Clinical trial NCT03381742
Conditions: Coronary Artery Disease
Sponsor: First Affiliated Hospital of Harbin Medical University
Start date: 2017-12-13; Completion date: 2019-02-13
Enrollment: 3043 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.

Detailed description:
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.

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. One-quarter standard-dose ticagrelor provided greater degree of platelet inhibition than standard dose clopidogrel in Chinese patients with stable CAD. But large-scale clinical trials are still needed to confirm the effects of low-dose ticagrelor on platelet function in Chinese patients with coronary heart disease.

Arms: arm 1: To observe the efficacy and safety of ticagrelor 45mg bidpo. in patients with coronary artery disease. arm 2: To observe the efficacy and safety of ticagrelor 90mg qdpo. in patients with coronary artery disease. arm 3: To observe the efficacy and safety of ticagrelor 90mg bidpo. in patients with coronary artery disease. arm 4: To observe the efficacy and safety of clopidogrel 75mg qdpo. in patients with coronary artery disease.
Interventions: intervention 1: Ticagrelor intervention 2: ticagrelor intervention 3: ticagrelor intervention 4: clopidogrel
Intervention descriptions: intervention 1: ticagrelor 45 mg twice daily for 5 consecutive days at least. intervention 2: ticagrelor 90 mg once daily for 5 consecutive days at least. intervention 3: ticagrelor 90 mg twice daily for 5 consecutive days at least. intervention 4: clopidogrel 75 mg once daily for 5 consecutive days at least.

Protocol documents:
Prot_SAP_000.pdf: 
Official Title:
Efficacy and Safety of Different Ticagrelor Regimens Versus 
Clopidogrel in Patients With Coronary Artery Disease: a Retrospective Multicenter 
Study (SUPERIOR)
NCT number: 03381742
Document date: August 16, 2019


Objective
Current guidelines favor dual anti-platelet therapy with ticagrelor 90 mg BID 
(T90BID) over clopidogrel 75 mg QD (C75QD) in addition to aspirin for coronary 
artery disease (CAD). However, an increased risk of ticagrelor-related adverse events 
prompted evaluation of low-dose regimens. This study aimed to examine the efficacy 
and safety outcomes of two low-dose regimens of ticagrelor in a large-scale cohort of 
patients with CAD.
Design
This is a retrospective, multicenter, observational study of 3,043 consecutive 
inpatients and outpatients with CAD, who received either ticagrelor or clopidogrel 
therapy. 
Methods
We retrospectively analyzed the data from 11 hospitals on 3,043 CAD patients, 
who received C75QD, T90BID, ticagrelor 45 mg BID (T45BID), or ticagrelor 90 mg 
QD (T90QD) for at least 5 consecutive days before thromboelastography test. The 
main efficacy outcome was the ADP-induced inhibition of platelet aggregation (IPA), 
and other efficacy outcomes included ADP-induced platelet-fibrin clot strength (MA), 
rate of high on-treatment platelet reactivity (HTPR), and cardiovascular event 
(cardiovascular death, new-onset myocardial infarction, or stroke) rates. The primary 
safety outcome was bleeding rate (major or minor bleeding), and rate of new-onset 
dyspnea was also studied. All the patients had a 5-day follow-up period after the first 
dosing of study drugs to assess the efficacy and safety outcomes. The outcomes were 
compared between patients with clopidogrel treatment and patients who received 
different ticagrelor regimens (T90BID, T45BID and T90QD) using logistic regression 
model for total population and propensity score–matching analysis.
Primary data analysis was performed by investigators with cooperation from the 
First Affiliated Hospital of Harbin Medical University and the other participating 
hospitals. The study was approved by the Ethics Committees of the First Affiliated 


Hospital of Harbin Medical University.
Data are summarized as frequencies and percentages for categorical variables. 
Continuous variables are expressed as median and interquartile range. To compare 
differences in continuous variables among groups, Mann–Whitney U test or Kruskal–
Wallis rank sum test was performed, followed by Dunn’s multiple comparison test. 
The Fisher’s exact test or 
 test was used to compare categorical variables, followed 
by Bonferroni adjustments for multiple comparisons test. Univariate and multivariate 
logistic regression analyses were conducted to evaluate the association between 
platelet inhibition (HTPR/non-HTPR) and treatment group or other clinical 
characteristics. Odds ratios (OR) and their 95% confidence intervals (CIs) are 
presented as a measure of association.
Propensity score matching was performed to reduce selection bias and 
confounders between two groups at baseline. The propensity scores were estimated 
using a multivariate logistic regression model that included the following variables: 
age; gender; weight; cigarette smoking; hypertension; diabetes mellitus; chronic 
kidney disease; previous PCI; previous coronary artery bypass grafting; serum levels 
of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, 
creatinine and uric acid; aspirin use; and acute myocardial infarction. The propensity 
scores were used to match the clopidogrel and ticagrelor groups in a 1:1 ratio, with a 
caliper value of 0.05.
All statistical analyses were 2-tailed, and a P value < 0.05 was considered 
statistically significant. Statistical analyses were performed using SAS software 
version 9.4 (SAS Institute, Cary, NC, USA) and R version 3.2.1 (http://www.r-
project.org).