![]() In 1775 William Withering began his clinical investigation into the medicinal properties of the foxglove. Ten years later he published his results. “I soon found” he says, “that the foxglove is a very powerful diuretic of advantage in every species of dropsy except the encysted, and that it has a power over the motion of the heart to a degree yet unobserved in any other medicine, and that this power may be converted to salutary ends.” In the 1890s James Mackenzie advanced clinical knowledge of digitalis. He used the ink polygraph to recorded the venous and arterial pulses simultaneously and showed that the irregular pulse of atrial fibrillation was always associated the absence of the atrial wave in the venous pulse trace. In his clinical studies Mackenzie found that digitalis was particularly effective in patients with heart failure associated with atrial fibrillation. At the same time, chemists were trying to extract and purify the active components in the foxglove leaf. In 1869 crystalline digitoxin was isolated and shown to have similar medicinal properties to digitalis leaf extract. A similar substance was discovered in 1928 and called gitoxin. It was then reported that the leaf of digitalis lanata which grew in the Danube Valley was more than four times as potent as standard digitalis. In 1929 some of the dried leaves were brought to the Wellcome Research Laboratories in Beckenham in Kent where much work had already been done on the purple foxglove to work out methods of extracting and purifying the chemical components. Using the digitalis lanata leaves chemists found a new substance, which formed tiny canoe-shaped crystals, and they named it digoxin. Digoxin became more or less the standard treatment for heart failure associated with atrial fibrillation and also in patients with normal cardiac rhythm. Given by mouth at a dose of 1mg per day or intravenously for more rapid effect it was particularly effective in slowing the heart rate also had diuretic activity relieving the symptoms of congestive heart failure. At a time when the only other therapy was bed rest and mercurial diuretics the effects of digoxin were dramatic and important. Digoxin was introduced into cardiology before clinical trials were the norm and is still part of the current ACC/AHA guidelines. These state that digoxin can be beneficial in patients to decrease hospitalisations for heart failure. What is the evidence behind this recommendation? There are a series of old clinical trials conducted between 1977 and 1993 examining the effects of dioxin in chronic heart failure. Most of them are small and the only large randomised study is the Digitalis Investigation Group (DIG) study. In DIG patients with an ejection fraction of 45% or less were randomised to digoxin or placebo in addition to diuretics and angiotensin-converting enzyme inhibitors. Digoxin did not reduce mortality but did decrease the rate of hospitalization heart failure. Trying to evaluate the place of digoxin is difficult since at the time of the DIG trial β-blockers, spironolactone / eplerenone, ibvabradine or resynchronisation therapy were not recognised treatments for heart failure. So we simply don't know if digoxin is beneficial in patients today, worse still, could it be harmful? In the Valsartan Heart Failure Trial digoxin was associated with higher risk of death and hospitalization for heart failure. The only randomised trial conducted recently showed that in severely ill patients awaiting cardiac transplantation for advanced heart failure digoxin increased risk in death. A post hoc analysis of the DIG trial also showed higher risk of death among women and in a recent study published this year in patients with systolic heart failure showed that digoxin was again associated with a significantly increased mortality. These findings should cause us to reconsider the role of digoxin in the management of patients in sinus rhythm with systolic heart failure. Perhaps after more than 200 years of clinical use it might be time to say farewell to the foxglove as the flower of physic withers.
