Mean Sitting Diastolic Blood Pressure Research Articles

A comparative evaluation of fixed dose and separately administered combinations of lisinopril and hydrochlorothiazide in treatment-naïve adult hypertensive patients in a rural Nigerian community

BackgroundAntihypertensive drugs administered as fixed dose combination (FDC) therapy compared to separately administered combination therapy have been proposed to improve treatment compliance/adherence, and therefore the efficacy of blood pressure (BP) control treatment. AimThe aim of this present study is to compare the blood pressure control, renal end-organ protection and medication compliance/adherence in patients receiving FDC and those receiving separately administered combinations of Lisinopril and Hydrochlorothiazide in treatment-naive hypertensive adult patients in a rural Nigerian community. Methodology: This randomized two-arm prospective longitudinal 8-week parallel-group study was carried-out for 6-month at the Ajegunle Community between April 2018 and October 2018. Efficacy variables included the changes from baseline in mean sitting systolic BP (MSSBP) and mean sitting diastolic BP (MSDBP). Medication safety, compliance/adherence and renal end-organ protection were assessed. ResultsThe baseline characteristics of the two groups were similar. Prevalence of hypertension was found to be 32.9%. The mean blood pressure of all the participants was 165.6 ± 16.5 mmHg and 98.5 ± 11.5 mmHg for systolic BP and diastolic BP respectively, while the mean pulse rate of the participants was 85.0 ± 13.4 beats/min. At the 8-week end point, both regimens had achieved significant reductions from baseline in MSSBP (−33.18 and −37.16 mm Hg, respectively; both, P < 0.05) and MSDBP (−12.97 and −17.53 mm Hg; both, P < 0.05). Both regimens were generally well tolerated. Adherence was better in the FDC arm and there was no any reported case of proteinuria occurrence in both arms. ConclusionThe high prevalence of hypertension in the community shows that there is unmet need in diagnosis and awareness of the disease. Both combination therapies were well tolerated; but the FDC antihypertensive therapy resulted in statistically significant amount of BP reductions than the separately administered combination antihypertensive therapy. Making FDCs available and affordable will help many hypertensive patients to achieve their target BP control goals easily.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low‐density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow‐up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least‐Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were −19.3 (2.68) mm Hg and −6.69 (2.76) mm Hg. The difference between the two groups was significant (−12.60 (2.77) mm Hg, 95% CI −18.06 to −7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were −52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (−55.13 (3.20) %, 95% CI −61.45 to −48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter, Randomized, 4-arm, Double-blind, Placebo-controlled, Phase III Study

PurposeHypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations. MethodsThis multicenter, 8-week, randomized, double-blind, Phase III study evaluated the efficacy and safety of FDC treatment with telmisartan (80 mg) and rosuvastatin calcium (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. Patients were randomly assigned to 4 groups: (1) FDC drug (80 mg of telmisartan and 20 mg of rosuvastatin); (2) 80 mg of telmisartan; (3) 20 mg of rosuvastatin; or (4) placebo. After 8 weeks of treatment, the change in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP) between the FDC group and the rosuvastatin group, and the percent change in LDL-C between the FDC group and the telmisartan group, were compared. FindingsA total of 210 patients were enrolled in the study (84 in the FDC group, 42 in the rosuvastatin group, 43 in the telmisartan group, and 41 in the placebo group). The reduction in blood pressure was significantly greater in the FDC group than in the rosuvastatin group after 8 weeks of treatment (least squares mean change from baseline, –16.1 [1.6] mm Hg vs –1.7 [2.2] mm Hg [P < 0.001] for MSSBP; –8.8 [1.0] mm Hg vs –1.6 [1.4] mm Hg [P < 0.001] for MSDBP). Least squares mean percent change in LDL-C from baseline was also significantly greater in the FDC group compared with the telmisartan group (–49.3% [2.2%] vs 1.5% [3.0%]; P < 0.001). FDC therapy also had a higher rate of achieving the treatment goal in both blood pressure (60% vs 45%; P = 0.024) and LDL-C (88.8% vs 16.3%; P < 0.001) compared with rosuvastatin or telmisartan alone, respectively. In regression analysis, higher baseline MSSBP, female sex, and lower body mass index were associated with increased reductions in MSSBP, whereas higher baseline LDL-C level and lower body mass index were associated with greater reductions in LDL-C. There were 48 adverse events in 36 patients (17.3% [36 of 208]), and 17 adverse drug reactions in 12 patients (5.8% [12 of 208]), indicating no significant differences in short-term safety among study groups. ImplicationsTreatment with an FDC drug containing telmisartan and rosuvastatin showed similar efficacy in lowering blood pressure and LDL-C levels compared with that of each single drug. ClinicalTrials.gov identifier: NCT01914432.

