Slow and steady wins the race when it comes to heart failure
Heart failure is a major cause of death all over the world, but also causes a lot of disability as a chronic condition, especially with ageing populations. 2-3% of the population suffer with heart failure. Heart failure patients are often prescribed a whole range of medicines to treat their blood pressure, kidney disease and many other conditions. One more tablet called IVABRADINE (or Procoralan) looks set to join the list. I just saw the results of the SHIFT trial presented at the European Congress of Cardiology in Stockholm today and they were simultaneously published in the Lancet online.
50% of heart failure patients have a high heart rate (defined as greater than 70 beats per minute). Beta-blockers reduce the heart rate and have been shown to reduce mortality in heart failure. However, they are not always tolerated well, partly because they also cause a drop in blood pressure. Ivabradine is a new drug which reduced heart rate without much effect on blood pressure, and so may be a new option to treat heart failure.
The SHIFT trial was a double-blinded, placebo-controlled, randomised controlled trial of ivabradine in 6500 patients with moderate to severe heart failure and a regular heart rhythm. This trial specifically looked at the heart rate of patients at the start of the trial (“baseline”) and throughout the trial. The main or primary outcome of the trial was death or hospitalisation due to heart failure. Double blinding means that neither the patients nor the researchers knew which treatment the patients received. Controlling with a placebo allows the researchers to estimate the effect of the drug beyond no treatment. Randomisation means that patients randomly received placebo or the drug (in this case, ivabradine), and removed bias in the selection of patients. The trial lasted for just under 2 years.
Basically, ivabradine reduced death and hospitalisations by 18%, and the drug was very well tolerated, with few side effects of unduly low heart rate (bradycardia) or low blood pressure. The authors concluded that for every 1 beat per minute increase in heart rate, there was a 3% increase in mortality in a continuous relationship. They also found that baseline heart rate predicted the degree of risk of death, and interestingly, patients with the highest heart rate at baseline had the greatest reduction in heart rate with the drug, ivabradine. High heart rate has been shown to be a “risk marker” for outcome of patients with heart failure. This trial seems to suggest that a high heart rate may also be a “risk factor” for heart failure, i.e. it may have a role in causing the disease. Either way, “the slower, the better” seems to be the motto for the heart when it is failing.
Delay in treatment increases mortality after heart attack : time means muscle
Evidence-based guidelines recommend that after a heart attack, the blocked coronary artery needs to be reopened quickly by either fibrinolysis (or “clot-busting” drugs) or primary percutaneous coronary intervention (primary PCI), which aims to open the artery using balloons and stents. However, there are several reasons for delay in these treatments.
Firstly, “patient delay” is the delay from the onset of chest pain or symptoms to when a call is made to emergency medical services, and can only really be reduced by better public education about heart attacks. Secondly, “system delay” is a combination of “transportation delay” (the time taken for the patient to get to the hospital) and “door-to-balloon delay” (the time taken for the patient to receive the artery-opening therapy once they are in the hospital). In terms of training of doctors and measurement of outcomes within hospitals and across health systems, there has been a huge focus on the “door-to-balloon” delay. However, to know the effect of delaying therapy on outcome, we need to look at “system delay”, which is what a Danish study does in this week’s JAMA.
Due to excellent public medical databases in Denmark, the authors were able to study over 6000 patients with the particular form of heart attack (“STEMI”) which is best treated by primary PCI, and obtain estimates for the various types of delay outlined above. The authors excluded patients with a treatment delay greater than 12 hours or a system delay greater than 6 hours.
Interestingly, treatment delay and patient delay were not associated with mortality, but the authors are quick to assert that “should not deter encouraging patients to seek medical help as soon as possible after the onset of symptoms”. On the other hand, system delay predicted mortality, with a hazard ratio of 1.10 per 1-hour delay. In other words, for every one hour of system delay, there is a 10% increase in mortality. When the authors analysed further, they found that a 1-hour transportation delay led to 10% increase in mortality, whereas a 1-hour door-to-balloon delay led to a 14% increase in mortality. In other words, time does really mean muscle (and life) when it comes to the heart.
autism and brain scan test: the real predictive value
A brain scan that detects autism in adults could mean much more straightforward diagnosis of the condition, scientists say. Reported the BBC, Sky the Guardian and many more.
I had great difficulty getting hold of this paper, it wasn’t published online at the time of the press release. I managed to get a copy via Ben Goldacre at Bad Science and Evidence Matters who sent me the full text. Given this problem in getting the paper, it is highly likely no one who released the story has actually read the paper.
The news all report the headline ‘The researchers detected autism with over 90% accuracy, the Journal of Neuroscience reports.’
Sounds impressive, but this is one of the most obvious mistakes to make in interpreting a diagnostic test result. Never mind this is not the correct study type.
What has happened is the sensitivity has been taken for the positive predictive value, which is what you want to know: if I have a positive test do I have the disease?
Sensitivity: The proportion of people with disease who have a positive test.
Positive predictive value (+PV): The proportion of people with a positive test who have disease.
So, for a prevalence of 1% the actual positive predictive value is 4.5%. That is about 5 in every 100 with a positive test would have autism. Even at a prevalence of 2%, only 8.5% would be correctly identified.
Suddenly, not that great a test. This has to be one of the worst examples of misinterpreting diagnostic test results in the media I’ve ever seen.
Developing world surgery: no operating theatres and no basic anaesthetic equipment
There are few surgeons who are as passionate as Atul Gawande about improving the desperate state of surgery in the poorest parts of the world. I met him a few years back at the launch of his bestselling book, “Complications”. He is a surgeon, academic, author, public health guru and heads Safe Surgery Saves Lives, a WHO group, formed to improve patient safety within surgical specialities. You cannot help but be impressed by the simplicity and the far-reaching consequences of research coming from the group. For example, a 19-point surgical checklist was introduced in eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) for 1 year. Use of the checklist reduced death rate from 1.5% to 0.8% and reduced complications occurring in hospital from 11% to 7%.
The Lancet Online First includes the latest study from Gawande’s group. Apparently, 11% of the world's disability-adjusted life years (a measure of the disability caused by diseases) are due to diseases that are often treated with surgery, whether coronary artery bypass graft surgery in coronary heart disease, carotid surgery in the setting of stroke, cancer surgery, or trauma surgery following road traffic accidents. There are huge global inequalities in terms of the operations performed. Out of 234 million surgical procedures done every year, the richest third of the world’s population has three-quarters of the operations, whereas the poorest third has only 4%. The latest study looks at how much of that inequality is due to two integral parts of surgery. One is the operating theatre, and the other is pulse oximetry, the simple process by which a patient’s blood oxygen levels are monitored during an operation. The study used WHO data from 769 hospitals in 92 countries. Importantly there were no differences in patients, health systems or wealth between countries that did have data about operating theatres and pulse oximetry and those which did not. Therefore, these factors are unlikely to be confounders.
The results make sombre reading. Rich countries like the UK had at least 14 operating theatres per 100 000 people, while all poor regions of the world (accounting for more than 2 billion people, or a third of the world’s population) had fewer than two operating theatres per 100 000 people. This is in spite of having more surgically treated diseases per head than do rich countries. As the authors state, “People in such regions are effectively without access to surgical care”. The fact that over half of operating theatres in sub-Saharan Africa did not have the facility to measure oxygen levels and therefore could not monitor a patient’s breathing during anaesthetic is horrifying and is probably the tip of the iceberg in terms of lack of other essential surgical and anaesthetic equipment. Whilst showing these inequalities does not solve them, it does the vital job of highlighting where global health initiatives need to focus.