Dual Antiplatelet Therapy

after PCI in Patients at

High Bleeding Risk
Outline
• Background
• Methodology
• Results
• Conclusion
2016 ACC/AHA Guidelines on Duration of Dual Antiplatelet
Therapy in Patients With Coronary Artery Disease
2021 ACC/AHA/SCAI Guideline for Coronary
Artery Revascularization
 OBJECTIVE
Conducted a RCT in patients who are at high risk for bleeding who had PCI with a
biodegradable-polymer sirolimus-eluting stent to evaluate 1 month of DAPT as
compared with a longer course of DAPT to assess clinical outcomes of ischemic events
and bleeding
II. METHODOLOGY
 Management of High bleeding Risk Patients Post Bioresorbable
Polymer Coated Stent Implantation with an Abbreviated versus
Standard DAPT Regimen (MASTER DAPT) trial

• Multicenter, randomized, open-label, noninferiority trial conducted from February

2017 to December 2019 at 140 sites in 30 countries
• Criteria
• Patients who had an acute or chronic coronary syndrome
• Had undergone PCI for one or more lesion with biodegradable-polymer sirolimus-eluting stent
(Ultimaster, Terumo)
• No further revascularization of additional lesions
• 1 or more criteria for high bleeding risk
 Criteria for High Bleeding Risk

Post-percutaneous coronary intervention (PCI), patients are at high bleeding risk if at least
one of the following criteria applies:
1. Clinical indication for treatment with oral anticoagulant (OAC) for at least 12 months
2. Recent (<12 months) nonaccess site bleeding episode(s) that required medical attention (i.e. actionable
bleeding).
3. Previous bleeding episode(s) that required hospitalization if the underlying cause had not been definitely
treated (i.e. surgical removal of the bleeding source).
4. Age ≥ 75 years
5. Systemic conditions associated with an increased bleeding risk (e.g. hematological disorders, including a
history of current thrombocytopenia defined as a platelet count <100.00/mm3 (<100 x 109/L) or any known
coagulation disorder associated with increased bleeding risk.
6. Documented anemia, defined as repeated hemoglobin levels <11g/dL or transfusion during the 4 weeks before
inclusion
7. Need for chronic treatment with steroids or nonsteroidal anti-inflammatory drugs.
8. Diagnosed malignancy (other than skin) considered at high bleeding risk including gastrointestinal,
genitourethral/renal and pulmonary.
9. Stroke at any time or transient ischemic attack in the previous 6 months
10. PRECISE-DAPT score ≥ 25
SCREENING PATIENTS PRIOR TO RANDOMIZATION

Patients who did not have any (1) ischemic complications or (2)
active bleeding events AND who (3) adhered to DAPT were
screened for inclusion in trial 30-44 days after PCI

Patients were randomly

(1) Abbreviated DAPT, or
Assigned in a 1:1 ratio to (2) Standard DAPT
either open-label

1 month = 60 days (within a window ± 14 days) after randomization

Follow-up visits 6 months = 150 days (± 14 days window) after randomization
1 year = 335 days (± 14 days window) after randomization
DAPT = aspirin + P2Y12 inhibitor
SAPT = either aspirin or P2Y12 inhibitor
For Patients on Oral Anticoagulation

In patients on OAC: Aspirin and clopidogrel were continued for at least 2 months (i.e. 3 months after index
PCI) and up to 11 months post randomization (i.e. 12 months after index PCI). Thereafter, either aspirin or
clopidogrel was continued up to 11 months post randomization (i.e. 12 months after index PCI). OAC was
continued until at least 11 months post randomization (i.e. 12 months after PCI).

