Nonfatal MI (nonfatal + mi)

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PRESCRIBER, Issue 22 2007
Article first published online: 28 DEC 200
Glitazones: benefits outweigh the risks Following a review of the safety of rosiglitazone and pioglitazone, the European Medicines Agency (EMEA) has concluded that their benefits outweigh their risks in the approved indications. The review was prompted by reports of an increased risk of fractures in women and, in patients taking rosiglitazone, ischaemic heart disease. The EMEA concluded that prescribing information for rosiglitazone should now include a warning that, in patients with ischaemic heart disease, it should only be used after careful evaluation of each patient's individual risk, and the combination of rosiglitazone and insulin should only be used in exceptional cases and under close supervision. No change was considered necessary to the prescribing information for pioglitazone. Modern dressings no better? A systematic review has found only weak evidence that modern dressings are better than saline gauze or paraffin gauze for healing acute and chronic wounds (Arch Dermatol 2007;143: 1297-304). The analysis, which included 99 studies, found that only hydrocolloids were demonstrably better than older dressings for healing chronic wounds, and alginates were superior to other modern dressings for debriding necrotic wounds. There was no evidence that modern dressings offered superior overall performance to the older alternatives. Hospital inflation twice primary care level The cost of drugs prescribed in secondary care but dispensed in the community increased by 6.4 per cent in 2006 - twice the rate of inflation in primary care - according to the latest statistics on hospital prescribing in England. The increase follows a reduction in costs in 2005 after the introduction of the new PPRS scheme. Data from The Information Centre ( show that hospital medicines make up about 24 per cent of the NHS drugs budget. Secondary care has a consistently better record than primary care in prescribing lower-cost alternatives within therapeutic categories, eg simvastatin and pravastatin among the statins, omeprazole and lansoprazole among PPIs, and ACE inhibitors among drugs acting on the renin angiotensin system. The most expensive drug prescribed by hospital specialists and dispensed in the community is interferon beta. MHRA limits the use of fibrates The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that fibrates should now be reserved for the treatment of isolated severe hypertriglyceridaemia. They should be considered for hypercholesterolaemia only when a statin or other treatment is contraindicated or not tolerated. In the latest Drug Safety Update, the MHRA says there is insufficient evidence of long-term benefits from fibrates, and first-line use is no longer justified because the evidence for the benefits of statins is robust. The MHRA also warns that some breastfeeding infants have increased susceptibility to the adverse effects of codeine taken by their mother, and that St John's wort may affect the hepatic metabolism of any anticonvulsant. Annual zoledronic acid infusion cuts mortality after hip fracture Once-yearly infusion of zoledronic acid (Aclasta) after hip fracture reduces deaths over a two-year period by 28 per cent compared with placebo, US investigators say (N Engl J Med 2007;357:1799-809). The HORIZON Recurrent Fracture Trial randomised 2127 men and women (mean age 75) within 90 days of surgery for hip fracture to zoledronic acid 5mg yearly or placebo. Mortality over 1.9 years of follow-up was 9.6 per cent with zoledronic acid and 13.3 per cent with placebo. Zoledronic acid also significantly reduced the rate of any new clinical fractures (by 35 per cent) and new clinical vertebral fractures(by 45 per cent),but the lower rate of hip fracture (2.0 vs 3.5 per cent with placebo) was not statistically significant. Rivastigmine patch for mild to moderate AD Rivastigmine (Exelon) is now available as a transdermal patch for the treatment of mild to moderate Alzheimer's disease. Applied once daily, the patch delivers 9.5mg per 24 hours and, says manufacturer Novartis, is associated with a lower incidence of nausea and vomiting than a comparable oral dose. The patch is available in two strengths: 4.6mg per 24hr is equivalent to oral doses of 3 or 6mg per day, and the 9.5mg per 24hr patch is equivalent to 9 or 12mg per day orally. The recommended dose of the patch is 9.5mg per day; both strengths cost 83.84 for 30 patches. Women more aspirin resistant than men? The cardioprotective effect of low-dose aspirin may be lower in women than men, say Canadian investigators (BMC Medicine 2007;5:29 doi: 10.1186/1741-70155-29). Their meta-analysis of 23 randomised trials involving a total of 113 494 participants found that aspirin significantly reduced the risk of nonfatal but not fatal myocardial infarction (MI). About one-quarter of the variation in its effects on nonfatal MI was accounted for by the sex mix of the trial population. Separating the results by sex showed the reduction in risk with aspirin use was statistically significant in men (relative