Richard Lehman’s journal review—20 November 2017

Richard Lehman reviews the latest research in the top medical journals

richard_lehmanNEJM 16 Nov 2017 Vol 377

Cardiac arrest during sport

Some people enjoy playing physical games, and lots of people enjoy watching them. It was the great Michael O’Donnell who taught me the distinction between games—fun, voluntary, human—versus “sport”, with its connotations of obsessive competitiveness and commercial capture. I guess it’s hard to have the first without it turning into the other. Here’s a Canadian observational study called “Sudden Cardiac Arrest during Participation in Competitive Sports” and it finds that many more people die suddenly during games (“non-competitive sports”: 58 deaths per 18.5 person-years of observation) than during competitive sport (16 deaths). “Just three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening.” I will leave it to sportier people to mull over these data and their implications for screening.

Diuretics in heart failure

Now if you asked an ordinary member of the public what these sportsmen (12 men, 3 women) died of, I bet you about a half would say “heart failure.” Only among doctors does “acute heart failure” mean anything other than sudden death. For us it is synonymous with pulmonary oedema of rapid onset, which often responds quickly to the administration of an intravenous loop diuretic. So far, so satisfying. But while diuretics have an essential role in heart failure management, every clinician (in primary care, especially) knows that responses vary and tailoring of treatment can be very difficult. Long term treatment with loop diuretics induces profound renal changes which can often result in diuretic resistance. Here is a really excellent review which should be read by everyone who manages heart failure. Moreover, it is lavishly illustrated with those pink, purple, and green illustrations of loops of Henle and basement membrane ion exchange blobby things which keep us slavering for the next sheeny paper issue of the NEJM.

Thrombectomy for occlusive stroke, again

The first stroke management revolution was thrombolysis: clot retrieval (thrombectomy) is the second, and it is reshaping the provision of stroke services. For both procedures, time means brain. But the DAWN trial
shows that even after 6 hours, some patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery may benefit from thrombectomy. These are the ones with a mismatch between the severity of the clinical deficit and the infarct volume. I won’t go into detail—I am just conveying the fact the acute stroke care is still in a state of progress.

Open data: 27 years and counting…

1990: “Failure to publish an adequate account of a well-designed clinical trial is a form of scientific misconduct that can lead those caring for patients to make inappropriate treatment decisions.” Iain Chalmers, JAMA.

2011: “Past failures to ensure proper regulation and registration of clinical trials, and a current culture of haphazard publication and incomplete data disclosure, make the proper analysis of the harms and benefits of common interventions almost impossible … Our patients will have to live with the consequences of these failures for many years to come.” Richard Lehman & Elizabeth Loder, The BMJ.

2017:”It is simply unacceptable that the data from published clinical trials are not made available to researchers and used to their fullest potential to improve health.”
The Wellcome Trust, the Medical Research Council, Cancer Research UK, and the Bill and Melinda Gates Foundation, NEJM.

JAMA 14 Nov 2017 Vol 318

The broken tibia: nail it or fix it?

Descended from a long line of military and naval surgeons and sawbones, British orthopaedic consultants have a reputation for getting on with as many operations as they can and then roaring off in their new Porsche. But this stereotype will no longer do. They have developed a passion for assessing the benefits of their treatments which exceeds that of many medical specialties. Here they assess the relative benefits of locking plate fixation vs intramedullary nail fixation on 6-month disability among adults with displaced fracture of the distal tibia. Given that both procedures carry a significant risk of infection and/or reoperation, and often result in residual disability, their conclusion is somewhat downbeat: “Among patients 16 years or older with an acute, displaced, extra-articular fracture of the distal tibia, neither nail fixation nor locking plate fixation resulted in superior disability status at 6 months.”

JAMA Intern Med Nov 2017

When to lower BP, again

In this systematic review and meta-analysis, including 74 trials and more than 300 000 patients, treatment to lower blood pressure was associated with a reduced risk for death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or above. Below 140 mm Hg, the treatment effect was neutral in primary preventive trials, but with possible benefit on nonfatal cardiovascular events in trials of patients with coronary heart disease.”

This comes in the week that the American Heart Association published its new hypertension guideline, based on its own systematic review. That sets the threshold at 130mm Hg, and at last introduces the idea of an assessment of total CV risk. But it reclassifies about half the population as “hypertensive”. Here lies a glimmer of hope. When this level of absurdity is reached, people might start questioning the notion of “hypertension” altogether, in favour of seeing how their own BP affects their personal risk. They might want to use an interactive risk calculator, so they can get some idea of the likely benefit to themselves as individuals if they opt for particular lifelong treatments. Our job is to provide them with easily updated, road-tested tools, and let them choose for themselves, without bothering them with our arbitrary population-based thresholds. I hope I live to see it happen.

