Very Low-dose Aspirin (30mg) vs. Standard Low-dose Aspirin (75mg) Among Patients Aged 65 Years or Above Undergoing PCI for Acute Coronary Syndrome: an Open-label Randomized Crossover Design Trial.
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Platelet reactivity (ASPI)
Study Overview
Brief Summary
Elderly patients undergoing percutaneous coronary intervention (PCI) face a high risk of both ischemic and hemorrhagic complications necessitating antiplatelet therapy. Previous data indicate that even at a dose of 20-30 mg/day, aspirin (ASA) allows almost complete inhibition of thromboxane (TX) A2 biosynthesis in healthy volunteers. However, ASA at a dose of 30 mg/day has not been evaluated in the acute phase of myocardial infarction or among elderly patients, where it may achieve an optimal balance between bleeding risk and ischemic complications.
This randomized study will include 40 patients over 65 years undergoing PCI for acute coronary syndrome (ACS). It compares a new dual antiplatelet therapy (DAPT) strategy consisting of a P2Y12 antagonist (ticagrelor) and ASA at a very low dose of 30 mg/day (n=20) against the current standard treatment (P2Y12 antagonist and ASA at a dose of 75 mg) (n=20) in the control group.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •age above 65 years
- •acute coronary syndrome (ACS)
- •positive results for myocardial necrosis markers (troponins)
- •undergoing successful coronary angioplasty with stent implantation within the last 24-48 hours before enrollment in the study
- •dual antiplatelet therapy (DAPT) containing ticagrelor
Exclusion Criteria
- •indications other than ACS and PCI for DAPT use
- •history of stent thrombosis during the course of DAPT
- •planned subsequent coronary artery revascularization
- •planned surgery requiring suspension or interruption of DAPT
- •planned discontinuation of ASA or P2Y12 antagonist during the study
- •use of doses other than 75 mg ASA once daily or non-use of a P2Y12 inhibitor - intake of diuretic drugs (e.g., loop diuretics, thiazides, potassium-sparing drugs)
- •intake or planned intake of oral anticoagulants, parenteral antithrombotic therapy (e.g., unfractionated heparin, low molecular weight heparin, bivalirudin), glycoprotein IIb/IIIa inhibitors (e.g., abciximab, tirofiban), fibrinolytic agents (e.g., tissue plasminogen activator), or nonsteroidal anti-inflammatory drugs
- •history of acute or chronic liver disease; severe kidney disease requiring dialysis; pregnancy; comorbidities associated with a predicted life expectancy of less than 1 year
- •any other condition deemed by the investigator to impact hemostasis, coagulation, bleeding risk, or the ability to adhere to the study protocol; receiving a strong inhibitor of cytochrome P450 3A, simvastatin or lovastatin at doses greater than 40 mg per day, a narrow therapeutic index cytochrome P450 3A substrate (e.g., cyclosporine or quinidine), or a strong inducer of cytochrome P450 3A (e.g., rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital)
- •hemodynamic instability; clinical condition preventing obtaining informed consent.
Arms & Interventions
Very low-dose aspirin first
Patients will receive ASA 30mg per day (in the morning) for 14 days, followed by ASA 75mg per day (in the morning) for the next 14 days.
All the participants will receive standard maintenance dose of ticagrelor 90mg twice a day as part of the DAPT therapy. All the participants will receive the loading dose of ASA 300mg before the PCI procedure.
Intervention: Low-dose aspirin (Drug)
Standard low-dose aspirin first
Patients will receive ASA 75mg per day (in the morning) for 14 days, followed by ASA 30mg per day (in the morning) for the next 14 days.
All the participants will receive standard maintenance dose of ticagrelor 90mg twice a day as part of the DAPT therapy. All the participants will receive the loading dose of ASA 300mg before the PCI procedure.
Intervention: Low-dose aspirin (Drug)
Outcomes
Primary Outcomes
Platelet reactivity (ASPI)
Time Frame: 14th day of treatment, 2h before ASA 30mg dose (through effect), and 2h after ASA 30mg dose (peak effect), in regards to group treated with DAPT with standard ASA 75mg dose after 14 days of therapy
Comparison of platelet reactivity dependent on arachidonic acid (ASPI test) in low-dose ASA therapy, assessed in impedance aggregometry in regards to group treated with DAPT with standard ASA 75mg dose after 14 days of therapy.
Secondary Outcomes
- PGI2 levels(Measured on days 7, 14, and 28 of treatment, 2 hours after the administration of the ASA dose)
- Platelet reactivity (ADP)(Days 7, 14, and 28 of treatment, 2 hours before the administration of the next ASA dose (pre-dose - representing the trough effect), and 2 hours after the ASA dose (post-dose - representing the peak effect))
- Platelet reactivity (TRAP-6)(Days 7, 14, and 28 of treatment, 2 hours before the administration of the next ASA dose (pre-dose - representing the trough effect), and 2 hours after the ASA dose (post-dose - representing the peak effect))
- Bleeding time(Days 7, 14, and 28 of treatment 2 hours after the administration of the ASA dose)
- Platelet reactivity (ASPI)(Days 7, and 28 of treatment, 2 hours before the administration of the next ASA dose (pre-dose - representing the trough effect), and 2 hours after the ASA dose (post-dose - representing the peak effect))
- TXB2 levels(Days 7, 14, and 28 of treatment, 2 hours before the administration of the next ASA dose, and 2 hours after the ASA dose)
Investigators
Mariusz Tomaniak
Tomaniak Mariusz MD PhD Assoc. Prof.
Medical University of Warsaw