risk, RR, 0.62) but not in women (RR 0.87). Look after physical health of mentally ill GPs and other primary care workers should take more responsibility for the physical health of their mentally ill patients, say advocacy groups. Mind and Body: Preventing and Improving Physical Health Problems in Patients With Schizophrenia points out that the mental health needs of patients with schizophrenia are met in secondary care, but their physical health needs should be met in primary care. In particular, the metabolic effects of antipsychotics may lead to obesity, diabetes and cardiovascular disease, and weight gain in particular is a frequent reason for nonadherence to treatment. The Mind and Body Manifesto was developed by SANE, The Mental Health Nurses Association, The National Obesity Forum and The Disability Rights Commission and sponsored by Bristol-Myers Squibb Pharmaceuticals Limited and Otsuka Pharmaceuticals (UK) Ltd. Copies are available from Health eCard costs Some costs quoted in our article on the Health eCard (The Health eCard: the way ahead for medical records?,5 October issue, pages 28-9) have been revised: the card and initial download will cost patients 39.50, and GPs will be entitled to charge patients 10 per annum for subsequent downloads. NICE appraisals of cytokine inhibitors in RA NICE has endorsed the use of the anti-TNF agents adalimumab (Humira), etanercept (Enbrel) and infliximab (Remicade), normally in conjunction with methotrexate, for the treatment of active RA when methotrexate and another DMARD have failed (also see New from NICE below). NICE has provisionally concluded, subject to consultation, that abatacept (Orencia) should not be recommended for the treatment of RA. Boots and BMJ launch health advice site is a new website providing information about health and medicines for the public produced by Boots using information provided by the BMJ Publishing Group. The website covers many of the topics already available from NHSDirect, with perhaps more information about available treatments. Diabetes care shows small improvement The third National Diabetes Audit in England and Wales has found that more people with diabetes were achieving the targets set by NICE for cholesterol levels, glycaemic control and blood pressure in 2005/06 - but younger patients were doing less well. Overall, the HbA1C target of ,7.5 per cent was achieved in 60 per cent of people with diabetes compared with 58 per cent in 2004/05. However, HbA1C was >9.5 per cent in 30 per cent of children and young people, of whom 9 per cent experienced at least one episode of ketoacidosis. More topics for NICE New topics referred to NICE include clinical guidelines on ovarian cancer, coeliac disease and stable angina, public health guidance on preventing cardiovascular disease, and technology appraisals on insulin detemir (Levemir) for type 1 diabetes, several treatments for cancer and hepatic and haematological disorders, and biological therapies for juvenile arthritis. New from NICE NICE appraisal on anti-TNFs for RA Since NICE published its first appraisal of agents acting against tumour necrosis factor-alpha (anti-TNFs) for the treatment of RA in 2002, the product licences for etanercept (Enbrel) and infliximab (Remicade) have changed and a new agent, adalimumab (Humira), has been introduced. The anti-TNFs act in different ways. Infliximab is a chimeric monoclonal antibody that binds to TNF-alpha, neutralising its activity. Etanercept, a recombinant human TNF-alpha receptor fusion protein, and adalimumab, a human-sequence antibody, both bind to TNF-alpha and block its interaction with cell surface receptors. Adalimumab also modulates some biological responses induced or regulated by TNF-alpha. These agents are recommended for adults with severe active RA (defined as a disease activity score - DAS28 - greater than 5.1) who have already tried two disease-modifying drugs, including methotrexate (if not contraindicated). Prior treatment should have been of at least six months' duration, including two months at the standard dose (unless limited by toxicity). Anti-TNFs should normally be prescribed with methotrexate; when this is not appropriate, etanercept and adalimumab may be prescribed as monotherapy. Treatment with an anti-TNF should be continued beyond six months only if there is an adequate response (defined as an improvement in DAS28 of at least 1.2). Data from the British Rheumatology Society Biologics register show that, after six months, 67 per cent of patients met NICE criteria for an adequate response; this declined to 55 per cent at 18 months. The basic annual cost of treatment is 9295 for adalimumab 40mg on alternate weeks or etanercept 25mg twice weekly; infliximab costs 3777 for a loading dose, then 7553-8812 depending on dose. Assuming no progression of disability, the incremental costs per QALY (compared with sequential DMARDs) were 30 200 for adalimumab, 24 600 for etanercept and 39 400 for infliximab. There are no direct comparative trials of the anti-TNFs, and their clinical trial findings are not directly comparable. Unless other factors determine treatment choice, NICE therefore recommends the least expensive. If the first anti-TNF is withdrawn within six months due to an adverse event, a second may be tried. [source]

