{"id":33144,"date":"2012-11-19T11:34:04","date_gmt":"2012-11-19T16:34:04","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=33144"},"modified":"2012-11-19T11:34:47","modified_gmt":"2012-11-19T16:34:47","slug":"selections-from-richard-lehmans-literature-review-november-19th","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/11\/19\/selections-from-richard-lehmans-literature-review-november-19th\/","title":{"rendered":"Selections from Richard Lehman\u2019s Literature Review: November 19th"},"content":{"rendered":"

CardioExchange is pleased to reprint selections from Dr. Richard Lehman\u2019s\u00a0weekly journal review blog<\/a>\u00a0at\u00a0BMJ.com<\/a>. Selected summaries are relevant to our audience, but we encourage members to engage with the\u00a0entire blog<\/a>.<\/em><\/p>\n

JAMA\u00a0 14 Nov 2012\u00a0 Vol 308<\/strong><\/p>\n

Multivitamins and Cancer Prevention in Men (pg. 1916):<\/strong> Last week we learned that male doctors who were randomised to take a daily multivitamin preparation had cardiovascular events and died from them at exactly the same rate as those who took placebo for a median of 11.2 years. This week we learn<\/a> that they also died of cancer at the same rate, but by aggregating all the cancers you can just squeeze a statistically significant reduction in total cancer incidence out of the data. So come on, fellow male physicians: if 83 of us take a daily multivitamin for 11 years, one of us may avoid a cancer, though all of us will die at the same rate. Golden docs in trials all must\/ As chimney-sweepers, come to dust.<\/p>\n

Atorvastatin with or without a PCSK9 Antibody in Primary Hypercholesterolemia (pg. 1891):<\/strong> After a while, it gets a bit boring restating the fact that the only lipid lowering agents which have been shown to reduce clinical events are the statins. I believe that this is true of people with primary hypercholesterolaemia as well as of the general population, but if I am wrong, I know I will quickly be corrected. The most potent dose of statin that most people can tolerate is atorvastatin 80mg, but in some individuals even this is not enough to reduce LDL-C sufficiently. In this phase 2 trial<\/a>, Sanofi and Regeneron Pharmaceuticals tried out their new monoclonal antibody targeted at serum proprotein convertase subtilisin\/kexin 9 (PCSK9), which has the effect of reducing degradation of LDL receptors and so gets more LDL removed from the circulation. This sounds very neat and ingenious, and it does actually work: SAR236553 lowers LDL-C more in primary hypercholesterolaemia than does atorvastatin 80mg, and can be added to it for extra effect. Time to give it a catchy name and start marketing it? I would say not. Just because monoclonal antibodies sound like magic bullets, that doesn\u2019t mean that they are either harm-free or as effective as surrogate end-point reduction would suggest. In the real world, there is no substitute for real time and real results: we need quite lengthy phase 3 studies.<\/p>\n

Lancet\u00a0 17 Nov 2012\u00a0 Vol 380<\/strong><\/p>\n

Type-2 Diabetes Screening and Population Mortality Over 10 Years (pg. 1741):<\/strong> Here is one of the most important papers to have come out of UK general practice for some years<\/a>. It reports a cluster randomised trial with 9.6 years of follow-up which shows that screening for diabetes in high risk individuals has no benefit. It used a validated risk score to identify 15,000 individuals at risk who were offered screening, with a control group of 4,137 who were not. Individuals identified with diabetes were then randomized to usual care or intensive multifactorial treatment. I know that at least one of the investigators was expecting the trial to demonstrate benefit, but there was simply no reduction in all-cause, cardiovascular, or diabetes-related mortality within 10 years. And this trial not only shows a lack of benefit from the early detection of diabetes, but also casts grave doubt on the doctrine of a \u201clegacy effect\u201d from early tight control, as claimed by the UKPDS investigators.<\/p>\n

