Platelets are parts of your blood that stick together to help form a clot. The stickier your platelets are, the greater your chance of having a heart attack. A clot in the wrong place can lead to a heart attack or stroke. Ticagrelor (Brilinta) keeps platelets from sticking together and it helps people from having a heart attack. The American College of Cardiology has recommended a combination of aspirin and Brilinta as one of the best treatments for the prevention of heart attacks, and death in patients who have had a heart attack or coronary stents. However, it is unknown if Brilinta may improve its work to keep platelets from sticking together giving a loading dose in patients already treated with Brilinta. A loading dose is a one-time increased dose of the same drug. The purpose of this study is to demonstrate whether the platelets of patients treated with Brilinta become less sticky when Brilinta is re-loaded.

A higher degree of platelet inhibition remains the goal of peri-interventional and long-term anti-thrombotic therapy in patients with coronary artery disease. Previous observations have shown that in patients on clopidogrel therapy undergoing percutanoues coronary intervention who get re-loaded with clopidogrel obtain enhanced platelet inhibition. Ticagrelor represents a new class of nonthienopyridine platelet inhibitors designed to address the limitations of current oral antiplatelet therapy, which has been recently approved for clinical use. However, to date it is unknown if greater inhibition of platelet aggregation can be achieved by adding a ticagrelor loading dose in patients already on maintenance ticagrelor therapy (90 mg twice daily). In addition, how to manage patients undergoing coronary interventions already on chronic ticagrelor therapy with regards to ticagrelor loading is an emerging clinical question which has yet to be explored. Therefore, understanding the pharmacodynamic implications of a ticagrelor re-load strategy in patients on already on chronic ticagrelor therapy is warranted. The scope of the present study is to evaluate the impact of ticagrelor re-load in patients on chronic ticagrelor therapy. A total of 60 patients will be randomized into one of the following two arms of treatment: 1) 90 mg of ticagrelor; 2) 180 mg of ticagrelor. Pharmacodynamic assessments will be performed at baseline, 1-hour and 4-hour after dosing administration. Comparison between baseline and 4-hour values in term of platelet P2Y12 reactivity index determined by whole blood vasodilator-stimulated phosphoprotein will be the primary end-point of the study. Secondary endpoints will include other pharmacodynamic measures.

Inclusion Criteria:

1. Patients with a clinical indication to be on ticagrelor therapy (90mg/bid)
2. On treatment with ticagrelor 90mg twice daily for at least 14 days
3. Age between 18 to 80 years
4. On aspirin <100mg/day

Exclusion Criteria:

1. History of intracranial bleeding
2. Severe hepatic impairment (ALT >2.5 times the upper limit of normal)
3. Active bleeding or propensity to bleed
4. Recent antiplatelet treatment (< 14 days) with a glycoprotein IIb/IIIa antagonist

6. Platelet count <80x106/mL 7. Hemodynamic instability 8. Serum creatinine <30 mL/min 9. On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban) 10. Patients with sick sinus syndrome or II or III degree AV block without pacemaker protection 12. Drugs interfering CYP3A4 metabolism (to avoid interaction with Ticagrelor): ketoconazole, itraconazole, voriconazole, clarithromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromizycin 13. Hemoglobin < 10g/dL 14. Pregnant females [women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study].

All patients had experienced an ACS and had a guideline-based indication to be on DAPT with aspirin and ticagrelor

Adverse events, including bleeding, bradyarrhythmias, and dyspnea, were recorded up to 24 hours after study completition