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PRESCRIBER, Issue 21 2007
Article first published online: 3 DEC 200
NSAIDs and SSRIs increase GI bleeding Taking an NSAID and an SSRI increases the risk of GI bleeding more than six-fold compared with taking neither drug, a meta-analysis shows (Aliment Pharmacol Ther online: 5 Oct 2007; doi:10.1111/j.1365-2036.20 07.03541.x). The analysis included four observational studies involving a total of 153 000 patients, and 101 cases reported in postmarketing surveillance. Compared with nonuse, the odds ratio for upper GI haemorrhage in patients taking an SSRI alone was 2.36; the number needed to harm (NNH) was 411 for one year's treatment in patients aged over 50 with no risk factors. For those taking an SSRI and an NSAID, it was 6.33 (NNH 106). Of 22 cases where treatment duration was known, the median time to onset of bleeding was 25 weeks and five occurred within one month. The MHRA warns of this interaction in its latest issue of Drug Safety Update, noting: ,corticosteroids, antiplatelet agents, and SSRIs may increase the risk of GI ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin'. MHRA warning on NSAID safety The MHRA reminds prescribers of new restrictions on prescribing piroxicam and the risks associated with ketorolac and ketoprofen in its latest Drug Safety Update (2007;1:Issue 3). Treatment with piroxicam should now only be initiated by a specialist as a second-line drug; patients currently taking it should be reviewed at the next routine appointment. Piroxicam is no longer indicated for any acute indications. These restrictions do not apply to topical piroxicam (Feldene gel). Ketorolac and ketoprofen are associated with a higher risk of adverse GI effects than other NSAIDs. The MHRA advises prescribers to adhere to the licensed indications that limit oral ketorolac therapy to seven days (two days for continuous iv or im use) and the maximum dose of ketoprofen to 100-200mg. Inhaled steroids may increase the risk of pneumonia in patients with COPD. In the TORCH study (N Engl J Med 2007;356:775-89), fluticasone (Flixotide) and fluticasone plus salmeterol (Seretide) were associated with a significantly increased risk compared with salmeterol alone. The MHRA recommends vigilance for signs of pneumonia or bronchitis in patients with COPD who are treated with inhaled steroids; affected patients should have their treatment reconsidered. Other issues reviewed in Drug Safety Update include: a more intense reaction after revaccination with the pneumococcal vaccine, Pneumovax II; exacerbation of osteonecrosis of the jaw by dental surgery in patients taking a bisphosphonate; a lower maximum dose for lorazepam (4mg for severe anxiety, 2mg for severe insomnia) rare reactions with botulinum toxin; and the cardiovascular safety and risk of fractures with the glitazones. Antibiotic resistance GPs who reduce their antibiotic prescribing achieve a significant reduction in bacterial resistance, a study from Wales has shown (Br J Gen Pract 2007;57:785-92). The analysis of 164 225 coliform isolates from urine samples submitted from 240 general practices found a 5.2 per cent decrease in ampicillin resistance in practices with the greatest reductions in total antibiotic prescribing. Overall, ampicillin resistance decreased by 1 per cent for every reduction of 50 amoxicillin prescriptions per 1000 patients. Trimethoprim resistance showed a similar trend. Mortality risk with discontinuing statins Patients who discontinue statin therapy after acute stroke are almost three times more likely to die than those who do not, an Italian study shows (Stroke 2007;38:2652-7). Follow-up of 631 patients discharged after acute stroke revealed that 39 per cent discontinued statin therapy. The hazard ratio for all-cause mortality in the first 12 months was 2.78 compared with those who continued treatment; this compared with a hazard ratio of 1.81 for stopping antiplatelet therapy. The authors argue that patient care should be improved during the transition from hospital to outpatient primary care. ACEI ARB = ADRs Combining an ACE inhibitor and an angiotensin-II receptor blocker increases the risk of adverse effects in patients with symptomatic left ventricular dysfunction, according to a US study (Arch Intern Med 2007;167:1930-6). Meta-analysis of four trials involving a total of 17 337 patients followed up for about two years showed that, compared with therapy including an ACE inhibitor, combined treatment increased the risk of stopping treatment due to adverse events by 38 per cent in patients with heart failure and by 17 per cent in patients with MI. The authors estimate that, for every 1,000 patients treated, 25 will discontinue treatment due to adverse effects and 17 will develop renal dysfunction. WOSCOPS: statin protection continues Pravastatin reduces the risk of death years after treatment has stopped, according to a follow-up of the WOSCOPS study (N Engl J Med 2007;357:1477-86). The West of Scotland Coronary Prevention Study originally randomised men