Circulation

ORIGINAL RESEARCH ARTICLE

Ticagrelor or Prasugrel in Patients With ST-

Segment–Elevation Myocardial Infarction
Undergoing Primary Percutaneous Coronary
Intervention
BACKGROUND: Data on the comparative efficacy and safety of ticagrelor Alp Aytekin, MD
versus prasugrel in patients with ST-segment–elevation myocardial ⁝
infarction undergoing primary percutaneous coronary intervention are Adnan Kastrati, MD
limited. We assessed the efficacy and safety of ticagrelor versus prasugrel
in a head-to-head comparison in patients with ST-segment–elevation
myocardial infarction undergoing primary percutaneous coronary
intervention.
METHODS: In this prespecified subgroup analysis, we included 1653
patients with ST-segment–elevation myocardial infarction randomized
to receive ticagrelor or prasugrel in the setting of the ISAR REACT-5 trial
(Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action
for Coronary Treatment 5). The primary end point was the incidence of
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death, myocardial infarction, or stroke at 1 year after randomization.

The secondary end point was the incidence of bleeding defined as BARC
(Bleeding Academic Research Consortium) type 3 to 5 bleeding at 1 year
after randomization.
RESULTS: The primary end point occurred in 83 patients (10.1%) in the
ticagrelor group and in 64 patients (7.9%) in the prasugrel group (hazard
ratio, 1.31 [95% CI, 0.95–1.82]; P=0.10). One-year incidence of all-cause
death (4.9% versus 4.7%; P=0.83), stroke (1.3% versus 1.0%; P=0.46),
and definite stent thrombosis (1.8% versus 1.0%; P=0.15) did not differ
significantly in patients assigned to ticagrelor or prasugrel. One-year
incidence of myocardial infarction (5.3% versus 2.8%; hazard ratio, 1.95
[95% CI, 1.18–3.23]; P=0.010) was higher with ticagrelor than with
prasugrel. BARC type 3 to 5 bleeding occurred in 46 patients (6.1%) in
the ticagrelor group and in 39 patients (5.1%) in the prasugrel group
(hazard ratio, 1.22 [95% CI, 0.80–1.87]; P=0.36).
The full author list is available on page
2335.
CONCLUSIONS: In patients with ST-segment–elevation myocardial
Key Words: hemorrhage ◼ mortality
infarction undergoing primary percutaneous coronary intervention, there ◼ P2Y12 receptor antagonists
was no significant difference in the primary end point between prasugrel ◼ percutaneous coronary intervention
and ticagrelor. Ticagrelor was associated with a significant increase in the ◼ prasugrel hydrochloride
◼ ST elevation myocardial infarction
risk for recurrent myocardial infarction. ◼ thrombosis ◼ ticagrelor

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: Sources of Funding, see page 2335

NCT01944800. © 2020 American Heart Association, Inc.

