17ss oestradiol does not attenuate the response to angiotensin I and II during long term therapy in postmenopausal women.

PURPOSE: It is thought that oestrogen replacement therapy may reduce the conversion of angiotensin I to angiotensin II in postmenopausal women by inhibiting angiotensin converting enzyme. We sought to determine the effects of 3 months oestrogen replacement therapy (ERT) on the response to angiotensin I and II in postmenopausal women. METHODS: Eighteen postmenopausal women were randomised to either three months of 2 mg oral oestradiol or placebo in a double blind, placebo controlled, protocol. Change in forearm blood flow (FBF), in response to brachial arterial infusion of increasing concentrations of angiotensin I and angiotensin II was measured, pre-randomisation, after 1 months randomised therapy and after 3 months therapy, using venous occlusion plethysmography. RESULTS: Oestrogen treatment had no effect on baseline FBF. The mean (SD) peak reductions in FBF with 64 pmol/min angiotensin I pre-randomisation, after 1 month and after 3 months treatment with placebo were 62(11), 65(15) and 57(8)%. The corresponding reductions with the peak dose of angiotensin II (16 pmol/min) were 53(8), 48(12) and 47(11)%. In the oestradiol group, the peak responses to angiotensin I were 56(8), 53(11) and 44(29)% pre-randomisation, after 1 months treatment and after 3 months treatment. The corresponding reductions in response to angiotensin II were 37(15), 47(15) and 45(19)%. Oestradiol did not affect the response to either angiotensin I or angiotensin II. CONCLUSION: This study does not support the idea that ERT might exert a cardioprotective effect through inhibition of the renin-angiotensin system.

Esomeprazole 40 mg and 20 mg is efficacious in the long-term management of patients with endoscopy-negative gastro-oesophageal reflux disease: a placebo-controlled trial of on-demand therapy for 6 months.

BACKGROUND: On-demand therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease (GORD) without oesophagitis. AIM: To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-demand therapy in endoscopy-negative GORD. PATIENTS AND METHODS: Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment (n = 721) were randomized to esomeprazole 20 mg (n = 282), 40 mg (n = 293) or placebo (n = 146) on demand (maximum one dose/day) for 6 months. The primary and secondary efficacy endpoints were time to study discontinuation due to (i) unwillingness to continue and (ii) inadequate control of heartburn, respectively. RESULTS: Both doses of esomeprazole were more effective than placebo. During the 6-month period, 42% of placebo recipients discontinued treatment due to unwillingness to continue, compared with 8% and 11% of esomeprazole 20 mg and 40 mg recipients, respectively. Overall, more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-demand therapy. CONCLUSIONS: Esomeprazole 20 mg was superior to placebo for on-demand treatment of GORD; a higher dose did not confer additional clinical benefit. Over 90% of patients were willing to continue on-demand treatment with esomeprazole 20 mg over a 6-month period.