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![]() In 2010 NICE published a guideline on Chest Pain of Recent Onset. This was an important document for GPs and cardiologists. It has been widely cited and has had an effect on how Rapid Access Chest Pain clinics operate. NICE used their usual cost-effectiveness approach to review and then recommend which cardiac investigations were most appropriate in the assessment of patients with chest pain. Some of the recommendations e.g. to not use exercise treadmill testing to assess patients have been largely ignored by many cardiologists but the guidelines have stimulated an increase in the use of non-invasive imaging tests such as CT coronary angiography, myocardial perfusion scanning and stress echocardiography. A recent article in the BMJ “Rational Imaging” series sought to review the investigation of stable chest pain of suspected cardiac origin. Essentially this was a rehash of the 2010 NICE guidelines with focus on the estimation of likelihood of a patient having coronary artery disease and a strong bias to recommended CT and cardiovascular MR imaging (not surprising since all of the authors have specialist interests in this discipline). I think it is time to redress the balance around imaging investigations and critically review the NICE guideline approach. The BMJ article describes the following case: A 45 year old man, who was a non-smoker and did not have diabetes or hyperlipidaemia, presented to his doctor with chest discomfort after exercise. There were no relevant findings on clinical examination and resting electrocardiography (ECG) results were normal. On the basis of age, sex, risk factors, and symptoms, the patient’s pre-test probability of coronary artery disease was 21% and he was referred for calcium scoring. The calcium score was 11 and he proceeded to computed tomography coronary angiography, which identified a 70% stenosis of the left anterior descending coronary artery. Adenosine stress perfusion cardiac magnetic resonance imaging showed reduced perfusion of the septum within the territory of the left anterior descending coronary artery. He was managed for stable angina on the basis of these findings. I see very many patients with this type of clinical presentation and my approach would not be that recommended by the authors of this article. My clinical impression is that the patient has angina. I would recommend treatment with 75mg aspirin, a beta blocker and to give a GTN spray. I would recommend that the patient has an invasive coronary angiogram. The angiogram is done to define the pattern of coronary artery disease and to decide on the correct approach to further management which may or may not involve revascularisation. The patient starts treatment as soon as the diagnosis of angina is made to improve symptoms and reduce risk of cardiovascular events. So the diagnosis and treatment plan for the patient is completed in a timely manner and with a single test rather than three different tests. NICE and this rational imaging review recommend a different approach. First you estimate the likelihood of coronary artery disease. How? The authors use the table in the NICE guidelines (see below) and say it’s 21%. On that basis they recommend a CT calcium score. I would take issue with this on two counts. First I think the patient’s symptoms are consistent with angina and therefore his predicted risk, according to the NICE guidelines, is much higher at 51%. Second there is evidence that in a younger patient coronary artery disease may occur in the absence of calcification of the coronary arteries. So a zero calcium score does not confidently exclude coronary artery disease in a symptomatic patient. Calcium scoring of the coronary arteries is a relatively quick, cheap and simple test which is entirely non-invasive. CT coronary angiography involves pre-treatment of the patient usually with beta blockers to reduce the heart rate to 60 and pre-assessment of the renal function as intravenous contrast will be administered. The patient then has a CT coronary angiogram and now we see that rather than the predicted 21% chance of having coronary disease the patient does actually have the disease. He then has an adenosine perfusion cardiac magnetic resonance scan (not very widely available, certainly expensive but as all of the authors are experts in CMR scanning not surprising). This demonstrates cardiac ischaemia which is not surprising since there is a flow limiting lesion in a coronary artery and the patient has symptoms of chest pain. After that the patient is managed for stable angina. This management, not discussed in the article, most likely involves an invasive angiogram and consideration of angioplasty to relieve symptoms if not controlled by medical therapy. Whilst the approach described by the authors might be appropriate for an asymptomatic patient it seems a long and complicated route to identify and treat the disease which most cardiologists could have predicted was there from simply taking a proper history. The best predictor of the presence of obstructive coronary artery disease is the presence of symptoms of angina. That’s not to say that patients without angina don’t have coronary artery disease. They do and many patients with significant coronary artery disease do not have classical symptoms of angina. In my view there are two principle questions to address. First, what is the cause of the patient’s symptoms of chest pain? If the answer is coronary artery disease then appropriate investigation needs to be undertaken. If the answer to this is no, then apart from trying to determine the non-cardiac cause of chest pain the other question is could this patient have underlying coronary artery disease? If the risk is high then appropriate preventative measures need to be recommended with regards to lifestyle and other risk factors. It is frustrating that many patients leave a chest pain clinic or accident and emergency department with a diagnosis of “non-cardiac chest pain." ![]() Table from NICE Chest Pain Guidelines. Note the limited ages available for lookup and that "High Risk is defined as diabetes AND smoking AND hyperlipidaemia. This is often misquoted as it has been in the BMJ Rational Imaging Article as diabetes OR smoking OR hyperlipidaemia. Using the table in the NICE guidelines to predict risk of coronary artery disease is risky business itself. First only mid-decade ages are given so most patients fall between the categories of risk. Then with the risk factors you either have none and are low risk or you are a diabetic smoker with a cholesterol of >6.47mmol/l (it’s a strange number because the original study is from the USA and used an LDL cut off of >250mg/dl) and you are high risk. A single risk factor doesn’t count as high risk and so it is impossible from the table to estimate the risk for the majority of patients we see.