https://www.ahajournals.org/journal/circ

Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244 December 15, 2020 2329

 Aytekin et al
Clinical Perspective
ORIGINAL RESEARCH
What Is New?
ARTICLE
• In this prespecified analysis of the ISAR-REACT 5
trial (Intracoronary Stenting and Antithrombotic
Regimen: Rapid Early Action for Coronary Treat-
ment 5), there was no significant interaction
between diagnosis on admission (ST-segment–
elevation myocardial infarction, non–ST-segment–
elevation acute coronary syndrome) and treatment
effect of the study drug in terms of the primary
end point.
• The primary composite end point of death, myocar-
dial infarction, or stroke and the safety end point of
bleeding at 1 year were not significantly different
between ticagrelor and prasugrel in patients with
ST-segment–elevation myocardial infarction under-
going primary percutaneous coronary intervention.
• A significant increase in the risk of recurrent myo-
cardial infarction was observed with ticagrelor
compared with prasugrel.
What Are the Clinical Implications?
• Ticagrelor and prasugrel are associated with com-
parable bleeding risk in patients with ST-segment–
elevation myocardial infarction undergoing primary
percutaneous coronary intervention.
• Although overall efficacy of both drugs was not
significantly different, the advantage observed with
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prasugrel in terms of the risk of recurrent myocar-
dial infarction might be considered in the treatment
of patients with ST-segment–elevation myocardial
infarction undergoing primary percutaneous coro-
nary intervention who present with a particularly
higher risk for thrombotic complications.
D
ual antiplatelet therapy is the guideline-recom-
mended treatment for patients presenting with
ST-segment–elevation myocardial infarction
(STEMI) undergoing primary percutaneous coronary
intervention (PCI).1–3 This therapy has improved the
clinical outcome of patients with STEMI by reducing
the risk of subsequent ischemic events, including stent
thrombosis. However, patients with STEMI frequently
manifest high on-aspirin or -clopidogrel platelet reactiv-
ity, which increases the risk for recurrent atherothrom-
botic events.4–6 This emphasizes the need for a potent
antiplatelet therapy with an immediate and consistent
onset of antiplatelet action.7 Large randomized trials
showed that the third-generation P2Y12 receptor inhibi-
tors prasugrel and ticagrelor are superior to clopido-
grel in reducing ischemic events in patients with acute
coronary syndrome (ACS) predominantly undergoing
invasive therapy.8,9 This was also confirmed by a recent
large network meta-analysis.10 The results in the STEMI
cohorts of these trials were consistent with the overall
2330 December 15, 2020
Ticagrelor or Prasugrel in STEMI
results with respect to reduction in ischemic risk by pra-
sugrel or ticagrelor compared with clopidogrel.11,12 The
efficacy and safety outcomes with prasugrel or ticagre-
lor in these trials cannot be directly compared because
of inconsistency and incomparability in patient popu-
lations and interventions. Furthermore, observational
studies and registry data have produced inconsistent
results with respect to the efficacy and safety of pra-
sugrel versus ticagrelor in patients with STEMI,13–18 and
their results should be interpreted cautiously because
of unmeasured confounders. So far, only 2 clinical trials
have performed a randomized head-to-head compari-
son of prasugrel and ticagrelor in patients with ACS.19,20
The ISAR-REACT 5 trial (Intracoronary Stenting and
Antithrombotic Regimen: Rapid Early Action for Coro-
nary Treatment) showed superiority of prasugrel over
ticagrelor in reducing the 1-year incidence of ischemic
events with no significant excess in bleeding risk.20 In
the ISAR-REACT 5 trial, an analysis of efficacy and safe-
ty of ticagrelor versus prasugrel according to the clini-
cal presentation was prespecified. Here, we present the
results of this analysis assessing the efficacy and safety
of ticagrelor versus prasugrel in patients with STEMI un-
dergoing primary PCI.
METHODS
Study Design, Patients, and Drugs
The data that support the findings of this study are available
from the corresponding author on reasonable request. Parties
interested in collaboration and data sharing may contact the
corresponding author directly. The ISAR-REACT 5 study was
an investigator-initiated, phase 4, multicenter, randomized,
open-label trial that assessed whether ticagrelor is superior
to prasugrel in patients with ACS planned for an invasive
management strategy. Details of the study design, inclu-
sion/exclusion criteria, and outcomes were previously pub-
lished.20 Patients were recruited between September 2013
and February 2018. The diagnosis of STEMI was established
in the presence of chest pain lasting ≥20 minutes within 24
hours before randomization associated with electrocardio-
graphic changes (ST-segment elevation of ≥1 mm in at least
2 extremity electrocardiographic leads or ≥2 mm in at least
2 contiguous precordial leads or left bundle-branch block of
new onset). Patients were randomly assigned to ticagrelor or
prasugrel as soon as possible after admission and before coro-
nary angiography and PCI. Time 0 was defined as the time
of randomization. Therapy with ticagrelor was started with a
loading dose of 180 mg and continued with a maintenance
dose of 90 mg twice daily. Therapy with prasugrel was started
at a loading dose of 60 mg and continued with a mainte-
nance dose of 10 mg once daily. In the prasugrel group, a
reduced maintenance dose of 5 mg daily was recommended
in patients with a body weight of <60 kg and in patients ≥75
years of age. The time of study drug initiation was the same
for ticagrelor and prasugrel (ie, drug loading dose as soon as
possible after randomization and before PCI). Aspirin therapy
consisted of a loading dose of 150 to 300 mg of intravenous
Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244
 Aytekin et al
or chewed aspirin and a maintenance dose of 75 to 100 mg
daily in the ticagrelor and prasugrel arms. The study conforms
to the Declaration of Helsinki, and the study protocol was
approved by the local ethics committee at each participat-
ing center. Written informed consent was obtained from all
patients.
End Points and Definitions
The primary end point was a composite of death resulting
from any cause, myocardial infarction, or stroke at 1 year
after randomization. The secondary end point was the inci-
dence of bleeding, defined as type 3 to 5 bleeding accord-
ing to the BARC (Bleeding Academic Research Consortium)
criteria21 at 1 year after randomization. Other end points
analyzed were individual components of the primary end
point, cardiovascular death,22 and stent thrombosis (definite
or probable).22 The definition of the myocardial infarction
was based on the Third Universal Definition of Myocardial
Infarction.23 Detailed definitions of each end point are pro-
vided in the primary publication.20
Follow-Up and Monitoring
The clinical follow-up was scheduled at 30±10 days, 6±1
months, and 12±1 months. Source data were solicited in
case of potential end point–related adverse events. All serious
adverse events and primary and secondary end points were
monitored on site. Patients were monitored at the hospital, by
outpatient visits, or through telephone and structured follow-
up letters. The study flowchart is provided in Figure I in the
Data Supplement.
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Statistical Analysis
The analysis of outcomes according to clinical presentation was
prespecified.20 Continuous data are presented as mean±SD or
median with 25th to 75th percentiles and compared by use
of the Student t test or Wilcoxon rank-sum test as appropri-
ate. Categorical variables are presented as counts and propor-
tions (percent) and compared using the χ2 test. For all end
points incorporating all-cause death, Kaplan-Meier estimates
were calculated. For the other end points, the cumulative inci-
dence functions were computed to account for competing
risk. Intergroup comparisons were made with the Cox pro-
portional hazard model. The participating center was entered
into the Cox proportional hazard model as a covariate, along
with the study treatment group. Risk estimates are presented
as hazard ratios (HRs) with 95% CIs. The efficacy end point
was analyzed according to the intention-to-treat principle (ie,
including all patients as initially assigned regardless of the
actual treatment received). The safety end point (BARC type
3–5 bleeding) was analyzed in a modified intention-to-treat
population (ie, including all patients with at least 1 applica-
tion of the study drug with bleeding assessed for up to 7 days
after discontinuation of the study drug). The outcomes were
graphically displayed with the use of Kaplan-Meier estimates
or cumulative incidences accounting for competing risk along
with 95% CIs.24 Landmark analysis with a prespecified land-
mark at 1 month was performed to assess the early and late
risk of the primary and secondary end points in the ticagrelor
and prasugrel groups. The statistical analysis was performed
Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244
Ticagrelor or Prasugrel in STEMI
with the R 3.6.0 Statistical Package (The R Foundation for
ORIGINAL RESEARCH
Statistical Computing, Vienna, Austria). A 2-sided value of
P<0.05 was considered to indicate statistical significance.
ARTICLE
RESULTS
Baseline Data
There was no significant interaction between diagnosis
on admission (unstable angina, non–ST-segment–ele-
vation myocardial infarction or STEMI) and treatment
effect of the study drug in terms of the primary end
point (P for interaction=0.86). The STEMI cohort of the
ISAR-REACT 5 trial included 1653 patients (study flow is
shown in Figure I in the Data Supplement). The baseline
characteristics are shown in Table 1. The median time
interval (25th–75th percentiles) from symptom onset to
randomization was 3.2 (1.8–7.7) hours in the ticagrelor
group and 3.0 (1.9–8.4) hours in the prasugrel group
(P=0.90). Diagnostic angiography was performed in
1652 patients (>99.9%), and PCI was performed in
1568 patients (94.9%). Although fewer patients in the
ticagrelor group than in the prasugrel group underwent
PCI (P=0.040), the difference was reduced (97.2% ver-
sus 98.2%; P=0.18) when the analysis was confined to
patients with final diagnosis of ACS. The angiographic
and procedural characteristics are shown in Tables I and
II in the Data Supplement. Angiographic and procedur-
al data, including periprocedural antithrombotic medi-
cation, appear to differ little in the ticagrelor or prasug-
rel groups. Therapy at discharge is shown in Table III in
the Data Supplement. Fewer patients in the ticagrelor
group than in the prasugrel group were discharged on
aspirin and statin therapy. Eighty-eight of 705 patients
(12.5%) in the ticagrelor group and 69 of 725 patients
(9.5%) in the prasugrel group (P=0.07) had discontin-
ued study medication at the 1-year follow-up (Figure II
in the Data Supplement). The assigned antithrombotic
medication after study drug discontinuation is shown in
Table IV in the Data Supplement.
Clinical Outcomes
One-year follow-up was complete in all but 15 patients
assigned to ticagrelor (1.8%) and 14 patients assigned
to prasugrel (1.7%). Clinical outcomes at 1 year are
shown in Table  2. The primary end point occurred in
83 of 833 patients (10.1%) assigned to ticagrelor and
64 of 820 patients (7.9%) assigned to prasugrel (HR,
1.31 [95% CI, 0.95–1.82]; P=0.10; Figure 1). The inci-
dence of all-cause death (4.9% versus 4.7%; P=0.83)
and stroke (1.3% versus 1.0%; P=0.46) did not dif-
fer significantly between patients assigned to ticagre-
lor and those assigned to prasugrel. The incidence of
myocardial infarction was 5.3% in the ticagrelor group
and 2.8% in the prasugrel group (HR, 1.95 [95% CI,
December 15, 2020 2331
 Aytekin et al Ticagrelor or Prasugrel in STEMI

