The Anglo-Scandinavian Cardiac Outcomes Trial

Abstract

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 end points 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 coronary heart disease (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 was to collaborate with the Gothenburg Trial Centre in Sweden, Pfizer would fund a major European outcome study. Preliminary discussions between United Kingdom and Swedish colleagues reviewed ongoing trials, including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, 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 because it was recognized that most patients required …