PP.02.03] EFFICACY AND TOLERABILITY OF NIFEDIPINE GASTROINTESTINAL THERAPEUTIC SYTEM 60MG IN CHINESE PATIENTS WITH UNCONTROLLED HYPERTENSION

Objective: Efficacy and tolerability of nifedipine gastrointestinal therapeutic system (GITS) 60 mg once daily (QD) in uncontrolled blood pressure (BP) is not completely explored in China. Therefore, we studied the efficacy and tolerability of nifedipine GITS 60 mg in Chinese hypertensive patients inadequately controlled with prior monotherapy. Design and method: This single-arm phase-4 study (NCT02413515) enrolled 278 hypertensive adults from 13 centers in China, in whom BP was uncontrolled after 4-weeks of antihypertensive monotherapy. The patients received oral nifedipine GITS 60 mg QD for 8-consecutive weeks. Primary endpoint was mean sitting systolic BP control rate (MSSBP; <130 mmHg for subjects with diabetes (DM) and <140 mmHg for others) at 8-weeks. Secondary endpoints included change in MSSBP and mean sitting diastolic BP (MSDBP), 24-h SBP and DBP reduction measured by 24 hour ABPM, and safety of nifedipine GITS 60 mg. Results: A total of 269 patients (mean age 55 ± 8.21 years, 62.8% males, 28.3% with DM) were included for efficacy and 278 for safety analysis. At week 8, overall MSSBP control rate was 64.7%. From baseline to 8-weeks, decrease in MSSBP and MSDBP was −15.2 ± 11.37 mmHg (147.9 ± 6.87 mmHg to 132.7 ± 11.82 mmHg) and −6.4 ± 7.87 mmHg (89.1 ± 7.13 mmHg to 82.7 ± 8.04), respectively (Table 1). The control rate was lower in patients with DM From baseline to 8-weeks, mean 24-h SBP was decreased from 138.5 ± 12.78 mmHg to 131.6 ± 12.29 mmHg (diff. −6.9 ± 11.30 mmHg, 95% CI −8.29, −5.56) and mean 24-h DBP was decreased from 86.4 ± 9.32 mmHg to 82.5 ± 9.12 mmHg (diff. −3.9 ± 7.63 mmHg, 95% CI −9.47, −6.42). Fifty (18%) cases of adverse events (AEs) and 25 (9%) cases of peripheral edema were reported. No drug related serious AEs and deaths occurred during the study.Conclusions: Nifedipine GITS 60 mg QD further improved control rate of MSSBP and MSDBP and was well tolerated in Chinese patients previously treated with standard dosage of antihypertensive monotherapy.

Efficacy and tolerability of once-daily 160 mg valsartan in Chinese patients with mild to moderate hypertension.

The present multicentre, prospective, open-label, single treatment arm study (Val-Perfect) examined the efficacy and tolerability of once-daily valsartan monotherapy (80 mg for two weeks, followed by 160 mg for eight weeks) in 195 Chinese patients with mild to moderate hypertension, using office, home, and ambulatory blood pressure (BP) monitoring. Significant mean reductions (P<0.0001) were observed in office BP from baseline to week 10, with mean sitting systolic BP (MSSBP) and mean sitting diastolic BP (MSDBP) values of 15.6±12.3 and 11.1±8.6 mmHg, respectively. The office BP control rate at week 10 was 56.9% (target MSSBP/MSDBP <130/80 mmHg for patients with type 2 diabetes or chronic kidney disease, <140/90 mmHg for others). Valsartan treatment significantly reduced mean 24-h SBP/DBP (-6.1/-4.4 mmHg; both P<0.0001) and mean home-monitored SBP/DBP (-13.3/-9.1 mmHg; both P<0.0001) at week 10. The incidence of adverse events (AEs) leading to discontinuation (1.5%) or drug-related AEs (3.1%) was low, with no instances of mortality or drug-related serious AEs. These results indicate that 160 mg valsartan is safe and effective at lowering BP in Chinese patients with mild to moderate hypertension. The significant reductions in office-based and out-of-office BP measures support the clinical relevance of moderate-dose valsartan monotherapy for effective 24-h BP control.

