February 25th, 2013

Selections from Richard Lehman’s Literature Review: February 25th

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.

NEJM   21 Feb 2013  Vol 368

Apixaban for Extended Treatment of VTE (pg. 368): These are stirring times in the wars of the fixed-dose oral clotbusters: drug companies are finally discovering if they have billion-dollar earners on their hands, or turkeys. Apixaban, a drug made by both Pfizer and Bristol-Myers Squibb, has had mixed fortunes so far, and is beginning to look rather like a large flavourless bird with a bib and a waddling gait. But all is not lost: turkey owners should take courage from Bernard Matthews and invent new ways of selling it. In this trial, Pfizer and BMS find a place where warfarin doesn’t already provide stiff competition and there is clinical equipoise. These are patients who have had unprovoked deep vein thrombosis and have completed their initial course of anticoagulation. The placebo arm shows a recurrence rate in this group of 8.8% in the first year; while those taking either 2.5mg or 5mg of apixaban twice daily had a recurrence rate of 1.7% and fewer bleeding events. So this is win-win-win: a reduction in VTE and bleeding and a lower than standard dose. Bootiful. But why no warfarin arm? Turkey is generally better than nothing, but is it generally better than chicken?

Extended Use of Dabigatran, Warfarin, or Placebo in VTE (pg. 709): And now to the competitor drug dabigatran, which is also beginning to show some signs of being a flightless bird. Boehringer Ingelheim, its manufacturer, again selected patients requiring long-term prophylaxis against recurrent venous thromboembolism for this trial, but very properly included a warfarin arm. Now the main emerging worry with dabigatran is that it increases coronary events, as well as bleeding events, for which there is no antidote. In this trial, there were 13 acute coronary events in the dabigatran group and 3 in the matched warfarin group. But in the warfarin group there were more bleeding events (treatable with vitamin K). In both the active groups there was a tenfold reduction of thromboembolism compared with placebo. So where does this take us? Certainly not straight on to a world without warfarin and INR testing. The big flaw in this trial was that it recruited from 33 countries with variable levels of INR control, such that the warfarin group were outside the target range for more than a third of the time. In all warfarin-comparator trials, this is the most important statistic. As a result, this trial strongly suggests that in a properly monitored population with VTE, warfarin is a safer drug than dabigatran, certainly in terms of cardiac events and possibly even for treatable bleeding.

Lancet  23 Feb 2013  Vol 381

Here is an issue of the Lancet which makes me think that all interventional cardiologists should have their equipment confiscated and be sent to a re-education camp called COURAGE, where they will have to parade at dawn and recite the entire contents of that key paper until they can do it without hesitation, repetition, or deviation. Release will be on condition that they never carry out any invasive procedure on a patient with stable angina without first ensuring that they are on optimal medical treatment. Any infringement will be followed by permanent detention in the notorious punishment block of the COURAGE camp.

CABG vs. PCI in patients with Three-Vessel Disease and Left Main Coronary Disease: 5-year follow-up of SYNTAX (pg. 629): The SYNTAX trial was set up long before COURAGE, when everyone assumed that if there is a narrowing in a coronary artery, the best outcomes must follow from unblocking or bypassing it. So in 85 centres across the US and Europe, 1800 patients with stable three-vessel disease were randomised to insertion of paclitaxel-eluting stents or coronary artery bypass grafting. Here are the five year results of the SYNTAX trial, reported as if COURAGE had never happened. “CABG should remain the standard of care for patients with complex lesions (high or intermediate SYNTAX scores). For patients with less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative. All patients with complex multivessel coronary artery disease should be reviewed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment.” No. no, no! Patients with stable angina of whatever cause should run a mile from all cardiac surgeons and interventional cardiologists, easing off a bit and taking GTN if they get any chest pain.

Development and Validation of SYNTAX Score II (pg. 639): There was a character called Dr Syntax who appeared in a series of comic novels from 1809 onwards, in which he stumbled pedantically through life insisting on the rules of grammar and little else. Perhaps he is the inspiration for this paper on the development and validation of the SYNTAX II score which looks at complex anatomical predictors of outcome from CABG versus stenting for stable angina, ignoring the fact that most patients will get the same outcomes from optimal drug therapy. Get real, SYNTAX doctors. Note that both these studies were paid for by Boston Scientific, which has an interest in selling TAXUSTM  stents.

COMPARE II: Abluminal Biodegradable Polymer Biolimus-Eluting Stent vs. Durable Polymer Everolimus-Eluting Stent (pg. 651): And so the Stent Wars go rumbling on, in trials which continue to recruit large numbers of patients with stable angina (1611 of them in this trial alone) selected for PCI for reasons which are not apparent in the text. This time it’s a biodegradable polymer-coated biolimus-eluting stent with a thin-strut everolimus-eluting stent coated with a durable biocompatible polymer. Like you care. These studies should really be hived off into a trade journal of some sort.

SORT OUT V: (pg. 661): Next article in Selling Stents, aka the Lancet: “Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention.” Worth a year’s subscription just to read it.

BMJ  23 Feb 2013  Vol 346

Efficacy and Safety of Dual Blockade of the Renin-Angiotensin System: When I learnt about the renin-angiotensin-aldosterone system in medical school 40 years ago, it was presented more as a physiological curiosity rather than a fundamental mechanism working with great rapidity to stabilise volume and electrolyte balance in most higher vertebrates. Then came the angiotensin-converting-enzyme inhibitors in the 1980s, followed by the angiotensin receptor blockers of the 1990s. Dual blockade of the RAAS became fashionable in both complicated hypertension and heart failure, until hard evidence started trickling in to show its harms and lack of effect. Even now, combining ACEIs and ARBs is written in to some guidelines and is widely practised in Europe and the USA. This meta-analysis adds in the direct renin blockers too. The ratio of harm to benefit of these combinations is almost always adverse—just don’t mix these drugs.

Diagnosis and Management of Pulmonary Embolism: How big is a piece of clot? A clottish question if ever there was, but one you need to answer if you are to have a useful discussion of pulmonary embolism. Our lungs are sieves for all sorts of debris: it is a part of their function, though largely unsung. Most of it does little harm, but big clots are bad news: “Pulmonary embolism is the most common cause of vascular death after myocardial infarction and stroke, and the leading preventable cause of death in hospital patients.” Here’s a really good review of the diagnosis and management of PE.

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