Previous trials and outcomes
Do these trials make a difference? Trials results from our patients have changed clinical practice.
ASCOT(Anglo-Scandinavian Cardiac Outcomes Trial) 1998-2005
- The results from the ASCOT study helped to change the UK standard treatment for high blood pressure.
- The results from the cholesterol part of the study influenced the national guidance on using statins to reduce cholesterol in people who are at risk of a heart attack, but who are not known to have heart disease.
- Results from ASCOT and the Heart Protection Study helped to inspire the new NHS health check programme.
It is very unusual for a single trial to have such big impact on practical treatments for more than one common problem.
We recruited 1,157 patients from all over east London and followed them for between 5 and 7 years for this study, which began recruitment here in 1998. In all, over 19,000 patients joined the study and the largest group of patients in the trial was at Barts and The London. The study was run by colleagues in Imperial College and in Gothenberg in Sweden.
All the patients had high blood pressure, and at least three risk factors for future heart disease (for example being male, having high cholesterol, smoking or diabetes). Patients were given either “traditional” blood pressure treatment based on beta-blocker and a water tablet, or a more “contemporary” regime based on a calcium channel blocker and an ACE inhibitor. Their blood pressure was treated to achieve blood pressure control, adding extra medication as needed. Patients’ progress was followed at least every 6 months until the end of the study in 2005.
Lipid Arm
More than half of the patients, 10,305 who did not have “high” cholesterol levels at the start of the study volunteered to take either a placebo (dummy) tablet, or the cholesterol-lowering tablet atorvastatin 10mg each day on top of their blood pressure pills. This was known as the lipid-lowering arm of the study (ASCOT-LLA). The cholesterol part of the study stopped early, after 3.3 years.
Patients who had the statin drug had 36% fewer heart attacks and 27% fewer strokes than those taking the placebo, and this was published in the Lancet and presented at the American Congress of Cardiology.
As a result of the ASCOT-LLA and other studies, the national guidelines for the treatment of cholesterol in people with high blood pressure were changed. Now people with high blood pressure and risk factors for heart disease are offered statins as part of the guidance of NICE, the National Institute for health and Clinical Excellence (www.nice.org.uk/CG067)
Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial
The Lancet, Volume 361, Issue 9364, 5 April 2003, Pages 1149-1158,
Peter S Sever, Björn Dahlöf, Neil R Poulter, Hans Wedel, Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O'Brien, Jan Östergren and for the ASCOT investigators.Blood pressure
Two years later the main ASCOT study was closed. The results showed that although the number of heart attacks in the newer drug group had not reached statistical significance, patients on the more modern drugs had died less frequently, had fewer strokes, and had been less likely to become diabetic than those who had had the more traditional beta-blocker and water tablet treatment.
After the results of ASCOT-BPLA, the British Hypertension Society and the National Institute for Clinical Excellence (NICE) produced new joint guidance for the treatment of high blood pressure in the UK (www.nice.org.uk/CG034 ).
We had so many patients in this study, and for so long, that both patients and GP surgeries used to think about us as “the ASCOT clinic” and so the name has stuck. More details can be found on the study website: www.ascotstudy.org
ASCOT substudies:
- CAFÉ
- Ethnicity
- Genetics
- CARAT
- Microalbuminuria and renal function
Illuminate Study 2005-2007
Although the study showed that the drug was harmful, it was very important for this to be known before the drug was launched for general use- so that harm was as little as possible. The study was praised by the Food and Drug Administration (FDA) in the USA for getting such an important result. If the drug had been made available for doctors to prescribe without the trial, then many hundreds or even thousands of people might have suffered before the problem was discovered. Many of these study patients with us have since taken part in other studies, so they seem to have agreed.
This trial was the first to test the idea that increasing levels of HDL “good” cholesterol could prevent heart attacks and strokes.
People with naturally high levels of HDL cholesterol have fewer heart attacks than those with low levels (it seems to help with removing fat from the walls of blood vessels and keeping them free from blockages).
We recruited 148 of the patients for this study, who had either had heart problems before, a stroke, or were diabetic- and so were at high risk of another heart attack. They were treated to reduce their bad cholesterol first with a statin drug, and then were given either Torcetrapib, or a placebo (dummy) tablet on top of this.
The study was stopped dramatically and early on December 2nd 2006 with the announcement that more patients on Torcetrapib had died than in the placebo group, and so the drug was withdrawn from trials. Thankfully all of our patients escaped major problems, but the blood pressure rise which was a known side-effect of the drug seemed to cause the problem. We had had to stop the study drug during the study because of blood pressure rise in many patients, and we now know that Torcetrapib increases a blood pressure hormone called aldosterone, which makes you keep more salt and water in your body.
The study was published in the prestigious New England Journal of Medicine…..
Barter, P. J., Caulfield, M., Eriksson, M., Grundy, S. M., Kastelein, J. J.P., Komajda, M., Lopez-Sendon, J., Mosca, L., Tardif, J.-C., Waters, D. D., Shear, C. L., Revkin, J. H., Buhr, K. A., Fisher, M. R., Tall, A. R., Brewer, B., the ILLUMINATE Investigators, (2007). Effects of Torcetrapib in Patients at High Risk for Coronary Events. NEJM 357: 2109-2122
Over 50 of our patients came to a meeting to hear the results of the study in 2007, and amazingly one volunteered for a trial involving the next drug in the same class.
The big question was whether any other manufacturer was going to risk testing the next drug in the same class (and if they did, you asked us would we be prepared to do it?)- this is now underway……….. the Dal-outcomes trial- see our current studies.