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.

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.

‘Poverty is as a strong a predictor of premature death today as it was a century ago’ reported a study on BMJ online this week. The study examined the geographical relationship between mortality and deprivation at the start of the 20th and 21st Century. Although there was a change in the number of deaths over this time, modern patterns of mortality and deprivation remain strongly linked to the patterns of a hundred years ago.

Their conclusion states ‘for all the medical and public health changes over this time, patterns of poverty and mortality and their relationship remain firmly entrenched.......... This relationship holds true for most major modern causes of death’.

If you bear with me for a few minutes I’ll explain why I think this occurs and the paradox that causes it.

Consider living in the most deprived areas of the country and survey one hundred 18 to 30 year-olds. Of these, 20 have long term health problems; for instance mental health problems. You decide over the next 10 years to invest considerably in health and for your investment you get a 20% reduction in chronic health problems, leaving you with 16 individuals still with chronic disease. However, 20 of the healthiest, educated and economically active individuals decide to become part of a common phenomenon: economic migration, whereby individuals emigrate from one area to another for the purposes of seeking employment or improved financial position. For the unhealthy this is normally not an option.

So what’s the paradox? Well when you resurvey you are left with 80 individuals of whom 16 have a chronic health problem. In effect 20% exactly the same figure we started with. Therefore, to me there seem only two solutions: one is to raise the average wealth of everyone, or second to take the economic activity to the areas which are the most deprived.