preminent and Hypertension

The main objective of this study was to evaluate non-inferiority of office mean systolic blood pressure (BP) reduction efficacy and superiority of 24-hour ambulatory central BP reduction efficacy between losartan combined with fixed dose amlodipine (L/A group) and dose up-titrated hydrochlorothiazide (L/H group) according to office BP.. We conducted a prospective, randomized, double-blind multicenter trial in 231 patients with hypertensive (mean age = 59.2 ± 12.2 years). Patients received losartan 50 mg monotherapy for 4 weeks, followed by additional use of amlodipine 5 mg or hydrochlorothiazide 12.5 mg for 20 weeks after randomization. The patients who did not achieve the BP goal after 4 weeks' randomization received an increased dose of 100 mg/5 mg for the L/A group and 100 mg/25 mg for L/H group, respectively. The 24-hour ambulatory central BP was measured at baseline and after 20 weeks' treatment.. Office mean systolic BP reduction of L/A group was not inferior to L/H group after 4 weeks' treatment (-17.6 ± 13.3 vs. -14.4 ± 12.6 mm Hg, P = 0.0863) and was not significantly different after 20 weeks' treatment. (-15.7 ± 14.0 vs. -14.7 ± 15.1 mm Hg, P = 0.6130) The 24-hour ambulatory central systolic BP was significantly more reduced in the L/A group compared with that in the L/H group after 20 weeks' treatment (-9.37 ± 10.67 vs. -6.28 ± 10.50 mm Hg, P = 0.0407). The 24-hour ambulatory central systolic BP at the completion of the study and its reduction magnitude were independently associated with reductions in aortic pulse wave velocity, pulse pressure, and wave reflection magnitude.. Office systolic BP reduction with L/A was not inferior to L/H after 4 week's treatment. The combination of losartan and amlodipine was more favorable in 24-hour ambulatory central hemodynamics beyond BP-lowering efficacy than the combination of losartan and hydrochlorothiazide, regardless of office BP.. NCT02294539.

Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Prospective Studies; Republic of Korea; Time Factors; Treatment Outcome

Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are available about their combinations on uricemia. In this study we evaluate the effect of two combinations of losartan, with amlodipine or with hydrochlorothiazide, on serum uric acid levels in hypertensive patients.. A total of 60 hypertensive patients were randomized in two groups; group LA received losartan/amlodipine (100/5 mg) once a day, whereas LH group received losartan hydrochlorothiazide (100/12.5 mg) once a day for 3 months. In both groups serum uric acid levels were measured at the beginning and end of the study. Patients were evaluated monthly for blood pressure (BP) and adverse events. Statistical analysis was performed with a two-way analysis of variance (ANOVA) for repeated measures.. All patients experienced a significant reduction of BP to the same extent (LA 155/94 to 123/79, LH 157/92 to 124/78 mmHg, p > 0.05). In the LA group, serum uric acid decreased from 6.5 ± 1.6 to 4.6 ± 1.3 mg/ml ( p = 0.0001), whereas in the LH group there was a nonsignificant increase from 5.82 ± 1.4 to 5.85 ± 1.5 mg/ml, ( p = 0.936). When both groups were compared, we found a significant reduction ( p < 0.00013) on serum uric acid levels in the LA group.. Both combinations decrease BP values to the same extent, however, LA combination showed a reduction on serum uric acid levels, which may contribute to a reduction in the metabolic risk in hypertensive patients.

Topics: Amlodipine; Antihypertensive Agents; Biomarkers; Blood Pressure; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Time Factors; Treatment Outcome; Uric Acid

