JOURNAL SNIPPETS November 3

NEJM 25 Nov 2010 Vol 363
2091 Quality improvement is actually, of course, a good thing in itself, and we need better ways of doing it and better ways of studying it. High quality outcomes research, carefully reflected on, is one essential input, and there are two good examples in this week's New England Journal. A general survey of North Carolina hospitals (see below, p.2124) produces a rather gloomy view of overall improvements in patient safety, but this study of mortality from allogeneic haematopoietic-cell transplantation is very much cheerier. The period 2003-7 showed an overall mortality fall of over 40% compared with a decade earlier, driven by significant decreases in the risk of severe GVHD; disease caused by viral, bacterial, and fungal infections; and damage to the liver, kidneys, and lungs. Further details are strictly for the haematologists: but it seems they have much to congratulate themselves about.
http://www.nejm.org/doi/full/10.1056/NEJMoa1004383

BMJ 27 Nov 2010 Vol 341
1144 Thrombolysis for acute occlusive stroke has been shown to be marginally beneficial in several RCTs, but the number of people over 80 in these trials is minuscule, whereas in real life, 30% of strokes occur in this age group. There is a presumption that the hazards of thrombolysis will be greater and the outcome difference less. This European registry study indicates that neither is true: thrombolysis remains beneficial for stroke beyond the age of 80.
http://www.bmj.com/content/341/bmj.c6046.full
1146 Any enthusiastic regular drinker of wine, will be delighted to note the PRIME study which confirms that by doing so you halve your chance of myocardial infarction. I suppose you also increase your chance of pancreatitis, cancers of the GI tract and stroke. Perhaps liver disease too, though the literature is surprisingly obscure at levels of intake below about 100u/week. The thing not to do is binge drink, which is a common pattern in Northern Ireland, and probably increases your baseline risk of MI. I think the further north you travel, the more dysfunctional alcohol use becomes, as warm oblivion becomes ever more desirable. As if to illustrate this point, a review of frostbite on p.1151 finds that nearly half of it is associated with alcohol use. I bet that means vodka or whisky in most cases, and wine alone hardly ever.
http://www.bmj.com/content/341/bmj.c6077.fullhttp://www.bmj.com/content/341/bmj.c5864.extract

Arch Intern Med 22 Nov 2010 Vol 170
1926 In studies of drugs that put people into hospital, warfarin usually comes near the top. This study looks at how combined platelet inhibition with aspirin plus clopidogrel compares in emergency department visits for haemorrhage-related events. The score is 2-1: 2.5 events per 1000 prescriptions of warfarin as compared with 1.2 events for aspirin/clopidogrel.
http://archinte.ama-assn.org/cgi/content/abstract/170/21/1892

JAMA 17 Nov 2010 Vol 304
2129 Like all doctors who survived their hospital jobs in the 1970s, I have some shocking memories. Oddly enough, though, some of them are happy too, as the shocks saved lives. The woman dragged out of a freezing canal with a core temperature of 28ºC who survived intact after 16 defibrillations; the 43-year old man with chest pain who went into VF just as we were putting the leads on his chest: all of us can still remember these kinds of event, while our futile attempts go forgotten days after. Surely an automated defibrillator must beat a sleep-deprived, dishevelled house doctor at achieving survival following in-hospital cardiac arrest? Actually no: another massive US cardiac outcomes study looks at the results of introducing automated defibrillators on to the wards of 204 hospitals and finds that results actually tend to be worse.
http://jama.ama-assn.org/cgi/content/abstract/304/19/2129
2137 The harmful effects of low-dose ionizing radiation are not well understood, but from about 100mSv upwards we are no longer talking about low doses, but the kind of exposures about which we have data from Hiroshima and Nagasaki. Alarmingly, such doses were received by a third of patients in this study of repeated myocardial perfusion scanning. OK, the majority of these people were over 60 and had heart disease, and would escape long-term harm: but it suggests that we are getting too gung-ho about exposing people to high energy photons from X-ray machines and unstable isotopes, and the cumulative damage which they cause.
http://jama.ama-assn.org/cgi/content/abstract/304/19/2137

