Christine Pollicino

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.

BACKGROUND Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant. METHODS A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site. INTERPRETATION Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individuals absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.

Randomized Controlled Trial of the Role of Positron Emission Tomography in the Management of Stage I and II Non-Small-Cell Lung Cancer

PURPOSE Positron emission tomography (PET) is a costly new technology with potential to improve preoperative evaluation for patients with non-small-cell lung cancer (NSCLC). There is increasing pressure for PET to be included in standard diagnostic work-up before decisions about surgical management of NSCLC. The resource implications of its widespread use in staging NSCLC are significant. METHODS A randomized controlled trial was conducted to investigate the impact of PET on clinical management and surgical outcomes for patients with stage I-II NSCLC. The primary hypothesis was that PET would reduce the proportion of patients with stage I-II NSCLC who underwent thoracotomy by at least 10% through identification of patients with inoperable disease. RESULTS One hundred eighty-four patients with stage I-II NSCLC were recruited and randomly assigned; 92% had stage I disease. Following exclusion of one ineligible patient, 92 patients were assigned to no PET and 91 to PET. Compared with conventional staging, PET upstaged 22 patients, confirmed staging in 61 and staged two patients as benign. Stage IV disease was rarely detected (two patients). PET led to further investigation or a change in clinical management in 13% of patients and provided information that could have affected management in a further 13% of patients. There was no significant difference between the trial arms in the number of thoracotomies avoided (P =.2). CONCLUSION For patients who are carefully and appropriately staged as having stage I-II disease, PET provides potential for more appropriate stage-specific therapy but may not lead to a significant reduction in the number of thoracotomies avoided.

Quality of Life and Survival in the 2 Years After Surgery for Non–Small-Cell Lung Cancer

PURPOSE Although surgery for early-stage non-small-cell lung cancer (NSCLC) is known to have a substantial impact on health-related quality of life (HRQOL), there are few published studies about HRQOL in the longer term. This article examines HRQOL and survival in the 2 years after surgery. PATIENTS AND METHODS Patients with clinical stage I or II NSCLC (n = 173) completed HRQOL questionnaires before surgery, at discharge, 1 month after surgery, and then every 4 months for 2 years. HRQOL was measured with a generic cancer questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ] C30) and a lung cancer-specific questionnaire (EORTC QLQ-LC13). Data were analyzed to examine the impact of surgery and any subsequent therapy, and to describe the trajectories of those who remained disease free at 2 years and those with recurrent cancer diagnosed during follow-up. RESULTS Disease recurred within 2 years for 36% of patients and 2-year survival was 65%. Surgery substantially reduced HRQOL across all dimensions except emotional functioning. HRQOL improved in the 2 years after surgery for patients without disease recurrence, although approximately half continued to experience symptoms and functional limitations. For those with recurrence within 2 years, there was some early postoperative recovery in HRQOL, with subsequent deterioration across most dimensions. CONCLUSION Surgery had a substantial impact on HRQOL, and although many disease-free survivors experienced recovery, some lived with long-term HRQOL impairment. HRQOL generally worsened with disease recurrence. The study results are important for informed decision making and ongoing supportive care for patients with operable NSCLC.

Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study

Objective:To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.Design, subjects and measurements:A nested case–control study examined circulating leptin and adiponectin levels in plasma obtained 4–6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events. The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis.Results:Relative risk (RR) increased across increasing leptin quartiles; the highest quartile compared with the lowest quartile was related to the highest risk (P for trend=0.002); the increased risk remained after adjustment for risk factors (P=0.018) or for obesity (P=0.038), but in the final model (adjusted for randomized treatment, other drugs, LIPID risk score, age and body mass index), the risk was attenuated (RR=1.61, 95% CI: 0.72–3.57, P for trend=0.34). Adiponectin did not predict cardiovascular events. Subjects randomly allocated to pravastatin had 6% lower leptin levels (P=0.04) than those allocated to placebo.Conclusion:Plasma leptin was a significant and independent predictor of recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.