Central systolic blood pressure (CSBP) may be a better predictor of cardiovascular risk than clinic brachial (B)SBP. The effects of dose increment from medium dose of angiotensin II receptor blockers (ARBs) to the maximum dose of ARBs (maximum) and changing from medium dose of ARBs to losartan 50 mg/hydrochlorothiazide 12.5 mg combination (combination) were compared in hypertensive patients in whom monotherapy with a medium ARB dose did not achieve goal home SBP (135 mmHg). Four weeks after treatment with a medium ARB dose monotherapy, those whose home SBP level was above 135 mmHg were randomized to receive the maximum ARB dose (n = 101) or the combination (n = 99) once daily for 8 weeks. Both regimens significantly decreased BSBP and CSBP, while a decrease in BSBP and CSBP was greater with combination. The maximum significantly decreased augmentation index (AIx), while the combination did not. The rate of a decrease in reflection to decrease in CSBP was greater in the maximum than in the combination. In the elderly subgroup, the combination more effectively lowered BSBP than the maximum, and only the combination decreased CSBP. However, in the young subgroup, the maximum decreased AIx more than combination, while both regimens lowered CSBP and BSBP to a similar extent. It is explained in part that the maximum may affect pulse wave reflection more predominantly than the combination, especially in young subjects. A weak effect on pulse wave reflection and, thus, on CSBP, of the combination may be overcome by the potent antihypertensive effect of this regimen.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin II Type 1 Receptor Blockers; Blood Pressure; Dose-Response Relationship, Drug; Drug Combinations; Drug Synergism; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Treatment Outcome; Young Adult

Morning hypertension is an established risk factor for cardiovascular events. In the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy (MAPPY) study, a 50-mg losartan/12.5-mg hydrochlorothiazide combination (Los/HCTZ) lowered morning blood pressure (BP) more effectively than 100-mg losartan (High-Los) in treated hypertensive patients with morning hypertension. The aim of this MAPPY study sub-analysis was to determine whether Los/HCTZ was effective for controlling isolated morning hypertension (morning BP ≥ 135/85 mmHg and evening BP < 135/85 mmHg), sustained hypertension (morning and evening BP ≥ 135/85 mmHg), or both. Of the 110 patients studied, 25 (22.7%) had isolated morning hypertension, and 85 (77.3%) had sustained hypertension at baseline. After 3-month treatment, isolated morning hypertension developed into controlled hypertension (morning and evening BP < 135/85 mmHg) in 9 of 11 Los/HCTZ patients (81.8%) and 3 of 14 High-Los patients (21.4%) (p = 0.003, chi-square test). Sustained hypertension developed into controlled hypertension in 21 of 44 Los/HCTZ patients (47.7%) and 13 of 41 High-Los patients (31.7%)(NS). The rates of achievement of SBP < 135 mmHg both in the morning and evening were: 81.8% and 21.4% in Los/HCTZ- and High-Los-treated isolated morning hypertension (p = 0.003), respectively; and 61.4% and 36.6% in Los/HCTX- and High-Los-treated sustained hypertension (p = 0.022), respectively. In conclusion, Los/HCTZ was effective for controlling both types of morning hypertension, especially isolated morning hypertension. Los/HCTZ was superior to High-Los in treating both types of morning hypertension.

Topics: Aged; Blood Pressure; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Prospective Studies; Treatment Outcome

Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL).. Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS + HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ group: n = 22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated.. Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS + HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not.. LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.

Topics: Adult; Aged; Benzimidazoles; Benzoates; Blood Pressure; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Prospective Studies; Telmisartan; Treatment Outcome; Uric Acid

The aim of the present study was to assess changes in blood pressure and metabolism after switching treatment from maximum-dose angiotensin II receptor blocker (ARB) therapy to a mixture of conventional-dose ARBs and low-dose diuretics.. This study was conducted among 43 Japanese patients with type 2 diabetes complicated with hypertension in whom continuous treatment with high doses of ARBs did not reduce their blood pressure to the target level (a systolic blood pressure of 130 mmHg or lower and a diastolic blood pressure of 80 mmHg or lower). The antihypertensive and metabolic effects of switching from high-dose ARBs to a combination of losartan (50 mg/day) plus hydrochlorothiazide (12.5 mg/day) were examined. The primary endpoint was a decrease in blood pressure at 24 weeks.. The combination treatment significantly decreased both systolic (baseline: 147±11; 24 weeks: 133±13 mmHg) and diastolic (baseline: 79±8; 24 weeks: 72±10 mmHg) blood pressure. This treatment was also associated with a significant increase in the HbA1c level (baseline: 7.0±0.8%; 24 weeks: 7.2±0.9%) and a significant decrease in the urinary albumin-creatinine ratio (baseline: 280±590; 24 weeks: 110±253 mg/g creatinine). However, the combination treatment had no effect on lipid metabolism or the serum uric acid or potassium levels.. In patients with diabetes, sodium reabsorption in the renal tubules is enhanced, which leads to the development of salt-sensitive hypertension. Therefore, the concurrent use of a diuretic that promotes sodium excretion can increase the antihypertensive effects of other drugs. This study demonstrated that switching from high-dose ARB treatment to losartan/hydrochlorothiazide combination therapy results in significant control of blood pressure.

Topics: Aged; Angiotensin Receptor Antagonists; Antihypertensive Agents; Diabetes Mellitus, Type 2; Drug Combinations; Drug Substitution; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Japan; Losartan; Male; Middle Aged; Treatment Outcome

It is unknown whether the use of diuretics is optimal over other antihypertensive agents in patients with chronic kidney disease (CKD) whose blood pressure remains uncontrolled despite treatment with renin-angiotensin system (RAS) inhibitors. In this study, we assessed the additive effects of hydrochlorothiazide (HCTZ) on reducing proteinuria in CKD patients under treatment with losartan (LS). We conducted a multicenter, open-labeled, randomized trial. One hundred and two CKD patients with hypertension and overt proteinuria were recruited from nine centers and randomly assigned to receive either LS (50 mg, n=51) or a combination of LS (50 mg per day) and HCTZ (12.5 mg per day) (LS/HCTZ, n=51). The primary outcome was a decrease in the urinary protein-to-creatinine ratio (UPCR). The target blood pressure was <130/80 mm Hg, and antihypertensive agents (other than RAS inhibitors and diuretics) were added if the target was not attained. Baseline characteristics of the two groups were similar. After 12 months of treatment, decreases in the UPCR were significantly greater in the LS/HCTZ group than in the LS group. There were no significant differences in blood pressure or the estimated glomerular filtration rate between the two groups. LS/HCTZ led to a greater reduction in proteinuria than treatment with LS, even though blood pressure in the LS group was similar to that in the LS/HCTZ group following the administration of additive antihypertensive agents throughout the observation period. This finding suggests that LS/HCTZ exerts renoprotective effects through a mechanism independent of blood pressure reduction.

Topics: Adult; Aged; Creatinine; Diuretics; Drug Combinations; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Prospective Studies; Proteinuria; Renal Insufficiency, Chronic; Treatment Outcome; Uric Acid; Young Adult

We examined whether the level of highsensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation, predicted the response of clinic and ambulatory blood pressure (BP) to antihypertensive treatment.. A randomized, open-label, multicenter trial was performed in 88 hypertensive patients (mean age = 63.4 years) allocated to receive losartan 50 mg or amlodipine 5 mg for 4 weeks, and each treatment was changed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in combination or amlodipine 10 mg for a further 4 weeks. Clinic and ambulatory BP were measured before and after 8 weeks of treatment, and hsCRP was measured at baseline.. The patients were divided into groups with hsCRP levels above and below the median (0.47 mg/L) for the study population. In the total population, 24-hour systolic BP (SBP) (P = 0.03) and daytime SBP (P = 0.01) were significantly higher in the above-median hsCRP group after 8 weeks of treatment. In multivariable regression analysis, baseline hsCRP was a significant determinant of the percentage change in daytime SBP (β = 0.29; P = 0.02) in the total population. In the losartan/HCTZ treatment group, changes in 24-hour SBP, daytime SBP, and diastolic BP were significantly smaller in the above-median hsCRP group than the below-median hsCRP group, whereas the amlodipine group did not show these differences.. Baseline low-grade inflammation in patients with hypertension was associated with a poor ambulatory BP response, especially with losartan/HCTZ treatment. Initial measurement of hsCRP could be useful for selection of an appropriate antihypertensive drug.

Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Humans; Hydrochlorothiazide; Hypertension; Inflammation; Losartan; Male; Middle Aged; Treatment Outcome

The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure (BP).. Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg, 59 were randomized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27). Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was added if target BP was not achieved after 3 months. Body mass index, office and 24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory investigations, and electrocardiography were done at baseline and after 6 months of treatment.. Losartan + HCTZ was as effective as bisoprolol + HCTZ, with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour BP in 75% and 66.7% of patients, respectively, after 6 months. Effective treatment of BP led to significant lowering of central systolic BP, but this was decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (-23.0 ± 2.3 mmHg) than by bisoprolol + HCTZ (-15.4 ± 2.9 mmHg) despite equal lowering of brachial BP. Factors correlated with central systolic BP and its lowering differed between the treatment groups. Losartan + HCTZ did not alter arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly increased AIx. We noted differences in ΔPWVE, ΔPWVM, and ΔAIx between the groups in favor of losartan + HCTZ. Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not associated with increased AIx in the losartan + HCTZ group.. Although both treatments decreased both office and 24-hour BP, losartan + HCTZ significantly decreased central systolic BP and had a more positive influence on pulse wave velocity, with a less negative effect of decreased heart rate on AIx and central systolic BP.

Topics: Adrenergic beta-1 Receptor Antagonists; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Bisoprolol; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Chi-Square Distribution; Diuretics; Doxazosin; Drug Combinations; Drug Therapy, Combination; Electrocardiography; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Pulse Wave Analysis; Severity of Illness Index; Time Factors; Treatment Outcome; Ukraine; Vascular Stiffness

The aim of this study was to compare the differences in the levels of a highly sensitive cardiac troponin T (Hs-cTnT) between Losartan (LOS) plus hydrochlorothiazide (HCTZ) and amlodipine. Seventy-eight hypertensive patients were randomized to receive LOS/HCTZ or amlodipine for 8 weeks. Both treatments decreased clinic and 24-hour blood pressure to the same extent. The Hs-cTnT level was significantly reduced in the amlodipine group (P < .05), but such a reduction was not found in the LOS/HCTZ group in the upper half group of Hs-cTnT level at baseline. Amlodipine had a more beneficial effect than LOS/HCTZ in patients with high Hs-cTnT levels.

Topics: Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; Blood Pressure; Calcium Channel Blockers; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Troponin T

In order to achieve target blood pressure levels to prevent cardiovascular disease, combination therapy of antihypertensive drugs is often required, although it is thought that requiring a patient to take many different pills would reduce adherence to the medication regimen. Whether antihypertensive treatment with a single pill combining antihypertensive drugs would improve medication adherence and blood pressure control was investigated.. A total of 207 hypertensive subjects were randomly assigned to a combination pill group (losartan 50mg/hydrochlorothiazide 12.5mg; n=103) or a control group (an angiotensin receptor blocker and a thiazide diuretic; n=104). Medication adherence was evaluated by pill counts at 1, 3, and 6 months after randomization. The mean adherence rates over 6 months were not different between the 2 groups: 98% in the combination pill group and 98% in the control group. Moreover, the 2 groups included similar numbers of subjects with relatively poor adherence rates (<90%) in each treatment period. The mean blood pressures over the 6-month treatment period were not different between the groups: 131/75 mmHg in the combination pill group and 130/75 mmHg in the control group (P=0.84/0.96).. There were no appreciable effects of the combination pill of antihypertensive drugs on medication adherence or blood pressure control in Japanese patients over a 6-month period.

Topics: Administration, Oral; Aged; Analysis of Variance; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Asian People; Blood Pressure; Chi-Square Distribution; Diuretics; Drug Combinations; Female; Health Knowledge, Attitudes, Practice; Humans; Hydrochlorothiazide; Hypertension; Japan; Linear Models; Losartan; Male; Medication Adherence; Middle Aged; Tablets; Time Factors; Treatment Outcome

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.

Topics: Adult; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Asian People; Blood Pressure; Diuretics; Drug Combinations; Female; Follow-Up Studies; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Treatment Outcome

Angiotensin receptor blockers (ARBs) are the first-line antihypertensive agents. In clinical practice, it is often difficult to achieve the recommended blood pressure level by ARBs in their ordinal dosages alone. This study examined the practical efficacy of a combination therapy of ARB with thiazide diuretics for lowering morning home blood pressure (MHBP) in comparison to high-dose ARB therapy in patients with morning hypertension administered an ordinal dosage of ARB. This study was performed in a prospective, randomized, open-labeled and blind-endpoint fashion. Patients were considered to have morning hypertension when their self-measured systolic MHBPs were 135mmHg or higher, irrespective of their diastolic MHBP and office blood pressures (OBPs). Forty-eight outpatients with morning hypertension receiving the ordinal dosage of ARB were given either losartan/hydrochlorothiazide (n = 26) or high-dose ARB (n = 22) in place of their previously prescribed ARB. No change in any medication was permitted during this period. Decreases of both systolic and diastolic MHBP after 3 months of treatment were significantly greater in the losartan/hydrochlorothiazide group than in the high-dose ARB group (p < 0.05, respectively). The ratio of adverse events was somewhat high (23.1% in the losartan/hydrochlorothiazide group, 9.1% in the high-dose ARB group, respectively). However, there were no significant differences in any particular adverse event between groups. This study suggested losartan/hydrochlorothiazide might be superior to high-dose ARB for reducing morning home blood pressure.

Topics: Aged; Aged, 80 and over; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Prospective Studies; Treatment Outcome

Hypertension management guidelines recommend titrating antihypertensive drugs stepwise every 4-6 weeks.We compared efficacy and safety of early versus late titration after 10 weeks' treatment with irbesartan/hydrochlorothiazide. Hypertensive patients uncontrolled on monotherapy were randomized into two groups. In the early titration group (E), patients received irbesartan/hydrochlorothiazide 150/12.5 mg for 2 weeks; uncontrolled patients were up-titrated to 300/25 mg at weeks 2 and 6. In the late titration group (L), patients received 150/12.5 mg for 6 weeks; uncontrolled patients were up-titrated to 300/25 mg at week 6 (W6). The change of mean systolic (SBP) and diastolic blood pressure (DBP) from baseline to week 10 (W10) were studied using a covariance analysis model. The percentage of controlled patients at W10 was compared between groups using Fisher's exact test. Of 833 patients enrolled from 14 countries, the intent-to-treat (ITT) population included 795 (mean age 58 +/- 12 years, female 60%, obesity 38%, diabetes 22%). AtW6, mean SBP decrease was: E - 28.8 mmHg vs L - 26.3 mmHg (p = 0.02). At W10, there was similar mean SBP decrease: E - 29.5 mmHg vs L- 31.0 mmHg (p = 0.14). The control rate at W10 was 58% (E) and 64% (L), p = 0.06. Serious adverse events were more frequent in E (2.5% vs 0.7%, p= 0.044). Both early and late titration regimens provide similar BP decrease and control rate.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Prospective Studies

Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.

Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Diuretics; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Kidney; Losartan; Male; Middle Aged; Potassium; Time Factors; Treatment Outcome

Topics: Aged; Disease Progression; Drug Combinations; Female; Ficusin; Humans; Hydrochlorothiazide; Hypertension; Losartan; Photochemotherapy; Psoriasis; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy

We have previously shown that an association of losartan and hydrochlorothiazide, initiated 1 mo after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection could be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among the following four groups: untreated Nx rats, Nx rats that received losartan, Nx rats that received losartan + hydrochlorothiazide, and Nx rats that received losartan + furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis, and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As previously shown, the losartan + hydrochlorothiazide association normalized tail-cuff pressure and albumin, prevented renal injury, and reduced mortality to zero. The losartan + furosemide treatment failed to reduce tail-cuff pressure or albumin to normal and prevented renal injury less efficiently than the losartan and hydrochlorothiazide regimen. The reasons for the differing efficacies of the losartan + furosemide and losartan + hydrochlorothiazide schemes are unclear and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced chronic kidney disease stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced chronic kidney disease.

Topics: Albuminuria; Animals; Blood Pressure; Drug Combinations; Furosemide; Hydrochlorothiazide; Hypertension; Kidney; Losartan; Male; Rats; Rats, Wistar; Renal Circulation

The guidelines for hypertension require the presence of compelling indications for pharmacological management of hypertension associated with various diseases. Data mainly obtained through randomized controlled trials have provided evidence supporting effectiveness of the combination of losartan (Lo) and hydrochlorothiazide (HCTZ) for management of hypertensive patients. However, there have been few reports discussing the effectiveness of Lo/HTCZ (losartan 50 mg/hydrochlorothizide 12.5 mg) in the 'real world' in the management of isolated systolic hypertension (ISH). This study was designed to investigate the 'real world' effectiveness of Lo/HTCZ-based treatment of ISH associated with various diseases.. This was a retrospective, uncontrolled analysis of data derived from a large, cross-sectional web-based clinical database collected by physicians.. Of 24,825 eligible patients, 20,726 were followed during a 6-month period. Among these, subjects for analysis included those with systolic blood pressure (SBP) >140 mmHg and diastolic BP (DBP) <90 mmHg; patients with diabetes mellitus and chronic kidney disease were excluded. A total of 15,846 patients were analysed. Among the various complications, hypercholesterolemia was the most frequent concomitant cardiovascular (CV) risk factor (48.1%), followed by obesity (16.3%). Associated clinical conditions were cerebrovascular diseases (9.6%), ischemic heart disease (7.9%) and left ventricular hypertrophy (4.6%). Total numbers of patients exhibiting any type of complications were 62% (≤64 years old), 69% (65-74 years old) and 67% (≥75 years old) (stratification of age). Mean SBP/DBP measurements (mm Hg) were 156/78 at the start, 140/72 at 1 month and 134/72 at 6 months. Blood pressure (BP) reductions associated with various diseases were similar among patients. Laboratory data including serum levels of total cholesterol, uric acid, hemoglobin A1c and serum potassium did not change during the study. Adverse effects such as orthostatic hypotension and considerable reductions in BP (>30 mmHg SBP) were rare.. Lo/HTCZ is safe and effective in reducing and improving BP control in a 'real world' setting. Treatment with Lo/HTCZ enabled a substantial proportion of hypertensive patients with associated diseases to achieve the recommended goal of <140 mm Hg.

Topics: Adult; Aged; Cross-Sectional Studies; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Retrospective Studies; Systole

In the Netherlands, antihypertensive treatment for patients with mild hypertension is recommended if the 10-year cardiovascular disease (CVD) risk exceeds 20%. Recent evidence suggests that lifelong CVD risk estimates might be more informative than 10-year ones. In addition, the cost of antihypertensive treatment in the Netherlands has decreased during the last decade.. The aim of this study is to estimate the cost-effectiveness of lowering systolic blood pressure (SBP) in patients ineligible for treatment in both a 10-year and a lifetime horizon.. A Markov model was developed to assess the cost-effectiveness of SBP reduction compared with no reduction in patients with mild hypertension and low CVD risk. Modified SCORE (Systematic Coronary Risk Evaluation) risk estimates were used to predict fatal and nonfatal CVD events. We analyzed scenarios for different age groups, sexes, and SBP reductions. Specifically, SBP reductions due to hydrochlorothiazide (HCT) 25 mg and hypothetical reductions with HCT 12.5 mg-losartan 50 mg combination were assumed. Parameter uncertainty was assessed through a probabilistic sensitivity analysis.. In a 10-year horizon, in scenarios of SBP reduction with HCT 25 mg, the incremental cost-effectiveness ratio (ICER) estimates for men varied across different ages in the range of €6032 to €58,217 per life-year gained, whereas for women ICER estimates were in the range of €12,345 to €361,064 per life-year gained. In a lifetime horizon, the cost-effectiveness estimates were favorable for both sexes. In scenarios of hypothetical SBP reductions, more favorable ICER estimates compared with no reduction were found. A large uncertainty around the cost-effectiveness estimates was observed among all scenarios.. Larger SBP reductions were found to be cost-effective in both a 10-year and lifetime horizon. These findings might call for more aggressive SBP reductions in patients with mild hypertension. However, a high level of uncertainty surrounds these cost-effectiveness estimates because they are based on CVD risk prediction modeling.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Cost-Benefit Analysis; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Markov Chains; Middle Aged; Netherlands; Primary Prevention; Risk Factors; Smoking

Timing can greatly affect the response to a stimulus, including antihypertensive medications. Herein, we assess the response of 30 patients to losartan/hydrochlorothiazide (L/H), administered for at least 1 month at a given circadian stage to each patient, this stage being changed during consecutive spans to cover six treatment times from awakening to bedtime at approximately 3-hour intervals. At the end of each stage, each patient underwent a 7-day around-the-clock ambulatory blood pressure (BP) profile, analyzed chronobiologically. A larger reduction of the midline estimating statistic of rhythm (MESOR; a rhythm-adjusted mean) of diastolic BP was achieved by L/H administration in the early morning for more patients (P < .05), while treatment upon awakening was the best choice for most patients to reduce the circadian amplitude of BP the most (P < .01). The optimal treatment time varied considerably among patients, however. Special attention should be given to the effect on the circadian amplitude since treatment can increase it above a threshold, beyond which there is a marked increase in cardiovascular disease risk. The results indicate the desirability to individualize the optimization of the antihypertensive effect of L/H by timing along the circadian scale.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Drug Chronotherapy; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Models, Cardiovascular; Precision Medicine

It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases.. To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study.. An observational analysis from a randomized controlled trial.. A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization.. The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (<90%; n = 19), moderate-adherence (90-99%; n = 71) and high-adherence (100%; n = 113) groups. Clinical characteristics of the subjects including BP, sex, randomized treatments and past medical history did not differ significantly among the three groups. Achieved follow-up BPs over the 6-month treatment period, which were adjusted for age, sex, baseline BP and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; P = 0.02/0.02) and the moderate-adherence (128/74 mmHg; P = 0.003/0.02) groups.. Low adherence to an antihypertensive-drug regimen was associated with poor BP control.

Topics: Aged; Antihypertensive Agents; Blood Pressure; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Japan; Losartan; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Prospective Studies; Treatment Outcome

This multicenter, prospective, observational study assessed the renoprotective effects of losartan/thiazide combination therapy in terms of lowering the estimated glomerular filtration rate (eGFR).. Adult patients with angiotensin receptor blocker (ARB)-resistant essential hypertension (n = 104) were enrolled and switched to combination therapy with losartan (50 mg/day) and hydrochlorothiazide (12.5 mg/day).. eGFR values declined significantly during the first 3 months, and changes in eGFR were assessed according to tertiles of the eGFR decrease ratio at 3 months. Only the high eGFR decrease (1st tertile) group showed significantly greater decreases in baseline eGFR and albumin-to-creatinine ratio (ACR) during the first 3 months. Additionally, the assessment according to tertiles of the baseline eGFR showed a signifcant decrease in eGFR and ACR during the first 3 months in the high baseline eGFR (1st tertile) group, but not in the moderate (2nd tertile) and low baseline eGFR (3rd tertile) groups.. The present results revealed that losartan/thiazide combination therapy attenuated glomerular overload, indicating that this therapy may provide glomerular protection in patients with an elevated GFR without causing prolonged damage to renal function.

Topics: Aged; Aged, 80 and over; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Dose-Response Relationship, Drug; Drug Combinations; Essential Hypertension; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Kidney Glomerulus; Losartan; Male; Middle Aged; Prospective Studies

Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension.. The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study.. A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value.. Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Creatinine; Drug Combinations; Female; Glomerular Filtration Rate; Humans; Hydrochlorothiazide; Hypertension; Hyperuricemia; Japan; Losartan; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Uric Acid; Young Adult

When physicians prescribe a new antihypertensive drug, they do not know the extent of the drug's effect on lowering blood pressure. To resolve this dilemma, a Web-based program was constructed for real-time entry and analysis of treatment. This observational study evaluated the efficacy of losartan/hydrochlorothiazide (Lo/HCTZ) in lowering blood pressure (BP) and achieving BP target values.. Physicians prescribed Lo/HCTZ for patients with hypertension who failed to achieve target BP values of < 140/90 mmHg and < 130/80 mmHg in patients with diabetes or chronic kidney disease, respectively, with antihypertensive drugs including an angiotensin receptor blocker.. From December 2006 to December 2009, the data of 88,254 patients were entered into this database, and the data of 24,825 subjects were analyzed. At the first visit, a total of 88,254 patients received a first prescription of Lo/HCTZ daily. Among these, at the end of the present analysis, 24,825 (28%) outpatients had a follow-up visit at 1 month and 20,726 (23%) outpatients had a follow-up visit at 6 months. The prevalence of hypertensive patients achieving systolic blood pressure (SBP) control (< 140 mmHg) increased over time from 6.9% to 54.3% in females and 6.1% to 52.3% in males (p < 0.05). At the start of the study, the levels of SBP were significantly highest in the eldest patients (≥ 75 years) followed by the group of 65-75 years and lowest in the youngest patients (≤ 64 years). However, at the end of the study, there were no differences in levels of SBP among the three groups.. This Web-based system may provide useful information when a new drug is first released into the market. Treatment with Lo/HCTZ enabled a substantial proportion of hypertensive patients to achieve the recommended goal of < 140/90 mmHg.

Topics: Age Factors; Aged; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Comorbidity; Databases, Factual; Diabetes Mellitus; Diuretics; Drug Combinations; Drug Prescriptions; Female; Guideline Adherence; Humans; Hydrochlorothiazide; Hypertension; Japan; Losartan; Male; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Sex Factors; Time Factors; Treatment Outcome

We analyzed the efficacy and safety of Preminent(®) [losartan (50 mg/day)/HCTZ (12.5 mg/day)] compared to CodioMD(®) [valsartan (80 mg/day)/HCTZ (6.25 mg/day)].. In this study, 31 hypertensive patients after receiving 3 months of Preminent(®) (Stage A) were enrolled. We applied a changeover with switching from Preminent(®) to CodioMD(®) (Stage B). We then applied another changeover with switching from CodioMD(®) to Preminent(®) after 3 months (Stage C).. Average values of 24-h blood pressure (BP), daytime BP and nighttime BP using ambulatory BP monitoring (ABPM) significantly increased from Stage A to B [4/3 mmHg, 5/3 mmHg and 3/3 mmHg, respectively]. Average values of 24-h BP, morning BP, daytime BP, nighttime BP significantly decreased from the end of Stage B to C [-5/-5 mmHg, -4/-6 mmHg, -5/-5 mmHg and -6/-4 mmHg, respectively]. Interestingly, the serum levels of uric acid and the urinary albumin/creatinine ratio showed a significant increase after the change to CodioMD(®). Since these adverse effects did not disappear after the return to Preminent(®) at the end of Stage C, we performed an additional 3-month follow-up (extended stage). These adverse effects finally disappeared at the end of this extended stage.. Single-pill fixed-dose combination therapy using Preminent(®) showed significant 24-h BP-lowering effects and was safe when compared with CodioMD(®).

Topics: Aged; Blood Pressure; Drug Combinations; Drug Substitution; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Tetrazoles; Treatment Outcome; Valine; Valsartan

To analyse recent data on the treatment of arterial hypertension (AH) with other risk factors (RF) of cerebral stroke in the Russian Federation, assessment of effects of antihypertensive treatment with a combined drug Hyzaar on the risk of cardiovascular complications (including cerebral stroke), on affection of target organs and metabolic factors of atherosclerosis.. A total of 500 outpatients with primary AH and risk factors including the risk of stroke received Hyzaar (losartan 50/100 mg and hydrochlorthiaside 12.5/25 mg) for one year.. More frequent RF in hypertensive patients are the following: high blood cholesterol (86.7%), left ventricular hypertrophy (53.2%), familial history of AH (74.2%). A combination of three and two RF occurs in 49.1 and 37% hypertensive patients, respectively. A 6-month treatment with Hyzaar lowered systolic blood pressure by 28.4 mm Hg and diastolic one by 15.4 mm Hg. The target blood pressure was achieved in 83.5%. Real clinical practice showed that administration of a target Hyzaar dose for 6 months leads to a 6.5% regress of left ventricular hypertrophy, an 11% decrease of total cholesterol, a 4% decrease of glucose and a 8.9% decrease of uric acid.. A control of AH and correction of RF in hypertensive patients with a high RF of stroke and other cardiovascular complications is real in use of adequate antihypertensive therapy.

Topics: Aged; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Losartan; Male; Middle Aged; Risk Factors; Stroke

Topics: Antihypertensive Agents; Baroreflex; Blood Pressure; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Losartan; Muscle, Skeletal; Sympathetic Nervous System