September 16th, 2013

Selections from Richard Lehman’s Literature Review: September 16th

CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.

NEJM  29 Aug-12 Sep 2013  Vol 369

Oral Apixaban for the Treatment of Acute VTE (pg. 799): When comparing a new fixed-dose anticoagulant with conventional warfarin based anticoagulation, what do you look for? Thrombotic events, death, major bleeding? Yes, certainly. But what makes the comparison meaningful? That depends largely on how well the warfarin group were kept within the target INR range. In the AMPLIFY trial, 5395 patients with new episodes of venous thromboembolism were randomised to apixaban twice daily for 6 months or to conventional treatment with enoxaparin followed by warfarin. The context of the trial is not described in the main paper, but from the appendix it seems to have been conducted in 28 countries, and it takes 14 pages to list the contributing centres which recruited patients. Half of them recruited fewer than ten subjects, and 31 centres recruited only one. There were numerous exclusion criteria. Overall, these hundreds of centres only managed to keep their patients within the INR target area of 2-3 for 61% of the time. So if you’re happy to accept that as your comparator, then apixaban is non-inferior to warfarin and causes fewer major bleeds. Otherwise, you might want to ask yourself why the drug companies who paid for this trial chose this way of doing it, and whether that 61% figure is what you hope for when you give warfarin to your patients.

D2B Time and Mortality Among Patients Undergoing Primary PCI (pg. 901): Over the fifteen years I’ve been watching the journals, I’ve had a grandstand view of the shift from thrombolysis to immediate percutaneous intervention as the treatment of choice for myocardial infarction. And still the shift goes on towards ever-quicker PCI, because there is good evidence that time means myocardium. This important study shows that in the USA, median door-to-balloon time in hospitals fell from 83 minutes to 67 minutes over a three year period (the years July 2005 to June 2006 compared with July 2008 to June 2009). But in-hospital mortality did not change. This is interesting but hard to interpret: much depends on what happens to the patient before reaching the hospital door. My take on all the studies—including those of thrombolysis given by paramedics—is that the sooner you reopen the coronary supply, the better. What matters critically is blockage to reopening time, not any subset of that.

Pretreatment with Prasugrel in Non–ST-Segment Elevation Acute Coronary Syndromes (pg. 999): Moving swiftly on, we get to this week’s issue of the mighty journal. Here the first paper concerns itself with a comparatively small issue in the treatment of myocardial infarction: the timing of prasugrel administration in relation to percutaneous intervention for non-ST-elevation MI. Do I see your eyes glaze over? OK, we are not all interventional cardiologists, but for the record, if you give the prasugrel before coronary catheterization, you get more bleeds but no extra benefit.

JAMA Intern Med  9 Sep 2013  Vol 173

Contraindicated Initiation of β-Blocker Therapy in Patients Hospitalized for HF (pg. 1547): I got interested in heart failure in the early 1990s, and helped to draw up the first Oxfordshire guideline on the subject. Avoid beta-blockers, we said in 1993. Then, oops, in came the first carvedilol trials, and a couple of years later we said introduce them cautiously in all stable patients without contra-indications. Now it is a matter of dogma that all patients with systolic heart failure should be on one of the beta-blockers shown to reduce mortality in a randomized trial. No choice in the matter: you must take these because you will live longer. But most patients dying from heart failure don’t want to live longer but to feel better. And in unstable heart failure, going on a beta-blocker can make you a whole lot worse. Here is a short report on the way that beta-blockers are handed out in US hospitals to heart failure patients who are at risk of clinical instability. The lead author is Kumar Dharmarajan, a brilliant young researcher who is interested in all the ways we mishandle heart failure patients when they come to hospital. He will know he has succeeded when he has nothing left to write about.

Lancet  31 Aug – 14 Sep 2013  Vol 382

Vascular and Upper GI Effects of NSAIDS (pg. 769): The disclosure of concealed harms that led to the withdrawal of Vioxx (rofecoxib) in 2004 suddenly made us aware of the cardiovascular risks of non-steroidal anti-inflammatory drugs, and from then on league tables of harm have appeared regularly. Not that they have had all that much effect. Diclofenac, which carries a risk at least as great as Vioxx, remains a highly popular drug that is still prescribed long-term to innumerable high-risk patients. Now, from the Coxib and traditional NSAID Trialists’ (CNT) Collaboration, comes what is probably the definitive examination of the relative risks of the various NSAIDs. As usual naproxen comes out best for lack of cardiovascular risk, while the others jostle for position in the harm league.

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