ticagrelor vs clopidogrel effect on mfr in cad population

Conditions: Coronary Artery Disease

Summary: ticagrelor is one of 3 anti-platelet medications used in patients with acute coronary syndrome (acs) to prevent further clot formation and further ischemic damage to myocardial tissue. overall benefits of one drug over the other is neutral in this generally unstable population. in pre-clinical trials, ticagrelor showed secondary effects, involving the release of adenosine to heart muscle where the demand for blood was increased due to a stress condition. blood flow was increased, potentially preventing potential damage. this study will compare ticagrelor, currently only approved for use in acs patients, against clopidogrel by measuring the myocardial blood flow(mbf) during stress to validate this phenomenon. the effect on blood flow will be measurable by using two specific doses of adenosine as the pharmacologic stress and correlating with measurements of blood flow using positron emission tomography (pet) nuclear imaging. this study hypothesizes that the increase in mbf during intermediate dose adenosine infusion will be greater in ticagrelor treated subjects compared to clopidogrel treated subjects


Eligibility criteria:
inclusion criteria: 1. age ≥ 18 years old 2. stable coronary artery disease on stable medical treatment. 3. bmi equal to or less than 30 kg/m2 4. no clinically significant abnormalities in baseline laboratory work 5. no clinically significant arrhythmias on baseline 12-lead electrocardiogram 6. female subjects must be post-menopausal, surgically sterilized or have negative urine beta human chorionic gonadotropin pregnancy test at initial screening and maintain effective contraceptive methods throughout the trial and for 7 days following the end of dosing treatment. exclusion criteria: 1. any contraindication against the use of clopidogrel, ticagrelor and/or asa. 2. oral anticoagulation therapy. 3. history of intracranial bleeding. 4. recent or active pathological bleeding, such as peptic ulcer. 5. moderate or severe hepatic impairment. 6. history or risk of bradycardia. 7. known second- or third-degree av block without pacemaker 8. dyspnea (nyha iii/iv), wheezing asthma or copd. 9. coronary artery bypass graft (cabg) surgery within 90 days prior to screening or at any time after consent. 10. percutaneous coronary intervention (pci) within 90 days prior to screening or at any time following consent. 11. acute myocardial infarction or acute coronary syndrome within 60 days prior to screening or at any time following consent. 12. any scheduled surgery during the trial period, including dental. 13. concomitant therapy with strong cytochrome cyp 3a inhibitor or inducer. 14. recent use of dipyridamole, dipyridamole-containing medications (e.g. aggrenox) 15. known hypersensitivity to the investigational drug or any of its components. 16. known hypersensitivity to adenosine. 17. lactose intolerance 18. breastfeeding or pregnancy. 19. claustrophobia or inability to lie still in a supine position 20. unwillingness to provide informed consent

Keywords: myocardial blood flow myocardial perfusion imaging myocardial blood flow reserve positron emission tomography adenosine ticagrelor clopidogrel