The RAPID (Reassessment of Anti-Platelet therapy using InDividualized Strategies) Team

Derek So, MD, currently leads the RAPID research team, which consists of a group of interventional cardiologists, cardiovascular surgeons, anesthesiologists, pharmacologists, basic scientists and epidemiologists with a common interest in pursuing research in the personalization of anti-platelet regimen among patients with acute coronary syndromes and coronary disease.

Capitalizing upon expertise in genomics, proteomics, platelet testing and biostatistics, the RAPID group endeavours to: i) enhance mechanistic understanding of risk/benefits of novel anti-platelet therapy strategies, ii) develop novel strategies focused on personalization to minimize risks and costs to individuals/society, iii) develop novel tools to identify at-risk patients, iv) provide knowledge translation with an aim of incorporation of personalized anti-platelet strategies into guidelines.

Notably, the RAPID group has received Heart and Stroke Foundation of Canada (HSFC) and Canadian Institutes of Health Research (CIHR) grants in the field of personalized anti-platelet therapy including: OSA-CUPID, RAPID-AGAP, RAPID MANAGE and RAPID TITRATE CABG studies. In a seminal study, RAPID GENE (Lancet), we co-developed the first bedside genetic test and proved utility in personalizing antiplatelet drugs, resulting in knowledge translation to researchers and policy makers (>130 citations, stimulating application in other areas of medicine).

The RAPID STEMI (Pharmacogenomics Journal – Nature) study has further proved the application of point-of-care genetic testing using 3 SNPs in ACS patients; this assay is currently used clinically in parts of Europe and has recently received FDA approval for use. Accordingly, this has spurred ongoing international studies such as TAILOR-PCI (led by the Mayo Clinic), which will enrol over 5,000 patients world-wide. Data from our RAPID-AGAP study has enabled development of a combined genetic/demographic risk score (currently being evaluated in the ongoing CIHR sponsored RAPID MANAGE study).

Through collaborations with industry, the RAPID group has enabled the University of Ottawa Heart Institute and the Montreal Heart Institute to be the only centres in Canada to have dedicated labs for point-of-care genetic and platelet function testing with unique state-of-the-art equipment including: Spartan CYP2C19 genetic testing, Verify-Now, Multiplate, Aggredyne and VASP platelet analyzers.  

Projects 

A Randomized Pilot Vanguard Study of Patients with ACS Treated with Ticagrelor Requiring Coronary Artery Bypass Surgery

(RAPID TITRATE CABG) – recruitment to start fall 2015:

  • Multi-centred randomized study at the University of Ottawa Heart Institute and the Montreal Heart Institute
  • Comparison of an early vs. delayed approach to CABG among ACS patients initially treated with ticagrelor
  • Primary outcome: feasibility and safety of an early CABG strategy (with clinical outcomes to be used in a future large scale multi-centred study)
  • Key secondary outcomes: platelet function testing for evaluation of mechanisms of benefits of an early CABG strategy

A Pharmacodynamic Study of a Personalized Strategy for P2Y12 Inhibition versus Ticagrelor in Reducing Ischemic and Bleeding Risk

(RAPID MANAGE – Clinicaltrials.gov: NCT02044146) - recruiting:

  • Multi-centred randomized study at the University of Ottawa Heart Institute and the Montreal Heart Institute
  • Comparison of novel personalized strategy (combining pharmacogenomics [CYP2C19*2, *3] and demographic factors to identify patients at high risk for high on-treatment platelet reactivity) vs. ticagrelor in patients with NSTE-ACS
  • Primary outcome: proportion of patients achieving therapeutic window as measured by VerifyNow P2Y12 assay (PRU between 82 and 208)
  • Key secondary outcomes: therapeutic window measured with Aggredyne and multiplate platelet assays

Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not?

(OPTICROSS – clinicaltrials.gov: NCT02054663) – recruitment completed:

  • Randomized study to evaluate optimal strategy to transition between ticagrelor to clopidogrel among patients with ACS requiring a switch from ticagrelor to clopidogrel
  • Primary outcome: PRU measured (by VerifyNow P2Y12 assay) at 72 hours after initiation of strategy
  • Key secondary outcomes: high on-treatment platelet reactivity in first 72 hours

ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy in Patients with ST-Elevation Myocardial Infarction (RAPID STEMI)

– completed.  Pharmacogenomics J. 2015 Apr

  • Randomized study evaluating a pharmacgenomic strategy in patients with STEMI
  • Patients randomized to high-dose clopidogrel vs. personalized strategy (carriers of CYP2C19*2, ABCB1TT switched to prasugrel, while non-carriers continued with clopidogrel).  Proof-of-concept to identify 3 genetic variants concurrently (CYP2C19*2,*17 and ABCB1TT).
  • Primary outcome: proportion with high on-treatment platelet reactivity at 1 month

ReAssessment of Anti-Platelet Therapy Using an InDividualized Strategy based on GENetic Evaluation (RAPID GENE)

– completed. Lancet. 2012 May 5; 379(9827):1705-11. Epub 2012 Mar 29.

