Rationale, design and organization of the Second Chinese Cardiac Study (CCS-2): a randomized trial of clopidogrel plus aspirin, and of metoprolol, among patients with suspected acute myocardial infarction

Assessing combined anti-platelet therapy in suspected acute myocardial infa rction Aspirin has been shown to be effective in the emergency treatment of acute myocardial infarction. It irreversibly inhibits platelet cyclo-oxyge nase and thereby prevents the formation of the platelet aggregating agent t hromboxane A(2). Clopidogrel is an anti-platelet agent that acts by a diffe rent mechanism, inhibiting adenosine diphosphate-induced platelet aggregati on. Simultaneous inhibition of both of these pathways might produce signifi cantly greater anti-platelet effects than inhibition of either atone. The S econd Chinese Cardiac Study (CCS-P) will reliably determine whether adding oral clopidogrel to aspirin for up to 4 weeks in hospital after suspected a cute myocardial infarction can produce a greater reduction in the risk of m ajor vascular events than can be achieved by giving aspirin alone. In order to be able to detect a further reduction of 10-15%, some 20 000-40 000 pat ients in over 1000 Chinese hospitals will be randomized. Assessing early beta-blocker therapy in suspected acute myocardial infarcti on Although over 27 000 patients have been studied previously in randomized trials of short-term beta-blocker therapy in acute myocardial infarction, the reduction in early mortality (513 (3.7%) for beta-blocker therapy death s versus 586 (4.3%) for control deaths) was only just conventionally signif icant (P = 0.02) and, overall, the absolute benefits were small in the rela tively low-risk patients studied. Although there might be worthwhile benefi t in higher risk patients, there is currently little routine use of beta-bl ocker therapy in acute myocardial infarction. Hence, patients in CCS-P wilt also be randomly allocated to receive metoprolol (intravenous then oral) o r matching placebo for up to 4 weeks in hospital in a 2 x 2 factorial desig n. Such a design allows all patients to contribute fully to assessment of t he separate effects of the anti-platelet regimen and the beta-blocker (with out any material effect on study cost or sample size requirements) whilst a lso providing information about their combined effects. A streamlined trial in a wide range of patients In order to randomize 20 00 0-40 000 patients, the design of CCS-2 has been streamlined: data collectio n and other extra work for collaborators is minimal, allowing busy hospital s to take part easily. All patients presenting within 24h of the onset of s uspected acute myocardial infarction are eligible for the study provided th ey have a definite ECG abnormality and are not persistently hypotensive, an d provided the doctor responsible considers there to be no clear indication for or contraindication to either of the trial treatments. Apart from admi nistration of the trial treatments, all other aspects of individual patient management are entirely at the discretion of the doctor responsible. By in cluding many different types of patient from many different types of hospit al, with wide variation in ancillary management, the CCS-2 results will be of direct clinical relevance to the heterogeneous realities of future clini cal practice. The trial began in July 1999 and is expected to be completed by the year 2003. J Cardiovasc Risk 7:435-441 (C) 2000 Lippincott Williams & Wilkins.