Table 1.  Baseline Characteristics*

ORIGINAL RESEARCH

Characteristic Ticagrelor (n=833) Prasugrel (n=820) P value

Age, y 62.4±12.1 63.2±12.1 0.17
ARTICLE

Women, n (%) 168 (20.2) 176 (21.5) 0.56

Diabetes, n (%) 166/832 (20.0) 146 (17.8) 0.29
 On insulin therapy 45/832 (5.4) 42 (5.1) 0.88
Current smoker, n (%) 345/827 (41.7) 333/815 (40.9) 0.76
Arterial hypertension, n (%) 518/831 (62.3) 495/818 (60.5) 0.48
Hypercholesterolemia, n (%) 420/831 (50.5) 398 (48.5) 0.44
Prior myocardial infarction, n (%) 99/832 (11.9) 89/819 (10.9) 0.56
Prior percutaneous coronary intervention, n (%) 122/832 (14.7) 120/819 (14.7) 1.00
Prior aortocoronary bypass surgery, n (%) 27/832 (3.3) 22/819 (2.7) 0.60
Cardiogenic shock, n (%) 19 (2.3) 22 (2.7) 0.71
Systolic blood pressure, mm Hg 139±25.6 139±24.7 0.80
Diastolic blood pressure, mm Hg 82.2±15 81.6±13.8 0.40
Heart rate, bpm 78.3±16.9 77.4±17 0.25
Body mass index, kg/m 2
27.6±4.44 27.7±4.32 0.82
Body weight <60 kg, n (%) 41/829 (5.0) 38/810 (4.7) 0.90
Creatinine, µmol/L 88.2±28.4 87.7±32.6 0.74
Coronary angiography, n (%) 832 (99.9) 820 (100.0) 1.00
Treatment strategy, n (%) 0.040
 Percutaneous coronary intervention 779 (93.5) 789 (96.2)
 Coronary artery bypass grafting 6 (0.7) 3 (0.4)
 Conservative 48 (5.8) 28 (3.4)

Data are mean±SD or n (%).

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*Completeness of continuous data: Systolic blood pressure was not available in 3 patients (1 in the ticagrelor group
and 2 in the prasugrel group); diastolic blood pressure was not available in 16 patients (7 in the ticagrelor group and 9 in
the prasugrel group); heart rate was not available in 2 patients (1 in each group); body mass index was not available in
17 patients (6 in the ticagrelor group and 11 in the prasugrel group); body weight was not available in 14 patients (4 in
the ticagrelor group and 10 in the prasugrel group); and creatinine level was not available in 5 patients (4 in the ticagrelor
group and 1 in the prasugrel group). The remaining continuous data are complete.

1.18–3.23]; P=0.010; Figure III in the Data Supplement).
It is notable that the difference in the incidence of myo-
cardial infarction was driven mostly by an increase in
spontaneous and PCI-related myocardial infarction with
ticagrelor compared with prasugrel (Table 2). The inci-
dence of definite stent thrombosis was 1.8% in the ti-
cagrelor group and 1.0% in the prasugrel group (HR,
1.88 [95% CI, 0.80–4.44]; P=0.15). The results of the
landmark analysis for the primary end point are shown
in Figure IV in the Data Supplement (left), and for both
early and later time intervals, they follow the trend ob-
served for the overall result.
In addition, we performed an efficacy analysis in the
per-protocol population—that is, including all patients
who received at least 1 dose of the randomly assigned
study drug over the period from ingestion of the first
dose to the time of study drug discontinuation, death,
loss to follow-up, or 1 year. Its main results are summa-
rized in Table 3 and are in line with those shown for the
intention-to-treat population.
The secondary end point (BARC type 3–5 bleeding)
occurred in 6.1% of patients in the ticagrelor group
and 5.1% of patients in the prasugrel group (HR, 1.22
[95% CI, 0.80–1.87]; P=0.36; Figure 2). Landmark anal-
ysis for the secondary end point is shown in Figure IV in
the Data Supplement (right). BARC type 1 or 2 bleeding
occurred in 11.9% of patients (n=98) in the ticagrelor
group and 14.7% of patients (n=120) in the prasugrel
group (HR, 0.78 [95% CI, 0.60–1.02]; P=0.07).
DISCUSSION
The ISAR-REACT 5 trial assessed the efficacy and safe-
ty of ticagrelor versus prasugrel in patients with ACS
planned to undergo invasive treatment. In this pre-
specified analysis of patients with STEMI, only an an-
tiplatelet drug was investigated because the treatment
strategy (drug administration and invasive examination
and therapy followed as soon as possible after random-
ization) was the same in both study arms. The principal
findings of this study in patients with STEMI may be

