Another brick in the wall: The impact of ticagrelor use on the incidence of stroke in a large registry

The risk of ischaemic stroke is a common concern among physicians who care for patients with acute coronary syndrome (ACS). These patients typically have multiple cardiovascular risk factors and require treatment with a dedicated medical regimen. The interesting work of Ulvenstam and colleagues seeks to further explore the impact of recent changes in medical treatment following percutaneous coronary interventions (PCIs) on stroke, which is often considered a secondary endpoint in the field of interventional cardiology. In their manuscript, the authors retrospectively evaluated the one-year incidence of ischaemic stroke among 34,933 patients following PCI for acute myocardial infarction (AMI) from 2009 to 2013 in Sweden. They assessed the impact of ticagrelor on ischaemic stroke by dividing the population into two time-blocks based on the introduction of ticagrelor. The first period was from December 2009 to December 2011, during which only clopidogrel was used. During the second period, from December 2011 to December 2013, 40% of patients were treated with clopidogrel and 60% with ticagrelor. Interestingly, there was a 21% relative risk reduction of ischaemic stroke in the second time block with a significant absolute lower incidence of ischaemic stroke (2.2% vs. 1.8%, see Figure 1). Moreover, the authors identified several variables associated with increased stroke risk, including older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and STEMI. The authors concluded that ticagrelor was associated with a significant reduction of ischaemic stroke rate over the time. Dual anti-platelet therapy (DAPT) is considered a standard of care for patients with AMI treated with PCI. The favourable results of the randomized clinical trial PLATO (see Figure 1) led to a progressive replacement of clopidogrel with the newer P2Y12 receptor blocker ticagrelor in the setting of PCI for ACS. However, no difference was observed in ischaemic stroke at 12 months’ follow-up (1.1% in both groups). The difference between the paper of Ulvenstam and the PLATO trial lies in the different populations considered in the two studies, as the authors comprehensively discussed in their paper. In the modern era of evidence-based medicine, results from randomized controlled trials (RCTs) are promptly translated into guidelines that greatly impact our daily practice. Nevertheless, cohorts enrolled in RCTs are usually composed of highly selected patients, substantially different from that seen in real-world practice. Despite the presence of typical cardiovascular risk factors and a higher incidence of STEMI in the PLATO population, patients in the observational study by Ulvenstam et al. were older and more likely to have a history of prior ischaemic stroke, a recognized predictor of further ischaemic cerebral accidents. Moreover, patients with atrial fibrillation with an indication for oral anticoagulation were excluded from PLATO. On the other hand, physicians ordinarily deal with difficulties like the choice of a correct combination of anti-coagulant and anti-platelet drugs along with sub-optimal therapy regimens in patients suffering of both AF and other risk factors for cerebrovascular diseases. These baseline differences may make the real-world population at great risk for ischaemic stroke and help account for the beneficial effect of ticagrelor in regard to the reduction of ischaemic stroke in the real-world population.