Aspirin Dose Comparison in Elderly PCI Patients: 30mg vs. 75mg in Acute Coronary Syndrome (LowASA-PCI)

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.

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 Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Acute Coronary Syndrome
• Intervention / Treatment: Drug: Low-dose aspirin

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mariusz Tomaniak, PhD; Phone Number: +48 22 599-19-58; Email: mariusz.tomaniak@wum.edu.pl

Study Locations

• Poland
  • Mazowieckie Voivodenship
    • Warsaw, Mazowieckie Voivodenship, Poland, 02-097
      • Recruiting
      • 1st Department and Clinic of Cardiology, Medical University of Warsaw
      • Contact: Mariusz Tomaniak, PhD; Phone Number: +48 22 599-19-58; Email: mariusz.tomaniak@wum.edu.pl
      • Principal Investigator: Mariusz Tomaniak, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Drug: Low-dose aspirin; Implementation of low-dose aspirin (30 mg)
Other: 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.	Drug: Low-dose aspirin; Implementation of low-dose aspirin (30 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity (ASPI)	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity (ADP)	Comparison of platelet reactivity dependent on ADP (ADP test) in low-dose ASA therapy, assessed in impedance aggregometry in regards to the group treated with DAPT with standard ASA 75mg dose and level changes in individual patients.	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)	Comparison of platelet reactivity dependent on TRAP-6 protein activating the thrombin receptor (TRAP test) in low-dose ASA therapy, assessed in impedance aggregometry in regards to group treated with DAPT with standard ASA 75mg dose and level changes in individual patients.	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 (ASPI)	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 and level changes in individual patients.	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)
Bleeding time	Comparison of bleeding time (assessed with lancet method) between two groups (ASA 30mg and ASA 75mg) and among the individual patients.	Days 7, 14, and 28 of treatment 2 hours after the administration of the ASA dose
PGI2 levels	Comparison of PGI2 concentration in urine between two groups (ASA 30mg and ASA 75mg) and among the individual patients.	Measured on days 7, 14, and 28 of treatment, 2 hours after the administration of the ASA dose
TXB2 levels	Comparison of TXB2 concentration between two groups (ASA 30mg and ASA 75mg) and among the individual patients.	Days 7, 14, and 28 of treatment, 2 hours before the administration of the next ASA dose, and 2 hours after the ASA dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety monitoring	Clinical endpoints (safety monitoring) will include an assessment of the composite endpoint comprising adverse cardiovascular events (MACE): death, myocardial infarction, stroke, and non-elective coronary artery revascularization within 3 months of PCI. The frequency of bleeding complications (BARC 1,2,3,4, or 5), and the frequency of confirmed and probable stent thrombosis defined by the Academic Research Consortium will also be evaluated.	90th day

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Investigators: Principal Investigator: Mariusz Tomaniak, PhD, 1st Department and Clinic of Cardiology, Medical University of Warsaw

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: February 2, 2024
• First Posted (Actual): February 12, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: PCI; Acute Coronary Syndrome; Myocardial Infarction; Dual Antiplatelet Therapy; Very-low dose aspirin
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Myocardial Infarction; Infarction; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: LowASA-PCI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No