Lancet 20 Nov 2010 Vol 376
1741 Many doctors in the 1990s went through a phase of taking low dose aspirin and recommending it to many of their patients with high blood pressure and/or type 2 diabetes. Then came a series of trials which showed that it doesn't work for primary prevention of cardiovascular events, even in groups who are at increased risk. But it does prevent about 25% of bowel cancer, according to this long-term follow up study of participants in 5 large aspirin trials, matched at a median of 18.3 years with mortality registers. The results suggest that you need to take about 75mg of aspirin for at least 5 years to achieve such protection, and the effect may be specific to the proximal colon. Thus in theory universal aspirin consumption, combined with a universal programme of screening sigmoidoscopy, could prevent most bowel cancer. However, an analysis like this can tell us little about adverse events, and we will only know for certain after a prospective trial lasting at least ten years.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61543-7/abstract

JOURNAL SNIPPETS November 2

JAMA 11 Nov 2010 Vol 304
2028 It's not often that you see a paper in JAMA written by a real working British GP - so congratulations to Louis Levene from Leicester for an excellent study that seeks to inform US practice by showing what happens to coronary heart disease mortality in relation to the recorded characteristics of individual primary care trusts. This was quite a statistical feat in itself, but would have been even more useful had it been done on an individual practice basis - after all, the data are out there, literally for all to see. Anyway, rejoice: CHD in the UK has fallen by nearly a half in the last decade, and although there are regional variations, these are not due to variations in the quality of general practice, except in the detection of high blood pressure, which could easily be remedied.
http://jama.ama-assn.org/cgi/content/abstract/304/18/2028

2059 A neat Commentary piece discusses the dilemmas of interventional cardiology in the light of the COURAGE and SYNTAX studies which show that medical treatment is as effective as percutaneous coronary intervention for stable coronary artery disease. When the first study appeared in 2007, interventional cardiologists were asked if they would now have the conviction of their COURAGE and stop putting stents into every stenosis they happened to see at angiography - what has been described as the "oculo-stenotic reflex". All immediate stenting is lumped together as "ad hoc PCI" and accounts for more than 80% of PCI in the USA; done for acute syndromes, it is generally appropriate, but in other situations, often not. This is a thoughtful, balanced discussion which however tactfully bypasses one factor which may keep ad hoc PCI going in the USA - money. There may be a double incentive - patients and HMOs may want to save the cost of a second angiography; and cardiologists and their institutions may just want the extra dollars they get for putting in a stent there and then. This piece argues that there where there is clinical doubt there should always be informed patient decision-making, even if this means taking a two-week pause between the diagnostic angiogram and the procedure.
http://jama.ama-assn.org/cgi/content/extract/304/18/2059

Lancet 13 Nov 2010 Vol 376

1658 A huge trial called SEARCH was set up in Oxford in 1998 in the hope of demonstrating that 80mg of simvastatin would be better than 20mg at preventing further coronary events in survivors of MI, and that additional benefit would result from lowering homocysteine. In fact it has shown neither. The high dose simvastatin group showed a 26-fold increase in significant myopathy, an expected fall in lipid cholesterol (LDL-C), but no significant difference in vascular events at a mean of 6.7 years. Yet in the summary this is taken to mean that high dose simvastatin is preferable, since that fits into a general meta-analysis of statin trials on p.1670. Although medicine has been taught alongside logic in Oxford for 850 years there is still room for improvement. Consider the following three statements:
- there is a continuous association between the observed level of LDL-C and coronary heart disease (CHD)
- all statin drugs lower LDL-C
- all statin drugs lower CHD in the same proportion that they lower LDL-C.