Abstract 656: Efficacy and Safety of Valsartan/Amlodipine Single-Pill Combination in Chinese Elderly Hypertensive Patients with Chronic Kidney Disease: Subgroup analysis of the CHINA STATUS II study

Objective: To evaluate the efficacy and safety of Valsartan/Amlodipine SPC in a sub-group analysis of elderly hypertensive patients (aged ≥65 years) with Chronic Kidney Disease (CKD) treated for 8 weeks in the CHINA STATUS II study. Methods: This post-hoc analysis was conducted in 3297 hypertensive elderly patients from CHINA STATUS II study(CSII), whose blood pressure (BP) was not controlled by monotherapy . 116 patients had CKD (aged 75.5±6.8 years) while 3181 were without CKD (aged 74.4±6.3 years). All patients in CSII received Valsartan/Amlodipine 80/5 mg SPC for 8 weeks. The patients did not achieve BP control at the end of 4 weeks (BP≥ 130/80 mmHg for patients with diabetes or CKD and≥140/90 mmHg for others), an additional antihypertensive agent added. T -test and chi-square test were used for statistical analysis. Results: After valsartan/amlodipine SPC treatment for 8 weeks, mean sitting systolic blood pressure (MSBP) decreased, 25.4±13.3 mmHg and 28.3±12.5 mmHg from baseline in patients with and without CKD, respectively. Mean sitting diastolic blood pressure (MSDP) was reduced by10.4±9.3 mmHg and 13.5±9.5 mmHg from baseline in patients with and without CKD, respectively. 17.2%patients with CKD achieved their BP target of &lt;130/80 mmHg and 77.8% non-CKD patients achieved their BP goal, &lt;140/90 mmHg. The incidence of adverse events was 0.9% in patients without CKD, while none were reported in patients with CKD. Two serious adverse events (SAEs), which were not drug-related, occurred in non-CKD patients and no SAE was reported in CKD patients. 100% of the patients with CKD and 99.2% of patients without CKD rated the tolerance to therapy as ‘good’ or ‘very good’, respectively. Conclusions: Valsartan/amlodipine SPC showed good safety and tolerance in hypertensive patients aged ≥65 with CKD whose BP was uncontrolled by previous monotherapy. Lower proportion of elderly patients with CKD achieved the strict BP target compared to elderly patients without CKD. In view of the limitation of this being a post-hoc analysis, the reason for the observed low BP control rate in elderly patients with CKD needs further analysis and research.

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension

Objective:To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension.Research design:Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial.Methods:After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m2).Main outcome measures:Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg.Results:Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7–10.7 mmHg more than Val/HCTZ, 3.4–8.3 mmHg more than Aml/Val, and 4.4–9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (e.g., Blacks, elderly).Conclusions:Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI.Trial registration number:NCT00327587.

EFFICACY AND TOLERABILITY OF AMLODIPINE/TELMISARTAN COMBINATION THERAPY IN HYPERTENSIVE PATIENTS WITH CARDIOVASCULAR RISK FACTORS

ObjectivesMost patients with hypertension require more than one drug to attain recommended blood pressure (BP) targets. Initiating therapy with two agents is recommended for patients at high risk of a...

Amlodipine/valsartan 5/160 mg versus valsartan 160 mg in Chinese hypertensives

BackgroundA majority of hypertensives require treatment with ≥2 antihypertensive therapies to achieve blood pressure (BP) goals. Single-pill combinations (SPC) may improve convenience and adherence to therapy and reduce health care resource use and costs. The antihypertensive effects of amlodipine and valsartan are well established. This study evaluated the efficacy and safety of amlodipine/valsartan 5/160mg SPC for the treatment of hypertension in predominantly Chinese patients not adequately controlled on valsartan 160mg alone. MethodsIn this multicentre study (24 centres), adults with stage 1 or 2 hypertension not adequately controlled with valsartan monotherapy were randomised to receive double-blind amlodipine/valsartan 5/160mg SPC or valsartan 160mg once daily for 8weeks. ResultsThe least-square mean change (standard error) from baseline to endpoint in mean sitting diastolic blood pressure (MSDBP) at trough, the primary efficacy variable, was –10.3 (0.39) mm Hg with amlodipine/valsartan and –6.6 (0.40) mm Hg with valsartan (difference: –3.7 [0.54] mm Hg, p<0.0001). The corresponding results for mean sitting systolic blood pressure (MSSBP) were –14.9 (0.61) mm Hg and –7.0 (0.61) mm Hg, respectively (difference: –7.9 [0.84] mm Hg, p<0.0001). A significantly greater proportion of patients achieved overall BP control (MSSBP/MSDBP<140/90mm Hg) with combination therapy (61.3%) versus monotherapy (39.3%; p<0.0001). Both treatments were well tolerated. ConclusionAmlodipine/valsartan 5/160mg SPC is a safe and effective therapy for lowering BP in predominantly Chinese adults with stage 1 or 2 hypertension not adequately controlled with valsartan 160mg monotherapy.

