Coronary Artery Disease, Myocardial Infarction
Conditions
Keywords
1-year post myocardial infarction, P2Y12 inhibitor, antiplatelet regimen
Brief summary
In patients after myocardial infarction (MI) (heart attacks) and treated with percutaneous coronary intervention (PCI), the current standard is dual antiplatelet therapy (DAPT), with aspirin and a P2Y12 receptor inhibitor, for 1 year of treatment. At 1 year, there are several options including: i) Ongoing DAPT (with aspirin and ticagrelor), ii) Selective treatment use of a P2Y12 inhibitor based on risk profiles. This study is a pilot vanguard study to evaluate several strategies for choosing anti-platelet regimen among patients post MI and PCI at 1 year.
Detailed description
The present study is a pilot/vanguard 3-arm study that seeks to compare 3 possible strategies for patients that are 1 year post MI and PCI. The 3 randomized groups include: i) aspirin and ticagrelor 60 mg twice daily, ii) monotherapy with ticagrelor 60 mg twice daily and iii) a personalized arm (PA), where patients will get selective therapy based on demographic and genetic risks. The PA group will use a modified DAPT score based on patient demographics to decide whether P2Y12 treatment is warranted. For those patients where treatment is warranted, a bedside genetic test will be used to determine whether they are carriers of at-risk genotypes, which put them at risk for under-responsiveness to clopidogrel (one of the specific P2Y12 inhibitors). Those identified as carriers will be treated with ticagrelor while non-carriers will be treated with clopidogrel. The study will act as a vanguard study to prove feasibility of enrollment and document overall bleeding rates. The long-term goal of the study is determine whether a personalized approach will decrease bleeding versus an approach of DAPT with ticagrelor and versus an approach with ticagrelor monotherapy.
Interventions
DRUGActive Comparator: Dual Antiplatelet Therapy (DAPT) - Aspirin 81 mg + Ticagrelor 60mg twice daily
DAPT with aspirin and ticagrelor
DRUGTicagrelor Monotherapy: Ticagrelor 60 mg twice daily
Ticagrelor monotherapy
DRUGPersonalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily
Personalized therapy based on risk score and genotyping
Sponsors
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Double (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \>50 years old at 1-year after myocardial infarction (non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI)) during which they had percutaneous coronary intervention (PCI) * Compliant with dual antiplatelet therapy (DAPT) for ≥ 1 year without an ischemic or bleeding complication after PCI * Still on DAPT regimen at enrollment * Patients must have 1 of the following atherothrombotic risk enrichment criteria: i) Age≥ 65 years ii) Diabetes iii) 2nd Prior MI (\>1 year ago) iv) multi-vessel coronary disease v) creatinine clearance (CrCl) \<60 mL/min.
Exclusion criteria
* Intolerance to ticagrelor or clopidogrel * \>18 months post percutaneous coronary intervention (PCI) and myocardial infarction (MI) * Requirement of a P2Y12 inhibitor * Requirement of oral anticoagulation * Take concurrent CYP3A inducing drugs which may interact with ticagrelor (e.g. anti-epileptic drugs) * History of stroke, TIA or intracranial bleed * Recent GI bleed or major surgery * Life expectancy of \< 1 year * Platelet count \< 100,000/μl * Bleeding diathesis * On dialysis * Severe liver disease * At risk for bradycardia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding Academic Research Consortium (BARC) Bleeding | 2 years post randomization | BARC bleeding types 2,3 or 5 |
| Feasibility for Patient Enrollment and Follow-up - measured by number of patients enrolled and followed over 2 years | 2 years | Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Thrombolysis in Myocardial Infarction (TIMI) bleeding | 1-3 years post randomization | Incidence of TIMI bleeding - major and minor |
| Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding | 1-3 years post randomization | Incidence of GUSTO bleeding - severe, moderate, mild |
| All Cause Mortality | 1 - 3 years post randomization | Death due to any cause |
| Cardiovascular Mortality | 1 -3 years post randomization | Death due to cardiovascular cause |
| Myocardial Infarction | 1 -3 years post randomization | Myocardial infarction as defined by the 3rd universal definition on infarction |
| Stroke | 1-3 years | Strokes defined as focal neurological deficit of \>24 hrs and confirmed by imaging |
| Stent Thrombosis | 1 - 3 years post randomization | Probable and definite stent thrombosis per ARC definition |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORDerek YF So, MD FRCPC
Ottawa Heart Institute Research Corporation
Outcome results
None listed