Risk of Pneumonia with Ticagrelor Versus Clopidogrel: a Population-Based Cohort Study
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J Gen Intern Med DOI: 10.1007/s11606-020-06131-3 © Society of General Internal Medicine 2020
INTRODUCTION
Ticagrelor is a potent antiplatelet agent used in the management of acute coronary syndromes (ACS) that exerts pleiotropic effects, including anti-inflammatory1 and anti-Grampositive antibacterial2 activity, and may reduce pneumonia complications.3 The objective of this study was to compare the risk of community-acquired pneumonia (CAP), predominantly caused by the Gram-positive pathogen Streptococcus pneumoniae, with ticagrelor versus clopidogrel among ACS patients who underwent percutaneous coronary intervention (PCI).
ratios (HR) and 95% confidence intervals (CI) for ticagrelor versus clopidogrel were obtained using Cox proportionalhazard models, censored at time of P2Y12 inhibitor switch, prescription fill gaps (greater than days’ supply plus 15-day grace period) or death, and adjusted for potential confounders selected a priori: age, sex, Cardiac-Specific Comorbidity Index,6 smoking status, chronic pulmonary disease, proton pump inhibitor use, fiscal year, and adherence. Moreover, we evaluated the primary outcome based on P2Y12 inhibitor adherence (≥ 80% versus < 80%). A sensitivity analysis using propensity score matching was consistent with the primary analysis (not shown; available upon request). The University of Alberta Research Ethics Office approved this study with consent waived because investigators were provided deidentified data. Statistical significance was set at 2-sided p < 0.05. Analyses were performed using SAS 9.4 (SAS Institute) and R 3.4.3 (R Project for Statistical Computing).
METHODS
We conducted a population-based cohort study by linking the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry with administrative data for hospitalizations, emergency department (ED) visits, outpatient prescription fills, and laboratory data. We previously compared major adverse coronary events with ticagrelor versus clopidogrel.4 We included patients ≥ 18 years old, discharged alive after undergoing PCI for ACS from April 2012 to March 2016, who filled a prescription for ticagrelor or clopidogrel ≤ 31 days after PCI. We excluded individuals already prescribed these medications prior to index admission. Medication exposure and adherence (assuming an intended standard 1-year therapy duration) were defined using outpatient prescription fills.4 The primary outcome was hospitalization or ED visit for non-viral CAP (discharge International Classification of Diseases-10th Revision codes J13.x to J18.x5) within 1 year after PCI. Secondary outcomes were individual components of hospitalization for CAP and ED visit for CAP. Hazard Received April 1, 2020 Accepted August 11, 2020
RESULTS
Among 11,185 eligible patients, the median age was 61 years (interquartile range 54 to 71) and 2760 (24.7%) were women (Table 1). Ticagrelor users were younger, had fewer comorbidities, and were less likely to be women, current smokers, to have chronic pulmonary disease, or use a p
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