Multicentre clinical trials in acute coronary syndromes
| Name | Registration and funding | Population/objective | Sample size | Main finding and conclusion |
| CURE | Sanofi-Synthelabo Bristol-Myers Squibb | Acute coronary syndrome To assess the effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. | 12 562 | The primary endpoint, a composite of death from cardiovascular causes, non-fatal MI or stroke, occurred in 9.3% in the clopidogrel group and 11.4% in the placebo group (RR 0,80;95% CI 0.72 to 0.90; p<0.001). |
| CvLPRIT | ISRCTN70913605 BHF | STEMI with multivessel coronary artery disease To undertake an open-label randomised clinical trial comparing complete revascularisation at index admission with treatment of the IRA only. | 296 | The primary endpoint, a composite of all-cause death, recurrent MI, heart failure and ischaemia-driven revascularisation within 12 months, occurred in 10.0% of the complete revascularisation group vs 21.2% in the IRA-only revascularisation group (HR: 0.45; 95% CI 0.24 to 0.84; p=0.009). In patients presenting for P-PCI with multivessel disease, inpatient total revascularisation may be considered. |
| ERIC-PPCI | NCT02342522 BHF | STEMI To investigate whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. | 5401 | At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8.6%) patients in the control group and 239 (9.4%) in the remote ischaemic conditioning group (HR 1.10 (95% CI 0.91 to 1.32), p=0.32 for intervention vs control). Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. |
| ISIS-1 | BHF ICI Pharmaceuticals Ltd | Acute MI To determine is intravenous atenolol followed by oral atenolol would reduce vascular mortality when compared with placebo. | 16 027 | Vascular mortality during the treatment period (days 0–7) was significantly lower (p<0.04) in the treated group, 3.9% vs 4.6%), but this 15% difference has wide 95% confidence limits (about zero to about a 0.25) |
| ISIS-2 | BHF Sterling Drugs Behringwerke | Acute MI To determine if (1) intravenous streptokinase, (2) 1 month of aspirin, (3) both active treatments or (3) neither compared with placebo control would reduce vascular death. | 17 187 | Those allocated the combination of streptokinase and aspirin had significantly fewer reinfarctions (1.8% vs 2.9%), strokes (0.6% vs 1.1%) and deaths (8.0% vs 13.2%) than those allocated neither. The differences in vascular and in all-cause mortality produced by streptokinase and by aspirin remained highly significant (p<0.001 for each) after the median of 15 months of follow-up. |
| ISIS-3 | BHF Sterling Drugs Behringwerke | Acute MI To determine the differences in bleeding, stroke, reinfarction and death between randomisation to intravenous SK or TPA or APSAC complex with aspirin given to all patients and randomisation to additional intravenous heparin. | 41 299 | Addition of heparin to aspirin was associated with excess of transfused or other major non-cerebral bleeds (1.0% aspirin plus heparin vs 0.8% aspirin alone; p<01) and of definite or probable cerebral haemorrhage (0.56% vs 0.40%; p<0.05), but with no significant differences in total stroke (1.28% vs 1.18%). Reinfarctions were slightly less common among those allocated aspirin plus heparin (3.16% vs 3.47%; p=0.09). There was no significant difference in the prespecified endpoint of 35-day mortality (10.3% aspirin plus heparin vs 10.6% aspirin alone). There was no significant mortality difference during days 0–35, either among all randomised patients (10.6% SK vs 10.5% APSAC) or among the prespecified subset presenting within 0–6 hour of pain onset and with ST elevation on the ECG in whom fibrinolytic treatment may have most to offer. TPA was associated with significantly fewer reports of allergy causing persistent symptoms and of hypotension requiring drug treatment and with significantly more reports of non-cerebral bleeds, but not of transfused bleeds. There was a significant excess of strokes with TPA (1.04% SK vs 1.39% TPA; p<0.01). |