with hypercholesterolaemia but no history of myocardial infarction (MI) to treatment with pravastatin or placebo. After five years, the combined incidence of death from CHD or nonfatal MI was reduced from 7.9 to 5.5 per cent in the treatment group. During the 10 years after completion of the trial, the incidence of the combined end-point was 8.6 per cent in those originally assigned to pravastatin and 10.3 per cent in the placebo group. All- cause mortality was also reduced over the entire 15-year period. The proportions of patients still taking a statin in the middle of this period, ie five years after the trial ended, were 39 per cent of the placebo group. Prescribing policies on HRT need reappraisal Health authorities should reconsider their policy on prescribing HRT, the International Menopause Society (IMS) says. In an open letter, the IMS says current safety concerns over HRT use are founded, but have been misinterpreted in observational studies, such as the Women's Health Initiative, that led to changes in guidelines. The IMS says HRT is the most effective treatment for vasomotor and urogenital symptoms and the risk:benefit profile is favourable until age 60. Low-dose oestrogen or the transdermal route of administration may lead to a more favourable risk profile. Flu vaccine does cut morbidity and mortality Following The Lancet's commentary doubting the effectiveness of flu vaccination (Lancet Infectious Diseases 2007;7:658-66), a US cohort study has found that it does reduce morbidity and mortality (N Engl J Med 2007;357:1373-81). The observational study included 713 872 person-seasons in older people living in the community over a 10year period from 1990 to 2000. Vaccination was associated with a 48 per cent reduction in the risk of death and a 27 per cent reduction in admission for pneumonia or flu. These benefits changed little in subgroups or with age. Copyright 2007 Wiley Interface Ltd [source]

Clinical Implications of QRS Duration and QT Peak Prolongation in Patients with Suspected Coronary Disease Referred for Elective Cardiac Catheterization

M. Nadeem Attar M.D., M.R.C.P.
Background: The electrocardiogram (ECG) remains a simple, universally available, and prognostically powerful investigation in heart failure, and acute coronary syndromes. We sought to assess the prognostic utility of clinical, angiographic, and simple ECG parameters in a large cohort of patients undergoing elective cardiac catheterization (CC) for known or suspected coronary artery disease. Methods: Consecutive consenting patients undergoing CC for coronary disease were enrolled at a single tertiary center. Patient data, drug therapy, catheter reports, and ECG recordings were prospectively recorded in a validated electronic archive. The primary outcome measure was death or nonfatal myocardial infarction (MI) over 1 year or until percutaneous or cardiac surgical intervention. Independent prognostic markers were identified using the Cox proportional hazard model. Results: A total of 682 individuals were recruited of whom 17(2.5%) died or suffered a nonfatal MI in 1 year. In multivariate analysis QRS duration (ms) (HR 1.03 95% CI 1.01,1.05, P = 0.003), extent of coronary disease (HR 2.01 95% CI 1.24,3.58, P = 0.006), and prolonged corrected QT peak interval in lead I (HR 1.02 95% CI 1.00,1.03, P = 0.044) were independently associated with death or nonfatal MI. Receiver-operator characteristic (ROC) analysis for the multivariate model against the primary end point yielded an area under the curve of 0.759 (95% CI 0.660,0.858), P < 0.001. Conclusions: QRS duration and QT peak are independently associated with increased risk of death or nonfatal MI in stable patients attending for coronary angiography. [source]

Late outcomes of drug-eluting versus bare metal stents in saphenous vein grafts: Propensity score analysis

Robert J. Applegate MD
Abstract Objective: To compare late outcomes with the routine use of drug-eluting stents (DES) compared with bare-metal stents (BMS) during percutaneous intervention (PCI) of saphenous vein grafts (SVGs). Background: Safety concerns >1 year from stent implantation have been raised about DES used for PCI of SVGs in a small randomized clinical trial. However, there are few studies comparing late outcomes of DES and BMS in routine clinical practice. Methods: Clinical outcomes (nonfatal MI, cardiac mortality) were assessed in 74 consecutive patients who received BMS and 74 consecutive propensity score matched patients that received DES for PCI of SVGs. Clinical follow-up was censored at 2 years 30 days for both stent groups. Results: At 2 years, the hazard ratio for DES compared with BMS for PCI of SVGs for target vessel revascularization was 0.54 (0.21,1.36), nonfatal MI or cardiac death was 0.68 (0.27,1.68), cardiac mortality 1.19 (0.32,4.45), and stent thrombosis 0.49 (0.09,2.66). Similar outcomes were observed stratified by propensity score quintile. Conclusions: The routine clinical use of DES for PCI of SVGs was associated with a safety profile that was similar to that of bare metal stents with a clear trend toward a less frequent need for reinterventions. 2008 Wiley-Liss, Inc. [source]