Main results of major double-blind, randomized, controlled clinical trials with ticlopidine or clopidogrel
| Clinical trial . | Reference . | Patients . | Treatments . | Cardiovascular endpoints . | Follow-up . | Efficacy* . | Bleeding events† . |
|---|---|---|---|---|---|---|---|
| CATS | 55 | Recent thromboembolic stroke | 1. Ticlopidine | Stroke, MI, or vascular death | 24 mo | 6.5% | |
| 2. Placebo | 23.3% (1.0-40.5) | 3.0% 9.0% | |||||
| TASS | 56 | Recent transient or mild persistent focal cerebral or retinal ischemia | 1. Ticlopidine | Nonfatal stroke or death from any cause | 3 y | 12% (−2%-26%) | 10.0% |
| 2. ASA | |||||||
| ISAR | 57 | CAD patients: PCI and stent implantation | 1. Ticlopidine + ASA | Cardiac death or AMI, CABG, or repeated PCI | 4 wk | 0.25 | 0.00 |
| 2. Heparin/VKA + ASA | (0.06-0.77) | 0.00-0.019 | |||||
| SAR | 58 | CAD patients: PCI and stent implantation | 1. Ticlopidine + ASA | AMI, death, repeat PCI, stent thrombosis at angiography | 30 d | 1 vs 2: 0.20 (0.07-0.61) | 1 vs 2: 0.88 (0.55-1.43) |
| 2. Heparin/VKA + ASA | 1 vs 3: 0.15 (0.05-0.43) | 1 vs 3: 3.06 (1.57-5.97) | |||||
| 3. ASA | |||||||
| CAPRIE | 59 | Atherosclerotic vascular disease | 1. Clopidogrel | Ischemic stroke, AMI, or vascular death | 1.9 y | 9.27% vs 9.28% | |
| 2. ASA | 8.7% (0.3-16.5) | ||||||
| CHARISMA | 60 | Clinically evident CV disease or multiple risk factors | 1. Clopidogrel + ASA | MI, stroke, or | 28 mo | 0.93 | F: 1.53 (0.83-2.82) |
| 2. Placebo + ASA | CV death | (0.83-1.05) | M: 1.25 (0.97-1.61) | ||||
| Mod: 1.62 (1.27-2.08) | |||||||
| MATCH | 61 | Recent ischemic stroke or TIA and ≥ 1 risk factors | 1. Clopidogrel + ASA | Ischemic stroke, MI, vascular death, or rehospitalization for acute ischemia | 18 mo | 6.4% (−4.6-16·3) | LT: 1.26 (0.62-1.88) |
| 2. Clopidogrel + placebo | M: 1.36 (0.86-1.86) | ||||||
| CURE | 62 | Acute coronary syndromes | 1. Clopidogrel + ASA | CV death, | 12 mo | 0.80 (0.72-0.90) | LT: 1.21 (0.95-1.56) |
| 2. Placebo + ASA | Nonfatal AMI, or stroke | M: 1.38 (1.13-1.67) | |||||
| T: 1.69 (1.48-1.94) | |||||||
| COMMIT | 63 | Suspected AMI | 1. Clopidogrel + ASA | (1) Death, reinfarction, or stroke | Up to 28 d | (1) 0.91 (0.86-0.97) | F: −0.1 (SE: 0.5) |
| 2. Placebo + ASA | (2) Death from any cause | (2) 0.93 (0.87-0·99) | M: 0.4 (0.7) | ||||
| m: 4.7 (1.7) | |||||||
| PCI CURE | 64 | NSTE ACS undergoing PCI in the CURE study | 1. Clopidogrel + ASA | CV death, AMI, or urgent target vessel revascularization | 30 d | 0.70 | LT: 0.92 (0.38-2.26) |
| 2. Placebo + ASA | (0.50-0·97) | M: 1.13 (0.61-2.10) | |||||
| m: 1.33 (0.59-3.03) |
| Clinical trial . | Reference . | Patients . | Treatments . | Cardiovascular endpoints . | Follow-up . | Efficacy* . | Bleeding events† . |
|---|---|---|---|---|---|---|---|
| CATS | 55 | Recent thromboembolic stroke | 1. Ticlopidine | Stroke, MI, or vascular death | 24 mo | 6.5% | |
| 2. Placebo | 23.3% (1.0-40.5) | 3.0% 9.0% | |||||