Does it therefore follow that:
(1)statin drugs lower CHD entirely by means of lowering LDL-C
(2) all drugs that lower LDL-C will lower CHD to the same degree as statins?
It would be good to think that any canny medieval Oxford schoolman would immediately answer no to both deductions, or rather "quod non erat demonstrandum".

In the case of (1), the best we can say is that this is a reasonable hypothesis, but a hard one to test. In the case of (2) we can say that this is a weak hypothesis, since every drug class has a mixture of actions, and so far no LDL-C lowering drugs other than statins have been shown to lower CHD. Nor should we prescribe them until they have. But the writing committees of these two studies, sharing a number of Oxford notables, behave more like theologians than logicians. LDL-cholesterol to them is an infallible surrogate, and anything that lowers it must be good, even though they have only studied statins. It's enough to make you want to burn your gown. As for The Lancet: this is the second time in two weeks that they've let triallists write a summary which misrepresents the result of trial which was negative for its primary end-point (SEARCH this week, VITAL last) - not good enough.

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60310-8/abstracthttp://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61350-5/abstract

BMJ 13 Nov 2010 Vol 341
1034 Do you like PROMs? When I was 16, I didn't mind queuing for tickets outside the Albert Hall and standing in the top gallery, but now being older, if you buy tickets on-line you can sit down and actually hear the players. This abbreviation also applies to patient-reported outcome measures, of the kind looked at in the context of heart failure. Suddenly these kinds of PROMs have become fashionable politically and get repeated mention in the White Paper "Liberating the NHS" - although they were never designed for service development but as end-points for clinical trials. Their quality and relevance varies widely, as you learn rapidly. This ground-breaking study devised an instrument with a high degree of inter-observer agreement to allow the assessment of PROMs in cardiovascular trials. Suffice to say that in many of the trials where they appear, they are used badly or irrelevantly, while in 70% of trials where they should appear, they don't.
http://www.bmj.com/content/341/bmj.c5707.full

Arch Intern Med 8 Nov 2010 Vol 170
1834 Delay From Symptom Onset to Hospital Presentation for Patients With Non–ST-Segment Elevation Myocardial Infarction. If you're a veteran scanner of titles in the US cardiovascular outcomes literature, the next thing you'll look for is the name of Harlan Krumholz in the authors list - ah yes, there it is, and so too is the name of Brahmajee Nallamothu, co-author of the thoughtful commentary piece on PCI in this week's JAMA. As a result of their work, and that of Henry Ting and John Spertus, who also appear in the credits, we know a huge amount in great detail about the workings of acute cardiology in the USA, despite the great variety of institutional arrangements. As a result of this exercise, for example, we know the exact time delay and clinical characteristics of 104 622 patients admitted to 568 US hospitals with NSTEMI - and realise that there has been no reduction in the delay time between 2001 and 2006. http://archinte.ama-assn.org/cgi/content/abstract/170/20/1834

1842 Now the interventional trials for ST-Elevation MI tell us that time means myocardium, so great efforts have been made in the US as in the UK to ensure that door-to-balloon time should be as short as possible. But what have we here? A study of 8771 patients admitted to a Michigan hospitals group between 2003 and 2008 which shows that although door-to-balloon time improved dramatically, outcomes remained the same. More data from UK studies quickly please: and since we do not have 568 acute hospitals and they all belong to one organisation, this should be a piece of cake compared with Harlan's work.
http://archinte.ama-assn.org/cgi/content/abstract/170/20/1842

1858 From time to time, serious medical journals like to publish pieces about chocolate, which are sure to get them a mention in the global news media. This research letter also involves women, thus allowing journalists to trot out their very funny jokes about the dear ladies and their chocolate. A group from Perth, Australia followed up a female cohort for 10 years to examine the effect of calcium supplements, and happened to ask about chocolate intake in their questionnaire. Here they report that chocolate consumption seems to have a dose-related protective effect against vascular disease in women. Ooh, come on girls, have another. http://archinte.ama-assn.org/cgi/content/extract/170/20/1857

WEBSITES UPDATE

As well as those websites already listed here are some more...

