NEJM 15 July 2010 Vol 363
245 If anything can cause a company's profits to BLOOM, it's a new obesity drug. The BLOOM (Behavioural Modification and Lorcaserin for Overweight and Obesity Management) trial was funded by Arena Pharmaceuticals, who will be hoping for vast returns on the latest drug to target the serotonin receptor. Those with supernaturally good memories and profound knowledge of clinical pharmacology (OK, you can put your hand down, Jeff Aronson) will remember that there are actually three such receptors and that previous anti-obesity drugs such as fenfluramine and dexfenfluramine targeted them non-specifically. They worked fairly well for appetite suppression but were withdrawn because they could cause valvular heart defects and pulmonary hypertension. This is because cells around the heart valves and in the pulmonary vasculature contain 5HT2B receptors whereas the receptor you need to hit for appetite suppression is 5HT2C. Lorcaserin is powerfully specific for this receptor and Arena went out of their way to check their trial subjects regularly with echocardiograms which prove that it doesn't cause heart valve problems in the first two years. Whereas it certainly does help people lose weight and will be advertised as blooming wonderful if and when it gets it licence. http://content.nejm.org/cgi/content/abstract/363/3/245
266 In reviews of acute pulmonary embolism I look for two things: mention of it as a common cause of exacerbations in heart failure and COPD, and guidance about which patients need long-term anticoagulation. This article by two Italian authors doesn't fully satisfy either criterion. There's little mention of HF or COPD and although they say that "extended treatment requires a reassessment of the patient's risk-benefit ratio at periodic intervals" they fail to tell us how to calculate these risks and benefits.
http://content.nejm.org/cgi/content/extract/363/3/266
Lancet 17 July 2010 Vol 376
163 Droves of healthy people come to see doctors all year round to have blood pressure checks. If it's off target, their GP sees them every few weeks to make adjustments. Neither the timing, the place nor the health professional involved reflects any real logic. This ground-breaking study (TASMINH2) addresses these realities by passing management to the patient whose blood pressure is monitored at home with a reliable automatic device linked by an automated modem to the GP practice. If it remains high, the patient is given advice and if necessary additional drug treatment to reduce it. The group randomised to this intervention showed usefully better control of systolic BP at the end of a year. If this technology became widespread, we would save many GP appointments and improve control in most of our hypertensive patients.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60964-6/abstract
Lancet 10 July 2010 Vol 376
112 Exercise will also help you avoid a stroke; alcohol alas will not. Most of the other risk factors for stroke identified by the INTERSTROKE study are the ones you might expect, and the ten main ones account for nearly 90% of the risk. The oddest feature is the role of body mass index: when corrected for other factors, a high BMI actually seems protective, whereas a high waist-to-hip ratio is a substantial risk factor.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60834-3/abstract
NEJM 1 Jul 2010 Vol 363
36 Implantable cardioverter-defibrillators often go wrong due to lead failure, and they can lead to shockingly bad ends in heart failure. This trial assesses a new type of ICD which does not rely on venous access but is entirely subcutaneous, delivering shocks to the thorax close to the heart. Its success depended a lot on accurate positioning, and over the ten months of the trial it worked well and appropriately, though it's too soon of course to say anything about long-term reliability, let alone long-term mortality benefit.
http://content.nejm.org/cgi/content/abstract/363/1/36
1037 The well-conceived new Archives series called LESS IS MORE here lives up to its radical credentials: we are giving diabetic patients too many drugs for cardiovascular protection. Again, this flies in the face of what we have been taught over the last few years. It also seems to fly in the face of the calculation done by these authors that treating to targets for LDL-cholesterol and blood pressure results in gains of 1.5 and I.35 quality-adjusted years respectively. But they demonstrate that these overall gains are largely accounted for by the treatment of a small number of very high-risk individuals, and that the more drugs you put in, the more you are likely to achieve minimal benefit or actual harm. A key paper in the continuing debate about targets in type 2 diabetes.
http://archinte.ama-assn.org/cgi/content/abstract/170/12/1037
Arch Intern Med 28 Jun 2010 Vol 170
1024 If in doubt prescribe statins. Among patients with known cardiovascular disease, it is very hard to find any benefit once heart failure has set in. But prescribing statins to high-risk patients for primary prevention may be futile, according to this literature-based meta-analysis. It is a very hard paper to follow, however, with a fairly heterogeneous mix of studies which are not adequately characterised or analysed in these six pages: to do that would require twice the length, or ideally an entire database, which could then be analysed on an individual patient basis...
http://archinte.ama-assn.org/cgi/content/abstract/170/12/1024
1032 The JUPITER trial of rosuvastatin was stopped early and has been a source of controversy ever since. The acronym stands for Justification for the Use of Statins in Primary Prevention, but when JUPITER's data are fed into a meta-analysis like the one we've just seen, there is no such Justification. In fact the data of this trial are internally contradictory in a way that strongly suggests manipulation, according to this critical reappraisal, which suggests that Jove's ire should be directed at the role of commercial sponsors.
http://archinte.ama-assn.org/cgi/content/abstract/170/12/1032
1037 The well-conceived new Archives series called LESS IS MORE here lives up to its radical credentials: we are giving diabetic patients too many drugs for cardiovascular protection. Again, this flies in the face of what we have been taught over the last few years. It also seems to fly in the face of the calculation done by these authors that treating to targets for LDL-cholesterol and blood pressure results in gains of 1.5 and I.35 quality-adjusted years respectively. But they demonstrate that these overall gains are largely accounted for by the treatment of a small number of very high-risk individuals, and that the more drugs you put in, the more you are likely to achieve minimal benefit or actual harm. A key paper in the continuing debate about targets in type 2 diabetes.
http://archinte.ama-assn.org/cgi/content/abstract/170/12/1037
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