The value of N-terminal fragment of brain natriuretic peptide and tissue inhibitor of metalloproteinase-1 levels as predictors of cardiovascular outcome in the LIPID study

AIMS We sought to determine the association between two major biomarkers, the inactive N-terminal fragment of brain natriuretic peptide (NT-proBNP) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and long-term cardiovascular outcomes in a cohort of subjects who had a myocardial infarction or unstable angina 3-36 months previously. METHODS AND RESULTS Plasma NT-proBNP and TIMP-1 were measured in a nested case control study of 250 randomly matched subject pairs enrolled in the long-term intervention with pravastatin in ischaemic disease (LIPID) and LIPID extended follow-up studies. Cases (n = 250) were defined as those who had a cardiovascular death, non-fatal myocardial infarction or stroke during the studies. Controls (n = 250) remained event-free for the same follow-up duration (average 2.5 years) as the matched cases. The relationships between cases and plasma NT-proBNP and TIMP-1 were adjusted for the LIPID risk score, treatment allocation and other biomarkers (CRP, IL-6 and white cell count), and examined using a multivariable conditional logistic regression model. NT-proBNP levels were significantly higher in the cases than in the controls [389 (152-864) vs. 198 (93-416) pg/mL, median (25%-75% percentiles), P < 0.001]. The odds ratio (OR) of recurrent cardiovascular events in individuals in the highest quartile was three times higher than those in the lowest quartile (95% confidence interval (CI) 1.8-5.1; P < 0.001). Similarly, TIMP-1 levels were significantly higher among cases compared with controls (806 vs. 736 pg/mL, median: highest vs. lowest quartile: OR 2.8, 95% CI 1.6-4.7; P < 0.001). After adjustment for the LIPID risk score, treatment with pravastatin and other biomarkers, both NT-proBNP and TIMP-1 predicted cardiovascular events significantly and independently of each other. CONCLUSION The study suggests that in subjects with stable ischaemic disease, NT-proBNP and TIMP-1 are independent predictive markers of coronary heart disease outcome.

Modeling the long-term cost-effectiveness of the caries management system in an Australian population

OBJECTIVES The Monitor Practice Program demonstrated that regular monitoring and noninvasive management of dental caries is effective in reducing the incremental DMFT (decayed, missing, and filled teeth) in patients, within the construct of a 3-year randomized clinical trial. This analysis evaluates the long-term cost-effectiveness of the preventive approach underpinning the Caries Management System, used in the general practice setting and modeled to the Australian population. METHODS An individual patient-simulation Markov model was developed to compare the long-term costs and outcomes of the Caries Management System versus standard dental care in a hypothetical sample representative of the Australian population. Eight Markov submodels were developed, representing eight molar teeth (excluding wisdom teeth), each consisting of 11 health states simulating the incidence and progression of dental caries, and future interventions such as fillings and crowns. Transition probabilities and costs assigned to health states were based on claims data from the second largest private health insurer in Australia. The economic evaluation was performed from the Australian private dental practitioner perspective. The incremental cost per DMFT avoided was calculated at three time points: 2 years, 3 years, and lifetime. Univariate sensitivity analysis was conducted to test the robustness of the results. RESULTS The incremental cost per DMFT avoided at 2 years, 3 years, and lifetime was estimated to be

Costing the components of pain management. Analysis of Trans-Tasman Radiation Oncology Group trial (TROG 96.05): One versus five fractions for neuropathic bone pain

1287.07,

Neither plasma coenzyme Q10 concentration, nor its decline during pravastatin therapy, is linked to recurrent cardiovascular disease events: A prospective case–control study from the LIPID study

1148.91, and

Measuring health system resource use for economic evaluation: a comparison of data sources.

1795.06, respectively. CONCLUSION The analysis suggests that the Caries Management System is most cost-effective in patients with a high risk of dental caries.