One-Year Outcomes of Early Therapy With Ticagrelor vs Clopidogrel in CYP2C19 Loss-of-Function Carriers With Stroke or TIA Trial.

BACKGROUND AND OBJECTIVES: The Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial showed that among Chinese patients with minor ischemic stroke or transient ischemic attack (TIA) who were carriers of CYP2C19 loss-of-function alleles, dual-antiplatelet therapy with ticagrelor-aspirin reduced the 90-day risk of stroke without increased severe or moderate bleeding compared with clopidogrel-aspirin. However, whether dual-antiplatelet therapy with ticagrelor was superior to clopidogrel beyond the 90 days of follow-up remained unclear. In this study, we reported 1-year follow-up outcomes of the CHANCE-2 trial. METHODS: The CHANCE-2 trial is a randomized, double-blind, placebo-controlled trial at 202 centers in China. Patients with a minor stroke or TIA who carried CYP2C19 loss-of-function alleles were randomized within 24 hours after symptom onset, in a 1:1 ratio, to receive ticagrelor and placebo clopidogrel or to receive clopidogrel and placebo ticagrelor for 90 days; both groups received aspirin for the first 21 days. After day 90, treatment was as per the choice of the clinician and the patient. RESULTS: Among 6,412 patients, the proportion of patients on ticagrelor plus aspirin, clopidogrel plus aspirin, ticagrelor alone, clopidogrel alone, aspirin alone, other antiplatelet, and no antiplatelet beyond month 3 to 1 year was 0.09%, 1.56%, 0.13%, 2.66%, 73.65%, 0.78%, and 21.13% in the ticagrelor-aspirin group and 0.03%, 1.63%, 0.19%, 2.60%, 72.83%, 0.66%, and 22.06% in the clopidogrel-aspirin group, respectively. The primary outcome of new stroke occurred in 252 patients (7.91%) in the ticagrelor-aspirin group and 310 patients (9.73%) in the clopidogrel-aspirin group by 1 year of follow-up (hazard ratio 0.80; 95% CI 0.68-0.95; p = 0.007); new stroke beyond 3 months to 1 year occurred in 61 patients (2.07%) and 67 patients (2.32%) (p = 0.48), respectively. Primary safety outcome of severe or moderate bleeding occurred in 17 patients (0.53%) in the ticagrelor-aspirin group and 20 patients (0.63%) in the clopidogrel-aspirin group (p = 0.61). DISCUSSION: For CYP2C19 loss-of-function allele carriers, early dual-antiplatelet therapy with ticagrelor is superior to clopidogrel at 1 year in reducing recurrent stroke. TRIAL REGISTRATION INFORMATION: URL: clinicaltrials.gov. Unique identifier: NCT04078737. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with minor stroke or TIA with TIACYP2C19 loss-of-function, ticagrelor plus aspirin for 21 days is superior to clopidogrel plus aspirin in reducing the 1-year risk of recurrent stroke.

Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial.

BACKGROUND: In patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel-aspirin) or ticagrelor plus aspirin (ticagrelor-aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who were CYP2C19 loss-of-function (LOF) allele carriers, whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is unclear. AIM: To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial. DESIGN: CHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2-90), plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day 2-21. All will be followed for 1 year. STUDY OUTCOMES: The primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months. DISCUSSION: The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers. TRIAL REGISTRATION NUMBER: NCT04078737.

Comparative evaluation of stroke triage algorithms for emergency medical dispatchers (MeDS): prospective cohort study protocol.

BACKGROUND: Stroke is a major cause of death and leading cause of disability in the United States. To maximize a stroke patient's chances of receiving thrombolytic treatment for acute ischemic stroke, it is important to improve prehospital recognition of stroke. However, it is known from published reports that emergency medical dispatchers (EMDs) using Card 28 of the Medical Priority Dispatch System protocols recognize stroke poorly. Therefore, to improve EMD's recognition of stroke, the National Association of Emergency Medical Dispatchers recently designed a new diagnostic stroke tool (Cincinnati Stroke Scale -CSS) to be used with Card 28. The objective of this study is to determine whether the addition of CSS improves diagnostic accuracy of stroke triage. METHODS/DESIGN: This prospective experimental study will be conducted during a one-year period in the 911 call center of Santa Clara County, CA. We will include callers aged ≥ 18 years with a chief complaint suggestive of stroke and second party callers (by-stander or family who are in close proximity to the patient and can administer the tool) ≥ 18 years of age. Life threatening calls will be excluded from the study. Card 28 questions will be administered to subjects who meet study criteria. After completion of Card 28, CSS tool will be administered to all calls. EMDs will record their initial assessment of a cerebro-vascular accident (stroke) after completion of Card 28 and their final assessment after completion of CSS. These assessments will be compared with the hospital discharge diagnosis (ICD-9 codes) recorded in the Office of Statewide Health Planning and Development (OSHPD) database after linking the EMD database and OSHPD database using probabilistic linkage. The primary analysis will compare the sensitivity of the two stroke protocols using logistic regression and generalizing estimating equations to account for clustering by EMDs. To detect a 15% difference in sensitivity between the two groups with 80% power, we will enroll a total of 370 subjects in this trial. DISCUSSION: A three week pilot study was performed which demonstrated the feasibility of implementation of the study protocol.