This study evaluates how aspirin, clopidogrel and ticagrelor work in people with chronic kidney disease (CKD) compared to people with normal kidneys. In the first part of the study, half of CKD participants will be randomly assigned to ticagrelor and aspirin, while the other half will be assigned to clopidogrel and aspirin in a blinded fashion. The treatment duration will be two weeks. After recruiting CKD participants the investigator will recruit controls with normal kidney function that will receive only ticagrelor and aspirin for two weeks.

It is known that people with chronic kidney disease (CKD) are at higher risk to have heart and blood vessel problems like heart attack and stroke compared to people that do not have kidney problems. Aspirin, clopidogrel and ticagrelor prevent blood clots building up in the vessels. If a blood clot is present in one vessel, it could stop oxygen carrying blood to get to a specific organ, and that could cause problems like heart attack or stroke. There is very little knowledge about the way this group of medicines works in people with chronic kidney disease as well as it works in individuals with normal kidney function.

Inclusion Criteria:

1. Males and females, aged 18-91 years
2. Ability to understand and sign informed consent after the nature of the study has been fully explained
3. CKD participants: Non-dialysis CKD patients: Presence of CKD with an estimated GFR of <30 mL/min/1.73 m2 for a period of ≥3 months, as defined by the National Kidney Foundation (NKF) and determined with the CKD-EPI creatinine-based formula
4. Controls with normal kidney function: participants with an estimated GFR >90 mL/min/1.73 m2 as determined by the CKD-EPI creatinine-based formula and a urine albumin-to-creatinine ratio <30 mg/g as defined by the National Kidney Foundation

Exclusion Criteria:

• No healthcare power of attorney to sign informed consent

• Unwillingness or inability to participate in the protocol or comply with any of its components.

• Subjects unable or unwilling to stop taking:

  • Aspirin and other antithrombotic agents, like cilostazol, ranolazine, aggrenox, prasugrel, warfarin, xarelto, pradaxa, eliquis.
  • Glycoprotein IIb/IIIa antagonist (abciximab-ReoPro, eptifibatide-Integrilin, tirofiban-Aggrastal)
  • NSAIDs and PPIs
  • Fish oil, Vitamin E and herbal supplements

• Acute kidney injury superimposed on CKD

• Kidney transplant or any other solid organ transplant recipient

• End-stage kidney disease on maintenance dialysis (peritoneal or hemodialysis)

• Nephrotic syndrome defined as nephrotic range proteinuria, hypoalbuminemia, hyperlipidemia and generalized edema

• Recent hospitalization or surgery <3 months

• Acute coronary or cerebrovascular event in the last 12 months

• Blood dyscrasias, active bleeding, or bleeding diathesis

• Gastrointestinal bleeding in the last 6 months

• Recent treatment (<30 days) with a glycoprotein IIb/IIIa antagonist (Integrelin).

• Hematocrit <25%, white blood cell count >20,000/μL, or platelet count <50,000/μL

• Any active malignancy or liver disease.

• Pregnancy

• Positive urine pregnancy test in a woman of childbearing potential prior to study entry. A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

• Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

De-identified data for all primary and secondary outcome measures will be uploaded on clinicaltrials.gov website.

2 years after study closure indefinitely

Adverse events reported during the 2 weeks of treatment from baseline visit to the final visit

CKD participants will be randomly assigned into one of the 2 study groups: ticagrelor (90 mg) one pill in the morning and one pill in the evening, or, clopidogrel (75 mg) one pill in the morning + placebo one pill in the evening. Placebo looks like the study drug but has no medicine in it. Neither participant nor the study personnel will know about allocation. The study drugs will look the same, except aspirin pill which will be dispensed to everyone in an open label manner.

There is no masking for control with normal kidney function. Participants will be asked to take open label ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) and aspirin 81 mg/day.