| ISIS-4 | BHF Bristol-Nyers-Squibb Astra-Hassle Artesan Pharma Casselamed | Acute MI To assess early oral captopril, oral mononitrate and intravenous magnesium sulphate on reduction in 5-week mortality rates. | 58 050 | There was a significant 7% proportional reduction in 5-week mortality with captopril. There was no significant reduction in 5-week mortality with mononitrate. There was no significant reduction in 5-week mortality with magnesium. |
| HEAT-PPCI | Liverpool Heart and Chest Hospital UK NIHR The Medicines Company AstraZeneca | ST-elevation MI To compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. | 1829 | The primary efficacy outcome occurred in 8.7% in the bivalirudin group and 5.7% in the heparin group (absolute risk difference 3.0%; RR 1.52, 95% CI 1.09 to 2.13, p=0.01). The primary safety outcome occurred in 3.5% in the bivalirudin group and 3.1% in the heparin group (0.4%; 1.15, 0.70–1.89, p=0.59). |
| High-STEACS | NCT01852123 BHF | Acute coronary syndromes To determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent MI or cardiovascular death in patients with suspected acute coronary syndrome. | 48 282 | The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent MI or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted OR for implementation vs validation phase 1.10, 95% CI 0.75 to 1.61; p=0.620). |
| PRAMI | Barts and the London Charity | ST-elevation MI To assess the value of PCI in non-infarct coronary arteries with major stenoses (preventive PCI). | 465 | The primary outcome of death from cardiovascular causes, nonfatal MI or refractory angina occurred in 9% in preventive PCI group and in 23% in no preventive PCI (infarct-artery-only PCI) group, (HR in the preventive-PCI group, 0.35; 95% CI 0.21 to 0.58; p<0.001). |
| RAPID-CTCA | NIHR | Acute coronary syndromes To establish if the use of early CT coronary angiography improves 1 year clinical outcomes in patients presenting to the emergency department with acute chest pain. | 1748 | The primary endpoint of death or subsequent MI occurred in 5.8% participants randomised to CT coronary angiography and 6.1% participants who received standard of care only (adjusted HR 0.91 (95% CI 0.62 to 1.35), p=0.65). |
| REACT | None BHF | STEMI with failed reperfusion To undertake a multicentre trial in the United Kingdom involving 427 patients with ST-segment elevation MI in whom reperfusion failed to occur (less than 50% ST-segment resolution) within 90 min after thrombolytic treatment. The patients were randomly assigned to repeated thrombolysis (142 patients), conservative treatment (141 patients), or rescue PCI (144 patients). | 427 | The adjusted HR for the occurrence of the primary end point for repeated thrombolysis vs conservative therapy was 1.09 (95% CI 0.71 to 1.67; p=0.69), as compared with adjusted hazard ratios of 0.43 (95% CI 0.26 to 0.72; p=0.001) for rescue PCI vs repeated thrombolysis and 0.47 (95% CI 0.28 to 0.79; p=0.004) for rescue PCI vs conservative therapy. Rescue PCI should be considered for patients in whom reperfusion fails to occur after thrombolytic therapy. |
| RITA-3 | None BHF | Unstable angina or NSTEMI To test the hypothesis that an interventional strategy is better than a conservative strategy in such patients. | 1810 | At 4 months, 86 (9.6%) of 895 patients in the intervention group had died or had a MI or refractory angina, compared with 133 (14.5%) of 915 patients in the conservative group (risk ratio 0.66, 95% CI 0.51 to 0.85, p=0.001). In patients presenting with unstable coronary-artery disease, an interventional strategy is preferable to a conservative strategy, mainly because of the halving of refractory or severe angina and with no increased risk of death or MI. |
APSAC, anisolyated plasminogen-streptokinase activator; CTCA, CT coronary angiography; DAPT, dual antiplatelet therapy; FFR, fractional flow reserve; IRA, infarct-related artery; MI, myocardial infarction; PPCI, primary percutaneous coronary interventoin; RR, relative risk; SK, streptokinase; TPA, tissue plasminogen activator.