Patients with an indication for antithrombotic therapy are one of the most vulnerable and high-risk populations with SAB. S. aureus virulence is partly mediated through platelet injury and through virulence factors which act along the thrombotic pathways. No RCT thus far has ever studied antithrombotic therapies to improve outcomes for SAB patients.

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In many regions, clopidogrel bisulfate is indicated for the secondary prevention of atherothrombotic events in patients with documented atherosclerosis. While both aspirin and clopidogrel can be used to reduce cardiovascular risk, clopidogrel's mechanism of action may provide a benefit in the treatment of S. aureus infection. Platelets engage in the clearance of S. aureus through secretion of antimicrobial peptides, phagocytosis of bacteria, ad recruitment of lymphocytes to augment the immune response. Clopidogrel inhibits P2Y12 on the surface of platelets and is mechanistically important in the pathogenesis of S. aureus. Pharmacologic P2Y12 inhibition provides protection from lethal S. aureus challenge in murine modules. A multi-year observational study of SAB at VA hospitals in the US reported that clopidogrel users were less likely to die in a propensity score adjusted analysis. (30 day mortality HR was 0.43 [95% CI, 0.19 to 0.98]).

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Patients are eligible for this domain if they meet all platform-level inclusion and none of the platform-level exclusion criteria AND all of the domain-level inclusion and none of the domain-level exclusion criteria.

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Domain-specific inclusion criteria:

• Patient is taking aspirin for secondary prevention of cardiovascular disease (coronary, cerebrovascular, or peripheral vascular disease)
  
  • Patients taking aspirin for primary prevention or other indications not listed are not eligible as aspirin and clopidogrel are not interchangeable in this clinical scenario because clopidogrel does not have an approved indication

Domain-specific exclusion criteria:

• Active bleeding (as determined by site investigator after discussion with treating team)
• Anticipated major cardiac surgery, neurosurgery, or spine surgery within the next 3 days
• Pregnancy (confirmed and excluded based on testing) or lactation
• Known receipt of clopidogrel, prasugrel, or ticagrelor within the last month
• Concominant receipt of a direct oral anticoagulant (apixaban, rivaroxaban, edoxaban, dabigatran)
• Allergy to cllpidogrel

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Patients will be randomized to one of the following:

• Continue aspirin
• Change to clopidogrel. Clopidogrel to be given at 75mg PO daily without a loading dose or any adustment for renal function for 90 days

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Treatment interruption for procedures, bleeding, or surgery are managed according to local practices and policies. These interruptions are not considered to be a protocol deviation

Lead Investigator: Dr. Emily G. McDonald

Email: emily.mcdonald@mcgill.ca