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Blood Press. 2015 Feb;24(1):1-6. doi: 10.3109/08037051.2014.946787. Epub 2014 Aug 27.

Physician (investigator) inertia in apparent treatment-resistant hypertension - insights from large randomized clinical trials. Lennart Hansson Memorial Lecture.

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University of Oslo, Ullevaal Hospital , Oslo , Norway.



Treatment of resistant hypertension has attained much attention during the past few years and naturally so has the prevalence of resistant hypertension. In the search for sources of such documentation, the lack of blood pressure (BP) control in randomized clinical outcome trials in hypertension has been used as indication of treatment-resistant hypertension. In the present study, we aimed at using previously unpublished information from monitoring of clinical trials in investigating the mechanism explaining why large fractions of patients in the trials remained uncontrolled for their high BP.


We report insight information from LIFE (n = 9193), VALUE (n = 15,245), ASCOT (n = 19,257) and ACCOMPLISH (n = 11,506). Data stored during the course of the trials for monitoring purposes were scrutinized for fractions of patients with BP control, which was BP < 140/90 mmHg in all trials, and we identified monitoring data showing fractions of patients who had been uptitrated to the various dosing levels or combinations of study drugs in the trials. Fractions of patients who had not been uptitrated on drugs and who remained without BP control identified the level of physician (investigator) inertia in these trials.


In the LIFE Study the majority of patients remained with systolic BP > 140 mmHg throughout. Approximately 1500 patients remained on the first dose titration step despite not having reached target BP. In the VALUE Trial 59.5% had reached systolic BP target 2 years into the study; 23.9% of patients remained on the lowest study dose and only 15.1% had been uptitrated to the highest study dose. In the ASCOT Trial, as many as 28% of participants had not reached target diastolic BP at year 4 in the study, and of these patients 37% still remained on the first drug dose titration step. In the ACCOMPLISH Trial approximately 80% had achieved the systolic BP target at study end; however, during the course of the trial approximately 25% of participants remained uncontrolled and at 6 months almost 60% of these patients had not been titrated to the highest drug dose level.


These data, taken from the monitoring phases of large outcome trials in hypertension, show that inertia, the lack of titration of study drugs to higher dosing levels or drug combinations according to the study protocols, is a major cause of not reaching BP targets in the trials. Thus, fractions of patients not reaching BP targets in outcome trials cannot be taken as evidence of treatment-resistant hypertension.


Blood pressure; clinical trial; hypertension; inertia; treatment resistance

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