Patients (≥21 years) with ischemic stroke (retinal and lacunar infarction) with the following:
(i) Severe cerebral deficit likely to lead to patient being bedridden or demented
Minimum of 1 year and maximum of 3 year
Clopidogrel (3,233) 75 mg/d
64.7 ± 11.0
63
Angina: 17
(i) focal neurological deficit likely to be of atherothrombotic origin
(ii) Carotid endarterectomy after qualifying stroke
Mean follow-up: 1.91 years
Atrial fibrillation: 4
(ii) onset ≥ 1 week and ≤ 6 months before randomization
(iii) Qualifying stroke induced by carotid endarterectomy or angiography
Total person-time: Clopidogrel: 6,054 person-years at risk;
Cardiomegaly: 5
(iii) neurological signs persisting ≥1 week from stroke onset
(iv) Unlikely to be discharged alive after qualifying event
Aspirin: 5,979 person-years at risk
CHF: 4
(iv) CT or MRI ruling out hemorrhage or non-relevant disease
(v) Severe co-morbidity likely to limit patient’s life expectancy to <3 years
Diabetes: 26
(vi) Uncontrolled hypertension
Hyperlipidemia: 38
Hypertension: 65
Ischemic stroke: 19
Myocardial infarction: 11
TIA/RIND: 19
Aspirin (3,198) 325 mg/d
64.5 ± 11.2
64
Angina: 17
Atrial fibrillation: 4
Cardiomegaly: 6
CHF: 4
Diabetes: 25
Hyperlipidemia: 37
Hypertension: 65
Ischemic stroke: 17
Myocardial infarction: 13
TIA/RIND: 19
Chi et al. (2018) [24], Retrospective cohort, Taiwan
Adult patients from the Taiwanese Stroke Registry who had ischemic stroke and whose survival statuses one year after the index stroke were confirmed
(i) Received a combination of aspirin and clopidogrel,
For 1 year after the diagnosis of ischemic stroke
Clopidogrel (6,443)
71.4 ± 13.2
60.5
Atrial fibrillation: 4.3
(ii) Received other medicine including Aggrenox, ticlopidine, cilostazol, or warfarin
CHD: 2.20
CVA/TIA: 32.7
Diabetes: 42.1
Heart disease: 34.4
(iii) Died during hospitalization for acute ischemic stroke
Hyperlipidemia: 45.9
(iv) With missing data
Hypertension: 78.6
(v) Died at discharge
IHD: 17.1
(vi) Had recurrent stroke before discharge
Aspirin (6,443)
Myocardial infarction: 0.34
71.8 ± 16.3
60.2
Atrial fibrillation: 4.33
CHD: 2.20
CVA/TIA: 34.6
Diabetes: 42.3
Heart disease: 33.0
Hyperlipidemia: 45.0
Hypertension: 79.2
IHD: 17.9
Myocardial infarction: 0.25
Christiansen et al. (2015) [25], Retrospective cohort, Denmark
Patients with first-time ischemic stroke discharged from Jan. 2017 to Dec. 2010 and those who survived the first 30 days after stroke
Atrial fibrillation or anticoagulation therapy before or up to 30 days after discharge
From 30 days after discharge until patients had an outcome, died, emigrated, or 1 year after discharge, whichever comes first
Clopidogrel (3,885)
68.6 (59.2–77.6)
49
Diabetes: 11.7
Bleeding: 8.2
Median follow-up: 335 days [335–335]
Cancer: 6.3
Total person-time: Clopidogrel: 3,364 person-years; Aspirin: 2,475 person-years
COPD: 7.1
Heart failure: 5.9
Hypertension: 42.3
Myocardial infarction: 13.5
Aspirin (3,043)
PAD: 4.6
75.3 (64.5–83.7)
48
Bleeding: 13.3
Cancer: 6.8
COPD: 8.4
Diabetes: 12.5
Heart failure: 7.3
Hypertension: 43.2
Myocardial infarction: 11
PAD: 4.1
Lee et al. (2014) [22], Retrospective cohort, Taiwan
Hospitalized adults who were admitted with a primary diagnosis of ischemic stroke (index stroke) between 2003 and 2009 and received continuous aspirin treatment ≥30 days before the index stroke
(i) Atrial fibrillation, valvular heart disease, or coagulopathy
Mean follow up: 2.4 years
Clopidogrel‡ (384)
70.8 ± 9.5
60
Diabetes: 44.0
(ii) Those with poor drug adherence (medication possession ratio ≤80%)
Average daily dose: 74.6 mg
GI bleeding/peptic ulcer: 18.8
Hyperlipidemia: 20.3
Hypertension: 57.3
IHD: 16.7
Aspirin (1,500)
Stroke/TIA: 22.7
Average daily dose: 101.9 mg
71.1 ± 10.2
60
Diabetes: 49.1
GI bleeding/peptic ulcer: 2.6
Hyperlipidemia: 21.8
Hypertension: 52.0
IHD: 18.9
Stroke/TIA: 18.7
Milionis et al. (2011) [26], Retrospective cohort, Greece
Patients who were hospitalized due to an acute ischemic stroke (atherothrombotic, lacunar, cryptogenic) and had an indication to receive antiplatelet therapy
Those who were treated with coumadin
For 5 years from index stroke
Clopidogrel (348) Average daily dose: 75 mg/d
77.6 ± 11.0
73
CAD:18.4
Mean follow-up: Clopidogrel: 38.5 ± 20.4 months;
Diabetes: 66.1
Aspirin: 40.9 ± 22.2 months
Hyperlipidemia: 46.3
Hypertension: 31.3
PAD: 6.1
Aspirin (880)
TIA: 14.1
Average daily dose: 104 mg/d
67.6 ± 11.8
70
CAD: 18.9
Diabetes: 71.4
Hyperlipidemia: 38.4
Hypertension: 29.5
PAD: 5.5
TIA: 14.7
*Age presented as mean age ± standard deviation or median age with interquartile range. †Only subgroup of patients with ischemic stroke at baseline are presented. ‡The Taiwan National Health Insurance Bureau provided reimbursement for the use of clopidogrel in patients with ischemic stroke who are allergic to aspirin, have peptic ulcer, or aspirin treatment failure. CAD: coronary artery disease; CHF: congestive heart failure; COPD: chronic obstructive pulmonary disease; CT: computed tomography; CVA: cerebrovascular attack; IHD: ischemic heart disease; MRI: magnetic resonance imaging; PAD: peripheral artery disease; RCT: randomized controlled trial; RIND: reversible ischemic neurological deficit; TIA: transient ischemic attack.
