September 23rd, 2013
Selections from Richard Lehman’s Literature Review: September 23rd
CardioExchange is pleased to reprint this selection 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.
NEJM 19 Sep 2013 Vol 369
Randomized Trial of Preventive Angioplasty in MI (pg. 1115): Interventional cardiologists are gun dogs. A cardiologist who spots a stenosis wants to rush off and do something, like a springer spaniel hearing the rustle of a pheasant in the covert. Following the COURAGE study, we are trying to retrain our cardiology springers to ignore stable angina on optimal medical treatment: “No, Doc! Sit! Stay!” we tell them, as they quiver and make whimpering noises. But the PRAMI study will let them off the leash to stent at their hearts’ content when faced with acute myocardial infarction. Patients with ST elevation MI in five large British hospitals were randomised to receive immediate percutaneous intervention for the “culprit lesion” alone, or for as many significant stenoses as the cardiologist felt worth stenting. The trial was stopped early when it was clear that there was a big benefit from the latter approach: “Hazard ratios …were 0.34 (95% CI, 0.11 to 1.08) for death from cardiac causes, 0.32 (95% CI, 0.13 to 0.75) for nonfatal myocardial infarction, and 0.35 (95% CI, 0.18 to 0.69) for refractory angina” during a mean follow-up of 23 months. Woof!
JAMA 18 Sep 2013 Vol 310
Effect of Aliskiren on Progression of Coronary Disease in Patients With Prehypertension (pg. 1135): The AQUARIUS trial is just the latest in which Novartis fails to find a market for aliskiren, a renin blocker which was first licensed six years ago. They hoped to use it in people with “pre-hypertension” and coronary disease, and used a surrogate outcome: coronary atheroma measured by intravascular ultrasound. I can’t do better than to quote a tweet from Ken Covinsky: Rx of pre-htn (not a disease) wth aliskiren doesnt reduce atheroma volume (not an outcome) That was helpful. Not.
Anticoagulation With Otamixaban and Ischemic Events in NSTE-ACS (pg. 1145): At the moment my bedtime reading is Peter Gøtzsche’s damning indictment of the drug industry, Deadly Medicines and Organised Crime, which has just been published by Radcliffe. It’s a must-read. He describes all the ways that companies running trials manipulate the results or hide them altogether. But this week I am going to praise three industry run trials for their integrity, because they all show the opposite of what the manufacturer was hoping for. The first is the AQUARIUS trial described above, run by Steve Nissen, with company sponsorship, but without company control of the data; and the third is the HERA trial in The Lancet. In the middle lies this trial of otamixaban. It sounds like a treatment for otitis externa, but otamixaban is actually the latest direct factor X inhibitor to reach a crowded market. The TAO trial was designed by its manufacturer to “compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy.” But sadly for Sanofi, “Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding.” So onwards to another trial for some other indication—though it’s a fair bet it won’t involve a direct comparison with another drug in the same class.