Combination therapy with amlodipine/valsartan in essential hypertension: a 52-week, randomised, open-label, extension study

A majority of hypertensive patients require > or = 2 agents to achieve target blood pressure (BP). This 52-week, multicentre, open-label, randomised extension trial to a previously reported double-blind, placebo-controlled study evaluated the safety and efficacy of amlodipine/valsartan (Aml/Val) combination. Patients who successfully completed the core study without serious drug-related adverse events (AEs) and mean sitting systolic BP (MSSBP)/mean sitting diastolic BP (MSDBP) < or = 150/95 mmHg were eligible to enter the extension and be treated with Aml/Val 2.5/80 or 5/80 mg. After 4 weeks of treatment, patients underwent force-titration to receive 5/160 mg (low dose) or 10/160 mg (high dose) for 48 weeks. Addition of hydrochlorothiazide (HCTZ) 12.5 mg was permitted if BP was > or = 140/90 mmHg at Week 8 or later. Patients could be down-titrated to the prior lower combination dose with or without HCTZ if an intolerable AE occurred. Safety evaluations included monitoring of AEs. Efficacy variables were change from baseline in MSDBP (primary) and MSSBP (secondary). Of 1246 patients randomised, 1075 (86.3%) completed the extension study. At week 52 end-point, change in MSSBP/MSDBP from core study baseline was -22.1/-17.2 mmHg for low-dose regimen and -22.8/-18.1 mmHg for high-dose regimen. For both regimens, reductions in BP were sustained over 52 weeks and mean BP maintained below approximately 135/85 mmHg at all visits. Frequent AEs in the low- and high-dose regimens were peripheral oedema (9.7% and 17.1% respectively), nasopharyngitis (8.1% and 7.2%), and dizziness (5.2% and 7.0%). Incidence of serious AEs was 3.7% with low dose and 4.1% with high dose. The combination of Aml/Val with the optional addition of HCTZ produced clinically significant and persistent reductions in BP over 52 weeks with a favourable tolerability profile.

Amlodipine/valsartan/hydrochlorothiazide triple combination therapy in moderate/severe hypertension: Secondary analyses evaluating efficacy and safety

An 8-week trial of amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) for moderate or severe hypertension demonstrated more-pronounced blood pressure (BP)-lowering effects compared with dual-component therapies. To elucidate the effects of time and baseline BP on the observed responses, exploratory analyses were performed. Patients aged 18-85 years with mean sitting systolic BP (MSSBP) 145 to <200 mmHg and mean sitting diastolic BP (MSDBP) 100 to <120 mmHg were randomized to Aml 10 mg/Val 320 mg/HCTZ 25 mg; Val 320 mg/HCTZ 25 mg; Aml 10 mg/Val 320 mg; or Aml 10 mg/HCTZ 25 mg. During the first 2 weeks, regimens were force-titrated in two stages. All least-square mean reductions in MSSBP and MSDBP (baseline to Week 3 and end of study) were significantly greater with triple therapy than with each dual therapy in the overall population and the severe systolic subgroup (baseline MSSBP > or =180 mmHg; except vs. Aml 10 mg/Val 320 mg at Week 3). At Week 3, more patients on triple therapy achieved MSSBP reductions of > or =-60, > or =-50, > or =-40, > or =-30, and > or =-20 mmHg (2.5%, 9.7%, 23.2%, 46.9% and 74.5%, respectively) than those on dual therapy (1.1%-2%, 5.6%-5.9%, 14.5%-16.7%, 33.5%-39.1%, and 58.8%-65.5%, respectively); this was also true at study endpoint. End-of-study MSSBP reductions were greater in triple-therapy recipients who had higher (vs. lower) baseline MSSBPs. LSM reductions ranged from -27.2 mmHg for baseline MSSBP 145 to <150 mmHg, to > or =49.6 mmHg for baseline MSSBP > or =180 mmHg. All treatments were well tolerated regardless of baseline MSSBP. Aml 10 mg/Val 320 mg/HCTZ 25 mg triple therapy is highly effective in reducing BP compared with dual components early in therapy, and systolic BP-lowering effects were proportionate to hypertension severity.

