1Consultant, 3 Specialty Trainee, Department of Anaesthesia and Peri-operativeMedicine, Guy’s and St Thomas’NHS Foundation Trust, London, UK 2Honorary Senior Lecturer, King’s College London, UK 4 Research Fellow inMedical Statistics, 6 Professor ofMedical Statistics, London School of Hygiene and Tropical Medicine, London, UK 5Associate Professor, PennCentre for Peri-operativeOutcomes Research and Transformation, University of Pennsylvania, USA 7Consultant, Department of Anaesthesia, Peri-operativeMedicine and Intensive Care, TorbayHospital, UK 8Associate Professor, Department of Anaesthesiology and Intensive Care, Institute of Tuberculosis and LungDiseases, Warsaw, Poland 9Associate Professor, University of Auckland, NewZealand 10 Professor, Department of Anaesthesia and PerioperativeMedicine, University of Cape Town, South Africa 11Associate Professor, Department of Anaesthesia and PainMedicine, University ofOttawa, Canada 12 Professor, TheChineseUniversity of HongKong, Hong Kong 13Consultant, Division of Anaesthesiology, SingaporeGeneral Hospital, Singapore 14Associate Professor, Department of Anaesthesia and PainMedicine, University of Toronto, Canada 15 Professor, Department of Anaesthesia, University Hospital RWTHAachen, Germany 16Associate Professor, Peri-operativeMedicine and Intensive Care, Karolinska University Hospital, Sweden 17 Professor, Department of Anaesthesiology, Critical Care and Pain, TataMemorial Hospital, Mumbai, India 18 Professor, Department of Anaesthesiology and PerioperativeMedicine,MonashUniversity, Melbourne, Australia 19 Professor, St James’Hospital, Dublin, Ireland 20Consultant, Department of Anaesthesia and Intensive Care, AziendaOspedale-Universit a di Padova, Italy 21Associate Professor, Department of Anaesthesiology, Aga KhanUniversity Hospital, Pakistan 22 Professor andChair, DivisionAnaesthesia, Intensive Care and EmergencyMedicine, UniversityMedical Center Utrecht, Netherlands

Background and purposeElevated blood pressure (BP) is prevalent and modifiable and has been hypothesized to lead to increased risk of dementia.DataData on 2 593 629 people from the UK Clinical Practice Research Database aged ≥40 years with a BP measurement between 1992 and 2011 and no prior record of dementia were collected.MethodsPoisson regression models were used to study the association between BP and physician‐diagnosed dementia. BP is believed to fall during the prodromal phase of dementia development, so associations were investigated by categories of time since BP measurement (<5, 5–10, >10 years) and by subtypes of dementia.ResultsDuring a median follow‐up of 8.2 years, 65 618 cases of dementia were observed: 49 161 Alzheimer's, 13 816 vascular dementia and 2541 other subtypes. For each 10 mmHg higher systolic BP, the future dementia risk was 9.2% (95% confidence interval 8.4%–10.0%) lower, but this association varied markedly by time since BP measurement. Short‐term associations with dementia were inverse with a 15.8% (15.5%–17.0%) lower risk 0–5 years after BP measurement and a 5.8% (7.7%–4.4%) lower risk 5–10 years after BP measurement. During the period >10 years after BP measurement, dementia risk was only 1.6% (0.1%–3.0%) lower, with a 4.3% (2.5%–6.0%) lower risk of Alzheimer's disease and a 7.0% (3.8%–10.2%) higher risk of vascular dementia.ConclusionsElevated BP is associated with decreased risk of dementia in the short term, possibly due to reverse causation. Long‐term associations of BP with dementia are less marked and differ by dementia subtype.

