Some A-fib Patients May Need a Bit More Aspirin After PCI: AUGUSTUS

PHILADELPHIA, PA—Physicians shouldn’t be too hasty about dropping aspirin in all A-fib patients after PCI, as it appears those with a particularly high risk of stent thrombosis might benefit from up to 1 month of additional coverage, an analysis of the AUGUSTUS trial suggests.

Definite/probable stent thrombosis was relatively rare in the first 6 months after the procedure, with most of the 30 cases (80%) occurring in the first month, according to Renato Lopes, MD, PhD (Duke University Medical Center, Durham, NC).

In the 2 x 2 factorial trial, stent thrombosis tended to be lower in patients taking apixaban (Eliquis; Bristol-Myers Squibb) versus a vitamin K antagonist (VKA) and in those taking aspirin versus placebo, though the differences were not statistically significant, he reported here at the American Heart Association (AHA) 2019 Scientific Sessions. All patients were also taking a P2Y12 inhibitor.

What that means, Lopes told TCTMD, is that it might be wise to continue aspirin—in addition to oral anticoagulation and P2Y12 inhibition—for the first 30 days if a patient’s risk of stent thrombosis seems high and risk of bleeding is acceptable.

A blanket policy of stopping aspirin, particularly when it’s translated to our noninterventional colleagues, might put patients at risk of stent thrombosis if it’s stopped too early. Shamir Mehta

AUGUSTUS and similar trials involving the other non-VKA oral anticoagulants (NOACs) have provided a consistent message when it comes to the majority of patients who require chronic anticoagulation for A-fib and antiplatelet therapy following PCI, Lopes said: “Using a NOAC and using a P2Y12 inhibitor without aspirin is the way to go.”

What has not been resolved, however, is when aspirin should be stopped after the procedure. Lopes pointed out that all of the trials have shown a concerning trend toward more stent thrombosis after patients are no longer protected by aspirin.

This new analysis digging into stent thrombosis in AUGUSTUS “gave us a hint that if you have a patient that has a high risk of stent thrombosis and has an acceptable risk of bleeding, then instead of dropping aspirin after hospital discharge around 5 days, it’s reasonable to keep aspirin for 30 days after the PCI and then drop aspirin,” Lopes said, “because if you do that, your trade-off between a stent thrombosis and avoiding a major bleed will be almost one to one.” After 1 month, he added, the risk of bleeding far exceeds the risk of stent thrombosis.

Risk Highest With VKA, No Aspirin

AUGUSTUS enrolled patients who had A-fib and were eligible for chronic oral anticoagulation, presented either with an ACS or for elective PCI, and had planned use of a P2Y12 inhibitor for at least 6 months. The 4,614 patients were randomized both to apixaban versus a VKA and to aspirin versus placebo. The main results reported earlier this year showed that apixaban without aspirin reduced bleeding and hospitalizations without increasing overall ischemic events compared with regimens that contained a VKA, aspirin, or both. There was a nonsignificant trend toward more stent thrombosis in the placebo arm than in the aspirin arm (0.9% vs 0.5%).

This new analysis, which was also published as a research letter in Circulation, delves deeper into the cases of stent thrombosis. It included the 3,498 patients who received a stent during the index hospitalization.

I think we answered the timing question, but now we need to do further studies to try to find who those patients might be. Renato Lopes

The overall rate of definite/probable stent thrombosis was 0.86%, with 24 of the 30 cases occurring within the first 30 days and the rest occurring between 1 and 6 months. Over the entire 6-month period, stent thrombosis was numerically less frequent with apixaban versus a VKA (0.74% vs 0.97%; HR 0.76; 95% CI 0.37-1.56) and with aspirin versus placebo (0.63% vs 1.08%; HR 0.58; 95% CI 0.28-1.22).

When looking at combined treatment, the rate of definite/probable stent thrombosis was lowest with apixaban plus aspirin (0.57%), followed by VKA plus aspirin (0.69%), apixaban alone (0.91%), and VKA alone (1.26%).

Most patients who developed stent thrombosis had an MI as a consequence (70%) and required urgent revascularization (53%); four out of every 10 patients with stent thrombosis died.

Individualized Aspirin Therapy Key

Commenting for TCTMD, Shamir Mehta, MD (McMaster University, Hamilton, Canada), said that the reduction in bleeding by discontinuing aspirin in the context of triple therapy is important, but there is a small price to pay in terms of stent thrombosis.

The key message, he said, is that the decision about when to stop aspirin needs to be individualized and certain patients might require aspirin for a bit longer.

“I worry sometimes about a blanket policy of stopping aspirin in all patients, because different patients have different risks of stent thrombosis. Some patients who have very thrombotic lesions—for example, those that present with STEMI—may need a short course of aspirin,” Mehta said, explaining that a “short course” generally means 2 to 4 weeks. “And so a blanket policy of stopping aspirin, particularly when it’s translated to our noninterventional colleagues, might put patients at risk of stent thrombosis if it’s stopped too early.”

Patients with ACS are essentially presenting with thrombotic occlusion or subtotal occlusion, and probably need a short course of aspirin in addition to their anticoagulant and P2Y12 inhibitor, he said. For elective procedures, patients who have more complex lesions (eg, chronic total occlusions) and who are undergoing multivessel PCI likely also require a short extension of aspirin therapy because the risk of stent thrombosis is very high early on.

There are a couple of caveats when it comes to interpreting the stent thrombosis finding of AUGUSTUS, Mehta pointed out. Because randomization did not occur immediately at the time of presentation, patients in the trial were protected with aspirin for about a week, and in some cases up to 2 weeks, he said. Thus, it’s unknown what the risk of stent thrombosis would have been if aspirin was stopped on the first day.

“Sometimes the messaging is such that aspirin needs to be stopped as soon as possible, and I think that’s the wrong message to give,” Mehta said. “I think the correct message is that aspirin does increase the risk of bleeding and that the risk of bleeding and thrombotic events needs to be weighed individually in each patient.”

Lopes noted that there aren’t good tools to help clinicians make the decision about when to stop aspirin in the context of triple therapy. But intuitively, he said, patients who are elderly, have renal impairment, are undergoing complex PCI, or have bifurcation lesions, for example, have a high risk of stent thrombosis.

“So far, we are using those to make those decisions, but we really need better studies to try to identify better who these patients might be,” Lopes said. “I think we answered the timing question, but now we need to do further studies to try to find who those patients might be.”