| TASS | 56 | Recent transient or mild persistent focal cerebral or retinal ischemia | 1. Ticlopidine | Nonfatal stroke or death from any cause | 3 y | 12% (−2%-26%) | 10.0% |
| 2. ASA | |||||||
| ISAR | 57 | CAD patients: PCI and stent implantation | 1. Ticlopidine + ASA | Cardiac death or AMI, CABG, or repeated PCI | 4 wk | 0.25 | 0.00 |
| 2. Heparin/VKA + ASA | (0.06-0.77) | 0.00-0.019 | |||||
| SAR | 58 | CAD patients: PCI and stent implantation | 1. Ticlopidine + ASA | AMI, death, repeat PCI, stent thrombosis at angiography | 30 d | 1 vs 2: 0.20 (0.07-0.61) | 1 vs 2: 0.88 (0.55-1.43) |
| 2. Heparin/VKA + ASA | 1 vs 3: 0.15 (0.05-0.43) | 1 vs 3: 3.06 (1.57-5.97) | |||||
| 3. ASA | |||||||
| CAPRIE | 59 | Atherosclerotic vascular disease | 1. Clopidogrel | Ischemic stroke, AMI, or vascular death | 1.9 y | 9.27% vs 9.28% | |
| 2. ASA | 8.7% (0.3-16.5) | ||||||
| CHARISMA | 60 | Clinically evident CV disease or multiple risk factors | 1. Clopidogrel + ASA | MI, stroke, or | 28 mo | 0.93 | F: 1.53 (0.83-2.82) |
| 2. Placebo + ASA | CV death | (0.83-1.05) | M: 1.25 (0.97-1.61) | ||||
| Mod: 1.62 (1.27-2.08) | |||||||
| MATCH | 61 | Recent ischemic stroke or TIA and ≥ 1 risk factors | 1. Clopidogrel + ASA | Ischemic stroke, MI, vascular death, or rehospitalization for acute ischemia | 18 mo | 6.4% (−4.6-16·3) | LT: 1.26 (0.62-1.88) |
| 2. Clopidogrel + placebo | M: 1.36 (0.86-1.86) | ||||||
| CURE | 62 | Acute coronary syndromes | 1. Clopidogrel + ASA | CV death, | 12 mo | 0.80 (0.72-0.90) | LT: 1.21 (0.95-1.56) |
| 2. Placebo + ASA | Nonfatal AMI, or stroke | M: 1.38 (1.13-1.67) | |||||
| T: 1.69 (1.48-1.94) | |||||||
| COMMIT | 63 | Suspected AMI | 1. Clopidogrel + ASA | (1) Death, reinfarction, or stroke | Up to 28 d | (1) 0.91 (0.86-0.97) | F: −0.1 (SE: 0.5) |
| 2. Placebo + ASA | (2) Death from any cause | (2) 0.93 (0.87-0·99) | M: 0.4 (0.7) | ||||
| m: 4.7 (1.7) | |||||||
| PCI CURE | 64 | NSTE ACS undergoing PCI in the CURE study | 1. Clopidogrel + ASA | CV death, AMI, or urgent target vessel revascularization | 30 d | 0.70 | LT: 0.92 (0.38-2.26) |
| 2. Placebo + ASA | (0.50-0·97) | M: 1.13 (0.61-2.10) | |||||
| m: 1.33 (0.59-3.03) |
Doses of the antiplatelet agents are as follows: ticlopidine, 250 mg twice a day55-58 ; ASA, 650 mg twice a day55 ; 325 mg daily58,59 ; 100 mg twice a day57 ; 160 mg daily63 ; 75 to 325 mg daily62,64 ; 75 to 160 mg daily60 ; 75 mg daily61 ; clopidogrel, 75 mg daily in all randomized clinical trials, plus 300 mg loading dose in the CURE trial.62,64
MI indicates myocardial infarction; CAD coronary artery disease; AMI, acute myocardial infarction; VKA, vitamin K antagonist; CV, cardiovascular; and TIA, transient ischemic attack.
Results are reported as relative risk reduction55,56,59,60 and relative risk57,58,60,62-64 (95% confidence interval).
When available, data on major (M), life-threatening (LT), fatal (F), moderate (Mod), minor (m), and total (T) bleeding events are reported as total incidence,55,56,59 relative risk,57,58,60-62,64 and excess per 1000 patients63 (95% confidence interval).