AIMS The second Randomized Intervention Treatment of Angina (RITA-2) trial compares an initial strategy of PTCA with continued medical management in patients with arteriographically proven coronary artery disease. This paper employs resource use data collected in the trial to compare the health service costs of the two strategies over 3 years follow-up. METHODS AND RESULTS 1018 patients were randomized, 504 to PTCA and 514 to continued medical management. Health service resource use data were collected prospectively on all patients. Hospital unit costs were estimated in collaboration with five U.K. centres. PTCA patients underwent more subsequent coronary arteriograms, but subsequent (non-randomized) PTCAs were more common in patients randomized to medical management (118 procedures in 102 patients) compared to those randomized to PTCA (73 procedures in 62 patients). The likelihood of undergoing CABG was similar in the two groups. The use of antianginal medications was higher in patients randomized to an initial strategy of medical management. There was an overall mean additional cost per patient over 3 years in patients randomized to PTCA of pound 2685 (95% CI pound 2074- pound 3322). CONCLUSIONS In RITA-2, the cost of an initial strategy of PTCA exceeded the cost of an initial strategy of medical management by 74% over 3 years.

Background Results of trials, comparing percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass grafting (CABG), indicate that rates of death or myocardial infarction are similar. with either treatment strategy. Management with PTCA is, however, associated with an increased requirement for subsequent, additional revascularisation. Coronary stents, used as an adjunct to PTCA, reduce restenosis and the need for repeat revascularisation. The aim of the Stent or Surgery (SoS) trial was to assess the effect of stent-assisted percutaneous coronary intervention (PCI) versus CABG in the management of patients with multivessel disease.Methods In 53 centres in Europe and Canada, symptomatic patients with multivessel coronary artery disease were randomised to CABG (n=500) or stent-assisted PCI (n=488). The primary outcome measure was a comparison of the rates of repeat revascularisation. Secondary outcomes included death or Q-wave myocardial infarction and all-cause mortality. Analysis was by intention to treat.Findings All patients were followed-up for a minimum of 1 year and the results are expressed for the median follow-up of 2 years. 21% (n=101) of patients in the PCI group required additional revascularisation procedures compared with 6% (n=30) in the CABG group (hazard ratio 3.85, 95% CI 2.56-5-79, p<0.0001). The incidence of death or Q-wave myocardial infarction was similar in both groups (PCI 9% [n=46], CABG 10% [n=49]; hazard ratio 0.95, 95% CI 0.63-1.42, p=0.80). There were fewer deaths in the CABG group than in the PCI group (PCI 5% [n=22], CABG 2% [n=8]; hazard ratio 2.91, 95% CI 1.29-6-53, p=0.01).Interpretation The use of coronary stents has reduced the need for repeat revascularisation when compared with previous studies that used balloon angioplasty, though the rate remains significantly higher than in patients managed with CABG. The apparent reduction in mortality with CABG requires further investigation.

Objectives. This 6-month follow-up analysis sought to assess whether the early reduction of mortality obtained with a 6-week treatment course of lisinopril or glyceryl trinitrate, or both, in unselected patients with acute myocardial infarction outlasts therapy and is still present after 6 months. The primary outcome of the 6-month follow up was the combined end point of mortality and severe left ventricular dysfunction.Background. The assumption was that the early benefit on remodeling processes may be maintained over a longer period of time, even in the absence of treatment.Methods. A total of 19,394 patients with acute myocardial infarction were randomized, within 24 h of onset of symptoms to a 6-week treatment course of oral lisinopril or open control and, according to a 2 x 2 factorial design, to glyceryl trinitrate or open control. Randomized treatments were stopped after 6 weeks in the absence of specific indications, and the patients were followed up for 6 months.Results. At 6 months, among patients randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was found between patients with and without glyceryl trinitrate therapy (18.4% vs, 18.9%, 2p = 0.39).Conclusions. Although the systematic administration of glyceryl trinitrate started early and continued for 6 weeks after acute myocardial infarction does not yield evidence of benefit, early treatment with lisinopril appears to improve prognosis. This effect seems to carry over the first 6 months from randomization, even after treatment withdrawal.

