Nuffield Department of Population Health

Richard Doll Building, , Headington, OX3 7LF, UK ______

Date: 25 February 2015

To: WHO Essential Medications List Expert Committee

An application to recommend that fixed-dose combination therapy be added to the WHO model list of essential medicines for secondary prevention of cardio- vascular disease (ischemic heart disease and ischemic stroke)

We are writing in strong support of the above application.

For more than 30 years the Clinical Trial Service Unit of the , of which we are jointly the directors, has conducted large international trials and co- ordinated worldwide meta-analyses of trials, of anti-thrombotic drugs, beta-blockers, converting enzyme inhibitors, blood-pressure lowering drugs and cholesterol- lowering drugs, demonstrating moderate but definite benefits that, in combination, yield substantial benefits, reducing by well over half the likelihood of recurrence and death if taken regularly for several years. If taken for secondary prevention, the absolute annual benefit from appropriate combination of such drugs is substantial.

Each of these classes of drug is now available as an affordable generic product, but it is difficult to maintain compliance (both by prescribers and by patients) over many years with multiple medications. Different expert panels, including the WHO and the Combination Pharmacotherapy and Public Health Research Working Group, have recognized the potential value of fixed dose combination therapy for secondary prevention of cardiovascular disease. We agree strongly that affordable availability of low-cost fixed-dose combination therapy is highly desirable, and inclusion of such combinations in the WHO essential drugs list would encourage this.

Sir Richard Peto Professor of Medical Statistics and Epidemiology, University of Oxford, UK

Colin Baigent Professor of Epidemiology University of Oxford, UK

Sir Rory Collins Head, Nuffield Department of Population Health, University of Oxford, UK

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Head of Department Professor Sir Rory Collins FMed Sci FRCP