SUMMARY  

• XARELTO is not indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS).¹
• There are no specific recommendations on transitioning from or to a dual antiplatelet therapy (DAPT) regimen to XARELTO with aspirin in patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) within the XARELTO US Prescribing Information.¹
• SWAP-AC (Switching Anti-Platelet and Anti-Coagulant Therapy), a prospective, randomized, pharmacodynamic study evaluated the viability of transitioning from DAPT (aspirin plus either clopidogrel, prasugrel, or ticagrelor) to dual pathway inhibition (DPI; aspirin 81 mg once daily plus XARELTO 2.5 mg twice daily) and compared the pharmacodynamic profiles of these different treatment approaches.²
  • At 30 days, there were no significant differences in the peak levels of
    platelet-mediated global thrombogenicity between DAPT and DPI in the ticagrelor or prasugrel cohort; however, the clopidogrel cohort had lower platelet-mediated global thrombogenicity in DAPT compared to DPI (P=0.011).
  • Bleeding Academic Research Consortium type 2 bleeding (epistaxis) was reported in 1 patient in the DPI cohort. No adverse events were reported in the DAPT group.

CLINICAL DATA

COMPASS

COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) was a phase 3, double-blind, randomized study designed to evaluate whether XARELTO 2.5 mg twice daily plus aspirin 100 mg once daily or XARELTO 5 mg twice daily alone is more effective than aspirin 100 mg once daily alone in preventing major cardiovascular events in patients with stable CAD or PAD (N=27,395).³

• Patients were excluded from COMPASS if use of DAPT, anticoagulation, or other
  anti-thrombotic therapy was required.³
• If patients developed the need for DAPT during the study period (i.e. in event of an ACS, or in patients who underwent percutaneous coronary intervention with stenting), the protocol stated that investigators could make the decision to temporarily discontinue XARELTO until DAPT was no longer clinically required. Alternatively, the investigators could also have transitioned patients in need of DAPT to the 2.5 mg twice daily dose of XARELTO (or matching placebo).⁴ Study XARELTO and placebo were to have been restarted once DAPT was discontinued after completion of an adequate duration.⁵
• Within COMPASS patients with stable CAD (N=24,842), there were 1120 patients who developed a need for DAPT.⁴
  • In the XARELTO 2.5 mg twice daily plus aspirin arm, 358 (4%) patients had required DAPT during the study, in which 344 had XARELTO treatment discontinued and 14 continued XARELTO 2.5 mg twice daily.⁴
  • In the XARELTO 5 mg twice daily alone arm, 384 (5%) patients had required DAPT during the study, in which 369 had XARELTO treatment discontinued and 15 continued XARELTO at a dose of 2.5 mg twice daily.⁴

SWAP-AC

SWAP-AC (Switching Anti-Platelet and Anti-Coagulant Therapy), a prospective, randomized, pharmacodynamic study evaluated the viability of transitioning from DAPT (aspirin plus either clopidogrel, prasugrel, or ticagrelor) to dual pathway inhibition (DPI; aspirin plus XARELTO) in patients with CCS and compared the pharmacodynamic profiles of these different treatment approaches.²

Study Design/Methods

Patients were included if they were ≥18 years of age with known CCS and had completed ≥6 months of DAPT after an elective percutaneous coronary intervention or ≥12 months after experiencing an ACS event and were still on therapy.

• Patients with active bleeding, high risk for bleeding, stroke within 1 month, or a history of hemorrhagic or lacunar stroke were excluded.
• Ninety patients were randomized 1:1 to maintain DAPT or switch to DPI (aspirin 81 mg once daily plus XARELTO 2.5 mg twice daily). The primary endpoint was maximum platelet aggregation (MPA) peak levels at 30 days. Secondary endpoints comprised other markers of platelet reactivity and thrombin generation.

Results

• There were no significant differences in the peak levels of platelet-mediated global thrombogenicity (primary endpoint) between the ticagrelor cohort and DPI (14.5% [0.0-63.0] vs 20.0% [0.0-70.0]; P=0.477) or the prasugrel cohort and DPI (20.0% [0.0-66.0] vs 4.0% [0.0-70.0]; P=0.482). Global platelet thrombogenicity was significantly lower in the clopidogrel cohort compared to DPI (27.0% [0.0-68.0] vs 53.0% [0.0-81.0]; P=0.011) at 30 days.
• No differences were observed between DAPT and DPI at any time during the study across all cohorts in terms of tissue factor-induced platelet aggregation.
• Markers of platelet P2Y₁₂ signalling showed significant increases following the switch from DAPT to DPI in each of the 3 DAPT cohorts.
• Bleeding Academic Research Consortium type 2 bleeding (epistaxis) was reported in 1 patient in the DPI cohort. No adverse events were reported in the DAPT group.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 12 July 2024.