· balanced between ticagrelor and clopidogrel groups.
· 16,237 patients enrolled, 13,885 randomized and monitored for primary events until the completion of trial. · Ticagrelor: 6930 assigned and included in the primary analysis, 20 never received ticagrelor so were not included in the safety analysis – 123 withdrew consent, 2083 discontinued the study drug, 7 had unknown vital status, 1 lost to follow-up · Clopidogrel: 6955 assigned and included in primary analysis, 23 never received clopidogrel so were not included in the safety analysis – 113 withdrew consent, 1803 discontinued the study drug, 7 had unknown vital signs, 4 lost to follow-up · Well balanced between ticagrelor and clopidogrel groups. · Global population including patients from Europe, Asia, North America, and South America · Median age 66 years old, 72% male · ~56% had had previous revascularization (ABI .78) and ~43% met ABI(.
63)/TBI(.49,.55) criteria · ~19% were asymptomatic and 76% had mild-sever claudication · Medical history, Tobacco use and medications were nearly identical between the two groups.
· The primary composite endpoint occurred in 10.8% of the ticagrelor arm and 10.6% of the clopidogrel arm which is a hazard ratio of 1.02 and not a statistically significant difference. · CV death (HR1.07) and MI (HR1.
06) had nonsignificant differences favoring clopidogrel. · Ischemic stroke had a significant difference favoring ticagrelor, hazard ratio (HR) of 0.78 (P = 0.03) · There were no significant differences in secondary endpoints. · Composite – CV death, MI, Ischemic stroke, hospitalization for acute limb ischemia – HR 1.02 (CI .92-1.
12) · All-cause mortality – HR 0.99 (CI 0.89-1.11) · Lower extremity revascularization – HR 0.
95 (CI 0.87-1.05) · Composite of all revascularization – HR 0.
97 (CI 0.90-1.05) · Safety results were relatively comparable across both groups. There was one statistically significant difference in the patient populations; ticagrelor had to be discontinued more often than clopidogrel due to adverse events HR 1.21 (P = <0.
001). Ticagrelor caused respiratory adverse effects on 5.4% on patients while clopidogrel only negatively affected 1.3%. The authors noted it was due to high rates of dyspnea in the ticagrelor group. · There were no statistical differences between groups in: TIMI major bleeding, fatal bleeding, intracranial bleeding, minor bleeding, and fatal events · TIMI major bleeding was stratified by geographic region, age, sex, revascularization history, antiplatelet therapy, diabetes, smoking, etc.
and no statistically significant differences were found between study groups. (Supplementary appendix figure S5) · Strengths: International study, Similar baseline characteristics, Trial met power, all patients accounted for, Large sample size, reported all AE and broke them down into classes and subgroups. · Weaknesses: Majority male patients, Large percentage of patients discontinued study drug, adherence not addressed.