{"id":31016,"date":"2012-08-13T13:00:30","date_gmt":"2012-08-13T17:00:30","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=31016"},"modified":"2012-08-13T13:00:30","modified_gmt":"2012-08-13T17:00:30","slug":"selections-from-richard-lehmans-literature-review-august-13th","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/08\/13\/selections-from-richard-lehmans-literature-review-august-13th\/","title":{"rendered":"Selections from Richard Lehman\u2019s Literature Review: August 13th"},"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 8 Aug 2012\u00a0 Vol 308<\/strong><\/p>\n

More Research is\u2026Readily Available (pg. 575):<\/strong> When Stephen Lock was editor of the BMJ, he banned the expression \u201cfurther research is needed\u201d on the grounds that further research is always needed. Here is a piece by John Oiannidis which argues that further research is very often badly needed – and that it is very often instantly achievable, simply by using data that has already been collected. But to do that, researchers need to know where the data are to be found, and to have automatic access to it. The rather clunky title of this essay, \u201cThe Importance of Potential Studies That Have Not Existed and Registration of Observational Data Sets<\/a>\u201d, does little justice to a powerful discussion of issues that lie at the very heart of the coming revolution in research methodology. We are \u2013 I hope \u2013 on the verge of an era where all data from every human trial ever carried out will be available to any researcher; and more than that, an era when every clinical encounter will in principle be available for analysis after the removal of patient identifiers. As Ioannidis points out, much of this is already possible and is not being done. The \u201cpotential studies that have not existed\u201d which he refers to are investigations that could settle contentious issues \u2013 if only people would take the trouble to look at datasets that are already in existence.<\/p>\n

(Note for pedants: I have deliberately used \u201cdata\u201d both as a plural and as a singular in two sentences, because this is common practice. I bet that within ten years, data will have followed \u201cmedia\u201d and become uniformly singular. Personally, I don\u2019t like it; but that\u2019s language for you. It\u2019s like a bacteria. Neuter plurals counted as singular in ancient Greek.)<\/p>\n

Normal Weight, Diabetes, and Risk of non-Cardiovascular Death (pg. 581):<\/strong> Here\u2019s another significant insight<\/a> into the enigma that is labelled \u201ctype 2 diabetes\u201d. We all know of people who have this condition despite being of normal weight (BMI less than 25), and in fact in the five large cohorts looked at here, the proportion of subjects with normal BMI at the time of onset of diabetes varied between 9 and 21%, with a mean of 12%. The striking finding of this analysis is that these individuals have a doubling of mortality risk at 15 years compared with overweight or obese individuals with T2DM. And oddly enough, this is mainly accounted for by non-cardiovascular causes of death.<\/p>\n

Total Cholesterol Levels in U.S. Kids (pg. 591):<\/strong> But now for a really puzzling observation: between 1988 and 2006, the mean level of total cholesterol in American children has declined. During this period, US kids aged between 6 and 19 have become fatter and less active. I don\u2019t know what can account for this, and nor does the writer of the editorial<\/a> that accompanies it, except to call it a reason for optimism.<\/p>\n

Lancet\u00a0 11 Aug 2012\u00a0 Vol 380<\/strong><\/p>\n

Statins and Diabetes (pg. 565):<\/strong> One way to push people over the arbitrary threshold of 7.0 mmol\/L fasting glucose is to give them a thiazide diuretic: another is to give them a statin. They are then officially \u201cdiabetic\u201d, but does that mean that they are condemned to progressive beta-cell failure? In the case of thiazides, the answer is simply no. In the case of statins, we don\u2019t know: but we do know that the cardiovascular benefits of continuing the drug easily outweigh any negative effects from hyperglycaemia. This analysis of data from the JUPITER trial<\/a> confirms that this applies across the glucose range, including people at high risk of diabetes.<\/p>\n

HDL-C and MI Protection (pg. 572):<\/strong> I tried counting the authors of this celebrated mendelian randomisation study of plasma high density lipoprotein cholesterol and myocardial infarction<\/a>, but I had to give up due to vertigo. There must be about 120. If you believe them, there is no likelihood of any causal link between HDL-C levels and protection from MI. If you don\u2019t believe them, you can start all over again: perform two mendelian randomisation analyses. First, use as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and test this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, use as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, also test a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.<\/p>\n

