Importance Guidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea. This is likely the most compelling evidence of this study for which the authors deserve congratulations, as it underscores the role of tailored antiplatelet therapy, considering drug tolerability and expected adherence: adherence appears more strongly associated with risk of MACE than choice of the P2Y12 inhibitor itself. However, adherence to P2Y12 inhibition was associated with 21% lower relative risk of MACE compared with non-adherence. Altogether, these counterintuitive observations suggest that unmeasured residual confounders might have not been accounted for. Conversely, ticagrelor users experienced more dyspnea and bleeding, events known to induce discontinuation of P2Y12 inhibitors, and more stent thrombosis, a likely consequence of discontinuation. Since factors associated with low adherence to P2Y12 inhibitors were more prevalent in (sicker) patients receiving clopidogrel, the Authors hypothesize that this may have caused lower adherence and persistence in clopidogrel than in ticagrelor arm. Higher rates of dyspnea and bleeding are related to the mechanism of action of ticagrelor, and they likely account for the known 25% higher risk of discontinuation than comparators5. ![]() Being also smaller than PLATO-invasive, this study might be actually underpowered to detect differences favoring ticagrelor: indeed, the direction of ischemic benefit in adjusted models is consistent with the unadjusted ones. This likely happened both because events occurring within hospitalization were not captured and because all patients had received PCI, resulting a lower-risk population. The absolute rate of 1-year composite incidence of death/ACS/stroke in ticagrelor arm of this study (8.0%) is ≈10% lower than that of PLATO-invasive (9.0%), and all-cause mortality is ≈60% lower (1.5% vs 3.9%), thus suggesting that this study cohort might be at a somehow lower risk than PLATO-invasive. By externally validating the conclusions of randomized trials and generating hypotheses for subsequent investigations, such cohort studies have a definite role in the hierarchy of evidence. This study challenges the results of the landmark PLATO-invasive trial and current guidelines supporting the preference of ticagrelor (or prasugrel) over clopidogrel in patients with ACS. The main finding was that ticagrelor, after adjusted Cox modeling or propensity-score matching, was not associated with a lower risk of major adverse coronary events (MACE) compared to clopidogrel, whereas it was associated with significantly higher rates of bleeding and dyspnea. Turgeon et al explored effectiveness and safety of ticagrelor compared to clopidogrel in outpatients discharged after acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI) in a registry-based cohort study of 11,185 patients. Shared Decision Making and Communication.Scientific Discovery and the Future of Medicine.Health Care Economics, Insurance, Payment.Clinical Implications of Basic Neuroscience. ![]() ![]() Challenges in Clinical Electrocardiography.
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