You can get around this by going back to the original paper which contains the risk model equations and building your own model to allow the exact age and individual risk factors. NICE didn’t do this in the guideline because it would be too complicated but it is ideally suited to an online version which I will publish soon on my website. Sadly however that doesn’t solve the problem. If you deconstruct the data in the table and go back to the original source you will be surprised and also disappointed. The original data comes from a paper published in the Annals of Internal Medicine in 1993 and reports the experiences of the Duke University Chest Pain Clinic. At Duke they collected sequential data on 1030 patients attending the clinic who were assessed for suspected ischaemic heart disease. 168 patients went on to have a coronary angiogram and from this cohort the risk prediction model was built and this produced the data in the table above. The tiny small sample size and the population on which it is based should make anyone use the NICE table with great caution. One wonders how many 35 year old females with no risk factors and typical angina were really studied by angiography in the 1980's when the data was collected. Certainly to use the numbers as a basis for determining the behaviour of different non-invasive investigation techniques would lead to a very high likelihood of inaccuracy. In the end there is as they say no substitute for experience. The most appropriate way to manage a patient with chest pain is for the assessment to be performed by an experienced cardiologist who can recommend the most appropriate strategy for that individual patient to get to the diagnosis and formulate a treatment plan as quickly and efficiently as possible. References: National Institute for Health and Care Excellence. Chest pain of recent onset: assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin. CG95. 2010. Declan P O’Regan, Stephen P Harden, Stuart A Cook, Investigating stable chest pain of suspected cardiac origin BMJ 2013;347:f3940 Pryor DB, Shaw L, McCants CB et al. (1993) Value of the history and physical in identifying patients at increased risk for coronary artery disease. Annals of Internal Medicine 118(2):81–90. How do patients give feedback on their experience in hospital or A+E? ![]() I'm reading a book at the moment. Actually its more of a manual than a book and it's called "Making Hospitals Work: How to improve patient care while saving everyone’s time and hospital’s resources". It tells the story of a fictional hospital and its new CEO. The CEO doesn't have any NHS experience but comes from an industry where they worship at the alter of "lean." The hospital in trouble. The CEO has been appointed by the board to turn the ship around. The troubles are not new or surprising. Patients waiting too long in A+E, delays to ward discharges, longer length of stay, medical patients on surgical wards, cancelled operations and so the list goes on. These are very familiar to anyone who has worked in the NHS. The manual tells the story of a the lean approach to assessing and making changes. Now I haven't finished the book but what strikes me so far in its analysis is the large amount of wasted time which occurs in the NHS. We are constantly waiting for things to happen, duplicating work (patients re-clerked and reviewed multiple times during admission) and dealing with huge amounts of apparent inefficiency. The book make you start to think about you own experiences and practice and here is an example. Its a Saturday afternoon and I happen to be in my office catching up on paperwork, The phone rings and the caller display flashes up a colleagues name. "I wonder if you can help us" he starts, "we have a patient where we suspect a pericardial effusion. The patient needs an echo, we tried to refer them elsewhere but there are some administrative difficulties." I stop him at that point because although they don't know I am in the hospital the decent thing is for me to just go to the ward and do the echo myself. This is good because it saves the patient being transferred and it gets the test done soon. Better patient care, consultant delivered, on the weekend - no argument with that. So I get the machine, go to the ward and do the echo. There is a large effusion - it needs to be drained. The patient is transferred to the coronary care unit and while this is happening I scurry round CCU to find all the bits of equipment I need. First a metal clinical trolley - I can't find the large one we usually use - no one has seen it. Then we find it acting as a stand for a "clinical wipe warmer". No I hadn't heard of that either but I guessing clinical wipes are a bit chilly on the skin so the patient experience is better if they are warmed before use. The pericardial drain set comes in a nice sterile pack with a bag and other bits and pieces so that is good but I also need other things. A sterile gown, sterile drapes, green needle, 50ml syringe, 10ml syringes, a silk straight needle suture, sample bottles, lignocaine and a dressing. I have to locate all of these items. There are spread throughout the ward in multiple locations - the clinical room, the sluice, the store