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.

The debate on the best way forward for primary prevention continues, and today cebmblog published:

Heneghan C. Considerable uncertainty remains in the evidence for primary prevention of cardiovascular disease [editorial]. The Cochrane Library 2011 19 Jan.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, and therefore strategies that aim to improve prevention in people without existing disease (primary prevention) are important for managing the overall burden of disease. This edition of The Cochrane Library adds to the evidence-base in this area with publication of two Cochrane Reviews on such preventive strategies: multiple risk factor interventions for primary prevention of coronary heart disease, and statins for the primary prevention of CVD. read more

One of my major issues with primary prevention is:
'Given the current limitations of the evidence-base, the alternative approach for policy is to focus on population-wide prevention. Widely publicised by Geoffrey Rose,legislating for smoke-free public spaces, re-designing public spaces to improve exercise or reducing daily dietary salt intake prove generally effective and can be cost-saving interventions.'

If you haven't already read a copy of Rose's book, you should,
get yourself a copy now. It should be compulsary reading for commissioners, docs and anyone involved in health prevention.