December 1st, 2014
Selections from Richard Lehman’s Literature Review: December 1st
Richard Lehman, BM, BCh, MRCGP
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 27 November 2014 Vol 371
Atenolol vs. Losartan in Children and Young Adults with Marfan’s Syndrome (pg. 2061): Antoine Bernard-Jean Marfan (1858-1942) was a French paediatrician who lived in the happy era of medicine when you could affix your name to new signs, symptoms, laws, and syndromes, and Marfan bagged at least one of each for himself. But, ironically, his name is immortalised by a syndrome distinctly different from the one he described—a fate which has also overtaken Drs Alzheimer and Asperger. Marfan (pronounced to rhyme with enfant) presented a girl with arachnodactyly and digital contractures, whereas Marfan (to rhyme with bar-fan) describes a hereditary disorder of connective tissue without contractures. In the full blown form of this autosomally dominant condition, the leading cause of death is cardiovascular disease, mainly progressive aortic root dilatation and dissection. To prevent this, beta-blockers have been generally used since an open label trial showed survival benefit in 1994. But theoretical reasons have been put forward that angiotensin receptor blockers might work better, and this trial pitted atenolol against losartan. At the end of three years, in 608 subjects aged 6 months to 25 years, there was no detectable difference between the agents. The primary outcome was a surrogate—the aortic root z score. And the trial was not adequately blinded. Be that as it may, it is good to note that in both groups the aortic root actually decreased in diameter as the study progressed.
JAMA 26 November 2014 Vol 312
Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients (pg. 2135): Back in those heroic days of medicine I alluded to above, a second year medical student at Johns Hopkins called Jay McClean isolated an anticoagulant from dog’s liver and called it heparin. This was in 1916, and had he called it McCleanin we might still remember him. It took another 20 years for a sufficiently pure and non-immunogenic liver extract to be produced for use as a human anticoagulant, and a further 50 years for low molecular weight heparins to be manufactured. However, although new is always more expensive, it is not necessarily better. A distinguished international line-up of authors use data from 2344 patients in the Prophylaxis for Thromboembolism in Critical Care Randomized Trial to determine whether LMWH dalteparin is worth the extra asking price compared with unfractionated heparin in ICU inmates. They conclude that it is. In fact, there is a cost saving driven by lower rates of pulmonary embolism and heparin induced thrombocytopenia, and corresponding lower overall use of resources with LMWH. Incidentally, old fashioned heparin is now made largely from pig intestine and bovine lung, which you’d think might preclude its use among hundreds of millions of religionists.
Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Japanese Patients 60 Years or Older With Atherosclerotic Risk Factors (OL): By far the most dangerous ingredient in the proposed polypills is aspirin, and the evidence that it prevents cardiovascular disease in the general population is very slender. But populations vary, and so do risk scores in those populations. Officially, 98.5% of people living on the islands of Japan are “ethnically Japanese,” but according to Wikipedia this has no established veracity, or indeed meaning. However, we can take it that they are ethnically largely similar, and may have subtly different physiological traits from Europeans or North Americans. The Japanese Primary Prevention Project (JPPP) was designed to determine whether once daily, low dose, enteric coated aspirin reduces the total number of atherosclerotic events (ischaemic heart disease and stroke) compared with no aspirin in Japanese people 60 years or older with hypertension, dyslipidemia, or diabetes mellitus. Nearly 15 000 people were randomised. Result: “Once daily, low dose aspirin did not significantly reduce the risk of the composite outcome of cardiovascular death, nonfatal stroke, and nonfatal myocardial infarction among Japanese patients 60 years or older with atherosclerotic risk factors.”
JAMA Intern Med November 2014 Vol 174
Outcomes After Out-of-Hospital Cardiac Arrest Treated by Basic vs. Advanced Life Support (OL): Probably the aspect of clinical medicine I will miss least is the requirement to waste three hours annually undergoing “life support training.” I can now confess that for several years I managed to go under the radar and skip these sessions. And I have been a doctor for 40 years without ever encountering an out of hospital cardiac arrest. If I do, I shall pump the chest as hard and frequently as I can and hope that someone has called an ambulance. Even this may be too much—nobody knows, because this is an evidence free area. This Less is More paper reports on outcomes following out of hospital cardiac arrest, according to whether basic or advanced life support was employed. There was a considerable difference. Those given advanced life support were less likely to survive and significantly more likely to suffer neurological damage.
Lancet 29 November 2014 Vol 384
Mechanical vs. Manual Chest Compression for Out-of-Hospital Cardiac Arrest (OL): While the basic concept of performing chest compressions for out of hospital cardiac arrest has never been subjected to a randomised trial, mechanical chest compressors have been compared with humans. By mechanical criteria, they perform better. But in trial after trial, PARAMEDIC being the latest, they make no difference to mortality. Which really makes you want to do that trial with no compressions as the control; but nobody would let you. A huge, earnest industry of well meant meddling stands to suffer. If you so much as lift an eyebrow during a CPR training lecture, you are made to feel at best like an incompetent, at worst like a murderer.
Relation Between D2B Times and Mortality After Primary PCI Over Time (OL): The leading figures in US cardiac outcomes research combine to examine trends in door to balloon (D2B) time and mortality after ST elevation myocardial infarction in 423 American hospitals, between January 2005 and December 2011. Their findings are paradoxical. Shorter patient specific door to balloon times were consistently associated at the individual level with lower in-hospital mortality and six month mortality. And during those six years, the median D2B fell from 86 minutes to 63. “By contrast, risk adjusted in-hospital and six month mortality at the population level, independent of patient specific D2B times, rose in the growing and changing population of patients undergoing pPCI during the study period.” So the investigators are explaining a paradox of worsening overall outcomes by a change in the population over that period. But if that is true, don’t we have to repeat all the trials comparing pPCI with thrombolysis, for example? I’m not entirely sure what is going on here. I leave these things to Harlan Krumholz, who is final author on this paper.