As the UK descends into hysteria around petrol and pasties, I have been reflecting for the last week on Peter Rothwell’s recent Lancet papers about cancer prevention and the role of aspirin. Basically, daily low-dose aspirin not only prevents development of new cancer, but also the spread of cancer. Aspirin is one of the oldest drugs in the drug cabinet of hospital wards and GP surgeries, but we continue to discover more about its roles in medicine. As new evidence appears on the horizon, the information and guidelines for practising doctors and their patients still continues to change. There are inevitably time delays in how quickly new information filters through healthcare settings and broader society, and how it is interpreted by both the patient and the doctor.

Aspirin has several different uses which are proven by large bodies of evidence, including as a painkiller, prevention of cardiovascular disease in people at risk (primary prevention) and people with known cardiovascular disease (secondary prevention) and now for prevention of cancer. I always love to refer back to the Hippocratic Oath, and so we have to weigh aspirin’s harms with these many benefits. The main harm with aspirin is bleeding, particularly people who have a tendency towards bleeding anyway, e.g. individuals with history of gastric ulcers.

Interestingly, as the new data is emerging about the long-term preventive effects on cancer, the use of aspirin for two other indications is in decline due to evidence of not that much good when weighed against the risk of bleeding. First, most doctors do not recommend low-dose aspirin for primary prevention of cardiovascular disease, largely due to available data from meta-analyses showing that it does not change mortality in diabetics or non-diabetics. Second, in patients with atrial fibrillation, a heart rhythm problem which increases risk of stroke, aspirin is no longer recommended, yet most guidelinesaround the world still include it. So while we can recommend aspirin for long-term cancer prevention, we may not be able to recommend it in healthy individuals for long-term stroke prevention.

Evidence-based medicine is following a moving target of diseases and treatments and so the evidence is also always changing, even for drugs as old as aspirin. So for newer drugs, you can begin to imagine how little we know. The challenge is to keep all people, both doctors and patients up-to-date with all available evidence and guidelines. However, we know that this is difficult, given that both doctors do not always follow guidelines and people do not generally like to take tablets. Notably, most news reports covering the “aspirin and cancer” story advised people to go and see their doctor before starting the drug. Fergus Walsh, of the BBC, quoted a notable academic, “Doctors were good at treating disease, but when it came to preventing ill-health then people had to make their own judgements”. I agree. I wonder whether people have as much chance of making the “right decision” themselves. And before you ask, I do not take an aspirin a day yet, but I did start cycling to work again this week. One preventive step at a time.

Since the early trials of beta-blockers and thrombolysis, or “clot-busting” drugs, in cardiovascular disease, the American Heart Association Scientific Sessions and other international cardiology meetings have been dominated by highly-anticipated “late-breaking” or “hot trials” sessions. During these talks, thousands of conference attendees would clamour to hear the results of trials of new drugs reported for the first time. As well as being highly talked about, they greatly influence projections of how the drug will perform in the real market: akin to a stockmarket floor for pharma. Today new drug trials are still by the dozen, but difficult economic times, increased regulation of pharma and wider and quicker dissemination of results may be changing the role of these sessions.

Aside from the trials, three messages are coming through loud and clear from this year’s meeting in Orlando. First, although the best-attended sessions are still the trials of new interventions and drugs for the range of cardiovascular disease, the number of talks devoted to primary prevention and primordial prevention is growing. In other words, prevention of the development of disease and prevention of the development of risk factors of disease, respectively

Second, there is a shifting focus on risk factors as continuous exposures over the whole lifespan. For example, we have talked about “pack-years” of smoking for a long time, i.e. an individual’s lifetime exposure to cigarette smoke. Rather than looking at arbitrary cut-offs for risk factors such as hypertension or high cholesterol, it may make more sense to look at the burden of that risk factor over their lifespan, and in combination with other risk factors.

Third, in the aftermath of the September UN high-level meeting, there is an increasing recognition of the global health aspects of heart disease and stroke. In a session chaired by Professor Sir Magdi Yacoub, eminent cardiac surgeon and long-term activist for improved health services for heart disease in low-income countries, a researcher from Mozambique showed the huge disease burden how feasible screening for common heart diseases can be, even in rural settings.

All three of these changes are welcome and signal gradual, encouraging paradigm shifts among both researchers and health professionals to look at the bigger picture of prevention and population approaches to cardiovascular disease.

We have blogged a lot about statins in the past here at Trusttheevidence.net, partly because they are so commonly used and partly because they are so often in research and in the media. Their role in secondary prevention is not in question and they are arguably one of the greatest advances in cardiovascular disease prevention in modern times in this respect. However, for quite a while, the role of statins in primary prevention has been doubtful, and last week a Cochrane review and a related editorial added to the already strong evidence base that if you are at low risk of coronary heart disease or stroke, you probably should not bother with statins.

The WHO’s Bulletin included research this week which showed that high cholesterol is undertreated even when it is diagnosed. “The proportion of undiagnosed individuals was highest in Thailand (78%) and lowest in the United States (16%). Time series estimates showed improved control of high total serum cholesterol over the past two decades in England and the United States.” One reason for these observations may be the fact that many of these patients with high cholesterol had no history of cardiovascular disease, and so the lack of definitive evidence for statins in primary prevention may have led to their omission. Another reason may be that the most aggressive marketing of statins for primary prevention occurred in US and European health systems. The authors of the study called for increased treatment of high cholesterol to stem the world’s cardiovascular epidemic, despite continued doubts about the role of statins in primary prevention. This research received wide media coverage and adds to the confusion in policy around statins for primary prevention

So I am wondering how come all this data and controversy about primary prevention data for statins has tended to appear so late in the patent life of the drugs. Of course, part of the issue is that it takes time to organize trials, and to gather enough data for meta-analyses. However, the entry about statins on Wikipedia made me think:

“To market statins effectively, Merck had to convince the public about the dangers of high cholesterol, and doctors that statins were safe and would extend lives.”

Did you know that “Lipitor” (aka “atorvastatin”), made by the world’s pharmaceutical giant, Pfizer, is the biggest blockbuster drug of all time? If you look at the list of top-selling drugs of all time, simvastatin, rosuvastatin and pravastatin are all high on the list. The problem for big pharma is that the statins are going off patent. Atorvastatin is already off patent in several countries and most of Pfizer’s patents for this drug expire in 2011. This is a big financial problem for Pfizer and other companies, and only yesterday, the close of Pfizer’s main UK base was announced. Drug companies are being forced to change their old research and development paradigms. They are also not going to be able to get away with withholding data or encouraging “off-label” use of their drugs. It is surely possible to develop safe and effective drugs with more openly available information to both clinicians and patients.