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John Simes

Publications and source records attributed to John Simes.

21 records · Page 2Linked to original sources

Effect of pravastatin on cardiovascular events and mortality in 1516 women with coronary heart disease: results from the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study.

BACKGROUND: The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study showed that cholesterol-lowering therapy prevented further events in patients with coronary heart disease and average cholesterol levels. The aim of this subgroup analysis was to assess the effects of pravastatin in women. METHODS: A total of 1516 women (756 assigned to take pravastatin) in a cohort of 9014 patients with previous myocardial infarction or unstable angina and a baseline plasma cholesterol level of 4.0 to 7.0 mmol/L (155-271 mg/dL) were assigned to receive pravastatin (40 mg/d) or placebo. Major cardiovascular disease events in 6 years were measured. RESULTS: Women were at a lesser risk than men for death from any cause (10.3% vs 14.8%, P <.01), death from coronary heart disease (6.6% vs 8.6%, P =.04), and coronary revascularization (13.6% vs 16.2%, P =.05) and at a similar risk of myocardial infarction (9.2% vs 10.5%, P =.26), stroke (3.6% vs 4.7%, P =.11), and hospitalization for unstable angina (25.1% vs 24.5%, P = 0.90). Pravastatin significantly reduced the risk of all prespecified cardiovascular events in all LIPID patients. Relative treatment effects in women did not differ significantly from those in men (P >.05) for any events except hospitalization for unstable angina. There were too few events to demonstrate separately significant effects in women; the estimated relative risk reduction with pravastatin was 11% (95% CI -18%-33%) for coronary heart disease death or nonfatal myocardial infarction, 18% (95% CI -25%-46%) for coronary heart disease death, 16% (95% CI -19%-41%) for myocardial infarction, and 17% (95% CI -2%-33%) for coronary heart disease death, myocardial infarction, or coronary revascularization. CONCLUSIONS: The study had the largest secondary-prevention female cohort studied thus far, but was not adequately powered to show separate effects in women. Nevertheless, the results were consistent with the main results of this and other trials in showing reduced risks with cholesterol-lowering treatment.

Adult↗

Accuracy of the Australian National Death Index: comparison with adjudicated fatal outcomes among Australian participants in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study.

OBJECTIVE: To assess the accuracy of the Australian National Death Index (NDI) in identifying deaths and recording cardiovascular and cancer causes of death. METHODS: Adjudicated mortality data from Australian participants in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study up until September 1999 were used as reference. Nine hundred and eighty deceased subjects and 4,841 surviving subjects were matched to the NDI by name, date of birth, date of death and postcode. Matching rigour was confirmed by manual review. Deaths ascribed to cardiovascular and cancer causes within the NDI were also compared against LIPID-adjudicated causes. RESULTS: The NDI displayed 93.7% sensitivity and 100% specificity for the identification of deaths. Mis-recording of identifiers was responsible for 69% of known deaths not matching to the NDI and, if eliminated, would have increased the sensitivity to 98.0%. Among deceased subjects who matched to the NDI, cause of death was recorded in 96.2%. The sensitivity and specificity for cardiovascular deaths were 92.5% and 89.6%, respectively, and for cancer deaths 95.2% and 99.2%, respectively. CONCLUSION: Much of the inaccuracy of the NDI could potentially be overcome by the use of unique identifiers. Among deaths identified by the NDI, those due to cardiovascular disease are more likely to be inaccurately recorded than cancer-related deaths, probably because less uncertainty surrounds the presence or absence of terminal malignant disease.

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Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials.

BACKGROUND: Platelet glycoprotein IIb/IIIa inhibitors have been shown to reduce cardiac complications in patients undergoing percutaneous coronary intervention. The clinical efficacy of these drugs in acute coronary syndromes, however, is still unclear. We did a meta-analysis of all large randomised trials designed to study the clinical efficacy and safety of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes who were not routinely scheduled to undergo early coronary revascularisation. METHODS: Inclusion criteria were: randomisation of patients with acute coronary syndromes but without persistent ST elevation; comparison of a glycoprotein IIb/IIIa inhibitor with placebo or control therapy; non-recommendation of early coronary revascularisation during study-drug infusion; and enrollment of at least 1000 patients. Data on individual patients were obtained from all participants in these trials. FINDINGS: Six trials, enrolling 31402 patients, fulfilled the inclusion criteria. 30 days after randomisation, 3530 (11.2%) patients died or developed a myocardial infarction. At 30 days, a 9% reduction in the odds of death or myocardial infarction was seen with glycoprotein IIb/IIIa inhibitors compared with placebo or control (10.8% [1980/18297] vs 11.8% [1550/13105] events; odds ratio 0.91 [95% CI 0.84-0.98]; p=0.015). The relative treatment benefit was similar in subgroups of patients according to important clinical baseline characteristics; hence, the absolute treatment benefit was largest in high-risk patients. An unexpected and significant interaction was seen between sex and allocated treatment, with a treatment benefit in men (0.81 [0.75-0.89] but not in women (1.15 [1.01-1.30]). However, once patients were stratified according to troponin concentration, there was no evidence of a sex difference in treatment response, and a risk reduction was seen in men and women with raised troponin concentrations. Major bleeding complications were increased by glycoprotein IIb/IIIa inhibitors (2.4% [445/18297] vs 1.4% [180/13105]; p<0.0001), but intracranial bleeding was not (16 [0.09%] vs 8 [0.06%]; p=0.40). INTERPRETATION: Glycoprotein IIb/IIIa inhibitors reduce the occurrence of death or myocardial infarction in patients with acute coronary syndromes not routinely scheduled for early revascularisation. The event reduction is greatest in patients at high risk of thrombotic complications. Treatment with a glycoprotein IIb/IIIa inhibitor might therefore be considered especially in such patients early after admission, and continued until a decision about early coronary revascularisation has been made.

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