2332 December 15, 2020 Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244

 Aytekin et al Ticagrelor or Prasugrel in STEMI

Table 2.  Clinical Outcomes

ORIGINAL RESEARCH
Ticagrelor Prasugrel Hazard ratio
Characteristic (n=833) (n=820) (95% CI) P value

ARTICLE
Primary end point (death, myocardial 83 (10.1) 64 (7.9) 1.31 (0.95–1.82) 0.10
infarction, or stroke)
Death resulting from any cause 40 (4.9) 38 (4.7) 1.05 (0.67–1.64) 0.83
 Cardiovascular 29 33
 Noncardiovascular 11 5
Myocardial infarction 44 (5.3) 23 (2.8) 1.95 (1.18–3.23) 0.010
 Type 1 24 (2.9) 12 (1.5) 2.06 (1.03–4.13) 0.041
 Type 2 1 1
 Type 4 19 (2.3) 10 (1.2) 1.92 (0.89–4.14) 0.09
 Type 4a 5 3
 Type 4b 14 7
 Type 5 0 0
ST-segment–elevation myocardial infarction 17 6
Stroke
 Any 11 (1.3) 8 (1.0) 1.41 (0.57–3.50) 0.46
 Ischemic 8 6
 Hemorrhagic 3 2
Definite or probable stent thrombosis 17 (2.1) 11 (1.3) 1.55 (0.72–3.30) 0.26
Definite stent thrombosis 15 (1.8) 8 (1.0) 1.88 (0.80–4.44) 0.15
Secondary safety end point: BARC type 46/830 (6.1) 39/810 (5.1) 1.22 (0.80–1.87) 0.36
3–5 bleeding
 BARC 3a 21 21
 BARC 3b 20 16
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 BARC 3c 2 0
 BARC 4 1 0
 BARC 5a 1 0
 BARC 5b 1 2

Data are number of events with Kaplan-Meier estimates (percent) for the primary end point and death or cumulative
incidence (percent) after accounting for competing risk for the remaining end points.
BARC indicates Bleeding Academic Research Consortium.

summarized as follows: First, there was no significant
difference in the 1-year incidence of the primary end
point (a composite of death, myocardial infarction, or
stroke) between prasugrel and ticagrelor. Second, ther-
apy with prasugrel was associated with a significant re-
duction in the risk of myocardial infarction. Third, the
incidence of major bleeding (defined as BARC type 3–5
bleeding) was not significantly different in patients as-
signed to the ticagrelor or prasugrel group up to 1 year
after primary PCI.
Implantation of coronary stents in a highly thrombo-
genic milieu such as infarct-related arteries in patients
with STEMI requires a potent antiplatelet inhibition to
prevent stent thrombosis. Earlier meta-analyses includ-
ing trials of patients with ACS have confirmed a greater
clinical efficacy of prasugrel and ticagrelor over clopi-
dogrel and suggested a greater efficacy of prasugrel
compared with ticagrelor in reducing the risk of stent
thrombosis.25,26 However, ACSs are heterogeneous in
terms of pathophysiology and prognosis after PCI,27
and the relative efficacy of newer P2Y12 inhibitors may
differ according to the ACS type.17 Subgroup analyses
of patients with STEMI recruited in the TRITON-TIMI 38
trial (Trial to Assess Improvement in Therapeutic Out-
comes by Optimizing Platelet Inhibition With Prasugrel–
Thrombolysis in Myocardial Infarction)11 and PLATO trial
(Platelet Inhibition and Clinical Outcomes)28 confirmed
the superiority of prasugrel and ticagrelor over clopi-
dogrel in reducing the risk of myocardial infarction and
stent thrombosis in patients with STEMI after primary
PCI. Observational studies and registries also showed
superiority of prasugrel and ticagrelor in reducing the
risk for ischemic events after primary PCI, but they gave
conflicting signals as to whether prasugrel or ticagrelor
should be preferred as an antiplatelet agent in these
patients. In a large registry of >89 000 patients under-
going primary PCI for STEMI in the United Kingdom,
prasugrel was associated with a lower 30-day and

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 Aytekin et al Ticagrelor or Prasugrel in STEMI

Table 3.  Primary End Point, Its Individual Components, and Stent
Thrombosis in Per-Protocol Analysis*
ORIGINAL RESEARCH

Ticagrelor Prasugrel Hazard ratio

Outcome (n=830) (n=810) (95% CI) P value
ARTICLE

Primary end 76 (9.6) 56 (7.2) 1.39 (0.98–1.96) 0.06

point (death,
myocardial
infarction, or
stroke)
Death resulting 36 (4.5) 33 (4.2) 1.08 (0.68–1.74) 0.74
from any cause
Myocardial 41 (5.2) 21 (2.7) 2.05 (1.21–3.47) 0.008
infarction
Stroke 10 (1.2) 7 (0.9) 1.43 (0.55–3.77) 0.46
Definite or 17 (2.1) 10 (1.2) 1.72 (0.79–3.77) 0.17
probable stent
thrombosis
Definite stent 15 (1.8) 7 (0.9) 2.20 (0.90–5.40) 0.08
thrombosis