Randomized, Double-blinded Trial Evaluation of Valsartan/Hydrochlorothiazide Combination Therapy in Mild to Moderate Essential Hypertension in North-east China

In this randomized, double-blind study, 126 mild to moderate essential hypertensive patients from northern China were studied to determine the efficacy and safety of a combination therapy of valsartan and hydrochlorothiazide. Patients were randomized to the V80/H12.5 (80 mg valsartan/12.5 mg hydrochlorothiazide) group or the V80 (80 mg valsartan) group. Six weeks after treatment, the mean decrease from baseline in mean sitting systolic blood pressure (MSSBP) was significantly higher in the V80/H12.5 group than the V80 group, but there was no difference in the change of mean sitting diastolic blood pressure (MSDBP) in the two groups. Overall, 80.33% and 70.97% had a controlled response (normalized MSDBP), and 85.25% and 77.42% had a diastolic response (normalized MSDBP or > 10 mmHg reduction in MSDBP) in the V80/H12.5 and V80 groups, respectively (not significantly different). The incidence of adverse events was also similar between the two groups. The combination of 80 mg valsartan/12.5 mg hydrochlorothiazide was efficacious and well tolerated in mild and moderate essential hypertensive patients.

Combination therapy with valsartan/hydrochlorothiazide at doses up to 320/25 mg improves blood pressure levels in patients with hypertension inadequately controlled by valsartan 320 mg monotherapy

Objectives. To investigate the efficacy and tolerability of valsartan (Val) 320 mg once daily (o.d.), Val/hydrochlorothiazide (HCTZ) 320/12.5 mg o.d. and Val/HCTZ 320/25 mg o.d. in patients with hypertension not adequately controlled by Val monotherapy. Methods. This double‐blind, active‐controlled, parallel‐group, randomized trial recruited patients ⩾18 years with mild‐to‐moderate essential hypertension, defined as mean sitting diastolic blood pressure (MSDBP) of ⩾95 mmHg and <110 mmHg without treatment. After washout, 3805 eligible patients received Val 320 mg o.d. single‐blind for 4 weeks. Subsequently, patients with MSDBP ⩾90 and <110 mmHg (n = 2702) were randomized to double‐blind treatment with Val 320 mg, Val/HCTZ 320/12.5 mg or Val/HCTZ 320/25 mg for 8 weeks. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) from the start of the single‐blind period were analysed, as well as the proportion of responders (MSDBP <90 mmHg or ⩾10 mmHg decrease from the start of the double‐blind period). Tolerability and safety were also assessed. Results. Reductions in MSDBP and MSSBP were observed in all groups. Both combinations were associated with significantly greater reductions than monotherapy for MSDBP and MSSBP at Weeks 8 and 12 (all p<0.0001). Both combinations also resulted in significantly greater proportion of responders at study end (74.9% and 68.8% for Val/HCTZ 320/25 mg and Val/HCTZ 320/12.5 mg, respectively) than monotherapy (52.7%; both p<0.0001). In addition, a dose–response was observed with increasing dose of HCTZ with respect to MSSBP. All treatments were well tolerated. Conclusions. The combination of Val and HCTZ at doses of 320/12.5 mg and 320/25 mg increases antihypertensive efficacy in patients with mild‐to‐moderate hypertension inadequately controlled with Val 320 mg monotherapy, without compromising tolerability.

