January 13, 2020
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Post-PCI ticagrelor does not lower MACE risk vs. clopidogrel in cohort study

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Among patients with ACS who underwent PCI and received an outpatient prescription for ticagrelor or clopidogrel, ticagrelor was not associated with a significant reduction in risk for MACE, and those who received ticagrelor had more major bleeding and dyspnea, according to data from a population-based cohort study published in JAMA Internal Medicine.

Researchers analyzed 13,897 adults with ACS who underwent PCI primarily with second-generation drug-eluting stents from April 2012 to March 31, 2016, and were included in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Of those, 11,185 patients received and filled an outpatient prescription for ticagrelor (Brilinta, AstraZeneca) or clopidogrel within 31 days after PCI.

Risk for MACE — defined as a composite of all-cause death, hospitalization for ACS, unplanned revascularization or stent thrombosis within 1 year of PCI — was not lower with ticagrelor compared with clopidogrel (adjusted HR = 0.97; 95% CI, 0.85-1.1).

Use of ticagrelor was associated with elevated risk for major bleeding (aHR = 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR = 1.98; 95% CI, 1.47-2.65), compared with clopidogrel. The difference in major bleeding between the two groups was primarily driven by increases in gastrointestinal hemorrhage and pulmonary hemorrhage, according to the findings.

The researchers further examined the association between medication adherence and MACE. Overall, patients who were adherent — defined as a medication refill adherence of at least 80% — had lower risk for MACE compared with those who had an adherence value below 80% (aHR = 0.79; 95% CI, 0.69-0.9).

During the study, 81.6% of patients who received a prescription for ticagrelor were adherent compared with 73.9% of those who received clopidogrel (P < .001).

Clopidogrel was used more often than ticagrelor in this cohort (63.6% vs. 36.4%); however, use of ticagrelor increased steadily during the study period and was used in more than half of patients during the second half of the study, according to the researchers. A switch from one P2Y12 inhibitor to the other occurred in 14% of ticagrelor users and 2.3% of clopidogrel users. Switching initial treatment was not associated with increased MACE risk.

In this cohort study, the median age was 61 years and one-quarter were women. Ticagrelor users were younger and presented with fewer comorbidities compared with clopidogrel users, according to the findings.

“Our findings differ from prior studies on this topic, and this may be due to differences in methodology, patient populations and advances in interventional cardiology,” Ricky D. Turgeon, BSc(Pharm), PharmD, from the department of pharmacy at Vancouver General Hospital, Vancouver, Canada, and colleagues wrote in the study.

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The researchers noted that this cohort study “included patients at higher risk of bleeding than those generally included in clinical trials.”

Moreover, “[t]his study found that adherence to a P2Y12 inhibitor was more strongly associated with risk of MACE than choice of the P2Y12 inhibitor itself. ... These results should encourage clinicians to routinely ask patients whether they are taking their medications as prescribed and identify and resolve barriers to adherence, including cost, adverse events (including dyspnea with ticagrelor) and burden from number or frequency of medications administered.”

Turgeon and colleagues noted that the steady decline in adherence observed during the course of this study “warrants ongoing assessment of medication adherence starting at hospital discharge and continuing at every follow-up visit.” – by Scott Buzby

Disclosures: Turgeon reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.