Data are number of events with Kaplan-Meier estimates (percent) for

Figure 1. One-year cumulative incidence of the primary end point
(death, myocardial infarction, stroke) in patients assigned to ticagrelor
or prasugrel.
Dotted lines are the 95% CIs. Primary end point was evaluated in the
intention-to-treat population.
1-year mortality compared with clopidogrel or ticagre-
lor.16 Both prasugrel and ticagrelor showed a similar risk
of bleeding, which was higher than the risk of bleeding
associated with clopidogrel. In another registry in the
United Kingdom, prasugrel was associated with lower
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primary end point and death or cumulative incidence (percent) after accounting
for competing risk for the remaining end points. Risk estimates are obtained
from the Cox proportional hazard model with stratification for the participating
center.
*The per-protocol analysis included all patients who received at least 1 dose
of the randomly assigned study drug over the period from ingestion of the
first dose to the time of study drug discontinuation, death, loss to follow-up,
or 1 year.
versus 2.7%) did not differ significantly in the ticagre-
lor or prasugrel assigned groups.19 The 1-year results
also did not show a significant difference in the occur-

adjusted 30-day mortality than ticagrelor or clopidogrel
and lower adjusted 1-year mortality compared with
clopidogrel. Of note, prasugrel and ticagrelor reduced
the risk of myocardial infarction after primary PCI with-
out an increase in the adjusted risk for bleeding.14 Other
registries have reported neutral results with respect to
efficacy or safety of prasugrel or ticagrelor-based dual
antiplatelet therapies after primary PCI.15,17,18 One regis-
try that used propensity score matching to minimize the
effect of baseline differences in cardiovascular risk (with
1290 pairs) reported lower 12-month incidence of net
adverse clinical events and major adverse cardiovascular
events with prasugrel versus ticagrelor driven mainly by
a reduction in the recurrent myocardial infarctions and
lower incidence of bleeding with prasugrel. However,
the benefit of prasugrel was confirmed in patients with
non-STEMI but not in patients with STEMI.17
So far, only 2 clinical trials have performed a ran-
domized head-to-head comparison of prasugrel and ti-
cagrelor in patients with ACS undergoing PCI.19,20 In the
PRAGUE 18 trial (Comparison of Prasugrel and Ticagre-
lor in the Treatment of Acute Myocardial Infarction), the
7-day composite of death, reinfarction, urgent target
vessel revascularization, stroke, or serious bleeding re-
quiring transfusion or prolonging hospitalization (4.1%
versus 4.0%) and 30-day composite of cardiovascular
death, nonfatal myocardial infarction, or stroke (2.5%
rence of the composite efficacy end point (cardiovascu-
lar death, myocardial infarction or stroke) or individual
end points such as cardiovascular (or all-cause) death,
myocardial infarction, stroke, definite stent thrombosis,
all bleeding, or TIMI major bleeding.29 Although the
PRAGUE-18 trial was the first study to perform a head-
to-head comparison between prasugrel and ticagrelor
in patients presenting with ACS (95% with STEMI or
bundle-branch block) and >99% of patients underwent
primary PCI, the premature trial termination (after re-
cruiting 1230 patients) and the high rate of switching
to clopidogrel (34.1% of patients assigned to prasugrel
and 44.4% of patients assigned to ticagrelor) impede a
true comparison between the drugs over the follow-up.
The present analysis included the STEMI cohort of the
ISAR-REACT trial with 95% of patients undergoing pri-
mary PCI. Although the difference did not reach statisti-
cal significance, the primary end point was numerically
lower with prasugrel compared with ticagrelor. It is no-
table that the difference in the occurrence of myocardial
infarction was statistically significant and driven mostly
by fewer spontaneous and stent thrombosis–related in-
farctions in the prasugrel group. Although the mecha-
nisms underlying a stronger anti-ischemic protection by
prasugrel in patients with STEMI remain poorly investi-
gated, some supportive evidence exists. A recent ran-
domized study showed that prasugrel compared with

