7. Study Rationale & Objective
Study Rationale:
Dual antiplatelet therapy consists of aspirin combined with an adenosine diphosphatase receptor antagonist,
which remains the cornerstone for the treatment of acute coronary syndromes (ACS). Both Ticagrelor and
Prasugrel have proven to have more rapid and consistent inhibition of platelets compared to clopidogrel. However,
no head-to-head trials have compared Ticagrelor and Prasugrel directly. This study was designed to be the first to
compare the efficacy and safety of these two medications.
Objective:
To assess if Ticagrelor is superior to Prasugrel in the management of ACS in patients with the planned
intervention.
8. Trial: Prospective, randomized, open-label, multicenter (21 centers in Germany, 2 in Italy, N=4018). Enrollment September
2013-February 2018 with 1-year follow-up.
Intervention: Patients who presented with ACS and for whom invasive evaluation was planned received eitherTicagrelor
or Prasugrel.
9. Outcomes:
Primary Outcome:
Composite of death, myocardial infarction, or stroke 1 year after randomization
Secondary Outcomes:
1. Safety endpoint: Bleeding (BARC class 3-5)
2. Incidence of individual components of the primary endpoint
3. Stent thrombosis (ARC criteria: definite and probable)
10. 1. 4018 patients recruited from 23 centers (21
in Germany, 2 in Italy); 2012 patients assigned
Ticagrelor and 2006 patients assigned
Prasugrel
2. Suspected diagnosis on admission: 41.1%
STEMI, 46.2% NSTEMI, 12.7% unstable
angina
3. Before admission, 34.7% of patients in the
Ticagrelor group and 35.6% of patients in the
Prasugrel group were taking aspirin; 5.0% of
patients in the Ticagrelor group, and 4.7% of
patients in the Prasugrel group were taking
clopidogrel
No significant demographic differences
between the two groups
11.
12. Limitations & Considerations
1. Open label trial making it more subject to bias.
2. Population included patients โฅ 75 years and < 60 kg who received reduced prasugrel maintenance dose of 5 mg daily instead of 10 mg daily after initial 60 mg
load without documented increased risk of bleeding; this information could potentially change our management in this patient population by encouraging more
frequent use of Prasugrel
3. High compliance rates at 99.6% and 99.1% in Ticagrelor and prasugrel groups, respectively, raise concern for potential over-reporting of medication
adherence, particularly in the setting of only 10% of follow-ups being face-to-face (with the remaining 83% being over the phone and 7% in written
correspondence).
4. Questionable skewed results given intention-to-treat model due to 20.4% of patients in each of the ticagrelor and prasugrel groups being discharged without the
antiplatelet therapy they were initially assigned. Additionally, 243 patients from the ticagrelor group and 199 patients from the prasugrel group discontinued
treatment after discharge. 37 patients were lost to follow-up, resulting in 1299 patients included in the analysis who were not receiving their assigned medication.
5. 233 patients (11.6%) from the prasugrel group were excluded from safety analysis vs. 23 (1.14%) in the ticagrelor group, potentially underestimating the rate of
major bleeding with prasugrel.
6.Ticagrelor was discontinued more frequently and earlier on in the trial than prasugrel possibly biasing the primary outcome away from ticagrelor
7. Despite the fact that ticagrelor was administered immediately vs delayed administration of prasugrel, rate of primary outcome was still significantly lower in
the prasugrel group. This may be due to the irreversible activity of prasugrel which last a platelets lifetime (10 days) vs reversible binding of ticagrelor to P2Y12
receptors.This also highlights that immediate loading by P2Y12 inhibitors in the setting of ACS may not be necessary.
8. Important to note that difference in primary outcome was largely due to individual component of myocardial infarction (higher rates of type 4a and 4b
myocardial infarction in ticagrelor arm) raising question of compliance in ticagrelor patients or effect of patients being switched from initial ticagrelor dose at
discharge
9.When compared to their original major studies, primary end point for ticagrelor was similar to PLATO trial (9.3% vs 9.8%) while prasugrel was different when
compared toTRITON-TIMI38 trial (6.9% vs 9.9%)