Efficacy and safety of valsartan 160/HCTZ 25 mg in fixed combination in hypertensive patients not controlled by candesartan 32 mg plus HCTZ 25 mg in free combination

ABSTRACTObjective: Free combination hypertension medication is associated with a lower compliance and less persistence compared to fixed combination therapy and can, there­fore, be associated with insufficient blood pressure reductions. This non-randomized study investigated whether valsartan 160 mg/ hydrochlorothiazide 25 mg (Val 160/HCTZ 25) in fixed dose combination could provide additional blood pressure control in hypertensive patients not adequately controlled by the free combination of candesartan 32 mg plus HCTZ 25 mg.Research design and methods: One hundred and ninety-seven patients with a mean sitting diastolic blood pressure (MSDBP) between 100 and 110 mmHg entered a 4-week treatment phase with 32 mg of candesartan in free combination with 25 mg of HCTZ once daily. One hundred and thirty-eight patients with uncontrolled BP at Week 4, entered a second 4-week treatment phase with Val160/ HCTZ 25 once daily.Main outcome measures: The primary efficacy parameter was the reduction in MSDBP at trough between Week 4 and Week 8 in the intent-to-treat population.Results: At baseline, MSDBP was 103.0 ± 2.8 mmHg. After Week 4, MSDBP had decreased to 93.8 ± 4.5 mmHg. Subsequent treatment with Val 160/HCTZ 25 for 4 weeks reduced MSDBP to 88.7 ± 8.6 mmHg. This represented an additional decrease in MSDBP of 5.1 ± 7.9 mmHg ( p < 0.0001). Val 160/ HCTZ 25 reduced mean sitting systolic BP by 3.4 ± 13.0 mmHg ( p = 0.0029).Conclusions: The fixed dose combination of valsartan 160/HCTZ 25 mg provided a statistically and clinically significant additional BP reduction in patients not controlled by the free combination of candesartan 32 mg and HCTZ 25 mg.

Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide

Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed. A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers. Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated. Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ.

Effect on blood pressure control of switching from valsartan monotherapy to losartan/hydrochlorothiazide in Asian patients with hypertension: results of a multicentre open-label trial

ABSTRACTStudy design: An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50 mg plus hydrochlorothiazide 12.5 mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80 mg.Methods: A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95–115 mmHg and a mean trough sitting systolic blood pressure (SiSBP) < 190 mmHg entered the baseline period of treatment with valsartan 80 mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90 mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50 mg/hydrochlorothiazide 12.5 mg combination once daily for a further 4 weeks.Results: Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80 mg to losartan 50 mg/hydrochlorothiazide 12.5 mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively ( p ≤ 0.001 for both outcomes). The goal of SiDBP ≤ 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80 mg/day. Combination therapy with losartan 50 mg/hydrochlorothiazide 12.5 mg was generally well tolerated. Mean compliance with the losartan 50 mg/hydrochlorothiazide 12.5 mg combination was > 99%.Conclusion: These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBP ≤ 90 mmHg with valsartan monotherapy at 80 mg once-daily, switching to a single-tablet combination of losartan 50 mg/hydrochlorothiazide 12.5 mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.

Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension.

Pharmacological treatment of hypertension reduces the risk of cardiovascular disease; however, randomized, controlled clinical trials and population studies have also shown that abnormally high blood pressure (BP) can be lowered with diet modification and exercise. The objective of this pilot study was to determine whether daily dietary supplementation with 10 g Chlorella tablets and 100 ml Chlorella extract for 2 months would reduce BP in subjects with a mean sitting diastolic BP (SiDBP) between 90 and 115 mm Hg. Thirty-three people were enrolled and underwent a 4-week washout period from all antihypertensive medications, during which they consumed placebo. At completion of this washout/placebo period, 24 subjects were considered evaluable (i.e., had a SiDBP between 90 and 115 mm Hg) and were continued in the study. After 1 or 2 months of dietary Chlorella supplementation, the average heart rate, sitting systolic BP, and SiDBP changed only slightly; after 2 months of Chlorella consumption, the group's mean SiDBP was 96.5 +/- 6.6. However, a heterogenous response pattern to Chlorella existed, with 25% (6/24) of the subjects achieving their BP goal (SiDBP less than 90 mm Hg). Furthermore, the BP of nonresponders did not increase significantly above washout values. Quality-of-life questionnaires indicated an overall perception that health had significantly improved in conjunction with Chlorella consumption. The results indicate that, for some subjects with mild to moderate hypertension, a daily dietary supplement of Chlorella reduced or kept stable their SiDBP.

Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension

Background: African Americans with hypertension, particularly those with more severe blood pressure elevations, are generally less responsive to monotherapy from any antihypertensive class. These patients usually require treatment with drugs from ≥2 antihypertensive classes to achieve adequate blood pressure control. Objective: The purpose of this study was to assess the antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide (HCTZ) in African American adults with mild to moderate hypertension. Methods: In this 12-week, multicenter, double-blind, randomized, parallel-group, placebo-controlled study, African American patients were randomized in a 3:3:1 ratio to 1 of 3 treatment groups: placebo, losartan monotherapy (50 to 150 mg), or losartan plus HCTZ (50/0 to 50/12.5 to 100/25 mg). Doses were titrated at weeks 4 and 8 if sitting diastolic blood pressure (SiDBP) was ≥90 mm Hg. Safety was assessed by determining the incidence of clinical and laboratory adverse events and evaluating mean changes in pulse, body weight, electrocardiographic parameters, and laboratory test results. Results: A total of 440 patients were randomized—188 to placebo, 193 to losartan monotherapy, and 59 to losartan/HCTZ; 391 completed the study. At week 12, the response rate with losartan monotherapy was 45.8%, with a significant ( P ≤ 0.01) lowering in mean SiDBP by 6.6 mm Hg compared with placebo; the response rate with placebo was 27.2%, with a mean SiDBP reduction of 3.9 mm Hg. Sitting systolic blood pressure (SiSBP) was significantly lowered with losartan monotherapy, by 6.4 mm Hg, compared with placebo (reduction of 2.3 mm Hg). The response rate with losartan/HCTZ was 62.7%, with reductions in SiSBP and SiDBP of 16.8 mm Hg and 10.8 mm Hg, respectively ( P ≤ 0.01 vs placebo and losartan monotherapy). The incidence of clinical adverse events was comparable in the 3 treatment groups. Conclusions: The results of this study suggest that in African American patients, losartan monotherapy was significantly more effective than placebo in lowering SiSBP and SiDBP. Moreover, the losartan/HCTZ combination regimen resulted in significant and clinically meaningful additional reductions in SiSBP and SiDBP compared with losartan monotherapy or placebo. Losartan monotherapy and the losartan/HCTZ regimens were generally as well tolerated as placebo.

Efficacy and safety of valsartan compared with enalapril at different altitudes

Objective: To compare the safety, tolerability, and antihypertensive efficacy of valsartan with enalapril at different altitudes. Method: A total of 142 adult Colombian outpatients with mild to moderate essential hypertension were recruited in 3 cities at different altitudes (Bogotá at 2600 m, Medellı́n at 1538 m and Barranquilla at 100 m) and randomized in an open label fashion to receive either valsartan 80 mg once daily or enalapril 20 mg once daily for 8 weeks. Those patients not responding at 4 weeks received additional 1.25 mg indapamide daily during the remaining trial period. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to 4 weeks. Secondary efficacy variables included the change in mean sitting systolic blood pressure (SSBP). The primary criterion for tolerability was the incidence of adverse experiences. Results: Both valsartan and enalapril reduced mean SDBP and SSBP with similar efficacy, independent of altitude. Adverse events irrespective of relationship to trial drug were reported by 12 patients (18.8%) on valsartan and by 15 (23.4%) patients on enalapril. Enalapril was associated with a significantly ( P<0.05) higher rate of dry cough and more cases of headache than valsartan. Conclusions: Valsartan 80 mg once daily is as effective as enalapril 20 mg once daily in reducing blood pressure, with tolerability profile at least as good as enalapril’s.

A COMPARISON OF VALSARTAN AND CAPTOPRIL IN PATIENTS WITH ESSENTIAL HYPERTENSION IN INDONESIA

SUMMARYAdult Indonesian outpatients were randomised to receive either valsartan 80 mg once daily or captopril 25 mg twice daily for 8 weeks. The main criterion for tolerability was the incidence of adverse events. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to endpoint. No valsartan patients experienced dry cough, which was reported by 22 captopril patients (21.6%). Both drugs reduced mean SDBP and SSBP, with a trend in favour of valsartan. The percentage of valsartan patients whose BP normalised was higher than in captopril patiente at week 4 (37% and 22%) and week 8 (45% and 34%), the difference being statistically significant at week 4 (p&lt;0.05). Valsartan 80 mg once daily is as effective as captopril 25 mg twice daily in reducing blood pressure in Indonesian patiente, and has a better tolerability profile in respect of dry cough.