Study Comparing Treatment Effectiveness of Guideline Indicated APT for ACS in Patients With CKD

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