Effect of telmisartan addition to amlodipine on ankle edema development in treating hypertensive patients (Publication with Expression of Concern. See vol. 19, 2018)

Objective: The objective of this research was to evaluate the effect of telmisartan addition to amlodipine, on peripheral edema in hypertensive patients. Research design and methods: Seventy-five outpatients were randomized to amlodipine (A) 10 mg or telmisartan (T) 80 mg, or amlodipine 10 mg plus telmisartan 80 mg, for 6 weeks, in three crossover periods. Main outcome measures: Blood pressure, ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP) were evaluated, as were plasma norepinephrine and plasma active renin (PAR). Results: Amlodipine-telmisartan combination induced greater SBP/DBP reduction (-28.1/21.7 mmHg, p < 0.0001 vs baseline) compared with monotherapy with both amlodipine and telmisartan. Amlodipine monotherapy increased AFV by 26.7%, and PSTP by 83.2% (both p < 0.01). Adding telmisartan to amlodipine produced a significantly lesser increase in both AFV (+7.9%, p < 0.01 vs amlodipine) and PSTP (+23.8%, p < 0.01 vs amlodipine). Plasma norepinephrine levels were increased by amlodipine (+134.3 pg/ml, p < 0.01); such an increase was attenuated by the addition of telmisartan (+55 pg/ml, p < 0.05 vs amlodipine). PAR was slightly increased by amlodipine (+21.5 pg/ml, p < 0.05) and more by telmisartan alone (+62.5 pg/ml) and telmisartan-amlodipine combination (+71.3 pg/ml; both p < 0.01). Conclusions: The addition of telmisartan to amlodipine significantly attenuated amlodipine-induced edema formation. The reduction of amlodipine-induced reflex-sympathetic activation by telmisartan might have contributed to such an effect.