Along with the current clinical trial, the efficacy and safety of ticagrelor and aspirin administered within the first 24 hours of first-ever ischemic stroke compared to cilostazol and aspirin were assessed through NIHSS, mRS, and possible adverse effects.

The investigators will conduct a randomized controlled trial between December 2021 and February 2024 after approval of the ethics committee of the faculty of medicine at Kafr el-Sheik University.

The investigators got written informed consent from all eligible patients or their first order of kin before randomization.

The study will be composed of 2 arms ticagrelor arm, which consisted of 450 patients who received 180 mg loading dose followed by 90 mg b.i.d from the 2nd to the 90th day), and the cilostazol arm consisted of 450 patients who received (a 200mg loading dose during the first 24 hours of stroke onset followed by 100mg twice daily from the 2nd day to the 90th day), All the patients in the two groups received open-label aspirin at a loading dose of 75 to 300 mg, followed by 75 mg daily for 21 days.

Study Procedures:

Every patient in our study will undergo:

Clinical workup: History, clinical assessment & NIHSS were recorded on admission, day 7, and the Modified Rankin Scale as a follow-up after one week and 3 months.

Detection of Risk Factors & Profiles:

Echocardiography& TOE: in indicated patients ECG Monitoring: daily ECG monitoring will be performed in indicated patients. - Carotid Duplex: carotid duplex in indicated patients.

4- ESR & Lipid Profile& liver functions: All will be tested routinely for all patients.

Imaging Follow UP Non-contrast CT brain on admission Day 2 MRI: after 2 days of admission, all the patients in this study will have a brain MRI (stroke protocol; T1W, T2W, FLAIR, DWI, T2 Echo Gradient, MRA of all intra-cerebral vessels).

CT brain: Any patient with unexplained clinical deterioration at any time throughout his/her hospital stay will be urgently imaged by CT.

Primary End Point:

The primary efficacy outcome was the rate of new stroke at 90 days, and the primary safety outcome was the rate of drug hemorrhagic complications using the PLATO bleeding definition.

• Secondary End Point: the secondary efficacy outcomes were to evaluate the rates of patients who achieved a significant reduction in NIHSS (decrease of four points or more) at the seventh day or discharge compared to baseline, the rates of a favorable outcome with (mRS = 0-2) after one week and after 90 days in a face-to-face interview in the outpatient clinic, rates of the composite of recurrent stroke, myocardial infarction and death due to vascular events after 90 days of follow-up, while the secondary safety outcome was the rate of treatment-related adverse effects assessed by a follow-up questionnaire.

Inclusion Criteria:

• the investigators included both genders with eligible ages ranging between 18-75 years, with the first-ever presentation with acute minor ischemic stroke or TIA who received antiplatelet treatment within the first 24 hours of the onset of ischemic stroke. Patients are not eligible for rt-PA treatment

Exclusion Criteria:

• Exclusion Criteria: The investigators excluded patients who had not been followed up on for 90 days after enrollment, those with NIHSS > 4, and patients with a known history of persistent or recurrent CNS pathology (e.g., epilepsy, meningioma, multiple sclerosis, history of head trauma with a residual neurological deficit).

We excluded patients who had clinical seizures at the onset of their stroke, as well as those who had symptoms of any major organ failure, active malignancies, or an acute myocardial infarction within the previous six weeks, and those who were on warfarin, regular ticagrelor during the week before admission, or chemotherapy within the previous year.

For safety measures and to avoid associated confounders, we excluded patients with active peptic ulcers, GIT surgery, bleeding history within the last year, and those with a history of major surgery within the last three months.

We ruled out of our trial patients who had a known allergy to the study drugs and those with INR > 1.4 or P.T. >18 or blood glucose level < 50 or > 400 mg/DL or blood pressure < 90/60 or > 185/110 mmHg on admission or Platelets < 100,000.

The investigators considered pregnant and lactating patients or those with stroke due to venous thrombosis, those with wake-up stroke and stroke following cardiac arrest or profuse hypotension ineligible for our trial.

An independent statistician generated a blocked randomization sequence using computer-generated random numbers; in a one-to-one ratio, participants were randomly assigned to receive either loading doses of ticagrelor and aspirin or cilostazol and aspirin by a specially trained and qualified nurse. We prepared Sequentially numbered opaque sealed envelopes and 900 labels for each drug labeled Drug A or B. According to the randomization chart, put them into envelopes numbered 1 to 900. Envelopes were attached to the patient's files. Patients were recruited sequentially and were given enrolment numbers starting from 1, which were mentioned on their files. Files with the same number as the patient enrolment number were opened, and the patients were assigned to receive drugs A or B. Drug A included ticagrelor and aspirin, and Drug B included cilostazol and aspirin. The statistical analysis was performed by an independent statistician who did not know the treatment protocol of groups A or B.