Design of trials included in meta-analysis
| Trial, year | n | Population | Drug/comparator | Dosage | Duration of treatment | Primary efficacy endpoint | Primary safety endpoint | Follow-up |
| CURE, 2001 | 12 562 | Patients presenting to hospital with acute coronary syndrome* within 24 hours after onset of symptoms and did not have ST elevation | Clopidogrel/placebo | 300 mg loading dose followed by 75 mg once daily | 3–12 months (mean duration of treatment, 9 months) | CV death, non-fatal MI or stroke | Major bleeding (requiring transfusion of ≥2 units of blood) | 12 months |
| COMMIT, 2005 | 45 852 | Patients admitted within 24 hours of suspected acute MI onset with ST elevation, left-bundle branch block or ST depression. | Clopidogrel/placebo | 75 mg | Hospital discharge or 28 days (mean 14.9 days) | Death, MI or stroke | Haemorrhagic stroke or non-cerebral bleeding (requiring transfusion or fatal) | Hospital discharge or 28 days. |
| CLARITY-TIMI 28, 2005 | 3491 | Patients 18–75 years of age presenting within 12 hours after onset of STEMI | Clopidogrel/placebo | 300 mg loading dose followed by 75 mg once daily | Up to day of coronary angiography, day 8 or hospital discharge | Death, MI or occluded infarct-related artery (TIMI flow grade of 0 or 1). | TIMI major bleeding | 30 days |
| TRITON-TIMI 38, 2007 | 13 608 | Patients with acute coronary syndrome* with scheduled PCI | Prasugrel/clopidogrel | 60 mg loading dose followed by 10 mg once daily | 6–15 months (median, 14.5 months) | CV death, non-fatal MI or non-fatal stroke | TIMI non-CABG major bleeding | 15 months |
| PLATO, 2009 | 18 624 | Patients hospitalised for an acute coronary syndrome* with an onset of symptoms during previous 24 hours | Ticagrelor/clopidogrel | 180 mg loading dose followed by 90 mg twice daily | 12 months | CV death, MI or stroke | Study defined major bleeding | 12 months |
| CHANCE, 2010 | 5170 | Patients within 24 hours after the onset of minor ischaemic stroke or high-risk TIA | Clopidogrel/placebo | 300 mg loading dose followed by 75 mg once daily | 90 days | New stroke (ischaemic or haemorrhagic) | GUSTO moderate to severe bleeding | 90 days |
| TRILOGY ACS, 2012 | 7243 | Patients with unstable angina* or NSTEMI selected for medical management without revascularisation within 10 days after the index event | Prasugrel/clopidogrel | 30 mg loading dose followed by 10 mg once daily | 30 months | CV death, non-fatal MI or non-fatal stroke | TIMI non-CABG major bleeding | 30 months |
| SPS3, 2012 | 3020 | Patients with recent symptomatic lacunar infarcts identified by MRI. | Clopidogrel/placebo | 75 mg | 3.4 years | Stroke recurrence (ischaemic stroke or intracranial haemorrhage, including subdural haematomas) | Study defined major extracranial haemorrhage | 3.4 years |
| SOCRATES, 2016 | 13 199 | Patients with a non-severe ischaemic stroke or high-risk transient ischaemic attack who had not received intravenous or intra-arterial thrombolysis and were not considered to have had a cardioembolic stroke | Ticagrelor/aspirin | 180 mg loading dose followed by 90 mg twice daily | 90 days | Stroke, MI or death | PLATO major bleeding | 90 days |
*For trials that included patients with unstable angina as well as MI (CURE, PLATO, TRITON-TIMI 38 and TRILOGY ACS), the overall treatment effect estimate and the effect estimates having excluded patients with unstable angina were very similar (online supplementary appendix for additional detail).
Trial acronyms: CHANCE, Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events Trial; CLARITY-TIMI 28, Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28 Study; COMMIT, Clopidogrel and Metoprolol in Myocardial Infarction Trial; CURE, Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial; PLATO, Platelet Inhibition and Patient Outcomes Trial; SPS3, Secondary Prevention of Small Subcortical Strokes Trial; SOCRATES, Acute Stroke or Transient Ischaemic Attack Treated with Aspirin or Ticagrelor and Patient Outcomes; TRILOGY ACS, Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes; TRITON-TIMI 38, Trial to Assess Improvement in Therapeutic Outcomes by Optimising Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38.
CABG, coronary artery bypass grafting; CV, cardiovascular; GUSTO, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries; MI, myocardial infarction; NSTEMI, non-ST elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST elevation myocardial infarction; TIA, transient ischaemic attack; TIMI, Thrombolysis in Myocardial Infarction.