2334 December 15, 2020 Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244

 Aytekin et al
Figure 2. Cumulative incidence of the safety end point at 1 year (BARC
[Bleeding Academic Research Consortium] type 3–5 bleeding).
Dotted lines are the 95% CIs. BARC type 3 to 5 bleeding was evaluated in the
modified intention-to-treat population.
ticagrelor or clopidogrel in patients with ACS under-
going PCI with coronary stenting was associated with
stronger platelet inhibition, improved endothelial func-
tion, and reduced interleukin-6 levels.30 Whether these
effects lead to a stronger anti-ischemic protection by
Downloaded from http://ahajournals.org by on December 1, 2022
prasugrel compared with ticagrelor remains to be inves-
tigated. Last, consistent with the results of the primary
publication20 and other studies,14,16–18 our study showed
that prasugrel and ticagrelor did not differ significantly
with respect to the risk of bleeding. One possible expla-
nation for the lack of excess risk of bleeding with prasu-
grel despite its stronger antithrombotic efficacy might
be the adapted prasugrel dose regimen used in elderly
and underweight patients.31
The present study has limitations. First, the analysis
carries the known limitations of subgroup analyses in
general; in particular, the size of the investigated pa-
tient subgroup reduces the power of the analysis to
detect a significant difference. Therefore, the present-
ed effect measures and CIs should be used primarily
for exploratory inference and hypothesis generation.
Second, as an open-label study, the analysis remains
susceptible to bias even though the adjudication of
end points was performed in a blinded manner by
study evaluators. Third, the follow-up was performed
mostly by telephone and not face-to-face contact in
hospital or outpatient visits. In addition, 29 patients
were lost to follow-up, which represents 37% of the
total number of patients who died. Fourth, there were
certain imbalances between the 2 treatment arms of
the study in terms of the prescription of aspirin and
statins at discharge. Last, age- and weight-dependent
Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244
Ticagrelor or Prasugrel in STEMI
dose adjustment was done only for prasugrel in the
ORIGINAL RESEARCH
present study.
ARTICLE
CONCLUSIONS
In patients with STEMI undergoing primary PCI, there
was no significant difference in the primary end point
between prasugrel and ticagrelor. Ticagrelor was asso-
ciated with a significant increase in the risk for recurrent
myocardial infarction.
ARTICLE INFORMATION
Received July 14, 2020; accepted October 8, 2020.
Continuing medical education (CME) credit is available for this article. Go to
http://cme.ahajournals.org to take the quiz.
The Data Supplement, podcast, and transcript are available with this article
at https://www.ahajournals.org/doi/suppl/10.1161/circulationaha.120.050244.
Authors
Alp Aytekin, MD; Gjin Ndrepepa, MD; Franz-Josef Neumann, MD; Maurizio
Menichelli, MD; Katharina Mayer, MD; Jochen Wöhrle, MD; Isabell Bernlochner,
MD; Shqipdona Lahu, MD; Gert Richardt, MD; Bernhard Witzenbichler, MD;
Dirk Sibbing, MD; Salvatore Cassese , MD; Dominick J. Angiolillo , MD,
PhD; Christian Valina, MD; Sebastian Kufner, MD; Christoph Liebetrau , MD;
Christian W. Hamm, MD; Erion Xhepa , MD, PhD; Alexander Hapfelmeier ,
MSc; Hendrik B. Sager , MD; Isabel Wustrow , MD; Michael Joner, MD;
Dietmar Trenk , PhD; Massimiliano Fusaro, MD; Karl-Ludwig Laugwitz, MD;
Heribert Schunkert , MD; Stefanie Schüpke, MD; Adnan Kastrati, MD
Correspondence
Adnan Kastrati, MD, Deutsches Herzzentrum München, Lazarettstrasse 36,
80636 Munich, Germany. Email kastrati@dhm.mhn.de
Affiliations
Deutsches Herzzentrum München, Cardiology and Technische Universität
München, Munich, Germany (A.A., G.N., K.M., S.L., S.C., S.K., E.X., H.B.S.,
M.J., M.F., H.S., S.S., A.K). Department of Cardiology and Angiology II, Uni-
versity Heart Center Freiburg·Bad Krozingen, Germany (F.J.N., C.V., D.T.). Os-
pedale Fabrizio Spaziani, Cardiology, Frosinone, Italy (M.M.). Department of
Cardiology, Medical Campus Lake Constance, Friedrichshafen, Germany (J.W.).
Medizinische Klinik und Poliklinik Innere Medizin I (Kardiologie, Angiologie,
Pneumologie), Klinikum Rechts der Isar, Munich, Germany (I.B., I.W., K.L.L).
German Center for Cardiovascular Research (DZHK), partner site Munich Heart
Alliance, Germany (I.B., D.S., K.L.L., H.B.S., M.J., H.S., S.S., A.K.). Heart Center
Bad Segeberg, Germany (G.R.). Helios Amper-Klinikum Dachau, Cardiology &
Pneumology, Germany (B.W.). Klinik der Universität München, Ludwig–Maxi-
milians–University, Cardiology, Munich, Germany (D.S.). Division of Cardiology,
University of Florida College of Medicine, Jacksonville (D.J.A.). Heart Center,
Campus Kerckhoff of Justus-Liebig-University, Giessen, Germany (C.L.,C.W.H.).
German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main,
Germany (C.W.H.). Technical University of Munich, School of Medicine, Institute
of General Practice and Health Services Research, Germany (A.H.).
Sources of Funding
This work was supported by a grant (FKZ 81X1600501) from the German Cen-
ter for Cardiovascular Research and the Deutsches Herzzentrum München,
Germany.
Disclosures
Dr Neumann reports lecture fees, paid to his institution, from Amgen, Daiichi
Sankyo, Novartis, and Ferrer; lecture fees, paid to his institution, and consulting
fees, paid to his institution, from AstraZeneca and Boehringer Ingelheim; grant
support, and lecture fees, paid to his institution, from Pfizer, Biotronic, Edwards
Lifesciences, Bayer HealthCare, and GlaxoSmithKline; and grant support from
December 15, 2020 2335
 Aytekin et al
Medtronic, Abbott Vascular, and Boston Scientific. Dr Bernlochner reports re-
ceiving grant support from MSD Sharp & Dohme and lecture fees from Sys-
ORIGINAL RESEARCH
mex Europe. Dr Sibbing reports personal fees from Bayer AG, Sanofi Aventis,
AstraZeneca, Pfizer, Ferrer, and Daiichi Sankyo and grants and personal fees
ARTICLE
from Roche Diagnostics. Dr Angiolillo reports grants and personal fees from
Amgen, Aralez, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb,
