The Anglo-Scandinavian Cardiac Outcomes Trial
At a meeting of the European Blood Pressure Group held in Madonna di Campiglio, Italy, in the spring of 1988, concern was expressed that there were no plans to evaluate the long-term efficacy of newer classes of blood pressure lowering drugs, including the calcium channel blockers and the angiotensin converting enzyme inhibitors, in morbidity and mortality outcome trials. These drugs were being increasingly used in clinical practice, worldwide, and there was a view that industry perceived there was no need for long–term studies. Much had been made of the potential benefits of these newer drugs in short-term studies on surrogate endpoints, compared with older therapies, but there was little pressure for investment in outcome trials in hypertension.
At a further meeting of the European Blood Pressure group the following year, in 1989, a steering group outlined a proposal for a factorial designed study to investigate not only whether newer treatments were better than old, but also whether cholesterol- lowering in a hypertensive population would confer benefits on CHD events. At approximately the same time in the United States, proposals along similar lines were being discussed by the National Heart, Lung and Blood Institute.
However, further progress was delayed until September 1995, when it was proposed that if a group of United Kingdom trialists were to collaborate with the Gothenburg Trial Centre in Sweden, Pfizer would fund a major European outcome study.
Preliminary discussions between UK and Swedish colleagues reviewed ongoing trials, including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), and focused on the design of a 2-way comparison trial comparing older treatment strategies with a newer treatment strategy based a calcium channel blocker and an angiotensin converting enzyme inhibitor. The concept of a “combination treatment” trial germinated, particularly since it was recognised that most patients that most patients required more than one drug to control blood pressure and that no other trial was designed to compare specific treatment regimens.
In addition, there was further discussion on a factorial design, involving a comparison of a lipid-lowering agent with placebo in a subgroup of patients with normal or modestly raised cholesterol levels for whom, at the time, there was no indication for lipid-lowering. Further details on the background to ASCOT are given in Appendix 1, online supplement data -: Hypertension. 2012;60:248-259.
An independent steering committee was set up in 1996. The trial protocol was agreed and finalised, named the Anglo-Scandinavian Cardiac Outcomes Trial, and recruitment commenced in February 1998.