Is Ticagrelor Superior to Clopidogrel in Real-World ACS Patients?
Clinical trial data don't always reflect real-world experience.
Platelet inhibition is fundamental to acute coronary syndrome (ACS) treatment, and newer antiplatelet agents like ticagrelor and prasugrel are more potent than clopidogrel.
Results from the PLATO trial show ticagrelor reduced the incidence of vascular death, nonfatal myocardial infarction (MI), and stroke compared with clopidogrel, although at the expense of an increased risk of major non-coronary artery bypass grafting-related bleeding. Accordingly, both European and American guidelines recommend ticagrelor over clopidogrel for ACS patients.
However, clinical trial data don’t always reflect real-world experience, given the rigorous structure of a study. Therefore, registry data can be valuable in confirming the findings of regimented trials.
In line with this logic, a large registry database from Sweden was recently analyzed to determine the real-world effects of ticagrelor in ACS patients. The main study population comprised 45,073 patients, of whom 11,954 were discharged on ticagrelor and 33,119 on clopidogrel.
An interesting note from this dataset: unlike the slow uptake seen in North America, ticagrelor captured almost half of the market for dual antiplatelet therapy within 9 months of its introduction across Sweden.
The cumulative probability of the combined outcome of death, MI, and stroke at 24 months was 11.7% with ticagrelor and 22.3% with clopidogrel. As for secondary outcomes, the probability of death was 5.8% with ticagrelor and 12.9%with clopidogrel. The corresponding figures for MI were 6.1% with ticagrelor and 10.8% with clopidogrel, and for stroke, they were 1.8% with ticagrelor and 3.8% with clopidogrel.
The cumulative probability of bleeding requiring admission was similar between patients treated with ticagrelor and clopidogrel (5.5% vs. 5.2%). However, a higher risk of bleeding was associated with ticagrelor after correcting for confounders.
Percutaneous coronary intervention (PCI)-related in-hospital bleeding occurred in 413 of 11,221 patients on ticagrelor versus 634 of 23,501 patients on clopidogrel. ACS type (STEMI vs. NSTEMI) didn’t interact with the association between ticagrelor treatment and patient outcomes.
Invasive strategy (PCI vs. non-PCI) didn’t interact with regards to the primary outcome, but an interaction was noted between invasive strategy and type of antiplatelet therapy with regards to death, as the association between ticagrelor treatment and reduced risk of death was more pronounced in patients undergoing PCI than non-PCI patients.
Overall, these results provide important real-world outcomes in ACS patients treated with ticagrelor or clopidogrel. These findings appear similar to the benefit achieved in the PLATO trial, as patients discharged on ticagrelor had lower incidence of the composite of death, MI, or stroke, as well as lower mortality alone. Patients prescribed ticagrelor were also at higher risk of bleeding, as evidenced by more readmissions with bleeding and more PCI-related in-hospital bleeding events.
These results must be viewed within the observational study design, as it opens up the possibility of residual confounding that’s a known potential source of error in registry studies. Furthermore, the rates of bleeding in this cohort were lower than what was seen in randomized trials, suggesting under-reporting.
Nevertheless, the results confirmed the clinical trial benefits of ticagrelor in a large, real-world cohort of patients. This is important for pharmacists because we often advise patients and physicians on choosing appropriate antiplatelet therapy for ACS patients. Pharmacists should take confidence in following the current guideline recommendations favoring ticagrelor over clopidogrel.
Sahlén A, et al. Outcomes in patients treated with ticagrelor or clopidogrel after acute myocardial infarction: experiences from SWEDEHEART registry. Eur Heart J. 2016.