Personalization of Long-Term Antiplatelet Therapy – RAPID EXTEND


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.

Full Title of Study: “Personalization of Long-Term Antiplatelet Therapy Using a Novel Combined Demographic/Pharmacogenomic Strategy – The RAPID EXTEND Randomized Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2022

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.


  • Drug: Active Comparator: Dual Antiplatelet Therapy (DAPT) – Aspirin 81 mg + Ticagrelor 60mg twice daily
    • DAPT with aspirin and ticagrelor
  • Drug: Ticagrelor Monotherapy: Ticagrelor 60 mg twice daily
    • Ticagrelor monotherapy
  • Drug: Personalized Therapy Arm: Aspirin 81 mg or Ticagrelor 60mg twice daily or Clopidogrel 75 mg once daily
    • Personalized therapy based on risk score and genotyping

Arms, Groups and Cohorts

  • Active Comparator: DAPT – Aspirin and Ticagrelor
    • As per results of the PEGASUS trial, patients will be treated with aspirin 81mg daily and ticagrelor 60mg twice daily
  • Experimental: Ticagrelor Monotherapy
    • Patients will only receive ticagrelor 60mg twice daily.
  • Experimental: Personalized Therapy Arm
    • Patients allocated to the personalized arm (PA) will have a DAPT score calculated. For those with a score of < 2, only aspirin at 81 mg daily will be prescribed. For those with a score of ≥ 2, P2Y12 inhibitor choice will be dependent on carrier status of CYP2C19 LOF alleles. Heterozygous or homozygous carriers will receive be prescribed ticagrelor 60mg twice daily and non-carriers with will be prescribed clopidogrel 75mg daily.

Clinical Trial Outcome Measures

Primary Measures

  • Bleeding Academic Research Consortium (BARC) Bleeding
    • Time Frame: 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
    • Time Frame: 2 years
    • Number of participants enrolled and followed: Target of 260 patients over 2 years with over 90% follow-up (Vanguard Study target)

Secondary Measures

  • Thrombolysis in Myocardial Infarction (TIMI) bleeding
    • Time Frame: 1-3 years post randomization
    • Incidence of TIMI bleeding – major and minor
  • Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding
    • Time Frame: 1-3 years post randomization
    • Incidence of GUSTO bleeding – severe, moderate, mild
  • All Cause Mortality
    • Time Frame: 1 – 3 years post randomization
    • Death due to any cause
  • Cardiovascular Mortality
    • Time Frame: 1 -3 years post randomization
    • Death due to cardiovascular cause
  • Myocardial Infarction
    • Time Frame: 1 -3 years post randomization
    • Myocardial infarction as defined by the 3rd universal definition on infarction
  • Stroke
    • Time Frame: 1-3 years
    • Strokes defined as focal neurological deficit of >24 hrs and confirmed by imaging
  • Stent Thrombosis
    • Time Frame: 1 – 3 years post randomization
    • Probable and definite stent thrombosis per ARC definition

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 50 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ottawa Heart Institute Research Corporation
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Derek YF So, MD FRCPC, Principal Investigator, Ottawa Heart Institute Research Corporation


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