An international Phase III clinical trial to assess whether a low-cost, once-daily ‘polypill’ can reduce the risks of heart attacks, strokes and other cardiovascular conditions is underway in the UK and three other countries.

The two-year UMPIRE (Use of a Multidrug Pill in Reducing cardiovascular Events) trial of the new fixed-dose Red Heart Pill has launched in London, through Imperial College Healthcare NHS Trust, and at centres in Dublin, Ireland, Utrecht, the Netherlands and – pending regulatory approval – in Hyderabad and New Dehli, India.

Parallel trials were launched earlier this year in New Zealand and Australia, while there are plans for further studies in Brazil, Canada, China and South Africa. Collectively, these trials will involve some 7,000 patients in 10 countries, taking one of two versions of the polypill formulated by India’s Dr Reddy’s Laboratories or their usual individual cardiovascular medicines.

The primary endpoint is whether patients are more likely to stick with a preventive treatment regime comprising a single, once-daily polypill than one involving multiple tablets. The researchers will also be looking at whether the Red Heart Pill is effective at lowering blood pressure and cholesterol levels.

The target population for the UMPIRE study is around 1,000 adults with established cardiovascular disease (CVD) or a high CVD risk at the European sites and around the same number of patients in India. The scheduled completion date is January 2013, with final data collection for the primary outcome measure expected in June 2012.

In the randomised, controlled design, patients will receive either usual care or one of the two versions of the Red Heart Pill: version 1, comprising aspirin 75mg (platelet function), simvastatin 40mg (cholesterol reduction), lisinopril 10mg and atenolol 50mg (both to lower blood pressure); or version 2, containing aspirin 50mg, simvastatin 40mg, lisinopril 10mg and hydrochlorothiazide.(diuretic).

In general, trial participants with a history of coronary heart disease will be given version 1 and patients with a history of stroke or cerebrovascular disease version 2. The primary outcome measures are adherence to medication, changes in blood pressure and changes in total cholesterol.

The partners in UMPIRE are Imperial College London; the Royal College of Surgeons in Ireland; University Medical Centre in Utrecht, the Netherlands; The George Institute and New Dehli’s Centre for Chronic Disease Control in India, as well as the Public Health Foundation of India; The George Institute for International Health in Sydney, Australia; and Dr Reddy’s Laboratories. Project funding has come from the European Union’s Seventh Framework Programme.

Original polypill

The original polypill concept, advanced in June 2003 by Professors Nicholas Wald and Malcolm Law of London’s Wolfson Institute of Preventive Medicine, involved a six-ingredient combination of a statin, aspirin, folic acid and three antihypertensives (a thiazide, a beta-blocker and an ACE-inhibitor), to be given to everyone over the age of 55 years and to people with existing high blood pressure, heart disease or diabetes.

In a much-discussed paper in the British Medical Journal, Wald and Law said taking the polypill daily could reduce the rate of ischaemic heart disease events by 88% and strokes by 80%, with minimal side-effects. The proposal generated a good deal of debate, quite a lot of it hostile. There were concerns about unforeseen adverse reactions from the six ingredients in combination and about people using the polypill as an excuse to continue leading unhealthy lifestyles.

In December 2006, Dr Reddy’s Laboratories announced a tie-up with researchers from the University of Aukland, led by Professor Anthony Rodgers, to conduct a clinical trial in New Zealand, India, Australia, Brazil, China, South Africa, the US and the UK with a polypill comprising aspirin, a statin and two antihypertensives. Professor Rodgers is one of the principal investigators for the UMPIRE trial, working out of The George Institute in Australia.

If the treatment strategy in UMPIRE is successful, the researchers aim to establish how the Red Heart Pill could be made available to patients on low incomes in countries such as India, where the majority of people do not currently have access to cardiovascular medicines.

In countries such as the UK, where cardiovascular therapy is more readily available, the idea is to see whether the polypill could provide a more convenient alternative to existing multiple medication and improve adherence. Evidence shows that, at present, many patients who start on these individual drugs do not continue to take them in the long term, Imperial College notes.