The rationale for mandating clopidogrel as the only acceptable P2Y12 inhibitor in the OAC population in
both study arms came from the absence of safety and efficacy data regarding the combination of ticagrelor or
prasugrel with aspirin and OAC (as patients requiring OAC were excluded from approval RCT) and a
recommendation of Class III (i.e. not indicated) in the European guidelines.
 Anti-Platelet Dosing

3.3. Implementation of randomized study regimens

Study regimens were implemented by regular drug prescription as described above. The
investigators provided the necessary prescription to the study participants. The following are
recommended according to the current guidelines and local practice.
• Aspirin is prescribed at the standard dose of at least 75 mg/day and up to 162 mg/day.
• Clopidogrel is prescribed in standard dose of 75 mg once daily.
• Prasugrel is prescribed at the standard dose of 10 mg/day or 5 mg/day in patients weighing less
than 60 kg or who are over 75 years old. In regions where other standard dose exists (i.e.
Japan), prasugrel dosage is adjusted according to the locally approved dose.
• Ticagrelor is prescribed at the standard dose of 180 mg/day (90 mg b.i.d.).
 PRIMARY OUTCOMES
• Net adverse clinical events
= composite of death from
any cause, myocardial
infarction, stroke, or major
bleeding

• Major adverse cardiac or

cerebral events
= Composite of death from
any cause, myocardial
infarction, or stroke

• Major or clinically relevant

nonmajor bleeding,
occurring between
randomization and 335 days
 SECONDARY OUTCOMES

Secondary outcomes
• Individual components of 3 primary outcomes
• Composite of death from cardiovascular causes, myocardial infarction, or stroke
• Death from cardiovascular or non-cardiovascular causes
• Definite or probably stent thrombosis
• All bleeding events
 STATISTICAL ANALYSIS
• Determined by difference in cumulative incidence at 335 days (abbreviated-therapy group
minus standard-therapy group)
• Primary analyses of (1) net adverse clinical events and (2) major adverse cardiac and
cerebral events were performed in per-protocol population = excluded patients who did
not meet selection criteria or did not implement protocol-mandated therapy within 14 days
after randomization
• Primary analysis of bleeding outcomes was performed in intention-to-treat population,
included all patients who had undergone randomization
 RESULTS
From February 28. 2017, to December 5, 2019 a total of n = 5204 patients underwent
screening.
• A total of 4579 patients (88%) were randomly assigned to either abbreviated-therapy
group (2295 patients) or standard-therapy group (2284 patients)
• Median time from the index PCI to randomization was 34 days in each group
Was randomization effective?
How high risk was the patient population?
Procedural characteristics of PCI were similar between groups
Treated lesion characteristics were similar between groups
Clopidogrel was most frequently used
P2Y12 inhibitor in standard-therapy
group and was most frequently used
monotherapy in abbreviated-therapy
group at time of randomization and
thereafter
Abbreviated DAPT was non-inferior to standard DAPT in
terms of net adverse clinical events
Abbreviated DAPT was non-inferior to standard DAPT in
terms of major adverse cardiac or cerebral events
Abbreviated DAPT was superior to standard DAPT in terms
of major or clinically relevant nonmajor bleeding
Secondary Outcomes
Subgroup analysis for net adverse clinical events
Subgroup analysis for major or nonmajor bleeding
IV. CONCLUSION
Discontinuation of DAPT after 1 month of PCI was vs.
standard DAPT therapy
 STRENGTHS & LIMITATIONS
Strengths
• 1st trial in high bleeding risk population powered to demonstrate non-inferiority for ischemia
• Did not exclude patients with acute coronary syndrome nor did they limit number, location, or
complexity of treated lesions
Limitations
• Unclear if results can be extended to patients who are not at high bleeding risk
• Unclear if results can be extended to other stent devices (biodegradable-polymer-sirolimus-
eluting stent)
• Excludes patients from randomization that had events during first month following PCI
potentially resulting in selection bias
• Variability in the type of single antiplatelet therapy used in abbreviated treatment group
 Take Home Points
• 1 month of DAPT may preserve ischemic benefits and reduce bleeding
risk in patients with high bleeding risk following PCI with DES