BMJ\u00a0 17 Nov 2012\u00a0 Vol 345<\/strong><\/p>\n

Primary and Secondary Prevention with New Oral anticoagulants for Stroke Prevention in AF:<\/strong> The newer anticoagulants are at least as good as warfarin for the primary and secondary prevention of stroke in atrial fibrillation, but it is hard to know which is best among them\u2014the direct thrombin inhibitors (dabigatran) and the factor Xa inhibitors (for example, rivaroxaban, apixaban). Several cardiovascular academics here<\/a> look at the differences between them in the trials and reach the conclusion that only head-to-head new trials will tell us anything substantive.<\/p>\n

Arch Int Med\u00a0 12 Nov 2012\u00a0 Vol 172<\/strong><\/p>\n

New Oral Anticoagulants in Patients Receiving Antiplatelet Therapy After ACS (pg. 1537):<\/strong> The Archives are beginning to annoy me, by printing too many interesting papers which I have to report on. Here is a piece with the cumbrous title \u201cUse of New-Generation Oral Anticoagulant Agents in Patients Receiving Antiplatelet Therapy After an Acute Coronary Syndrome: Systematic Review and Meta-analysis of Randomized Controlled Trials<\/a>.\u201d Those of you who have been following these reviews for some years (or actually reading the primary literature\u2014heaven forbid) will know what a keenly fought-over field this is. But for pharma companies hoping for their next blockbuster drug, a very disappointing one. \u201cThe use of anti-Xa or direct thrombin inhibitors is associated with a dramatic increase in major bleeding events, which might offset all ischemic benefits in patients receiving antiplatelet therapy after an ACS\u201d is the conclusion of these Hungarian meta-analysts. How dramatic? Well, at least three-fold: not quite all the rooms in Bluebeard\u2019s castle, but enough to warn you off opening any more doors.<\/p>\n

Prediction Rule for Death and Severe Disability After Acute Ischemic Stroke (pg. 1548):<\/strong> Now here is a hen\u2019s tooth: a clinical prediction rule that doctors may actually use<\/a>. It is called the PLAN Score and it is a bedside prediction rule for death and severe disability following acute ischaemic stroke. Not the first ever, of course, but perhaps the least cumbersome, factoring in just 9 easily available clinical variables. It had a C statistic (look this up if you don\u2019t know what it is) in the mid 0.8 range for death by 30 days, severe dependence, and death within one year.<\/p>\n

Drugs that Target the Renin-Angiotensin-Aldosterone System and Risk for\u00a0Angioedema (pg. 1582):<\/strong> Angio-oedema is a common side effect of angiotensin-converting enzyme inhibitors (ACEIs) and this American database study seeks to compare these with\u00a0 angiotensin receptor blockers (ARBs), and much less-used the direct renin inhibitor aliskiren, while adjusting for a range of possible confounding factors. It\u2019s a reasonable study <\/a>which reaches the conclusion you\u2019d expect: ARBs are less likely to cause your face to swell up while aliskiren is too seldom used for us to be sure, but it\u2019s probably worse than ACEIs. Researchers using the vastly bigger UK Clinical Research Database should be churning out this kind of thing by the shedload every week.<\/p>\n","protected":false},"excerpt":{"rendered":"

This week’s topics include multivitamins and cancer prevention in men, a comparison of atorvastatin with or without a PCSK9 Antibody in primary hypercholesterolemia, type-2 diabetes screening and population mortality over 10 years, and more.<\/p>\n","protected":false},"author":475,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[1566,1497,1567,585,341,416,329,1565,1139,1519,1563,1564,489],"class_list":["post-33144","post","type-post","status-publish","format-standard","hentry","category-general","tag-acute-coronary-syndrome","tag-acute-ischemic-stroke","tag-angioedema","tag-atorvastatin","tag-atrial-fibrillation","tag-cancer","tag-cardiovascular-risk","tag-diabetes-screening","tag-men","tag-multivitamins","tag-pcsk9-antibody","tag-primary-hypercholesterolemia","tag-stroke-prevention"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/33144","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/475"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=33144"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/33144\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=33144"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=33144"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=33144"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}