room, trolleys on the ward, a hidden cupboard. It takes time, the Sister, feels sorry for me, helps but even she's not sure where some of the things are. We start talking. "Who is responsibility for stocking up?" I ask, "Well it's all of our responsibility" she says. "When the stock arrives who deals with it?" I ask, "Well whoever is on duty is supposed to put it away" she says. It's clear I know very little about how the ward actually operates but In my experience anything that is everyone's responsibility rapidly becomes no ones responsibility. It makes me see how the nurses must think of the doctors as a bit like guests in a hotel who visit for short periods, use the facilities but don't know anything about how the rooms get cleaned or the toiletries get replaced or how any of the supplies are ordered. I start to think about the lean manual I am reading and the what if questions begin? What if all the things I needed for my drain were in one clinical room? What if every clinical room on every medical ward in the hospital had the same layout with the same stock in the same places? What if the labelling systems were the same? What if there was a person who visited the ward twice a week to stock take, restock and organise these rooms? What if the stationary on the ward was in standardised cabinets so I didn't have to look though 3 filing cabinets to find the consent form. The amount of time wasted looking for things would be reduced. More time could be spent on direct patient care. I suspect that stock control on the wards is not as efficient as it should be and my what if might even save money by reducing the amount of waste and over-ordering. This isn't rocket science it's just common sense so why aren't we doing it? ![]() Calcium channel blockers or CCBs such as amlodipine, diltiazem or verapamil are widely prescribed for the treatment of high blood pressure, angina and heart arrhythmias. Since these conditions make up a large part of a cardiologists workload most of us will have prescribed these medications to hundreds of people. Since the conditions they are used for are chronic patients are likely to be taking the medications for many years and this makes the long term safety of the medicines very important. Over the last 20 years there have been a number of scares about the safety of CCBs. In 1995 it was the association between increased risk of heart attack that made headlines such as "Drug for Blood Pressure Linked to Heart Attacks: Researchers Fear 6 Million Are Imperiled” and this generated considerable public concern. This scare came and went and the prescription of CCBs continued. Skip forward 18 years and now we have another scare - CCBs are associated with an increase risk of breast cancer. A paper in JAMA Internal Medicine released on the 5th August reports that long-term current use of CCBs is associated with an increased risk of breast cancer. Except that this is not a new scare as there have been rumblings about an association of CCBs with cancer for many years. In the late nineties two papers reported increases in risk of all cancers among elderly people but both studies were small and subsequent larger studies failed to confirm the CCB-cancer association. In 3 randomized clinical trials over 5 years no cancer signal was seen and after this the CCB-cancer hypothesis gradually faded away that is until just recently. So what does the current study show. There are two main types of invasive breast cancer - ductal and lobular. The researchers looked at women aged 55-74 years old. They took 1055 women with lobular and 905 women with ductal breast cancer type and compared then to 891 control women without a history of breast cancer. The control women were matched for age and other known risk factors for breast cancer. About half the women in each group had a history of high blood pressure and the researchers noted the type and duration of anti-hypertensive medication. In the control group 12 women had been taking a CCBs for more than 10 years. In the women with breast cancer 27 in the ductal group and 31 in the lobular group had been taking CCB for more than 10 years. In other words if you were a women with hypertension and breast cancer then you were more likely to be taking a CCB for 10 years or more. The results in the study are reported as odds ratios and this statistical measure gives an idea about the strength of association between the CCB exposure and breast cancer. When the authors looked at other blood pressure medication they did not find a significant association with increased risk of breast cancer. So essentially this studies shows a significant association between chronic CCB consumption and breast cancer risk but like all such studies it does not prove a causal relationship. So far so good but what women on CCBs and their doctors want to know is how much is the individual patient's risk of breast cancer is increased. This is where it gets more difficult, but not impossible. First you need to think about the women's baseline risk of breast cancer. There are web-base calculators which allow us to predicted this. The lifetime risk of developing breast cancer is 1 in 8 for a women in the UK. The average 60 year women has a risk of developing