Seminar 15: Is the polypill the panacea that will reduce CVD?

Dr Denis Xavier is professor and head of pharmacology at St John’s Medical College, Bangalore, and is also the principal investigator of a Center of Excellence in Bangalore, part of the Chronic Disease Initiative on which Cristina Rabadan-Diehl presented in the previous breakfast seminar (here >>). He presented on the polypill in C3’s series of International Breakfast Seminars on 18 July 2012.

  • Slides from the event are available here >>
  • A full report of the seminar can be downloaded here >>
  • An interview with Dr Xavier on the Dr Xavier on the BBC’s World Service Health Check radio programme (18 July 2012) here >>

It is almost 10 years since an article in the BMJ suggested that the polypill could be a panacea for cardiovascular disease (CVD), the world’s leading cause of death. Primary prevention can be cumbersome, and individual lifestyle modification – while natural and safe – may not be low cost, simple or sustainable. Reductions in deaths in developed countries have been due to good treatment, not good prevention – and even in developed countries, only 10% of people with a history of CVD take all the basic drugs (statins, aspirin, beta-blockers, folic acid). This is much lower (0.2%) in developing countries, and in the lowest-income countries, nearly 90% are getting no treatment at all.

The polypill combines a number of generic drugs in a single pill – the original calculation in the BMJ was that this could, if taken by everyone over the age of 55, potentially reduce the risk of ischaemic heart disease by 88% and stroke by 80%. Potential advantages of the polypill include few side-effects, lower costs (fewer visits to the doctor, reduced prescription costs, etc.), better adherence when taking just a single pill, and fewer medication errors.

Denis is involved with several studies of a ‘polycap’, originally developed in India:

  • The Indian Polycap Study (TIPS) (2005) combined antiplatelet, statin, ACE-inhibitor, a beta-blocker and a diuretic (the latter four in half the usual dose), and investigated different combinations (including all the drugs) to see if it worked as well as the drugs separately. The study ran for 12 weeks, and the 2,000 participants, aged 45–80, had at least one CVD risk factor. The polypill was found to be well tolerated over 12 weeks compared to the other combinations of drugs, and, based on actual data in the trial, the polycap led to a 62% risk reduction of CHD and 48% reduction in stroke. In other words, the polycap is similar to the effects of its components (e.g. aspirin does not interfere with blood-pressure- lowering effects), and it could reduce CVD risk by about half. (One participant noted that a new trial of the polypill with people aged 50+ who had, up to that point, been taking the components of the polypill, saw resulting blood pressure and lipid reductions that were exactly as predicted in the original BMJ article.)
  • The TIPS-2 study was conducted among patients with stable CVD or with elevated risk, and looked at the benefit of giving two doses of the polycap, rather than a single dose. The double dose did give greater risk reduction (blood pressure and lipids), translating into a 50–60% reduction in long-term risk.
  • TIPS-3 is the International Polycap Study, looking at the polycap, low-dose aspirin and vitamin D supplementation. It is a study of men aged over 55 and women over 60, who have known risks but no known vascular disease. This study has started in India, and will run across 10 countries.

The development of the polypill has not been universally welcomed – particularly by those who are afraid that it could medicalise risk and act as a disincentive to those who need to adopt healthier lifestyles. Denis stressed that the polypill should always be complementary to lifestyle change.

Health professionals, too, are not always supportive of the polypill – perhaps because of vested interests, and a failure to appreciate that any reduction in risk is beneficial. The media and policy-makers also may not be aware of the potential benefits: strong policies on access and pricing are needed if the polypill is to become widely available.

There is still research to be done: it is not yet known if the polypill will reduce CVD events, nor do we know its long-term safety, the ideal dose, or the ideal drugs to include. There will probably not be one polypill appropriate for all – it would not be for those at very high risk, for example. But we do now have the data to show that it can be used in secondary prevention and high-risk primary prevention.

Denis concluded by saying that the polypill seems to be the only current panacea for global CVD prevention.

Discussion focused on:

  • engaging the pharmaceutical industry to take on the polypill and produce it at very low cost – for example, by governments agreeing to buy it in bulk. This would also require the governments to accept that current investment may not be being invested in the best places for maximum benefit;
  • the polypill as part of a lifestyle strategy, which can itself have huge health benefits – for example, one participant suggested that the polypill be withdrawn if efforts are not also made to change lifestyles;
  • the need for regulators to recognise the benefits of polypills (not just for CVD), and work to facilitate sensible trials of the components that allow rapid progress to be made, rather than delaying development for years; and
  • how the polypill will be perceived in the UK – patients are more likely to be receptive to it than health professionals.