Discontinuation of Therapy in Hypertension Research
Value, Ethics, Risk, and Role in Renal Denervation Trials
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See related article, pp 927–932
Less than 60 years ago, 2 studies were published that when read together constitute a surrogate for the first clinical trial in hypertension research. In the first, Priscilla Kincaid-Smith et al1 described the fate of untreated malignant hypertension in 197 subjects. In the second,2 the same group reported their experience with results of treatment in 94 subjects over 7 years. The first series was not an intentional placebo-control group but simply the reflection of lack of provision of treatment at that time because epidemiological evidence about the risks of hypertension was in its infancy, and documentation that reducing blood pressure would produce any benefit was nonexistent. Experts even argued whether fibrinoid necrosis, the hallmark pathology for malignant hypertension, was caused by blood pressure elevation or by a toxic factor.3 The second series subjected patients to therapy with ganglionic blocking agents without a comparison group. Therapy produced side effects that we would call horrendous nowadays, particularly, paralysis of parasympathetic ganglia, which required additional pharmacological therapy.
Medical students and trainees with the mindset and knowledge of 2017 are astonished by both aspects of this history: the lack of use of therapy for a rapidly fatal disease and the uncontrolled nature of the first intervention. However, in the context of the evidence at the time (total uncertainty about the benefit of therapy and lack of solid knowledge about risk), it is unquestionable that there was no ethical breach. Further, taking into consideration that 1-year mortality was reduced from 90% to 50% from the first series to the second, the results of these studies were instrumental for all future developments in the field of hypertension.
When research on benefit of reducing blood pressure was extended to patients with nonmalignant hypertension, a proactive decision was made to …