[ad_1]
NEW ORLEANS – The risk / benefit dilemma of antithrombotic therapy in patients with both atrial fibrillation (AF) and dual antiplatelet therapy (DAPT) may become a little less daunting given the results of the randomized trial AUGUSTUS.
In the study, which involved people with both AF and acute coronary syndromes (ACS) or recent percutaneous coronary intervention (PCI), all undergoing treatment with a P2Y12 inhibitor, such as the clopidogrel, presented the two lower on apixaban (Eliquis, Bristol-Myers Squibb / Pfizer) only on a vitamin K antagonist (VKA), such as warfarin.
In another conclusion based on a separate randomization in the trial, which had a 2×2 factorial design, the DAPT appeared unnecessary and even more risky in case of major bleeding compared to a P2Y12 inhibitor alone in most patients with recent AF and SCA or PKI.
Combining the two independent results, treatment with apixaban over a P2Y12 inhibitor appeared to have the lowest risk of bleeding and clinical events, whereas neither of the two comparisons showed effect on the risk of ischemic events, observed the principal investigator of AUGUSTUS, Renato Lopes D, MD, MHS, Ph.D., Duke Clinical Research Institute, Durham, Carolina North, in an interview.
But the trial does not say that such a "double therapy" is necessarily the best option for all patients with AF and a recent SCA or PKI, does it? he warned; the design of the test was not designed to draw such a conclusion.
In addition, the results do not necessarily exclude the role of triple therapy, he said. theheart.org | Medscape Cardiology. With a P2Y12 inhibitor on board, there were significantly fewer major bleeds and fewer clinical events with apixaban plus aspirin than with AVK plus aspirin.
"That's another important message of the lawsuit," Lopes said. "If you want to use triple therapy because you feel that aspirin is important – for example, your patient has a very high risk of stent thrombosis or ischemic events – the study shows that Use of aspirin with apixaban is better than that with VKA. "
Lopes was to present the AUGUSTUS trial here at the 68th Annual Scientific Session 2019 (ACC.19) of the American College of Cardiology (ACC.19) around the time of its online publication today in the New England Journal of Medicine.
"It is clear that it is unlikely that a uniform policy for all patients will apply to these patients," writes Shamir R. Mehta, MD, McMaster University, Hamilton, Ontario, Canada, in an accompanying editorial.
"Based on these data, clinical decision making should continue to be based on a balanced badessment of three competing risks: cardioembolic stroke, coronary ischemic events and bleeding" for each patient, he said.
For example, in patients with low thrombotic risk or high risk of bleeding, "early omission of aspirin therapy and direct oral anticoagulant therapy with clopidogrel is fully warranted".
But for those who are undergoing complex or high-risk PCI or who have high-risk SCA, "aspirin probably should not be routinely missed for at least several weeks or more, depending on the risk of bleeding," Mehta writes.
AUGUSTUS enrolled 4,614 patients in centers in North America, Europe, Asia, and South America presenting with AF as an indication for chronic oral anticoagulation and recent SCA or stent-based ICP. More than 90% started clopidogrel and the rest, other P2Y12 inhibitors.
Patients were randomized to receive either open apixaban (at the established dosage for non-valvular AF) or an AVK (2306 and 2308 patients, respectively), and a separate, double-blind randomization to receive aspirin. 81 mg / day. day or placebo (2307 and 2307 patients, respectively). They were followed for 6 months.
In the comparison between apixaban and VKA, the adjusted risk ratio for the primary endpoint, major or clinically significant non-significant bleeding, was 0.69 (95% CI, 0.58 – 0.81; P <0.001 for non-inferiority and superiority), report Lopes and his colleagues.
For aspirin versus placebo, the CF for the same endpoint was 1.89 (95% CI, 1.59-2.24; P <0.001).
The main event rate for 100 patient-years was highest with AVK and aspirin (49.1), followed by apixaban and aspirin (33.6), VKA and placebo (26.7), and apixaban and placebo ( 16.8).
For the secondary endpoint of death or hospitalization, the HR for apixaban versus AVK was 0.83 (95% CI, 0.74-0.93; P = 0.002); for aspirin versus placebo, it was not significant at 1.08 (95% CI, 0.96 to 1.21).
And for the secondary endpoint of death or ischemic events (stroke, myocardial infarction, definitive or probable thrombosis of a stent or urgent revascularization), the heart rate was reduced in a non-significant manner for apixaban to 0.93 (95% CI, 0.75 – 1.16) and for aspirin vs placebo at 0.89 (95% CI, 0.71 to 1.11).
Bleeding in the primary endpoint was prospectively defined according to the criteria of the International Society of Thrombosis and Hemostasis (ISTH). But Lopes said the bleeding results during the test were "consistent and robust", whether they were defined by the ISTH or by the alternative criteria of GUSTO or TIMI.
[Notedel'editor:[Editor'snote:[Notedel'éditeur:[Editor’snote:theheart.org | Medscape Cardiology plans to update this story soon with expert commentary]AUGUSTUS was funded by Bristol-Myers Squibb and Pfizer, whose Lopes discloses that he has received grants and personal fees while conducting the trial. Lopes also reports receiving personal fees from Boehringer Ingelheim and Bayer AG and grants from Amgen, GlaxoSmithKline, Medtronic and Sanofi Aventis. Disclosures about other authors are available on the journal's website. Mehta says he has received grants from AstraZeneca, Boston Scientific and Boehringer Ingelheim.
American College of Cardiology 68th Annual Scientific Session 2019 (ACC.19). Joint American College of Cardiology / Journal of the American Medical Association Clinical Trials Last Minute 405-08. Presented on March 17, 2018.
N Engl J Med. Posted online 17 March 2019. Full text, Editorial
Follow Steve Stiles on Twitter: @ SteveStiles2. For more information on theheart.org, follow us on Twitter and Facebook.
[ad_2]
Source link