National Heart Forum
http://www.heartforum.org.uk/
Membership organisation bringing together organisations dealing with all areas and
risk factors in the field of chronic disease prevention. Information on NHF position
statements and policy work areas is available from the site, along with publications
such as the Healthy weight, Healthy lives toolkit, and the NHF modelling team’s
reports on obesity trends.

Heartstats
http://www.heartstats.org/
The British Heart Foundation’s regularly updated statistics website. Includes a wide
range of statistics on risk factors for chronic disease such as blood cholesterol,
smoking, physical activity and diet.

Blood Pressure Association
http://www.bpassoc.org.uk/
A charity supporting patients as well as healthcare professionals managing
hypertension. The site includes guides to the effects of high blood pressure, available
medication for its treatment and monitoring.

British Hypertension Society
http://www.bhsoc.org/
The British Hypertension Society acts as a medical and research forum for
hypertension. The Society produces guidelines on management of hypertension,
which are available from their site, and also links to NICE guidance.

Heart UK
http://www.heartuk.org.uk/
Website includes resources such as a cardiovascular disease prediction chart, JBS
risk assessor, and links to NICE guidelines and various publications.

ARTICLE ABSTRACTS FROM WATCH

NEJM 11 Mar 2010 Vol 362
886 This study looked at nearly 400,000 elective coronary angiographies performed in US hospitals over 4 years. Although preliminary investigations had been done in 84% of cases, the pick-up rate for significant coronary stenosis on angiography was 37.6%. Even these patients may have had little benefit, since COURAGE tells us that in stable angina, people do as well with optimal medical treatment as with percutaneous intervention. So 250,000 of these angiographies were definitely of no value to the patients, and that probably applies to most of the rest too. We need much better case selection for the catheter lab, with all its attendant risks of radiation and bleeding, not to mention cost in money and cardiologist time.
http://content.nejm.org/cgi/content/abstract/362/10/886

906 Thyroxine lowers cholesterol, as most of you will know from treating hypothyroid patients. Statins also lower cholesterol, as most of you will also know: but not always enough for the liking of lipidologists. They and the drug companies are forever in search of the next lipid lowering drug, an easy and potentially lucrative quest based on serum fat measurements of various kinds, as in this study of eprotirome, a thyromimetic compound. My word, it lowers LDL-cholesterol in statin-treated patients without harmful effects over a period of 12 weeks. What a breakthrough. Why, in another five years we might know if it benefits patients, or kills them.
http://content.nejm.org/cgi/content/abstract/362/10/906

Lancet 13 Mar 2010 Vol 375
This issue is dominated by the question of blood pressure variability and stroke, and by the intellectual presence of Peter Rothwell, in both the papers (pp.895, 906) and in a long review on p.938. This is impressive, and a Good Thing. Rothwell is a neurologist and is most interested in what happens to link blood pressure with stroke - a sudden process. Not surprisingly, strokes are linked with labile visit-to-visit SBP, indicating a tendency to sudden surges. At the moment in clinical practice we throw these babies away as bathwater. We disregard both pulse pressure and variation, and relax the moment we can enter a BP of less than 150/90 on the patient record. This needs to change following these papers. The evidence is that the best drugs to reduce BP variability are calcium channel blockers and thiazide diuretic, whereas most other drug classes actually increase BP variability. Bendroflumethiazide may well go back in the Polypill, because we know that most people over 65 need a BP reducing agent and that BFZ reduces both stroke and heart failure - albeit at the expense of harmless induced hyperglycaemia which we are inclined to mislabel as diabetes.
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60308-X/abstracthttp://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60235-8/abstracthttp://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60309-1/abstract