  • Design and proof-of-concept of the first bedside genetic test in clinical medicine
  • Randomized study of patients with stable CAD or NSTE-ACS undergoing PCI
  • Patients randomized to standard therapy vs. personalized approach (carriers of CYP2C19*2 switched to prasugrel)
  • Primary outcome: proportion with high on-treatment platelet reactivity at 1 week

The above studies utilize our state-of-the-art pharmacogenomics and platelet function laboratory, which uniquely is one of two institutions in Canada with the capabilities to perform these tests.

Publications 

See current publications list at PubMed.
See Research Gate profile

Selected publications:

  1. Malhotra N,  Abunassar J,. Wells GA,  McPherson R, Fu A, Hibbert B, Labinaz M,  Le May M, Dick A,  Glover C, Froeschl M, Marquis JF, Tran L, Bernick J, Chong AY, So D.  on behalf of the CArdiovascular Percutaneous Intervention TriAL (CAPITAL) investigators. A Pharmacodynamic Comparison of a Personalized Strategy for Anti-platelet Therapy versus Ticagrelor in Achieving a Therapeutic Window. Int J Cardiol. 2015.
  2. So DY,   Wells GA,  McPherson R,   Labinaz M,   Le May MR,   Glover C,    Dick AJ, Froeschl M, Marquis JF,   Gollob MH,   Tran L,   Bernick J, Hibbert B,   Roberts JD   on behalf of the CAPITAL investigators. A Prospective Randomized Evaluation of a Pharmacogenomic Approach to Antiplatelet Therapy among Patients with ST-Elevation Myocardial Infarction: The RAPID STEMI Study. Pharmacogenomics J. 2015 Apr
  3. Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M, Dick A, Marquis JF, O’Brien E, Goncalves S, Druce I, Stewart A, Gollob MH, So DYF. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomized, proof-of-concept trial. The Lancet. 2012 May 5; 379(9827):1705-11.
  4. So DYF, Roberts, JD. Overcoming Obstacles in Pharmacogenomic Strategies for Antiplatelet Drugs – Are We RAPID enough? Pharmacogenomics. July 2012; 13(10):1105-8.
  5. Goncalves SC, Labinaz M, Le May M, Glover C, Froeschl M, Marquis JF, O'Brien E, Shukla D, Ruchin P, Sookur D, Ha A, So D. Usefulness of mean platelet volume as a biomarker for long-term outcomes after percutaneous coronary intervention. Am J Cardiol. 2011 Jan 15;107(2):204-9.
  6. So DY, Cook EF, Le May M, Glover C, Williams W, Ha A, Davie RF, Froeschl M, Marquis JF, O’Brien E, Labinaz M. Association of Aspirin Dosage to Clinical Outcomes after Percutaneous Coronary Intervention: Observations from the Ottawa Heart Institute PCI Registry. J Invasive Cardiol. 2009. 21(3):121-7.
  7. Le May MR, So DY, Dionne R, Glover CA, Froeschl MP, Wells GA, Davies RF, Sherrard HL, Maloney J, Marquis JF, O’Brien ER, Trickett J, Poirer P, Ryan SC, Ha A, Joseph PG, Labinaz M. A Citywide Protocol for Primary PCI in ST-segment Elevation Myocardial Infarction. New Engl J Medicine. 2008. 358(3):231-40
Staff 

Current Team Members

Team Leader:
Derek So, MD, Interventional Cardiology

Members:
Aun Yeong Chong, MD, Interventional Cardiology
Benjamin Hibbert, MD, Interventional Cardiology
Michel Le May, MD, Interventional Cardiology
Marino Labinaz, MD, Interventional Cardiology
Chris Glover, MD, Interventional Cardiology
Ruth McPherson, MD, PhD, Genetics and Atherogenomics
George A. Wells, PhD, Epidemiology
Fraser Rubens, MD, Cardiac Surgery
Marc Ruel, MD, Cardiac Surgery
Vincent Chan, MD, Cardiac Surgery
Jean-Yves Dupuis, MD, Anesthesia
Michael Bourke, MD, Anesthesia

Research Assistants and Coordinators:
Lyne Stuewe (RN) – Nurse Coordinator
Cheryl Charlebois (RN) – Nurse Coordinator
Colleen Chilton (RN) – Nurse Coordinator

Research Fellows:
Kuljit Singh, MD

Collaborating Investigators

Jean-François Tanguay. MD (Interventional Cardiology, Montreal Heart Institute)
Marie Lordkipanidze, MD (Pharmcology, Montreal Heart Institute)
Louis Perrault, MD (Cardiac Surgery, Montreal Heart Institute)

Previous Research Fellows

Joseph Abunassar, MD – Johns Hopkins University
Ali Pourdjabbar, MD – University of San Diego
Jason Roberts, MD – Western University
Sandro Goncalves, MD – Federal University of Rio Grande do Sul

Positions Available 

Opportunities:

To enquire about available positions, please submit your CV with a cover letter detailing what you can bring to the team.

Contact:
dso@ottawaheart.ca

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