EBM at the bedside-bicuspid aortic valves and familial screening
The original proponents of EBM have always argued for “evidence at the bedside” so that we can make the best decisions for patients nearest to the point “where the rubber hits the road”. How often do we clinicians actually look up the evidence in real time during or soon after a consultation to change the management or the advice we give to a patient?
I saw a lady in her 40s in our cardiology clinic this week. She has been followed up every 1-2 years in clinic for bicuspid aortic valve (BAV). Basically, the aortic valve is at the outflow of the left ventricle (the major pump of the heart) and usually has three cusps which open and close to ensure flow of blood in the right direction through and out of the heart. In bicuspid valves, people are born with only two cusps and over their lifetime, they are more prone to developing narrowing of the valve (“aortic stenosis”), with a significant probability of needing aortic valve replacement during their lifetime. The idea of screening and surveillance is that any narrowing or malfunction of the aortic valve can be picked up early, and the person can be referred for surgery more quickly and effectively than if their disease had progressed.
BAV is the most common abnormality of the heart valves, occurring in 1- 2% of the general population and is twice as common in males as in females. Reassuringly, a recent cohort study of patients with BAV found that they have similar survival rates to the normal population. However, “given that serious complications will develop in over a third of patients with BAV, the bicuspid valve may be responsible for more deaths and morbidity than the combined effects of all the other congenital heart defects”. The potential problems are narrowing or leaking of the aortic valve, infective endocarditis and enlargement or “dilatation” of the aorta. In other words, BAV is common, has serious complications and there is a treatment which improves survival (aortic valve replacement). Therefore, BAV is a condition which meets Wilson’s criteria for screening.
I was asked by the lady if her children were at risk of BAV and whether they should be screened. I did not know the exact answer so I looked online with the patient. There is a 30% risk of aortic dilatation or BAV in first degree relatives (parents, children or siblings) of people with BAV. A more recent study showed that 20% of first degree relatives of people with BAV may have undetected BAV themselves. It turns out there are no NICE guidelines or formal UK/European guidelines for whether we should be screening relatives or how we should be doing it.
Interestingly, across the pond, the Americans have guidelines for familial screening and the literature seems to suggest it. Therefore adult children of patients with BAV should have an echocardiogram to check that they do not have a BAV which would mean that they should also be followed up. Valvular heart disease is a bigger health issue than we imagine.
There are four take home messages for me. First, EBM can be done at the bedside-it is meant to be the most practical of clinical sciences. Second, there is no harm as a clinician in saying “I don’t know” and looking it up. Third, sometimes it is the obvious clinical questions which are still unanswered or debatable. Finally, practice can be changed.
Weighing up benefit and harm -net clinical benefit and subgroup analysis
The Hippocratic oath originally included the harm and good that doctors and their prescribed treatments can cause. The biggest challenge in today’s clinical practice is not much different. With increasing numbers of trials of different drugs in different patient groups with different comparison groups, how are patients and doctors ever going to see the wood from the trees? How do we make judgments about which drug to use in which situation?
NICE was set up in 1999 in order to help in these difficult matters. Broadly speaking, it looks at current trial evidence and uses the metrics of “cost-effectiveness” to decide whether to fund drugs and treatments in the NHS. It uses “quality-adjusted life years” (the ‘QALY') to measure effectiveness and then calculates the cost per QALY gained for a given drug. A drug must be effective in treating disease but the cost of the benefit must be below a certain threshold, usually £20000-30000 per QALY gained
One problem is that in trials, we tend to focus on benefits and not harms. Another problem is that the performance of drugs in different patients, even for simple characteristics like age and sex and poorly defined in many trials. Even more importantly, trials often do not report their outcomes based on the disease risk of the patients involved. Therefore we end up “painting all patients with one brush”. This has obvious problems. Cost effectiveness analysis is only as good as the trials which are studied and if those trials do not report outcomes (good and bad) properly, then analysis is difficult.
Atrial fibrillation (AF) is a heart rhythm problem which causes increased risk of stroke. Warfarin has been established as a safe treatment for over 50 years and reduces risk of stroke. However, it does lead to increased risk of bleeding, including intracerebral bleeds. Therefore, a way of quantifying the overall benefit of warfarin is to directly weigh up the risk of stroke and the risk of intracerebral bleeds as a “net clinical benefit”, as proposed by Singer and his colleagues in 2009. They reported that “Expected net clinical benefit of warfarin therapy is highest among patients with the highest untreated risk for stroke, which includes the oldest age category.” In other words, we should use the drug in the patients with the highest chance of benefit from the drug, or the highest chance of the adverse outcome (intracerebral bleeds).
Currently 3 new drugs (dabigatran, apixaban and rivaroxaban) have been evaluated in trials as alternatives to warfarin in the setting of AF. Each of these trials looks at different patients and uses different comparisons. In a recent analysis, we used data from the Danish National Patient registry to work out the net clinical benefit of these drugs at different levels of risk of stroke (potential benefit) and bleeding (potential harm) compared with warfarin. We also calculated the number of patients needed to treat and harm for each drug at each level of risk. Although, this is a modelling exercise, this type of analysis is needed in order to look at all the drugs side by side, using the best evidence we currently have. This idea of “net clinical benefit” could also be used in other disease areas in order to quantify to both health professionals and patients how good or bad a treatment is.
The choice between rail and road:perspectives from Delhi
This week I started a 3-week research trip to India, based at the Centre for Chronic Disease Control in New Delhi. Yesterday I rediscovered the joy of train travel. My morning began with a ride on the efficient Delhi metro at 6.15am. The service is state-of-the-art in South Asia, and in my view, compares very well with similar services in many high-income countries. Alongside the option of driving, sitting on the train from Delhi to Chandigarh was not only much more relaxing, but I actually had the time to take in the views as we travelled through colourful North Indian villages.
Contrast this with the situation on India’s roads. Even in urban centres such as Delhi, the chaos of road traffic makes you wonder at how survival statistics are not worse. India has a higher rate of road traffic accidents (RTAs) than anywhere in the world, according to the World Health Organisation’s report last year, with 14 people dying every hour on the road. Globally, RTAs make up a third of unintentional injury deaths, with double the death rate and three times the burden of disability in low-middle income countries compared with high-income countries, which are less able to cover the huge economic and social costs. Children are more likely to be victims, and RTAs are projected to be fourth leading cause of death in 2030.
One recent post-mortem study from Kolkata found that a staggering 63.1% of deaths were due to accidents, mostly on the roads. The dire circumstances which can result from RTAs are shown by a case report from Jaipur, India, simply titled, “An unusual presentation of head injury: teeth in brain”.
Interestingly, an analysis from the UK estimated that walking to and from stations accounted for 65% of the overall door-to-door risk of being killed on rail journeys; with the rail system itself accounting for only 21% of the risk. In other words, it is the risk of the road which causes deaths on trains in England as well. There are calls for better data globally, since only 20 countries have the high-quality data needed to accurately estimate mortality from RTAs but I think I have read enough. I will use the train whenever possible. The urgent message for Indian policymakers is that a comprehensive policy for road safety is required and fast.

See Carl Heneghan in action in the CEBM's workshop videos. 
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