Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
Half-dose Ticagrelor Overcomes High-dose Clopidogrel in Acute Coronary Syndrome Patients With High On-Clopidogrel Platelet Reactivity
With the widespread use of clopidogrel, resistance to clopidogrel has been attracting
 increasing attention, and emerged as a new challenge adversely affecting patients clinical
 risk and outcome. Clopidogrel resistance means that blood platelets show little or no
 response to clopidogrel. It is closely associated with increased risk of serious
 cardiovascular events, seriously affects the prognosis of patients, and brings difficulties
 to clinical treatment.

 Guideline recommendations on the use of dual antiplatelet therapy have been formulated that
 ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg daily plus
 aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day orally could
 significantly reduce the occurrence of clopidogrel resistance and adverse cardiovascular
 events. The previous studies have reported that half-dose ticagrelor had the similar
 inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was
 significantly stronger than that in the clopidogrel group. But it is still not very clear
 that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel
 resistance and coronary heart disease.

 Therefore, we performed this randomized, single-blind clinical trial to observe the effects
 of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and
 prognosis in clopidogrel resistance's patients with coronary heart disease.
Dual Antiplatelet Therapy (DAPT) with aspirin and P2Y12 receptor inhibitor remains a
 cornerstone in the secondary prevention of coronary artery disease (CAD). Clopidogrel is one
 of the most commonly used antithrombotic agent that inhibits the platelet P2Y(12) adenosine
 diphosphate (ADP) receptor. With the widespread use of clopidogrel, resistance to clopidogrel
 has been attracting increasing attention, and emerged as a new challenge adversely affecting
 patients clinical risk and outcome. Clopidogrel resistance means that blood platelets show
 little or no response to clopidogrel. Recent studies have found that clopidogrel resistance
 rate was about 11% ~ 44%. Clopidogrel resistance is more common in patients with
 loss-of-function CYP2C19 genotypes, and closely associated with increased risk of serious
 cardiovascular events, including ischemic events, myocardial infarction, stent thrombosis,
 revascularization and so on. This seriously affects the prognosis of patients, and brings
 difficulties to clinical treatment.

 Ticagrelor is an oral, reversibly-binding, direct-acting P2Y12 receptor antagonist used
 clinically for the prevention of atherothrombotic events in patients with acute coronary
 syndromes (ACS). Guideline recommendations on the use of dual antiplatelet therapy have been
 formulated that ticagrelor 90 mg twice daily plus aspirin in preference to clopidogrel 75mg
 daily plus aspirin for ACS patients. Recent study found that ticagrelor 90mg twice a day
 orally could significantly reduce the occurrence of clopidogrel resistance and adverse
 cardiovascular events. The previous studies have reported that half-dose ticagrelor had the
 similar inhibitory effect on platelet aggregation as the standard-dose ticagrelor, which was
 significantly stronger than that in the clopidogrel group. But it is still not very clear
 that the effect of low-dose ticagrelor on platelet function in patients with clopidogrel
 resistance and coronary heart disease.

 Therefore, we performed this randomized, single-blind clinical trial to observe the effects
 of low-dose ticagrelor and double standard-dose clopidogrel on platelet aggregation and
 cardiovascular prognosis in clopidogrel resistance's patients with coronary heart disease.
Inclusion Criteria:

 1. Patients with oral clopidogrel treatment admitted to hospital within 24 hours or
 long-term follow-up outpatients with oral clopidogrel treatment;

 2. The platelet aggregation rate (PAgR) measured with light transmission aggregometry
 (LTA) is decreased no more than 10% from baseline level, or PAgR is more than 46% and
 the percentage of inhibition of ADP-induced platelet aggregation measured by
 thrombelastogram is not more than 30%;

 Exclusion Criteria:

 1. Planned use of glycoprotein IIb/IIIa receptor inhibitors, adenosine diphosphate (ADP)
 receptor antagonists, or anticoagulant therapy during the study period;

 2. Platelet count <100g/L;

 3. Creatinine clearance rate < 30ml/min;

 4. Diagnosed as respiratory or circulatory instability (cardiac shock, severe congestive
 heart failure NYHA II-IV or left ventricular ejection fraction < 40%);

 5. A history of bleeding tendency;

 6. Aspirin, ticagrelor or clopidogrel allergies;

 7. Severe liver injury.