Relation between patients’ variable compliance and office blood pressure in treatment-resistant hypertension.
Tousset, E.(1), H. Figueiredo (2),M.P. Schneider(2),O. Bugnon(2), B.Vrijens (1)
(1) Pharmionic Systems Ltd., Visé, Belgium , (2) University Outpatient Medical Clinic, Lausanne, Switzerland
Objectives: Suboptimal compliance with prescribed therapy results in variable exposure to the treatment and is recognized as a potential cause for non- or poor-response to prescribed anti-hypertensive drug regimens(1). The primary objective of this study is to assess the impact of variable dosing histories on blood pressure in unresponsive hypertensive patients treated with multiple drugs.
Methods: The study involved 89 patients coming from two different settings: 1) 44 resistant hypertensive patients treated with at least three anti-hypertensive drugs and recruited in a clinical trial aiming at improving patients' clinical outcome and compliance. 2) 45 uncontrolled patients followed by general practitioners in a clinical practice. Office blood pressures were measured at each clinic visit. Antihypertensive drug dosing histories were compiled electronically by medication event monitors (MEMS®), one monitor for each prescribed antihypertensive drug. Daily compliance with the treatments was summarised by a binary variable indicating whether the patient took at least one of the drugs as prescribed by the physician. Nonlinear mixed effect models were used to analyse the impact of variable dosing histories on systolic blood pressures (SBP). A sigmoid Emax model was selected to describe the relation between SBP collected over time and drug exposure recorded prior to the corresponding visits.
Results: The average proportion of patients who complied with at least one of the prescribed dosing regimens was stable over time and significantly higher in the clinical trial setting (92% vs 81%,p=0.0004). The daily indicators were used to define the average number of days with correct dosing in a window of 10 days prior to the measurement of blood pressure. The model was adjusted for baseline blood pressures (linear relation, p<0.0001) and drug exposure summary statistics (sigmoid Emax relation, p<0.0001). It estimated a 24 mmHg [11-37] decrease in SBP for a typical patient achieving a 100% drug exposure. Fifty percent of the maximal reduction in SBP was achieved at a drug exposure level of 51 % [26-76].
Conclusion: This analysis shows a statistically and clinically significant relation between SBP and electronically compiled dosing histories. It allows one to estimate the expected SBP over the entire spectrum of compliance with the prescribed antihypertensive drugs.
 Burnier M, Schneider MP, Chiolero A, Stubi CL, Brunner HR. Electronic compliance monitoring in resistant hypertension: the basis for rational therapeutic decisions. Journal of hypertension 2001, 19:335-341.