Ann Intern Med 14 Nov 2017 Vol 167

After PCI, should aspirin stopped for surgery?

The question here is whether patients who have had percutaneous coronary intervention would do better to stop or carry on with aspirin when undergoing non-cardiac surgery. The evidence comes from a subset of the POISE-2 (PeriOperative ISchemic Evaluation-2) trial, and comes out weakly in favour of carrying on. But, as the abstract states, “Limitation: Nonprespecified subgroup analysis with small sample.” This is just a hypothesis that needs its own trial.

The Lancet 18 Nov 2017 Vol 390

Population screening for vascular disease

In this trial, all men aged 65–74 years living in the Central Denmark Region were randomised to screening for abdominal aortic aneurysm, peripheral arterial disease, and hypertension, or to no screening. There was an absolute risk reduction of 0·006 (0·001–0·011) in mortality over a median follow-up of 4.4 years for the screened group. In their conclusion, the authors claim that this represents a breakthrough in screening effectiveness and should be adopted more widely. But this is questioned in an editorial containing this trenchant paragraph:

“The NNI of 169 compares favourably with previous abdominal aortic aneurysm screening studies showing NNIs of 667 and 352. Although an NNI of 169 for overall mortality is impressive and compares favourably with many common cancer screening programmes (which can have NNIs of more than a thousand), such benefit is insufficient to recommend population screening. In addition to efficacy, population-based screening must be shown to be sufficiently accurate (low false-positive and false-negative rates), not harmful (particularly with downstream testing, treatments, and procedures), cost-effective, acceptable to patients, and feasible in real-world settings. These requirements are particularly important because screening affects a large number of people who have no health complaints.”

Teriparatide v risedronate

This Lilly-sponsored trial report begins by stating that “No clinical trials have compared osteoporosis drugs with incident fractures as the primary outcome.” So what are drug regulators actually for? Even this trial only looks at events over two years. It shows that teriparatide 20 mcg daily by injection has the edge over risedronate 35mg weekly by mouth: the absolute difference in fractures was 5% in women with severe osteoporosis. The basic monthly cost of risedronate in the UK is 85p, while teriparatide currently costs £271.88. The latter may come down when the patent expires in 2019.

Rivers of rivaroxaban

Bayer’s fortune was made when it began to sell aspirin in 1899, though nobody then would have predicted that its main use 100 years later would be as an inhibitor of platelet aggregation. Nowadays it is taken by nearly everybody with coronary artery disease, peripheral vascular disease, or identified carotid stenosis. What if all these people could be persuaded to take another Bayer drug as well? The massive COMPASS trial was designed to test the effect of rivaroxaban, instead of aspirin or added to aspirin, in these populations. Although the papers declare the aspirin/rivaroxaban combination a success for reducing mortality both in stable coronary artery disease and in peripheral artery disease, this came at the cost of increased major bleeding. Moreover, it’s not clear how much the widespread prescribing of rivaroxaban for secondary prevention will help fill Bayer’s coffers, since the drug is protected by a handful of patents which are all due to expire.

The BMJ 18 Nov 2017 Vol 359

Weight loss in obesity and mortality

Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis” Nobody could call that an unimportant topic. And nobody should underestimate the work involved in searching the literature and then combining the results of 54 RCTs with 30 206 participants. However, all but one of them was a trial of a low-fat diet, so this can’t be extrapolated to all weight-reducing strategies. The effect was in the right direction and I like the modest way the conclusion is framed: “Weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity.”

Endovascular repair for AAA moves ahead
Set up a good trial, and the results will continue to benefit patients as long as the data keep coming in. Ruptured aortic aneurysm is just about the messiest surgical emergency there is, but the IMPROVE trial managed to randomise 275 with confirmed rupture to endovascular repair and 261 to open repair across 29 vascular centres in the UK and one in Canada. “At three years, compared with open repair, an endovascular strategy for suspected ruptured abdominal aortic aneurysm was associated with a survival advantage, a gain in QALYs, similar levels of reintervention, and reduced costs.” Great to see such an important paper published in The BMJ.

Plant of the Week: Rosmarinus officinalis “Severn Sea”

The various forms of rosemary are good garden plants in England, though they need sun and dry conditions or they will rot away within three years or so. “Severn Sea” is still flowering for us in mid-November, well after the first frosts. It is about the prettiest thing in the garden, and would be even better if pink kaffir lilies were peeping out amongst the bright blue flowers on every arching branch. I must remember to set this up for next year.

Some people bring sprigs of rosemary into their kitchens. This is all very well provided they do not come into contact with food. Around the Mediterranean littoral, meat dishes are often denatured with burnt rosemary and charred garlic. Jamie Oliver’s books supply many such recipes, so that people who like eating may avoid them.