breast cancer of 1.8% over 5 years. From this and the odds ratio in the paper it is possible to estimate that 18 women need to be treated with a CCBs for 10 years in order to produce one additional case of breast cancer. We call that the number needed to harm and 18 is a fairly low number. To place this in context treating people with raised cholesterol with statins to prevent heart disease has a number needed to treat of about 50 and we regard this as effective treatment. So should we advise all our female patients who have been on CCBs for more than 10 years to stop taking them? Before we do this it is important to remember that the association with CCBs and breast cancer reported in this study were not seen when the same research group looked at a completely separate population of women. In their previous study they found that some other blood pressure tablets (thiazide and potassium-sparing diuretics) but not CCBs were associated with 40% and 60% increase in risk of breast cancer. In the California Teachers Study cohort they found that diuretic use for 10 years or longer was associated with a 16% increased risk, while use of CCBs and ACE inhibitors was not. A case-control analysis derived from the United Kingdom–based General Practice Research Database found no associations with use of ACE inhibitors, CCBs or β-blockers for 5 or more years. Confused? You should be. How can all these differences be explained since there appears to be no consistency. These studies are all conducted in different populations with different methodology, correction factors and time periods and so it is not surprising differences are seen. One very important point is that the recently published study only found an association between breast cancer and the use of the CCB in women treated for 10 years or more. It is possible that the effects of CCBs take many years to develop and since most of the previously published studies looked at shorter time periods the effect was missed. This new study has generated a lot of interest because CCBs are one of the most commonly prescribed class of drugs in the UK and breast cancer is the most commonly occurring cancer among women. If the CCBs do produce a 2-3 fold increase then long term CCB treatment would be a major modifiable risk factor for breast cancer. The results from this study are interesting and hypothesis generating. It is too early to recommend that all women who have been on CCBs for 9.9 years should be switched to alternative medications since the results from this study are not entirely consistent with other studies and need to be repeated and confirmed. However in the mean time cardiologists and GPs should be able to discuss the results of this study with patients and give appropriate advice perhaps by converting the odds ratios which are inherently difficult to understand into the number needed to harm. If an individual women has been on CCBs for a long time and is very anxious about continuing them then there are alternative treatments that can be offered and this should be discussed. Li et al., Use of Antihypertensive Medications and Breast Cancer Risk Among Women Aged 55 to 74 Years. JAMA Internal Medicine Odds ratio to NNT converter ![]() Anyone who has been to Italy and needed to buy a medicine will have experienced the ‘farmacia’ or pharmacy. These shops, identified with the green cross symbol outside, give the impression of yesteryear. Enter and the farmacista, il dottore or la dotorressa will be wearing a white coat ready to greet you from behind a gleaming glass topped cabinet. Prego? This is your invitation to speak. If you want paracetamol you may well get a blank look, in Italy branded aspirin is the main painkiller of choice. If you want an alternative then there is the wonderfully named ‘Moment’ or ibuprofen. If you didn't have a headache when you arrived you certainly will when you are told the price. A small box of a dozen ibuprofen tablets will usually set you back around 8 to 9 Euro - an astonishing 60p per tablet. Shocked at the price you might think next time you can bypass the farmacia and get you medicine at the supermarket, think again. In Italy the farmacisti have a complete monopoly on the sale of medicines and until very recently medicines could only be sold in a designated farmacia. In 2006, in a feint nod towards the “free market” and following pressure from the Co-op, the government of Mario Monti passed a new law to allow the sale of some over the counter medicines in supermarkets. The Italian government was proud of the bill which was “rushed through” and became law in a record nine months! But wait for it, after intense lobbying, by guess who, it was agreed that there had to be a farmacista present at all times and the area where the medicines were sold had to be completely separate from the rest of the shop! Not surprisingly the status quo continues and there has been no change outside of very large supermarkets in big cities. Certainly there was of no benefit to the average Italian or the beleaguered tourist. When the new law was debated the main argument, proposed by the farmacisti, against the more liberal approach was that it would worsen the health of the population and thereby