Arch Intern Med 8 Mar 2010 Vol 170
433 The meticulous work of outcomes assessment in real life situations continues, and nobody does it better than Harlan Krumholz and his team at Yale. This week they turn their attention to differences in patient survival after myocardial infarction by hospital capability to perform percutaneous coronary intervention. In the USA, as here in the UK, there is a big debate about how best to regionalise services to ensure that as many people as possible can get timely PCI following MI. The real life situation proves to be far from simple: some regions might get better outcomes from centralisation, but others not.
http://archinte.ama-assn.org/cgi/content/abstract/170/5/433

SNIPPETS FROM JOURNALS

JAMA 27 Jan 2010 Vol 303
333 Paroxysmal atrial fibrillation can vary from a minor nuisance to a cause of intermittent angina and heart failure. This trial shows that catheter radiofrequency ablation is markedly effective in the first nine months for patients whose paroxysmal AF fails to respond to antiarrhythmic drugs. That said, they still carried on with these drugs (excepting amiodarone) and anticoagulation or antiplatelet therapy according to current guidelines. A particular joy for methodologists was the use in this trial of Bayesian boundaries to determine interim analysis times. Put like that, it instantly sounds boring, but honestly it isn't.
http://jama.ama-assn.org/cgi/content/abstract/303/4/333

BMJ 30 Jan 2010 Vol 340
249 Cardiac rehabilitation is now routinely recommended to everyone who survives a heart attack, but 60% don't turn up. From a large number of trials, reviewed in this paper, we know that it is equally effective when given at home. But this does mean that the rehab team has to be flexible, proactive and adequately staffed. Don't hold your breath as the recession cuts start to bite.
http://www.bmj.com/cgi/content/full/340/jan19_4/b5631
252 I suspect it's going to be increasingly common for anaesthetists to insist on patients having non-invasive cardiac stress testing before elective major non-cardiac surgery, and this large Canadian observational study lends some support to this policy - but only for people with known cardiovascular risk factors. I searched in vain for the Web Table A which might have gone some way to explaining the mechanism by which pre-op stress testing actually harmed some low risk patients - the text speculates that it might have been by foisting beta-blockers on them. Anyway, for those with 1-6 risk factors, there is a measurable mortality benefit, even though very few of them actually require an invasive cardiac procedure.
http://www.bmj.com/cgi/content/full/340/jan28_3/b5526

Arch Intern Med 25 Jan 2010 Vol 170
126 DASH it! As you read this paper showing that a low-fat, low salt diet really does bring down blood pressure by as much as a powerful antihypertensive drug - up to 16/10 mm Hg. That's when it's combined with a weight losing regime over 4 months. It would be very hard to maintain that over a longer period so let's settle for 11/7.5 as in the DASH alone group. http://archinte.ama-assn.org/cgi/content/abstract/170/2/126
136 But hang on - here is the opposite message. A diet of unlimited meat and a lot of fat (the low-carbohydrate ketogenic diet) achieved a much better BP reduction than a low-fat diet in this next study - 6/4.5 vs 4.5/O. Moreover the second group had help from orlistat. Both groups lost weight equally. The undoubted benefits of the DASH diet do not seem to derive from fat restriction. In fact they can probably be matched by a wide variety of less puritanical diets.
http://archinte.ama-assn.org/cgi/content/abstract/170/2/136

JAMA 20 Jan 2010 Vol 303
250 Snip, snip. You are a few seconds nearer to death. Your telomeres are shortening. Quick, grab some smoked salmon. "Among this cohort of patients with coronary heart disease, there was an inverse relationship between baseline blood levels of omega-3 fatty acids and the rate of telomere shortening over 5 years." If you can't get hold of oily fish, a good alternative source of omega-3 fatty acids is snake oil. Helps your telomeres. Live Longer With Snake Oil - it's official.
http://jama.ama-assn.org/cgi/content/abstract/303/3/250

NEJM 21 Jan 2010 Vol 362
217 The heart and lungs share a space in the thoracic cavity. When one gets bigger, the other gets squashed. This elementary fact is nicely illustrated by a study of 2816 people aged 45 to 84 without gross cardiovascular or lung disease. The more evidence of emphysema on lung CT scanning, the smaller the capacity of the left ventricle when filling. This means that the ejection fraction was not impaired but cardiac output was. This is nothing to do with cor pulmonale, mainly a problem of the right ventricle, or myocardial ischaemia, though in advanced COPD these may also play a part. O that cardiologists would remember that the chest contains lungs. It's difficult enough to get them to remember that the heart has two ventricles and a phase called diastole.
http://content.nejm.org/cgi/content/abstract/362/3/217
228 Which brings us nicely on to the topic of systolic heart failure, as reviewed here by John McMurray. Whenattending heart failure conferences there were ribs about trialling yet another drug on recumbent male patients aged 60 with reduced ejection fractions in hospital beds. It isn't the best way of informing us how to treat 75 year olds in the community with multiple morbidities including cardiac impairment. Still, we have to pick up what clues we can from what studies there are, though it would be a mistake to call this evidence-based medicine. It is called general practice, and it can be quite hard. Here are some of the easier bits for those who need an update.
http://content.nejm.org/cgi/content/extract/362/3/228
239 "The primary care physician remains the principal provider and care coordinator for patients with Williams-Beuren syndrome." Your practice may well contain such an individual, if your list is over 10,000. But you probably know this as Williams' syndrome without the Beuren - a microdeletion at chromosome 7 causing a characteristic facial appearance, hypercalcaemia, growth failure, heart abnormalities and learning difficulties. If you are a primary care physician who is the principal care provider for this person, you are not going to find a better review than this , so if you work in SWEssex you can have access to this via Athens
http://content.nejm.org/cgi/content/extract/362/3/239

Lancet 23 Jan 2010 Vol 375
283 Plato held that each earthly object was an imperfect approximation to an ideal object. Clopidogrel is your typical earthly product: expensive and disappointing, as it does nothing for about 30% of people who take it. Ticagrelor on the other hand sounds like the Platonic ideal for platelet inhibition - it works for everybody as it is not a pro-drug, but it is reversible and therefore should cause fewer bleeds. But how all the things of earth disappoint. The most striking thing about the PLATO trial is that ticagrelor is nowhere near 30% better than clopidogrel. This massive study in 13,408 people about to undergo invasive treatment for acute coronary syndromes showed a tiny difference in the composite end-point of death, myocardial infarction or stroke - 9.0% v 10.7% in favour of ticagrelor. There was no difference in bleeds. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)62191-7/abstract

Ann Intern Med 19 Jan 2010 Vol 152
69 Here's a study from the USA which examines three strategies for the primary prevention of coronary artery disease using statins. Two are based on measurement of LDL-cholesterol ("treat to target") and the other is based on total estimated 5-year coronary risk ("tailored treatment"). "We assumed that LDL cholesterol reduction is a statin's sole mechanism of action and that change in total LDL cholesterol is a perfect indicator of the amount of risk reduction that a patient receives from a statin, thereby conceding the 2 most important assumptions underlying the treat-to-target approach. We realize that the first assumption is controversial and that the second assumption is untrue (LDL cholesterol determinations have substantial measurement error)." Neatly put. This is a modelling exercise set by Harlan Krumholz for his scholars and they do it beautifully: the most effective way to use these drugs is to give simvastatin 40mg to everyone with a 5-15% CAD risk and 40mg atorvastatin to everyone with a risk above that - and never mind the LDL-C.
http://www.annals.org/content/152/2/69.abstract
78 By and large it doesn't matter what you give patients to reduce their blood pressure so long as it works and they keep taking it. However, you may wish to bear in mind that exclusive treatment with calcium channel blockers may carry a higher risk of atrial fibrillation than beta-blockers and ACE inhibitors.
http://www.annals.org/content/152/2/78.abstract

Cardiovascular disease

3 articles of interest

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysisBMJ

Lipid modification : Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular diseaseNICE

Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patientsJournal of the American College of Cardiology