Issue: May 2019

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March 17, 2019
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AUGUSTUS: Dual therapy with apixaban, P2Y12 inhibitor safe in Afib patients post-ACS or PCI

Issue: May 2019
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Renato D. Lopes
Renato D. Lopes

NEW ORLEANS — New data from the AUGUSTUS trial provide insight on the appropriate antithrombotic regimen after ACS or PCI in patients with atrial fibrillation.

An antithrombotic regimen that includes a P2Y12 inhibitor and apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), without aspirin, resulted in less bleeding and fewer hospitalizations, with no difference in ischemic events compared with other regimens that included a vitamin K antagonist, aspirin or both in this patient population.

The 2x2 factorial randomized controlled trial enrolled 4,614 patients with AF from 33 countries who had ACS or had undergone PCI. Patients were randomly assigned within 14 days of having an ACS or undergoing PCI to treatment with apixaban 5 mg twice daily or 2.5 mg twice daily based on dose-reduction criteria or warfarin, on top of planned P2Y12 inhibitor therapy, and then also low-dose aspirin 81 mg once daily or matching placebo for 6 months. Choice of P2Y12 inhibitor was left to the treating physician; clopidogrel was used in 92.6% of patients.

On the basis of the findings in this trial, “I think that routinely and for most patients a regimen that includes a P2Y12 inhibitor and a novel oral anticoagulant — in this case, apixaban — would be enough” to achieve the best net clinical benefit between bleeding and ischemic events for these high group of patients, Renato D. Lopes, MD, MHS, PhD, professor of medicine in the division of cardiology at Duke University Medical Center, said during a press conference.

Reduced bleeding

Patients who received apixaban had a 31% reduction in risk for major or clinically relevant nonmajor bleeding vs. those who received warfarin (10.5% vs. 14.7%; HR = 0.69; 95% CI, 0.58-0.81; P < .001 for both noninferiority and superiority). Bleeding risk was reduced by 47% among patients who received placebo vs. aspirin (HR = 1.89; 95% CI, 1.59-2.24; P < .001).

Putting the results together, Lopes said, the highest rate of bleeding occurred in patients who were treated with clopidogrel, warfarin and aspirin (18.5%) and the lowest rate was in those treated with clopidogrel, apixaban and placebo (7.3%).

New data from the AUGUSTUS trial provide insight on the appropriate antithrombotic regimen after ACS or PCI in patients with atrial fibrillation.
Source: Shutterstock

Other findings

AUGUSTUS also looked at secondary outcomes including death or hospitalization and a composite of ischemic events, including MI, definite/probable stent thrombosis, stroke or urgent revascularization.

Use of apixaban reduced the rate of death or hospitalization by 17% (23.5% vs. 27.4%; HR = 0.83; 95% CI, 0.74-0.93; P = .002). This was primarily driven by a reduction in hospitalization, Lopes said. With aspirin vs. placebo, the researchers observed no significant difference in this outcome.

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Again, putting the results together, the highest rate of death or hospitalization occurred in patients who were treated with clopidogrel, warfarin and aspirin (27.5%) and the lowest rate was in those treated with clopidogrel, apixaban and placebo (22%).

The treatment groups did not differ in ischemic events, except for a 50% lower risk for stroke with apixaban compared with warfarin.

The researchers noted, however, a greater number of coronary ischemic events in patients who did not receive aspirin. However, they cautioned in the NEJM study that “event rates were low and the trial was not adequately powered to assess differences in individual ischemic outcomes.

“Although this analysis should be considered exploratory, similar trials have shown a similar pattern of numerically more coronary ischemic events when aspirin was omitted. Thus, when clinicians consider aspirin as a component of antithrombotic therapy after PCI in patients with atrial fibrillation, a potential small absolute decrease in the risk of coronary ischemic events needs to be weighed against a larger absolute increase in the risk of clinically significant bleeding,” they wrote in NEJM.

In other results, the median age of AUGUSTUS participants was 71 years and 29% were women. Among those who underwent randomization, 37.3% had ACS and underwent PCI, 24% had medically managed ACS and nearly 39% underwent elective PCI. In the anticoagulation group, 12.7% of patients stopped apixaban and 13.8% stopped warfarin before the study concluded. In the antiplatelet group, 17% stopped aspirin and nearly 15% stopped placebo.

‘Less is more’

AUGUSTUS evaluated a high-risk population. It is estimated that 5% to 8% of patients undergoing PCI have AF, which complicates the choice of antithrombotic therapy after PCI, according to the researchers.

“For the majority of patients, if you look at the totality of data, one lesson learned that is now confirmed by AUGUSTUS is that less is more. ... If we use a P2Y12 inhibitor with one of the NOACS at the right dose for stroke prevention in atrial fibrillation — in this case, apixaban 5 mg twice daily — you have the safest strategy and you don’t seem to pay a high cost on ischemic events,” Lopes said during the press conference. – by Katie Kalvaitis, with additional reporting by Erik Swain

References:

Lopes RD. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.

Lopes RD, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1817083.

Disclosures: AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer. Lopes reports he received an institutional research grant from Bristol-Myers Squibb/Pfizer and received personal fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer.