Subject(s)
Adrenal Gland Neoplasms/history , Adrenomedullin/history , Pheochromocytoma/history , Adrenal Gland Neoplasms/chemistry , Adrenomedullin/blood , Adrenomedullin/isolation & purification , Adrenomedullin/pharmacology , Amino Acid Sequence , Animals , Blood Platelets/chemistry , Blood Platelets/drug effects , Blood Platelets/metabolism , Blood Pressure/drug effects , Calcitonin Gene-Related Peptide/history , Calcitonin Gene-Related Peptide/pharmacology , Cyclic AMP/analysis , Cyclic AMP/history , History, 20th Century , Humans , Hypotension/history , Hypotension/metabolism , Molecular Sequence Data , Pheochromocytoma/chemistry , RatsABSTRACT
Concerns about metabolic complications often disturb prolonged use of diuretics in Japan. We investigated 3-year safety and efficacy in Japanese patients with hypertension who were uncontrolled with angiotensin receptor blocker or angiotensin-converting enzyme inhibitor regimens and then switched to losartan (50 mg)/hydrochlorothiazide (12.5 mg; HCTZ) combinations. Blood pressure decreased favorably and maintained a steady state for 3 years (157 ± 16/88 ± 11 mm Hg to 132 ± 13/75 ± 9 mm Hg, P < .0001). Metabolic parameters maintained a limited range of changes after 3 years, and adverse events were markedly decreased after 1-year treatment. The losartan/HCTZ combination minimized diuretic-related adverse effects and thus may be useful for the treatment of Japanese patients with hypertension.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Hydrochlorothiazide/therapeutic use , Hypertension/drug therapy , Losartan/therapeutic use , Adult , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Asian People , Blood Pressure/drug effects , Diuretics/adverse effects , Diuretics/therapeutic use , Drug Combinations , Female , Follow-Up Studies , Humans , Hydrochlorothiazide/adverse effects , Losartan/adverse effects , Male , Middle Aged , Treatment OutcomeABSTRACT
The long-term antihypertensive efficacy and safety of losartan/hydrochlorothiazide (HCTZ) combinations have not been appropriately evaluated in Japan. In this study, treated hypertensive patients taking angiotensin-receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEI) regimens not at blood pressure (BP) goals proposed by the Japanese Society of Hypertension (JSH) were switched to losartan/HCTZ combinations and followed for 1 year. Data analysis included 244 patients aged 64.5+/-10.7 years, 56% male, 27% with diabetes mellitus and 36% with dyslipidemia. Pre-switching BP 157+/-16/88+/-10 mm Hg promptly decreased and maintained a steady state, reaching 132+/-15/77+/-9 mm Hg (P<0.001) 1 year later. After 1 year of treatment, 50% of patients cleared the goals of the JSH guideline for systolic BP and 79% for diastolic BP. Patients with maximal doses of ARBs tended to show larger decreases in BP (159+/-11/90+/-10 to 128+/-10/75+/-8 mm Hg, P<0.001, n=32). Clinical and laboratory adverse events were reported for 29 patients (11%), but serious abnormalities were not observed. In particular, plasma levels of uric acid (UA) were well-maintained for 1 year, and significant decreases in UA were observed in patients with higher levels of UA (>/=7.0 mg dl(-1)). Losartan/HCTZ combinations showed strong and steady hypotensive abilities and acceptable safety and tolerability in patients currently not at BP goals with regimens including ARBs or ACEIs in Japan.