Chiesi, Daiichi-Sankyo, and Eli Lilly, Janssen, Merck, Sanofi, CeloNova, and As-
traZeneca; personal fees from Haemonetics, PhaseBio, PLx Pharma, Pfizer, The
Medicines Company, and St. Jude Medical; and grants from CSL Behring, Eisai,
Gilead, Idorsia Pharmaceuticals Ltd, Matsutani Chemical Industry Co, Novartis,
Osprey Medical, Renal Guard Solutions, and Scott R. MacKenzie Foundation.
Dr Liebetrau reports that he has received consulting fees or honoraria from
AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb,
Daiichi Sankyo, Pfizer, and Thermo Fisher and research grants from Deutsche
Herzstiftung, Kerckhoff-Stiftung, and Kühl-Stiftung. He declares that his insti-
tution has received payments for participation in clinical study programs from
Abbott, AstraZeneca, Bayer, Biosensors, Boston Scientific, Daiichi-Sankyo, and
Neovasc. Dr Hamm reports personal fees from AstraZeneca. Dr Sager reports
having has received funding from the European Research Council under the Eu-
ropean Union’s Horizon 2020 Research and Innovation Program (STRATO), the
Else-Kröner-Fresenius-Stiftung, the Deutsche Herzstiftung, and the Deutsche
Forschungsgemeinschaft. Dr Joner reports receiving personal fees from Bio-
tronik, Orbus Neich, AstraZeneca, and Recor; grants and personal fees from
Boston Scientific and Edwards; and grants from Amgen. Dr Trenk reports that
he has received consulting fees or honoraria from Amgen, AstraZeneca, Bayer,
Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo,
Ferrer, Pfizer, and Sanofi and research grants from Deutsche Herzstiftung and
PharmCompNet Baden-Wuerttemberg: Kompetenznetzwerk Pharmakologie
Baden-Wuerttemberg. Dr Trenk declares that his institution has received pay-
ments for participation in clinical study programs from Amgen, AstraZeneca,
Bayer, Daiichi-Sankyo, Doasense, Esperion, Idorsia, and Otsuka. Dr Schunkert
reports personal fees from MSD Sharp & Dohme, Amgen, Bayer Vital GmbH,
Boehringer Ingelheim, Daiichi-Sankyo, Novartis, Servier, Brahms, Bristol-Myers
Squibb, Medtronic, Sanofi Aventis, Synlab, Pfizer, and Vifor, as well as grants
and personal fees from AstraZeneca. Dr Schüpke reports grants from DZHK
(German Center for Cardiovascular Research) and Else Kröner-Fresenius-Stif-
tung, personal fees from Bayer Vital GmbH, and lecture fees from Daiichi San-
Downloaded from http://ahajournals.org by on December 1, 2022
kyo. The other authors report no conflicts.
Supplemental Material
Data Supplement Tables I–IV
Data Supplement Figures I–IV
REFERENCES
1. O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA,
Ettinger SM, Fang JC, Fesmire FM, Franklin BA, et al. 2013 ACCF/AHA
guideline for the management of ST-elevation myocardial infarction: ex-
ecutive summary: a report of the American College of Cardiology Founda-
tion/American Heart Association Task Force on Practice Guidelines. J Am
Coll Cardiol. 2013;61:485–510.
2. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H,
Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, et al. 2017 ESC guide-
lines for the management of acute myocardial infarction in patients
presenting with ST-segment elevation: the Task Force for the manage-
ment of acute myocardial infarction in patients presenting with ST-seg-
ment elevation of the European Society of Cardiology (ESC). Eur Heart J.
2018;39:119–177.
3. Capodanno D, Alfonso F, Levine GN, Valgimigli M, Angiolillo DJ. ACC/
AHA versus ESC guidelines on dual antiplatelet therapy: JACC guideline
comparison. J Am Coll Cardiol. 2018;72:2915–2931.
4. Matetzky S, Shenkman B, Guetta V, Shechter M, Beinart R, Goldenberg I,
Novikov I, Pres H, Savion N, Varon D, et al. Clopidogrel resistance is associ-
ated with increased risk of recurrent atherothrombotic events in patients
with acute myocardial infarction. Circulation. 2004;109:3171–3175.
5. Dillinger JG, Saeed A, Spagnoli V, Sollier CB, Sideris G, Silberman SM,
Voicu S, Drouet L, Henry P. High platelet reactivity on aspirin in patients
with acute ST elevation myocardial infarction. Thromb Res. 2016;
144:56–61.
6. Sibbing D, Aradi D, Alexopoulos D, Ten Berg J, Bhatt DL, Bonello L,
Collet JP, Cuisset T, Franchi F, Gross L, et al. Updated expert consensus
statement on platelet function and genetic testing for  guiding P2Y12
2336 December 15, 2020
Ticagrelor or Prasugrel in STEMI
receptor inhibitor treatment in percutaneous coronary intervention. JACC
Cardiovasc Interv. 2019;12:1521–1537. doi: 10.1016/j.jcin.2019.03.034
7. Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with
STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14:361–379. doi:
10.1038/nrcardio.2017.18
8. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W,
Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, et al; TRITON-
TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute
coronary syndromes. N Engl J Med. 2007;357:2001–2015. doi: 10.1056/
NEJMoa0706482
9. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C,
Horrow J, Husted S, James S, Katus H, et al. Ticagrelor versus clopi-
dogrel in patients with acute coronary syndromes. N Engl J Med.
2009;361:1045–1057.
10. Navarese EP, Khan SU, Kołodziejczak M, Kubica J, Buccheri S,
Cannon CP, Gurbel PA, De Servi S, Budaj A, Bartorelli A, et al. Com-
parative efficacy and safety of oral P2Y12 inhibitors in acute coro-
nary syndrome: network meta-analysis of 52 816 patients from 12
randomized trials. Circulation. 2020;142:150–160. doi: 10.1161/
CIRCULATIONAHA.120.046786
11. Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM,
McCabe CH, Antman EM; TRITON-TIMI 38 investigators. Prasugrel com-
pared with clopidogrel in patients undergoing percutaneous coronary
intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): dou-
ble-blind, randomised controlled trial. Lancet. 2009;373:723–731. doi:
10.1016/S0140-6736(09)60441-4
12. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP,
Emanuelsson H, Finkelstein A, Husted S, Katus H, et al. Ticagrelor versus
clopidogrel in patients with ST-elevation acute coronary syndromes in-
tended for reperfusion with primary percutaneous coronary intervention:
a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis.
Circulation. 2010;122:2131–2141.
