For personal use only. Not to be reproduced without permission of The Lancet. ARTICLES THE LANCET • Vol 356 • December 2, 2000 1871 Summary Background The LIPID study is a major trial of secondary prevention of coronary-heart-disease events that includes hospital admission with unstable angina (as well as myocardial infarction) as a qualifying event. In this substudy of LIPID, we compared subsequent cardiovascular risks and the effects of pravastatin in patients with previous unstable angina or previous myocardial infarction. Methods 3260 patients diagnosed with unstable angina and 5754 with acute myocardial infarction 3–36 months previously were randomly assigned 40 mg pravastatin daily or placebo over a mean of 6·0 years. The risk reduction of a range of cardiovascular events was estimated by means of the hazard ratio in Cox’s proportional hazards model. Findings Among patients assigned placebo, survival in the two diagnosis groups was similar. The relative risk reduction for mortality with pravastatin was 20·6% in the myocardial infarction group and 26·3% in the unstable angina group (p=0·55). Pravastatin significantly reduced the rates of all prespecified coronary endpoints in the myocardial infarction group. In patients with previous unstable angina, coronary heart disease mortality, total mortality, myocardial infarction, a need for coronary revascularisation, the number of admissions to hospital, and the number of days in hospital were significantly lower with pravastatin. Overall, hospital admission for unstable angina was the most common endpoint (24·6% of the placebo group; 22·3% of the pravastatin group). Interpretation Patients who have survived acute myocardial infarction or unstable angina have a similar long-term prognosis, a high occurrence of subsequent unstable angina, and benefit similarly from therapy with pravastatin. Lancet 2000; 355: 1871–75 *Deceased National Heart Foundation of Australia, Melbourne (Prof A Tonkin FRACP); Wesley Medical Centre, Brisbane (D Colquhoun FRACP); National Health and Medical Research Council Clinical Trials Centre (J Emberson MSc, W Hague MBBS, A Keech FRACP, R J Simes FRACP); Fremantle Hospital, Perth (G Lane FRACP); Institute for International Health Research and Development, Sydney (Prof S MacMahon PhD); Sir Charles Gairdner Hospital, Perth (Prof P Thompson FRACP); Green Lane Hospital, Auckland (Prof H D White FRACP); and Royal Melbourne Hosptal, Melbourne, Australia (D Hunt FRACP) Correspondence to: Prof Andrew M Tonkin, National Heart Foundation of Australia, West Melbourne, Victoria 3003, Australia (e-mail: Andrew.Tonkin@heartfoundation.com.au) Introduction The number of patients with unstable angina who require admission to monitored beds for hospital treatment is increasing and, in many countries, is higher than the number of patients admitted with acute myocardial infarction. 1 However, although these patients have similar pathophysiology, 2 scientific data relating to the long-term prevention of further coronary-heart-disease events has generally been limited to the patients with myocardial infarction. For patients with unstable angina, the place of cholesterol-lowering therapy for secondary prevention of coronary-heart-disease events has had little attention. Overall results in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study—the largest trial of lipid-modifying therapy with a 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor—have been presented. 3 This is the only trial of prevention to include patients admitted to hospital with unstable angina as well as those with previous myocardial infarction. The trial design included stratification by this qualifying diagnosis, since whether the effects of treatment would be the same in both groups of patients was not known. In this substudy, our objectives were: (1) to ascertain the long-term risks of major cardiovascular events in patients qualifying for the LIPID study with unstable angina; (2) to compare the risks of major cardiovascular events in patients qualifying with unstable angina with those in patients who had had myocardial infarction; and (3) to compare the effects of pravastatin in the patients with previous unstable angina with those in the patients with previous acute myocardial infarction. Methods Patients The design of the LIPID study has been described in detail elsewhere. 4 9014 patients (7498 men and 1516 women, aged 31–75 years) were recruited in 87 centres in Australia and New Zealand between June, 1990, and December, 1992. Patients had had an acute myocardial infarction or a hospital discharge diagnosis of unstable angina 3–36 months before randomisation. Patients who had experienced both acute myocardial infarction and hospital admission for unstable angina within this period were included in the myocardial infarction stratum. The aim was for a third of the cohort to qualify for the study with previous unstable angina. Eligible patients were invited to take part in an 8-week, single-blind, placebo run-in phase, during which dietary advice was given with the aim of reducing fat to less than 30% of total energy intake, and dietary cholesterol to less than 300 mg/day. Patients were eligible for randomisation if they then had a total cholesterol concentration in plasma of 4·0–7·0 mmol/L and fasting triglycerides of more than 5·0 mmol/L. Major exclusion criteria included Effects of pravastatin in 3260 patients with unstable angina: results from the LIPID study Andrew M Tonkin, David Colquhoun, Jonathan Emberson, Wendy Hague, Anthony Keech, Geoffrey Lane, Stephen MacMahon, John Shaw,* R John Simes, Peter L Thompson, Harvey D White, and David Hunt, for the LIPID Study Group Articles