Practice Update: Cardiology

INTERVENTIONAL CARDIOLOGY 20

Long-term outcomes improve when patients are switched to clopidogrel after ACS European Heart Journal

Take-home message • The objective of this study was to assess the effects of switching from ticagrelor or prasugrel to clopidogrel 1 month after acute coronary syndrome (ACS). Investigators recruited 645 patients treated with aspirin plus ticagrelor or prasugrel. At 1 month after the ACS event, 322 patients were switched to dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel, and 323 patients continued with the aspirin plus ticagrelor or prasugrel. After 1 year, 43 patients (13.4%) in the switched DAPT group and 85 patients (26.3%) in the unchanged DAPT group had experienced the primary composite outcome of cardiovascular death, urgent revascularization, stroke, and bleeding (P <0.01). This difference was primarily due to higher rates of bleeding in the unchanged DAPT group; there were no differences in the ischemic endpoints between the two groups. • The investigators conclude that switching patients on DAPT to clopidogrel 1 month after ACS is superior to continuing long-term therapy with other P2Y12 blocking agents. This strategy reduced bleeding events with DAPT without increasing ischemic risk.

COMMENT By Deepak L Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC D ual antiplatelet therapy with aspirin and an oral adenosine diphosphate (ADP) receptor antagonist is indicated for at least a year in patients with acute coronary syndromes (ACS) undergoing percu- taneous coronary intervention (PCI). Historically, the ADP receptor antago- nist was clopidogrel. Then, ticagrelor and prasugrel were both found to be more efficacious than clopidogrel in this setting. However, both agents also cause more bleeding than clopidogrel. Therefore, the TOPIC trial randomized ACS patients treated with PCI and on DAPT with either ticagrelor or prasug- rel to receive continued therapy or to switch to clopidogrel at 1 month, if they were stable and event-free at that point. Not surprisingly, there was more bleed- ing in the continued DAPT arm vs the switched DAPT arm. There was no sig- nificant difference in ischemic events between the continued DAPT and switched DAPT arms, although, with 67 total ischemic events, the trial was very underpowered. The trial was also done in a single center and was open-label, which are further limitations. Although the results make sense and a strategy of DAPT-switching would be cheaper and also result in less bleeding, it is pos- sible that, if a properly sized multicenter, randomized, blinded trial were done, there would in fact be a significant ischemic risk to this strategy. Also, it is important to realize that, in the PLATO trial, ticagrelor reduced all-cause mor- tality compared with clopidogrel, and the TOPIC trial was not close to being powered for that important endpoint.

Abstract AIMS Newer P2Y12 blockers (prasugrel and ticagrelor) demonstrated significant ischaemic benefit over clopidogrel after acute coronary syndrome (ACS). However, both drugs are associated with an increase in bleeding com- plications. The objective of the present study was to evaluate the benefit of switching dual antiplatelet therapy (DAPT) from aspirin plus a newer P2Y12 blocker to aspirin plus clopidogrel 1month after ACS. METHODS AND RESULTS We performed an open- label, monocentric, and randomized trial. From March 2014 to April 2016, patients admitted with ACS requiring coronary intervention, on aspirin and a newer P2Y12 blocker and without adverse event at 1 month, were assigned to switch to aspirin and clopidogrel (switchedDAPT) or continuation of their drug regimen (unchangedDAPT). Theprimary outcomewas a compositeof cardiovascular death, urgent revascularization, stroke and bleeding as defined by the Bleeding Academic Research Consortium (BARC) classification ≥2 at 1 year post

ACS. Six hundred and forty six patients were randomized and 645 analysed, corresponding to 322 patients in the switched DAPT and 323 in the unchanged DAPT group. The primary endpoint occurred in 43 (13.4%) patients in the switched DAPT group and in 85 (26.3%) patients in the unchanged DAPT (HR 95%CI 0.48 [0.34–0.68]), P<0.01). No significant differences were reported on ischaemic endpoints, while BARC≥2 bleeding occurred in 13 (4.0%) patients in the switchedDAPT and in 48 (14.9%) in the unchanged DAPT group (HR 95%CI 0.30 [0.18–0.50], P<0.01). CONCLUSION A switched DAPT is superior to an unchanged DAPT strategy to prevent bleed- ing complications without increase in ischaemic events following ACS. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (Timing of Platelet Inhibition After Acute Coro- nary Syndrome) randomized study. Eur Heart J 2017 May 16;[EPub Ahead of Print], T Cuisset, P Deharo, J Quilici, et al.

Dr Bhatt is Executive Director of Interventional Cardiovascular Programs at Brigham and Women’s Hospital Heart & Vascular Center and Professor of Medicine at Harvard Medical School.

PRACTICEUPDATE CARDIOLOGY