In PCI treated ACS, switching from aspirin a newer P2Y12 blocker to aspirin clopidogrel reduced adverse events
Question In patients with an acute coronary syndrome (ACS) who were treated with percutaneous coronary intervention (PCI) and had no adverse events after a month of dual antiplatelet therapy (DAPT) with aspirin plus a newer P2Y12 blocker, does switching to a new DAPT regimen of fixed dose combination (FDC) aspirin plus clopidogrel reduce bleeding and ischemic events? Methods Design Randomized controlled trial (RCT) (Timing of Optimal Platelet Inhibition After Acute Coronary Syndrome [TOPIC] study) ClinicalTrials.gov NCT02099422. Allocation Unclear allocation concealment. Blinding Blinded* (outcome adjudicators) Follow up period 1 year after ACS. Setting 1 hospital in Marseille, France. Patients 646 adults >18 years of age (mean age 60 y, 82% men) who were admitted for an ACS and required PCI within 72 hours, were treated with aspirin plus a newer P2Y12 blocker (prasugrel, 10 mg/d, or ticagrelor, 90 mg twice/d) at discharge, and had no major adverse events (ischemic or bleeding events) within 1 month of the ACS. Exclusion criteria included thrombocytopenia; previous intracranial bleeding; major bleeding in the past 12 months; use of long term anticoagulation; or contraindication to aspirin, clopidogrel, prasugrel, or ticagrelor. Intervention Switch to a new DAPT single tablet FDC of aspirin, 75 mg, plus clopidogrel, 75 mg (n =323) or continue DAPT with aspirin plus the newer P2Y12 blocker (n =323) Outcomes Composite of ischemic and bleeding events (cardiovascular [CV] death, unplanned hospitalization leading to urgent coronary revascularization, stroke, or bleeding [Bleeding Academic Research Consortium classification 2] Secondary outcomes included components of the primary composite, any ischemic event, and any bleeding. Patient follow up 98% (modified intention to treat analysis) Main results The main results are in the Table. Conclusion In patients who had an acute coronary syndrome treated with percutaneous coronary intervention and had no adverse events after a month of dual antiplatelet therapy (DAPT) with aspirin plus a newer P2Y12 blocker, switching to a new DAPT regimen of fixed dose combination aspirin plus clopidogrel reduced a composite of ischemic and bleeding events. Switch to aspirin clopidogrel (switched) vs continuing aspirin newer P2Y12 (continued) 1 mo after an acute coronary syndrome (ACS) treated with percutaneous coronary intervention Outcomes Event rates At 1 y after ACS Switched Continued RRR (95% CI) NNT (CI) Ischemic and bleeding events 13% 26% 48% (29 to 63) 8 (7 to 14) Cardiovascular death 0.3% 1.2% 70% (72 to 95) Not significant Unplanned revascularization 8.7% 9.3% 7% (51 to 43) Not significant Stroke 0.3% 0.9% 63% (158 to 95) Not significant Bleeding (BARC 2) 4.0% 14.9% 68% (48 to 81) 10 (9 to 14) Any ischemic event 9.3% 11.5% 19% (27 to 48) Not significant Any bleeding 9.3% 23.5% 58% (40 to 70) 8 (7 to 11) BARC Bleeding Academic Research Consortium classification; other abbreviations defined in Glossary. RRR, NNT, and CI calculated from continued event rates and hazard ratios in article. Cardiovascular death, unplanned hospitalization leading to urgent coronary revascularization, stroke, or bleeding (BARC 2) Commentary Guidelines recommend DAPT for 1 year after an ACS event (1) Recurrent ischemic events are reduced further with the use of the more potent P2Y12 inhibitors, ticagrelor and prasugrel, compared with clopidogrel, although these agents increase bleeding risk (2, 3) The RCT by Cuisset and colleagues found that transitioning from aspirin plus a newer P2Y12 blocker to FDC aspirin plus clopidogrel 30 days after an ACS event reduced the risk for a composite of CV death, unplanned hospitalization leading to urgent coronary revascularization, stroke, or bleeding episodes at 1 year after ACS. However, the observed benefit was driven predominantly by a reduction in minor bleeding events, with no difference in ischemic events. Although this trial provides new insights into DAPT therapy after ACS, the single center, open label design limits its generalizability. The trial also was not powered to detect a difference between groups in the incidence of ischemic events. Although the results of Cuisset and colleagues suggest that the transition to a clopidogrel plus aspirin FDC reduced bleeding events (predominantly minor) larger blinded RCTs are needed to fully elucidate the effects on ischemic events and major bleeding before these results are applied in clinical practice.
Annals of Internal Medicine