Acute Coronary Syndrome, Percutaneous Coronary Intervention
Conditions
Brief summary
In patients with heart attacks, the treatment of choice is to restore blood flow with percutaneous coronary intervention (PCI) (use of stents (metal meshes) to open blockages). After PCI, the standard drug treatment includes aspirin and clopidogrel. These medications block full function of the platelet cells, which are responsible for clotting. Despite their use, patients after PCI are at risk for heart attacks, sudden clotting of stents or death. A major contributor may be resistance to clopidogrel. New more potent drugs, which can overcome the resistance, are now available; however, they come with an increase chance of severe bleeding and costs. An ideal solution would be to identify at-risk patients and selectively treat them with more potent drugs, while lower-risk patients continue with clopidogrel. This type of strategy (personalized strategy) would decrease heart attacks and death (compared to clopidogrel), while also preventing bleeding complications (compared to treating all patients with the new drugs). Of resistant patients, many carry genes (inherited units) that prevent proper absorption of clopidogrel. Our group has developed and tested a new bedside genetic test, which identifies carriers of at-risk genes. However, this technique alone does not identify all at-risk patients. Consequently, we have now devised a novel tool, which combines genetics with patient characteristics to identify high-risk patients. The present study combines this new tool into a strategy for personalized treatment. Patients with heart attacks who undergo PCI will be randomly assigned to 1 of 3 strategies: a) new personalized strategy, b) clopidogrel strategy (previous standard drug) or c) ticagrelor strategy (stronger approved drug). The function of the platelet cells will be measured at 1 month to determine potential benefits. Evaluation of this new personalized strategy is important for improving patient outcomes after PCI. The hypothesis is that patients receiving a personalized strategy will have decrease risk for future heart attacks and bleeding.
Interventions
DRUGTicagrelor, Prasugrel, Clopidogrel
Sponsors
Canadian Institutes of Health Research (CIHR)
Ottawa Heart Institute Research Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients: age \>18 yrs, \< 75yrs -\> 60 kg ( since March 2015 age \>75 and \< 60 kg eligible - but prasugrel reduced to 5mg daily if randomized to personalized therapy arm) * NSTEMI undergoing PCI will be eligible
Exclusion criteria
\- Patients will be excluded if they have: i) a contra-indication for clopidogrel or prasugrel or ticagrelor (as per monograph), ii) have an intolerance to aspirin, iii) have absolute requirement for ticagrelor or prasugrel (e.g. stent thrombosis, allergic reaction to clopidogrel), iv) requirement for anti-coagulation treatment, v) a history of stroke, TIA or intracranial hemorrhage , vi) a platelet count \< 100,000/μl, vii) a known bleeding diathesis, viii) hematocrit \<30% or \>52%, ix) severe liver dysfunction, x) renal insufficiency (creatinine clearance \< 30ml/min), xi) adjuvant therapy with a glycoprotein IIbIIIa inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients in Therapeutic Window | 1 month | The primary endpoint is the proportion of patients outside of the therapeutic window in the personalized therapy (PN) arm compared to the ticagrelor (TG) arm at 1 month. The therapeutic window will be defined by platelet function values (VerifyNow P2Y12 assay - P2Y12 reaction unit (PRU) ≤ 208 (correlated with decreased ischemic outcomes) AND PRU \>= 85 (correlated with decrease bleeding). This is a surrogate of NACE (net adverse clinical events) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| P2Y12 Reaction Unit (PRU) | Baseline, Day 1, 1 month | change in PRU from baseline, day 1 to 1 month in each of the groups |
| Bleeding | 1 month, 6 months | the incidence of bleeding (defined by TIMI minor and major bleeds) among groups |
| MACE | 1 month, 6 months | combined clinical endpoint (MACE) including death, myocardial infarction(MI) or urgent target vessel revascularization (TVR) |
| Stent thrombosis | 1 month, 6 month | stent thrombosis (ARC definite/probable) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cost | 1 month, 6 months | Evaluate cost involved in each strategy |
| Genetic factors associated to outcomes | 1 month, 6 months | Exploratory analysis of other potential genetic variants to outcomes |
Countries
Canada
Outcome results
None listed