COMPASS Antithrombotic Approach Works Well in Prior-PCI Patients

Patients with chronic coronary syndromes derive a benefit from low-dose rivaroxaban (Xarelto; Bayer/Janssen) plus aspirin regardless of whether they’ve undergone PCI in the past, the COMPASS-PCI study shows.

Compared with aspirin alone, dual-pathway inhibition reduced rates of MACE and mortality—at the cost of more major bleeding—in patients without a history of PCI and in those who had a coronary intervention 1 to 10 years prior to randomization, according to researchers led by Kevin Bainey, MD (University of Alberta, Edmonton, Canada).

Of note, the time that had elapsed since PCI was performed did not influence the magnitude of the reductions in MACE and mortality, the investigators report in a study published online recently in Circulation.

“This has practical implications when we see these patients in clinic because we’re seeing them a year, 2 years out, and they’re only on aspirin, and adding rivaroxaban in that setting appears to be of benefit provided that their bleeding risk is not excessive,” Bainey told TCTMD.

“Yes, there is going to be a higher risk of bleeding. You’re adding a more potent antithrombotic regimen,” he added. “But I think with our analysis, as well as the overall COMPASS trial, it’s very encouraging that what I call ‘bad bleeding’ is not more prevalent in patients with a dual-pathway-inhibition approach.”

The COMPASS trial randomized 27,395 patients with chronic coronary syndromes (ie, stable CAD) or PAD, showing that dual-pathway inhibition with rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily reduced MACE (CV death, MI, or stroke) and mortality but increased ISTH major bleeding compared with aspirin alone.

The investigators prespecified an analysis focused on patients with a prior history of PCI. Of the 16,560 patients with chronic coronary syndromes included in the trial, 59.6% had undergone PCI an average of 5.4 years and as long as 10 years before randomization.

Through an average follow-up of just under 2 years, the combination of low-dose rivaroxaban and aspirin reduced risks of MACE and all-cause and CV mortality, with an increase in major bleeding, compared with aspirin alone in patients both with and without prior PCI (all P = NS for interaction).

Outcomes at 2 Years, by PCI History

Rivaroxaban plus aspirin did not significantly reduce risks of MI or stent thrombosis or increase risks of fatal bleeding, bleeding into a critical organ, or intracranial hemorrhage, regardless of PCI history.

A composite outcome of net clinical benefit (CV mortality, MI, stroke, fatal bleeding, or bleeding into a critical organ) favored dual-pathway inhibition with rivaroxaban and aspirin both in patients with and those without a prior PCI (P = 0.98 for interaction).

In patients with prior PCI, reductions in MACE and all-cause mortality were unaffected by the time since PCI. And in both groups defined by PCI history, outcomes were improved regardless of whether they had had an MI.

Bainey said that COMPASS-PCI indicates that patients with chronic coronary syndromes who are at least a year out from PCI and typically would be taking aspirin alone stand to gain from the addition of low-dose rivaroxaban.

“I think that it is incumbent upon us to really think about this dual-pathway-inhibition strategy at that time,” he said. “I know a lot of people also contemplate a dual antiplatelet strategy in those patients, but I think what’s nice with this study compared to the dual antiplatelet story is that we have demonstrated an improvement in survival, and that’s not been seen with the dual antiplatelet therapy strategy long-term.”

In Canada, the approach is gaining traction out in practice, Bainey said, noting, however, that payment can vary from province to province. Nevertheless, he said, “I think there is widespread acceptance of this dual-pathway-inhibition approach, and yeah, we are using it.”