Large randomised trials have demonstrated that fibrinolytic therapy can reduce mortality in patients with suspected acute myocardial infarction (AMI). The indications for, and contraindications to, this treatment in some categories of patient are disputed, examples being late presentation, elderly patients, and those in cardiogenic shock. This overview aims to help resolve some of the remaining uncertainties. From all trials of fibrinolytic therapy versus control that randomised more than 1000 patients with suspected AMI, information was sought and checked on deaths during the first 5 weeks and on major adverse events occurring during hospitalisation. The nine trials included 58 600 patients, amongwhom 6177 (10·5%) deaths, 564 (1·0%) strokes, and 436 (0·7%) major non-cerebral bleeds were reported. Fibrinolytic therapy was associated with an excess of deaths during days 0-1 (especially among patients presenting more than12 h after symptom onset, and in the elderly) but this was outweighed by a much larger benefit during days 2-35. This "early hazard" should not obscure the very clear overall survival advantage that is produced by fibrinolytic therapy. Benefit was observed among patients presenting with ST elevation or bundle-branch block (BBB)—irrespective of age, sex, blood pressure, heart rate, or previous history of myocardial infarction or diabetes—and was greater the earlier treatment began. Among the 45 000 patients presenting with ST elevation or BBB the relation between benefit and delay from symptom onset indicated highly significant absolute mortality reductions of about 30 per 1000 for those presenting within 0-6 h and of about 20 per 1000 for those presenting 7-12 h from onset, and a statistically uncertain benefit of about 10 per 1000 for those presenting at 13-18 h (with more randomised evidence needed in this latter group to assess reliably the net effects of treatment). Fibrinolytic therapy was associated with about 4 extra strokes per 1000 during days 0-1: of these, 2 were associated with early death and so were already accounted for in the overall mortality reduction, 1 was moderately or severely disabling, and 1 was not. This overview indicates that fibrinolytic therapy is beneficial in a much wider range of patients than is currently given such treatment routinely.

It has yet to be established whether substantial reduction of plasma lipids will lead to retardation, and to what extent and how quickly, of diffuse and focal coronary atheroma.The Multicentre Anti-Atheroma Study (MAAS) is randomised double-blind clinical trial of 381 patients with coronary heart disease assigned to treatment with diet and either simvastatin 20 mg daily or placebo for 4 years. Patients on simvastatin had a 23% reduction in serum cholesterol, a 31% reduction in low-density lipoprotein cholesterol, and a 9% increase in high-density lipoprotein cholesterol compared with placebo over 4 years. Quantitative coronary angiography was done at baseline, and after 2 and 4 years. 167 patients (89%) on placebo and 178 (92%) on simvastatin had baseline and follow-up angiograms. In the placebo group there were reductions in mean lumen diameter (-0.08 mm) and in minimum lumen diameter (-0.13 mm). Treatment effects were + 0.06 (95% Cl 0.02 to 0.10) and + 0.08 mm (0.03 to 0.14) for mean and minimum lumen diameter, respectively (combined p = 0.006). Patients on placebo had an increase in mean diameter stenosis of 3.6% and the treatment effect of simvastatin was - 2.6% (- 4.4 to - 0.8). Treatment effects were observed regardless of diameter stenosis at baseline. On a per-patient basis, angiographic progression occurred less often in the simvastatin group, 41 versus 54 patients; and regression was more frequent, 33 versus 20 patients (combined p = 0.02). Significantly more new lesions and new tote I occlusions developed in the placebo group, 48 versus 28, and 18 versus 8, respectively. There was no difference in clinical outcome. The numbers of patients who died or had a myocardial infarction were 16 and 14 in the placebo and simvastatin groups, respectively. In the placebo group more patients underwent coronary angioplasty or re-vascularisation, 34 versus 23 on simvastatin.The trial showed that 20 mg simvastatin daily over 4 years reduces hyperlipidaemia and slows progression of diffuse and focal coronary atherosclerosis.