November 12th, 2012
Selections from Richard Lehman’s Literature Review: November 12th
CardioExchange is pleased to reprint selections from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA 7 Nov 2012 Vol 308
Multivitamins in the Prevention of CVD in Men (pg. 1751): Vitamins are vital amines; you need them to stay healthy; therefore the more you take, the healthier you will be. It’s amazing how pervasive this delusion is: it led even Linus Pauling, three times Nobel prizewinner, to make an ass of himself. And it sells billions of dollars’ worth of useless tablets. Did I really see a two-storey emporium called Ye Olde Vitamin Shoppe in New York City, or had someone slipped some absinthe into my Starbucks? Anyway, you are a doctor, so you should know better than to take this rubbish: here is the Physicians Health Study II. “Among this population of US male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.” Antioxidants, antischmocksidants.
Platelet Function During Extended Prasugrel and Clopidogrel Therapy for ACS Treated Without Revascularization: Of course there are sound mechanistic reasons why antioxidants should prevent cardiovascular disease; it is entirely perverse that that they don’t. And there are sound mechanistic reasons why prasugrel should lead to better outcomes than clopidogrel when used with aspirin to prevent ischaemic outcomes following ACS without ST-elevation. In the TRILOGY ACS trial, patients who had not undergone revascularization had their platelet reactivity measured, and sure enough prasugrel was uniformly more effective than clopidogrel at inactivating platelets. But O perversity! “Among those in the platelet substudy, no significant differences existed between prasugrel vs clopidogrel in the occurrence of the primary efficacy end point through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes.” Sound mechanistic reasons count for nothing in real life, yet again.
NEJM 8 Nov 2012 Vol 367
Statin Use and Reduced Cancer Mortality (pg. 1792): “Statin use in patients with cancer is associated with reduced cancer-related mortality. This suggests a need for trials of statins in patients with cancer.” Denmark stars again: the investigators assessed mortality among patients from the entire Danish population who had received a diagnosis of cancer between 1995 and 2007, with follow-up until December 31, 2009. They found a 15% reduction in overall mortality in people with 13 types of cancer taking statins of any kind and any dose, driven by a reduction in cancer-related mortality. So their conclusion is absolutely spot-on: we need trials of statins in cancer.
Ann Intern Med 6 Nov 2012
Comparative Effectiveness of Sulfonylurea vs. Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes (pg. 601): After the fall of the Roman Empire, the developed world entered centuries of intellectual darkness marked by minimal scientific progress, a period often called the “Dark Ages.” After many centuries, progress resumed and eventually accelerated during the Renaissance. In a similar fashion, knowledge about the comparative effectiveness of drugs to treat type 2 diabetes is finally beginning to emerge from 40 years of stagnation. This period of darkness and the current reawakening provide critically important lessons for contemporary medicine about the use of surrogate end points in drug development, regulatory oversight, and the hazards associated with reliance on commercial funding for pivotal clinical trials. OK, that’s the standard Lehman rant about diabetes trials. But it wasn’t written by me: there should be quotation marks around those opening sentences, which were actually written by Steve Nissen. That’s slightly ironic, given how much commercial funding he has received for conducting pivotal trials: but his editorial is still well worth reading. He is commenting on a large cohort study which compares the effects of sulfonylureas and metformin on CVD outcomes (acute myocardial infarction and stroke) or death. It’s nothing so ground-breaking as a randomized trial, and it simply confirms that use of sulfonylureas compared with metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death, of about 20%. It doesn’t tell us if metformin is beneficial, or sulfonylureas are harmful, or a bit of both. And these drug classes appeared half a century ago…