To compare clinical outcomes in patients with chronic kidney disease (CKD) presenting with an acute coronary syndrome (ACS) treated with clopidogrel or ticagrelor (both FDA approved and guideline indicated drugs for treating these patients upstream managed medically or with coronary revascularization).

The purpose of this trial is to see if ticagrelor is a better antiplatelet treatment option than clopidogrel for dual antiplatelet therapy (with aspirin) in chronic kidney disease (CKD) patients presenting with acute coronary syndrome (ACS). This study will be a comparative effectiveness trial of the two guideline-based treatments for patients with ACS with CKD, who are at a significantly higher risk of mortality and morbidity and often receive sub-optimal treatment. Ticagrelor and clopidogrel are the only two drugs in ACS that are approved for upstream (on admission) use both in CKD and non-CKD patients who are managed both medically (conservatively) or with coronary revascularization (with PCI-percutaneous coronary revascularization or CABG-coronary artery bypass graft surgery). Both of these drugs are not cleared renally and do not require dose adjustments in any stage of CKD.

Moreover, as a significant majority of CKD patients presenting with ACS are initially cared for by internists, hospitalists, and nephrologists, execution of this study at VA hospitals will strengthen collaboration between these specialties with cardiology and help adopt best practice pathways across multiple services participating in the care of this high-risk patient population. Finally, the study and its findings will for the first time provide randomized clinical trial evidence to guide the care of CKD patients with ACS who are at a high risk for both recurrent ischemia and bleeding complications.

Hypothesis to be tested: The Investigators hypothesize that use of guideline-indicated dual antiplatelet therapy (DAPT) with ticagrelor compared to clopidogrel in CKD patients presenting with ACS will reduce ischemic cardiovascular events at 1 year, additionally without a significant increase in severe bleeding (Bleeding Associated Research Consortium or BARC >3 category) over the same period. This hypothesis is based on prior subgroup analysis of published studies.

Randomized patients will be followed for 1 year from date of admission and events recorded through chart review. For patients who are event free, a phone follow-up will be done at the end of 1 year to note events, which will be recorded on the medical chart as well.

Inclusion Criteria:

• Hospital admission with non-emergent ACS qualifying diagnosis: chest pain, unstable angina or NSTEMI
• A decision to prescribe clopidogrel or ticagrelor in addition to aspirin (DAPT-dual antiplatelet therapy) by the attending physician
• A eGFR< 60 mL/min per 1.73 m.2 (as defined in the EMR or CPRS reported results)

Exclusion Criteria:

• Diagnosis of ST Elevation Myocardial Infarction (STEMI) at admission
• History of intra-cranial hemorrhage
• Bleeding requiring hospitalization, surgery, or transfusion within the past 3 months
• Life expectancy in the opinion of the provider < 6 months
• Chronic antithrombotic therapy
• Known allergy to clopidogrel or ticagrelor
• Patients on hemodialysis