increase the burden on the already struggling Italian healthcare system. Cheap flights, budget airlines and the internet give the impression that the world is a smaller place but there are still huge cultural and practical differences between countries. Here in the UK it would be unthinkable to have to go to a pharmacy simply to buy a paracetamol, in Italy it is normal. We are familiar with self-treatment using simple medicines and the likelihood of harm is deemed to be low. Wide availability and competition has led to medicines being sold at incredibly low cost. To the outsider the Italian appears to be at the mercy of a cartel of farmacisti who must be raking in huge profits at the expense of a population with little choice about where to buy their medicines. But maybe the Italians’ don’t see it that way. Reading the press and blogs there isn’t a groundswell against this apparently anti-competitive practice. Perhaps some of this can be explained by the Italians deep respect for the professional. In Italy if you have a university degree you have a title. The farmacista is a dottoressa, the mechanic an engineer and even a football manager is a maestro. The farmacisti have a five years of university education followed by a tough national examination, they are organised and respected for their advice and experience. The ubiquitous white coat emphasises the idea of a clinical, scientific and laboratory approach – they are the medicine professionals and why wouldn’t want to buy your medicine from them? Surely it must be safer and if the medicines are only available a farmacia this re-enforces their special status and not something that can be picked up with alongside the groceries. Experiencing different cultures and systems is revealing. In Italy is the strength of the professional groups and the population trust of the professional which goes a long way to support this practice. My simple advice for the traveller is to take your own medicines with you and save yourself some money. ![]() It usually goes like this. Mrs Jones is a lady in her mid-70s with a history of controlled hypertension. An irregular pulse is detected by a practice nurse usually during a routine blood pressure check. Atrial fibrillation is confirmed on an ECG and she is referred to cardiology outpatients. We go through the history, examination and then onto the management. I usually break this down into management of symptoms and reduction of stroke risk. In the asymptomatic patient the former is usually very easy so we rapidly move onto the latter which is usually more challenging. I explain that AF is associated with an increased risk of stroke. 10,000 people a year are admitted to hospital in the UK with a stroke and found to be in AF. Then we arrive at the moment of the consultation where the W word is mentioned. I have tried to introduce this gently using the word anticoagulation, talking about little clots in the heart, preventing them by thinning the blood but finally the W word has to come out: "So Mrs Jones I would recommend that we start you on Warfarin." A moment later the patient looks crestfallen. The reply is usually a combination of 1) I don’t want to go onto warfarin; 2) I have a friend/relative/neighbour who is on it and they have had terrible trouble; 3) I was dreading you would say that; 4) Can’t I just continue with the aspirin after all that thins the blood too doesn’t it? 5) Can I leave it for now and take it if things get worse. I usually ask the patient “What is your biggest worry?” and often the reply is: “I don’t want to have stroke!” We are recommending more and more anticoagulation. The awareness of the increased stroke risk associated with AF is rising and there are comprehensive guidelines recommending anticoagulation which apply to ever increasing numbers of patients. Anticoagulation in AF is now regarded by the pharmaceutical industry as big business. This made me consider the risks and benefits of different types of stroke prevention therapy for AF. Guidelines have made this easy. Calculate the CHADS2 or CHADSVASC score of the patient and if it is more than 1 for CHADS2 or 2 for CHADSVASC then anticoagulation is recommended. You don’t need to know or think about the absolute risk numbers just a simple addition. The guideline tells you when to start anticoagulation and of course if you follow the guidelines you can’t be criticised. On the other hand if the patient has a stroke and you didn't recommend warfarin then that is not good. If the patient has a serious bleed due to the warfarin then you can’t be criticised for following the guidelines, can you? Sometimes it helpful to think about the actual numbers behind these guidelines to see exactly the benefits and risks of the different treatments. It is common to tell the patient that anticoagulation reduces risk of stroke by two thirds - impressive. Consider Mrs Jones, she has an annual estimated stroke risk of 4.3% and an annual bleeding risk of 0.6% according to the risk calculators. Treating her with aspirin reduces the risk of stroke to 3.4% (22% RRR; 0.9% ARR, with a 1 in 106 chance of benefit per year). The risk of major bleeding rises to 1.1% (1 in 222 chance of being harmed). So a miniscule chance of