Statins: Treat Everyone, Treat to Risk, or Treat to Target? (pg. 581):<\/strong> You\u2019ll note that the preceding study did confirm that LDL-C is causal in adverse cardiovascular events; and only LDL-lowering strategy that we know to prevent CV events is statin therapy. Now there are three camps where statins are concerned: the \u201cput them in the water supply\u201d camp at one extreme, and the \u201ctreat to target\u201d camp at the other, and half way between the \u201ctreat to risk\u201d camp. This meta-analysis of individual data<\/a> from 27 randomised trials confirms that statins lower cardiovascular risk at all levels, with the most pronounced effect of course at the top of the risk scale. Some friends of mine would argue that statins taken from the age of say 16 would prevent atheroma altogether; others among my friends rail at the mass medication of society and seem to wish that statins had never been invented; I myself think they should be offered to everyone above some arbitrary age, say 50. In their editorial, Shah Ebrahim and Juan Casas appear to agree, though their last paragraph does offer the tempting alternative of moving to Mauritius.<\/p>\n

Reviewing Hypertension Treatment (pg. 591):<\/strong> The management of \u201chypertension\u201d in primary care is one of the most boring jobs we do, and I fear we don\u2019t do it very well. Most of the individuals who trudge regularly into our surgeries every six months gain no benefit whatsoever from the drugs we give them \u2013 the number needed to prevent one stroke is typically 100-400 – and most of the time we don\u2019t even measure their BP adequately anyway. We medicate the herd for small benefit, while often struggling with the patients at highest risk. Fortunately most of the drugs we use are cheap and safe, but the market is so huge that drug companies continue to develop new drugs which might work for some subgroups of patients with resistant hypertension. This review usefully lists them<\/a>, but the real revolution is likely to come from a different direction \u2013 devices and procedures which permanently reset the sympathetic nervous system. In ten years\u2019 time, I wouldn\u2019t be surprised to see renal sympathetic denervation becoming a routine procedure: or will it be continuous carotid stimulation?<\/p>\n

BMJ\u00a0 11 Aug 2012\u00a0 Vol 345<\/strong><\/p>\n

Clopidogrel and PPIs:<\/strong> In laboratory tests of platelet function, proton pump inhibitors cancel out the effect of clopidogrel because they inhibit the P450 2C19 enzyme. So if you look at a cohort of people who are taking clopidogrel (with aspirin) you might expect to find a higher rate of coronary events in those who are also taking a PPI. And in fact, as this study from the UK GP Research Database<\/a> shows, there is a 30% or so higher risk in this group, if you look at the cohort as a whole. In fact there is an even higher risk difference in non-vascular death, which begins to make you wonder whether there is something else going on in these people who are taking PPIs. Maybe the groups are not comparable: and the cunning authors then go on to test this hypothesis by looking at within individual differences in CV outcomes during periods on and off PPI treatment. Here the effect direction is reversed. This is intriguing, and probably means that most people can take clopidogrel and PPIs together with impunity: but there are some loose ends here. Somebody needs to repeat this exercise using another database, looking more precisely at the individual clinical reasons for co-treatment with PPIs, aspirin and clopidogrel.<\/p>\n

Pharma Innovation:<\/strong> The most important contribution to this week\u2019s BMJ is undoubtedly an analysis by Donald Light and Joel Lexchin<\/a> of the truth behind the \u201cinnovation crisis\u201d in the pharmaceutical industry. They demonstrate that it is a widely touted myth, aimed at putting pressure on regulatory agencies to help the poor ailing industry by setting a lower bar for licensing new products. In fact only one in ten products has any added clinical value, whereas the FDA is currently granting \u201cpriority status\u201d to 44% of new drugs. The remaining 90% simply drive up health costs without adding benefit, and most industry effort is put into developing such me-too drugs. And this is a highly successful business model: pharmaceutical R&D budgets rose by $34.2bn between 1995 and 2010, while profits rose by $200bn.\u00a0 The pharmaceutical industry could innovate if it had the incentives to, and indeed does do so one time in ten: but most of the time it is creaming off easy money from health systems that can ill afford it.<\/p>\n","protected":false},"excerpt":{"rendered":"

This week’s topics include using existing data for new research; normal weight, diabetes, and non-CVD death; cholesterol levels in U.S. kids; statins and diabetes; HDL-C and MI protection; statin treatment; hypertension treatment; clopidogrel and PPIs; and an analysis behind the “innovation crisis” of the pharmaceutical industry.<\/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":[283,210,334,1283,454,1314,1407,1406,1404,584,469,1405],"class_list":["post-31016","post","type-post","status-publish","format-standard","hentry","category-general","tag-children","tag-cholesterol","tag-clopidogrel","tag-hdl-c","tag-hypertension","tag-myocardial-infarction","tag-pharmaceutical-industry","tag-proton-pump-inhibitor","tag-research","tag-statins","tag-type-2-diabetes","tag-weight"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/31016","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=31016"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/31016\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=31016"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=31016"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=31016"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}