Literature
Clinical Pearls & Morning Reports
Published October 2, 2019
In the trial by Steg et al., was intracranial hemorrhage more frequent in patients who received ticagrelor as compared to those who received placebo?
Steg et al. conducted a randomized, double-blind trial that compared cardiovascular and safety outcomes with aspirin plus ticagrelor versus aspirin alone in patients 50 years of age or older who had stable coronary artery disease and type 2 diabetes mellitus, and who did not have a history of myocardial infarction or stroke. Read the Original Article here.
Clinical Pearls
Q: Describe some of the settings in which ticagrelor has been shown to be beneficial.
A: Ticagrelor, a reversible antagonist of the platelet P2Y12 receptor, has been shown to provide more consistent platelet inhibition than aspirin or clopidogrel. Ticagrelor has also been shown to provide protection against cardiovascular events when added to aspirin in patients with acute coronary syndromes and in high-risk patients with previous myocardial infarction. The relative benefit of ticagrelor in these patients has been consistent regardless of the presence of diabetes. Whether patients with stable coronary artery disease and diabetes who do not have a history of myocardial infarction or stroke also derive benefit from dual antiplatelet therapy with ticagrelor plus aspirin is unclear.
Q: How did ticagrelor added to aspirin (ticagrelor group) compare to aspirin alone (placebo group) with respect to cardiovascular outcomes in the trial by Steg et al.?
A: The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary composite efficacy outcome occurred in 736 of 9619 patients (7.7%) in the ticagrelor group and in 818 of 9601 patients (8.5%) in the placebo group, which corresponded to Kaplan–Meier rates of 6.9% and 7.6%, respectively, at 36 months (hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04). The lower frequency of the primary composite outcome in the ticagrelor group was driven by lower incidences of myocardial infarction and stroke than in the placebo group. There was no significant between-group difference in the incidence of cardiovascular death.
Morning Report Questions
Q: In the trial by Steg et al., was intracranial hemorrhage more frequent in patients who received ticagrelor as compared to those who received placebo?
A: There was a higher frequency of TIMI major bleeding in the ticagrelor group than in the placebo group (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001). Results that were consistent with the primary safety analysis were observed for other bleeding definitions. There was no significant between-group difference in the incidence of fatal bleeding episodes, although the number of events was higher in the ticagrelor group. Intracranial hemorrhage was more frequent with ticagrelor than with placebo, with 70 events and 46 events, respectively (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005).
Q: How did Steg et al. view the risk of “net irreversible harm” with ticagrelor as compared to placebo in their trial?
A: In an exploratory analysis that weighed both efficacy and safety events, the risk of a composite outcome of net irreversible harm was not significantly lower in the ticagrelor group than in the placebo group, which suggests that ticagrelor therapy does not have a favorable risk–benefit ratio in this trial population.