benefit and miniscule chance of harm. Giving warfarin reduces stroke risk to 1.4% (66% RRR; 2.9% ARR, with a 1 in 35 chance of benefit per year) but the risk of major bleeding rises to 3.1% (1 in 40 chance of being harmed). If there are 1000 patients similar to this then by doing nothing 43 will have stroke and 6 of them a major bleed over the next year. Treat them all with warfarin prevents 29 strokes but cause 25 major bleeds. Treated them with aspirin prevents 9 strokes but cause 5 major bleeds. I guess it all depends on whether you fear stroke or bleeding more, major bleeding provided it is not cerebral haemorrhage is not usually associate with long term disability and so may be trying to compare apples with pears and remember the patients biggest fear was of having a stroke. The current recommendation is that anyone with a CHADS2VASC score of 2 or more should be offered anticoagulation. It is clear that warfarin treatment is associated with a benefit. As doctors we tend to emphasise the positives and stress the 66% risk reduction with warfarin compared to the 22% with aspirin. We do not stress the 5-fold increase in the risk of major bleeding associated with warfarin. There has been a huge interest in atrial fibrillation recently. Some of this has been driven by the availability of the new oral anticoagulant drugs and the intense advertising war between the different companies to position their drug as the most effective. This has also been accompanied by an awareness campaign to doctors regarding the stroke risk associated with atrial fibrillation as well as community clinics funded by the pharmaceutical industry intent on finding cases of atrial fibrillation and reviewing the anticoagulation treatment. As physicians we tend to play down the harmful effects of the treatments and emphasise the positives. We want to practice according to the guidelines. If you were the patient with AF and you were told you there was a 1:35 chance of benefit with warfarin and 1:40 chance of harm what would you do? Calls this week for school lunch boxes to be produced in uniform drab brown colours to make them less attractive to children are being considered by the Government.
Campaigners have long argued that the contents of the school lunch box is harmful and that junk food and indequate nutrition contribute to the growing problem of childhood obesity rates and poor results in numeracy and literacy. One pressure group said: "We know that children become addicted to packed lunches at a young age. This is a major public health issue and action needs to be taken now." Recent research has shown that what you eat for your lunch as a child determines your food choices for the rest of your life. You only have to see how popular sandwiches and fizzy drinks are amongst adults. It can all be traced back to the school packed lunch. In Australia the government took the brave step of legislating to make lunch boxes have plain covers with standardised health messages on the outside. "These images are graphic and, we make no apologies for that," said a Ministry of Health official. "they're designed to put children off their lunch." Whilst the scientific evidence behind this move isn't strong at the moment, time will prove that we were right said a government spokesman. Other groups have called for a complete ban on the school packed lunch. This is a national emergency, if we can't have these packed lunches banned we need skilled staff to inspect school lunch boxes. Claims that one school was considering airport style security measures to scan lunch boxes at the school gate and to restrict juice containers to less than 100ml have been strongly denied. In other news the Government has shelved plans for minimum pricing on alcohol and plain packaging for cigarettes saying they would rather concentrate on issues that will really impact on public health. ![]() The first coronary stent was implanted in 1986 by Dr Ulrich Sigwart. Stents are metal scaffolds which have revolutionised coronary angioplasty. Prior to stents, coronary dissection, caused by balloon angioplasty, usually resulted in an emergency coronary bypass operation or at best a 90% stenosis was reduced to a 40% one. Stents solved these problems but led to different ones. First there was stent thrombosis. Patients were initially treated with aspirin and warfarin to inhibit the clotting pathways but the bleeding problems were terrible. Then we then realised that aspirin could be combined with ticlopidine and subsequently clopidogrel to provide a safe treatment to reduce stent thrombosis but without the bleeding. Then there was the problem of restenosis (re-narrowing) at the site of the coronary stent implant. This led to spot stenting to keep the length of stent as short as possible. After that and thanks to Antonio Colombo and the use of intra-vascular ultrasound we realised that stents needed to be implanted at high to reduce restenosis. However problems with restenosis still existed and cardiologists developed complex treatments such as brachytherapy (intra-arterial radiotherapy) which now have all but disappeared. In the early 2000's we were introduced to the drug eluting stent. First Cypher, then Taxus and then the second