13. Lee YS, Jin CD, Kim MH, Guo LZ, Cho YR, Park K, Park JS, Park TH,
Kim YD. Comparison of prasugrel and ticagrelor antiplatelet effects in Ko-
rean patients presenting with ST-segment elevation myocardial infarction.
Circ J. 2015;79:1248–1254. doi: 10.1253/circj.CJ-15-0270
14. Krishnamurthy A, Keeble C, Anderson M, Somers K, Burton-Wood N,
Harland C, Baxter P, McLenachan J, Blaxill J, Blackman DJ, et al. Real-world
comparison of clopidogrel, prasugrel and ticagrelor in patients undergoing
primary percutaneous coronary intervention. Open Heart. 2019;6:e000951.
doi: 10.1136/openhrt-2018-000951
15. Kim MC, Jeong MH, Sim DS, Hong YJ, Kim JH, Ahn Y, Ahn TH, Seung KB,
Choi DJ, Kim HS, et al. Comparison of clinical outcomes between ticagre-
lor and prasugrel in patients with ST-segment elevation myocardial infarc-
tion: results from the Korea Acute Myocardial Infarction Registry-National
Institutes of Health. Circ J. 2018;82:1866–1873.
16. Olier I, Sirker A, Hildick-Smith DJR, Kinnaird T, Ludman P, de Belder MA,
Baumbach A, Byrne J, Rashid M, Curzen N, et al. Association of different
antiplatelet therapies with mortality after primary percutaneous coronary
intervention. Heart. 2018;104:1683–1690.
17. De Filippo O, Cortese M, D Ascenzo F, Raposeiras-Roubin S, Abu-Assi E,
Kinnaird T, Ariza-Solé A, Manzano-Fernández S, Templin C, Velicki L, et al.
Real-world data of prasugrel vs. ticagrelor in acute myocardial infarction:
results from the RENAMI Registry. Am J Cardiovasc Drugs. 2019;19:381–
391. doi: 10.1007/s40256-019-00339-3
18. De Luca L, Zeymer U, Claeys MJ, Dorler J, Erne P, Matter CM, Radovanovic D,
Weidinger F, Luscher TF, Jukema JW. Comparison of P2Y12 receptor in-
hibitors in patients with ST-elevation myocardial infarction in clinical prac-
tice: a propensity score analysis of 5 contemporary European registries
[published online January 20, 2020]. Eur Heart J Cardiovasc Pharmacother.
doi: 10.1093/ehjcvp/pvaa002. https://academic.oup.com/ehjcvp/advance-
article/doi/10.1093/ehjcvp/pvaa002/5713517
19. Motovska Z, Hlinomaz O, Miklik R, Hromadka M, Varvarovsky I, Dusek J,
Knot J, Jarkovsky J, Kala P, Rokyta R, et al; PRAGUE-18 Study Group. Pra-
sugrel versus ticagrelor in patients with acute myocardial infarction
treated with primary percutaneous coronary intervention: multicenter
randomized PRAGUE-18 Study. Circulation. 2016;134:1603–1612. doi:
10.1161/CIRCULATIONAHA.116.024823
20. Schüpke S, Neumann FJ, Menichelli M, Mayer K, Bernlochner I,
Wöhrle J, Richardt G, Liebetrau C, Witzenbichler B, Antoniucci D, et al;
ISAR-REACT 5 Trial Investigators. Ticagrelor or prasugrel in patients with
acute coronary syndromes. N Engl J Med. 2019;381:1524–1534. doi:
10.1056/NEJMoa1908973
Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244
 Aytekin et al
21. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S,
Wiviott SD, Menon V, Nikolsky E, et al. Standardized bleeding definitions
for cardiovascular clinical trials: a consensus report from the Bleeding
Academic Research Consortium. Circulation. 2011;123:2736–2747. doi:
10.1161/CIRCULATIONAHA.110.009449
22. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA,
Steg PG, Morel MA, Mauri L, Vranckx P, et al; Academic Research Con-
sortium. Clinical end points in coronary stent trials: a case for stan-
dardized definitions. Circulation. 2007;115:2344–2351. doi: 10.1161/
CIRCULATIONAHA.106.685313
23. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD,
Katus HA, Lindahl B, Morrow DA, Clemmensen PM, et al; Joint ESC/
ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial In-
farction. Third Universal Definition of Myocardial Infarction. Circulation.
2012;126:2020–2035. doi: 10.1161/CIR.0b013e31826e1058
24. Scrucca L, Santucci A, Aversa F. Competing risk analysis using R: an easy
guide for clinicians. Bone Marrow Transplant. 2007;40:381–387.
25. Biondi-Zoccai G, Lotrionte M, Agostoni P, Abbate A, Romagnoli E,
Sangiorgi G, Angiolillo DJ, Valgimigli M, Testa L, Gaita F, et al. Adjusted in-
direct comparison meta-analysis of prasugrel versus ticagrelor for patients
with acute coronary syndromes. Int J Cardiol. 2011;150:325–331. doi:
10.1016/j.ijcard.2010.08.035
26. Chatterjee S, Ghose A, Sharma A, Guha G, Mukherjee D, Frankel R.
Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction
Downloaded from http://ahajournals.org by on December 1, 2022
Circulation. 2020;142:2329–2337. DOI: 10.1161/CIRCULATIONAHA.120.050244
Ticagrelor or Prasugrel in STEMI
of ischemic events: evidence from a network meta-analysis. J Thromb
Thrombolysis. 2013;36:223–232.
ORIGINAL RESEARCH
27. Ndrepepa G, Mehilli J, Schulz S, Iijima R, Keta D, Byrne RA, Pache J,
Seyfarth M, Schömig A, Kastrati A. Patterns of presentation and outcomes
ARTICLE
of patients with acute coronary syndromes. Cardiology. 2009;113:198–
206. doi: 10.1159/000201273
28. Velders MA, Abtan J, Angiolillo DJ, Ardissino D, Harrington RA, Hellkamp A,
Himmelmann A, Husted S, Katus HA, Meier B, et al; PLATO Investigators. Safe-
ty and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary
intervention. Heart. 2016;102:617–625. doi: 10.1136/heartjnl-2015-308963
29. Motovska Z, Hlinomaz O, Kala P, Hromadka M, Knot J, Varvarovsky I,
Dusek J, Jarkovsky J, Miklik R, Rokyta R, et al; PRAGUE-18 Study Group.
1-Year outcomes of patients undergoing primary angioplasty for myocar-
dial infarction treated with prasugrel versus ticagrelor. J Am Coll Cardiol.
2018;71:371–381. doi: 10.1016/j.jacc.2017.11.008
30. Schnorbus B, Daiber A, Jurk K, Warnke S, Koenig J, Lackner KJ, Munzel T,
Gori T. Effects of clopidogrel vs. prasugrel vs. ticagrelor on endothelial
function, inflammatory parameters, and platelet function in patients with
acute coronary syndrome undergoing coronary artery stenting: a random-
ized, blinded, parallel study. Eur Heart J. 2020;41:3144-3152.
31. Menichelli M, Neumann FJ, Ndrepepa G, Mayer K, Wöhrle J, Bernlochner I,
Richardt G, Witzenbichler B, Sibbing D, Gewalt S, et al. Age- and weight-
adapted dose of prasugrel versus standard dose of ticagrelor in patients
with acute coronary syndromes: results from a randomized trial. Ann In-
tern Med. 2020;173:436–444. doi: 10.7326/M20-1806
December 15, 2020 2337