mixed results.
Researchers randomly assigned 8,404 patients with ACS needing angiography and PCI to transradial access or transfemoral access, and 7,213 patients to anticoagulation with bivalirudin (Angiomax, The Medicines Company) or unfractionated heparin plus, if necessary, glycoprotein IIb/IIIa inhibition.
For both analyses, the primary outcomes were MACE, defined as death, MI or stroke, at 30 days, and net adverse clinical events, defined as MACE or BARC major bleeding not related to CABG, at 30 days.
Transradial superior to transfemoral
Marco Valgimigli, MD, PhD, reported that 8.8% of the radial group had MACE at 30 days vs. 10.3% of the femoral group (RR = 0.85; 95% CI, 0.74-0.99). The P value of .0307 was not significant because the two-sided alpha was prespecified at .025.
Marco Valgimigli
About 10% of the radial group had net adverse clinical events, compared with 11.7% of the femoral group (RR = 0.83; 95% CI, 0.73-0.96). The difference was driven by BARC major bleeding unrelated to CABG (radial, 1.6%; femoral, 2.3%; RR = 0.67; 95% CI, 0.49-0.92) and all-cause mortality (radial, 1.6%; femoral, 2.2%; RR = 0.72; 95% CI, 0.53-0.99), Valgimigli said.
While there was more crossover from radial to femoral than vice versa (5.8% vs. 2.3%; P < .001), rates of PCI failure were similar in both groups (radial, 6.3%; femoral, 6.1%; P = .77), he said.
Results were highly dependent on the operator’s experience with transradial intervention, he said.
The access-site analysis was simultaneously published in The Lancet.
Mixed results for bivalirudin
In the analysis by anticoagulant, patients assigned bivalirudin did not show significant improvement in 30-day MACE or 30-day net adverse clinical events compared with those assigned standard anticoagulation therapy, Valgimigli said.
However, compared with standard therapy, the bivalirudin group had lower rates of all-cause mortality (1.7% vs. 2.3%; RR = 0.71; 95% CI, 0.51-0.99), CV death (1.6% vs. 2.3%; RR = 0.7; 95% CI, 0.5-0.98) and cardiac death (1.5% vs. 2.2%; RR = 0.68; 95% CI, 0.48-0.97), he said.
Those results were likely driven by reductions in bleeding associated with bivalirudin, including BARC 3 (1.3% vs. 2.1%; RR = 0.61; 95% CI, 0.42-0.88), BARC 5 (0.1% vs. 0.4%; RR = 0.31; 95% CI, 0.11-0.85), TIMI major or minor (1% vs. 1.9%; rate ratio = 0.5; 95% CI, 0.33-0.75) and GUSTO (0.9% vs. 1.5%; rate ratio = 0.61; 95% CI, 0.39-0.95) bleeding, according to Valgimigli, from Thoraxcenter, Erasmus Medical Center, Rotterdam, Netherlands.
The bleeding results were “even more impressive for the thrombin comparison than for the access-site comparison,” Valgimigli said.
The effects from anticoagulation were independent from the access site used during the procedure, he said. – by Erik Swain
References:
Valgimigli M, 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.
Valgimigli M, et al. Lancet. 2015;doi:10.1016/S0140-6736(15)60292-6.
Disclosure: Valgimigli reports speaking for Abbott, AstraZeneca, CID Vascular and IROKO.
Perspective
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In the last year, there has been a lot of confusion regarding choice of the optimal anticoagulant during PCI in patients with ACS. MATRIX has put most of these issues to rest. The most important endpoint is all-cause mortality. Similar to what we saw in the HORIZONS-AMI trial in 3,600 randomized patients, in more than 7,200 randomized patients MATRIX also found a substantial reduction in all-cause mortality in patients treated with bivalirudin rather than a heparin based regimen. We have now seen a significant reduction in mortality from the two largest trials that have investigated bivalirudin in STEMI and ACS, including the most contemporary study compared to mostly heparin alone. Matrix should lead to increased use of bivalirudin once the results of this study are disseminated in the press and publication, which always takes a while. All-cause mortality trumps all other endpoints. That coupled with the large reduction in major bleeding, with similar preservation of ischemic MACE, makes bivalirudin the optimal choice for patients with STEMI and NSTEMI undergoing PCI. This held for both patients undergoing femoral and radial artery access.
I wasn’t surprised at all by the access-site results, although I’m sure some people will be. For many years, our studies and real-world studies demonstrated that bivalirudin reduces bleeding and mortality in patients receiving radial as well as femoral access, because bivalirudin reduces non-access-site related bleeds as well as access-site related bleeds. It’s actually the non-access-site related bleeds that are prognostically more important. We have now seen this replicated in a true 2x2 randomized trial, which is the optimal way to test the issue.
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I would like to see a subanalysis with regard to transfusion. I understand that the researchers are concerned that bleeding is more damaging than transfusion, but in the acute MI population, transfusions have been associated with poor outcomes in previous studies. It may be that the most important predictor of outcomes is whether the patient receives transfusion. I look forward to further analyses from this trial.
It is clear that bivalirudin is a useful drug; it already has a class I, level of evidence A recommendation. As long as there is a cost differential, there will be some limitations to its use. Classically, this becomes more cost effective in patients with high risk for bleeding. That wasn’t analyzed in this trial, but perhaps more information is coming on this.
Perspective
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The MATRIX trial is a very important trial. It built upon the findings of RIVAL in that it took high-volume operators and exquisitely showed that radial access not only reduced bleeding, but also reduced mortality. This will be the study to perhaps change guidelines to make radial access the default approach. Our next step is physician training and making sure that we translate this demonstrated benefit into clinical practice.
As for bivalirudin vs. heparin, this is the largest study conducted for that issue and is also important in that regard. Operators will have to think about their antithrombotic choice and their access site separately. I also think this is a second wind for bivalirudin, even though the primary outcome was not reduced. Mortality is the most important component of the primary outcome, so when you see a reduction in mortality, even if it’s hypothesis-generating, it generates further interest. Clinicians may be more likely to use bivalirudin again as a result of the MATRIX trial.