generation stents such as Xience, Promus and Integrity Resolute. No longer did interventional cardiologists have to worry about the length of stent they were implanting. Treat from normal vessel to normal vessel became the mantra. But the downside was stent thrombosis, originally thought to just be a short term problem it is clear that it could occur years after stent implantation. Also in some high risk patients such as those with diabetes the restenosis problem has not been completely solved. There are some patients with in-stent, in-stent re-stenosis for which the treatment options are limited. The holy grail of stenting has been seen as the biodegradable or resorbable stent. Implant the stent when it is needed for the first few months and then when it has done its job, like a self absorbing suture, it dissolves away. This sounds an attractive prospect and in 2012 the world of stenting was revolutionised by the entry of the first commercially available biodegradable stent called ABSORB. In the early phase after implantation the ABSORB revascularises like a drug eluting stent. It releases the anti-proliferative drug everolimus to minimise neo-intimal growth and restenosis. During the restoration the scaffold benignly resorbs and the stent gradually ceases to provide luminal support resulting in a discontinuous structure embedded within the coronary artery. As the scaffold degrades, the polymer is converted into lactic acid which is metabolised and is ultimately converted into benign by-products of carbon dioxide and water. Several studies support this concept and indicate that there is no clinical benefit of a permanent stent over time. The ABSORB eliminates the permanent mechanical restraint on the vessel and should allow for more normal blood vessel function. Three-year results from 101 patients in the second stage of the ABSORB trial have shown that the rate of major adverse cardiovascular events was 10% at three years, similar to a comparative set of data with a best-in-class drug eluting stent at the same follow-up period. In a subset of 45 patients, intravascular imaging techniques showed improvements in vessel movement and a 7.2% increase in late lumen gain (an increase in the area within the blood vessel) from measurements taken at one and three years. These findings are unique to the absorbable stent and are not typically observed with metallic stents that cage the vessel. The ABSORB stent is now available and patients interested in receiving it should discuss with their cardiologist to see if they are suitable for the device. References: ABSORB II Trial ABSORB-Extend Trial ![]()
![]() The data on angioplasty in the UK is out this week on the BCIS website and it appears that all 557 cardiologists whose data is reported have a MACCE (major adverse cardiac and cerebrovascular event) rate within that expected. MACCE is a measure of the number of patients who died, had a stroke or needed an emergency bypass operation after an angioplasty procedure. BCIS estimate the MACCE rate for each patient based on parameters which are reported in a study from data obtained some 10 years ago called NWQIP. This model predicts, apparently, with 70% accuracy according to the patient's age, sex, emergent PCI, urgency of treatment, cardiogenic shock and whether a bypass graft or the left main stem was intervened on. From this BCIS estimate the 95% confidence intervals (CI) of the predicted MACCE and provided the cardiologists actual MACCE rate is lower than the upper CI then everything is apparently fine. So statistically if there were 1000 cardiologists you would expect that by chance alone then 25 of them would be above the upper 95% confidence interval and 25 would lie below the lower confidence interval. So what is the chance that not one of the 557 cardiologists in the BCIS report would be outside the top 95% confidence interval? Well its a very small number (actually p=0.000000751). So currently this is an exam which a cardiologist has a 1 in 100 million chance of failing. Now as BCIS say you can't directly compared different operators but what you can do is look at people who have a similar practice. If you pool data from cardiologists who do more than 75 angioplasty procedures per year (the BCIS recommended minimum) and who do more than 10 primary PCI procedures (treating patients with acute heart attacks who are the sickest patients) then the average MACCE rate is 2.2%. This is much lower than 8.2% MACCE rate which is predicted by the BCIS model. Although we might like to regard interventional cardiologists are superhuman creatures what this data really tells us is that the model BCIS has used to predict risk vastly over predicts the actual MACCE making this truly an exam which cannot be failed. To be fair BCIS do acknowledge the limitations of the data but there is an urgent need for more contemporary risk prediction models going forward. |
Dr Richard BogleThe opinions expressed in this blog are strictly those of the author and should not be construed as the opinion or policy of my employers nor recommendations for your care or anyone else's. Always seek professional guidance instead. Archives
August 2023
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