Wilder's principle: pre-treatment value determines post-treatment response

Over more than half a century numerous studies have documented that pre-treatment blood pressure (BP) is a determinant of the anti-hypertensive response.1–9 This has been shown for systolic and diastolic BP, acute and long-term response, monotherapy and combination therapy, and for office BP as well as for 24 h ambulatory BP. The first observation along that line was perhaps made by Freis et al . who, in 1958, in a very careful in-patient study reported a decrease in BP with chlorothiazide in every single hypertensive patient whereas in 15 normotensive subjects followed under exactly similar dietary and hospital control conditions, no reduction in BP occurred.10 This phenomenon that the pre-treatment level determines to a large extent the change per se , that is, the principle of initial value (German: Ausgangswertgesetz) was first described by Josef Wilder in 1931 who proposed that the ‘direction of response of body function to any agent depends to a large degree on the initial valuable of that function’.11,12 In 1976, Dixon and Johnson put forward the hypothesis that ‘the magnitude of the fall in blood-pressure in response to an antihypertensive drug depends on the level of the pretreatment pressure, and there is a direct relationship between the two in that the higher the pretreatment pressure the greater the fall in pressure in response to treatment’.13 Subsequent testing of this hypothesis in 42 published small studies in a total of 971 patients with 23 anti-hypertensive drug regimens revealed that in clinical practice ‘most of the regimens failed to show ideal behavior’ but that the ‘hypothesis …