Mean Sitting Systolic Blood Pressure Research Articles

Efficacy and safety of standard dose triple combination of telmisartan 80mg/amlodipine 5mg/chlorthalidone 25mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25mg with telmisartan 80mg plus amlodipine 5mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40mg/amlodipine 5mg/chlorthalidone 12.5mg, TEL/AML/CHTD group) or dual combination (telmisartan 40mg/amlodipine 5mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age=60.9±10.7years, male=78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9±12.2/88.5±10.4mm Hg. After 8weeks treatment, the change of MSSBPs at week 8 are -19.1±14.9mm Hg (TEL/AML/CHTD) and -11.4±14.7mm Hg (TEL/AML) (p<.0001). The achievement rates of target BP (53.8% vs. 37.8%, p=.0017) and responder rate (54.8% vs. 35.6%, p=.0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age≥65years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p=.042) Our study showed standard dose triple combination of telmisartan 80mg/amlodipine 5mg/chlorthalidone 25mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Efficacy and Safety of Coadministered Ezetimibe–Rosuvastatin plus Telmisartan in South Korean Patients with Dyslipidemia and Hypertension: A Multicenter, Randomized, Double-Blind, Active-Controlled, Phase III Trial

The introduction of a fixed-dose combination (FDC) is expected to improve treatment compliance. There were 181 subjects who were randomized to three groups: ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg, ezetimibe-rosuvastatin 10/20 mg, and telmisartan 80 mg. The primary outcomes were change in mean sitting systolic blood pressure (MSSBP) and percentage change in low-density-lipoprotein cholesterol (LDL-C) compared to baseline at week 8. The least-square mean (SE) in MSSBP changes between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the ezetimibe-rosuvastatin 10/20 mg group were -25.81 (2.34) mmHg and -7.66 (2.45) mmHg. There was a significant difference between the two groups (-18.15 (2.83) mmHg, 95% CI -23.75 to -12.56, p < 0.0001). Changes in least-square mean (SE) in LDL-C between the ezetimibe-rosuvastatin 10/20 mg + telmisartan 80 mg group and the telmisartan 80 mg group were -63.82 (2.87)% and -2.48 (3.12)%. A significant difference was observed between the two groups (-61.34 (3.33)%, 95% CI -67.91 to -54.78, p < 0.0001). No serious adverse events were observed. Ezetimibe-rosuvastatin plus telmisartan treatment is effective and safe when compared to either ezetimibe-rosuvastatin or telmisartan.

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.

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.

Efficacy and safety of valsartan/amlodipine single-pill combination in 11,422 Chinese patients with hypertension: an observational study.

IntroductionSingle-pill combination (SPC) therapy of two drugs is recommended by international guidelines, including the Chinese guidelines (2010), for the treatment of hypertension in high-risk patients who require marked blood pressure (BP) reductions. Real-world data on the efficacy and safety of valsartan/amlodipine (Val/Aml) SPC are scarce. The present study is the first observational study in China to evaluate the efficacy (primary endpoint) and safety of Val/Aml (80/5 mg) SPC in Chinese patients with hypertension whose BP was not adequately controlled by monotherapy in a real-world setting.MethodsThis prospective, multicenter, open-label, post-marketing observational study included 11,422 Chinese adults (≥18 years) with essential hypertension from 238 sites of 29 provinces who were prescribed once-daily Val/Aml (80/5 mg) SPC. Patients were treated for 8 weeks. The primary efficacy variable of the study included changes in mean sitting systolic BP (MSSBP) and mean diastolic BP (MSDBP) from baseline to week 8 (end point). The secondary efficacy variable of the study included BP control rate and response rate at week 4 and 8. Safety assessments included recording and measurement of all adverse events (AEs) and vital signs in the safety population.ResultsA significant reduction of 27.1 mmHg in MSSBP (159.6 vs. 132.5 mmHg; P < 0.0001) and 15.2 mmHg in MSDBP (95.6 vs. 80.4 mmHg; P < 0.0001) from baseline was observed at week 8. The BP-lowering efficacy of Val/Aml SPC was independent of age and comorbidities. BP control of <140/90 mmHg was achieved in 76.8% (n = 8,692) of the patients. The most frequently reported AEs were dizziness (0.2%), headache (0.2%), upper respiratory tract infection (0.2%), and edema (0.2%). Only three serious AEs were reported and they were not drug-related.ConclusionThis is the first evidence-based real-world data in Chinese hypertensive patients which demonstrate the efficacy and safety of Val/Aml (80/5 mg) SPC.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-014-0132-x) contains supplementary material, which is available to authorized users.

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, Safety and Tolerability of High dose Valsartan Hydrochloride in Essential Hypertension

Background: Studies across the world have demonstrated the efficacy of valsartan in lowering blood pressure in a variety of patient populations, several of them investigated higher doses of the drug. This study focuses on revealing safety and efficacy of valsartan at higher doses in Bangladeshi population. Current study is planned to evaluate the efficacy, safety and tolerability of daily dose of Valsartan 160 or 320 mg in the treatment of essential hypertension. Method: This is a multi-center, open-label, observational, non-comparative, clinical decision based titration, involving about 31 centers in Bangladesh. A total of 334 newly diagnosed adult patients with essential hypertension received valsartan at a dose of 160 mg or 320 mg as deemed necessary by physician were included to allow for an assessment of efficacy, safety and tolerability. The total duration of treatment with valsartan was 16 weeks. Primary parameter for efficacy was percentage responders to valsartan at 16 weeks, reduction in Mean sitting systolic blood pressure (MSSBP) and Mean sitting Diastolic blood pressure MSDBP, control rate (% patients) achieving SBP &lt;140 mmHg and DBP &lt;90 mmHg at end point and Global assessment of efficacy and tolerability to valsartan treatment by the physician and patient. Result: Mean age of the patient was 53.31±8.8 years and 56.5% were male. A clearly evident decline is evident in mean Systolic BP and diastolic BP over the study duration. Average reduction of 30.4 ± 17.4 mmHg was seen in systolic BP, 18.4 ± 11.2 mmHg in diastolic BP and 3.5 ± 3.1/ minute in heart rate. The reduction was highly significant in both systolic BP and diastolic BP and heart rate as well (P&lt;.001). At 16 weeks only 3.4% were found to be refractory to the treatment. Global assessment of safety and efficacy was assessed on four point scale, around 30.2% of the physician rated the efficacy as excellent, around 56% rated as very good and 13.8% rated as good. Tolerability of the treatment was also assessed based on the opinion of the patient and physician concerned on four point scale. Around 34.1% of the physician rated the tolerability as excellent, around 49.7% rated as very good and 16.2% rated as good. Conclusion: Sixteen week treatment with valsartan at 160mg daily or 320 mg daily is an effective treatment for patients with essential hypertension. The drug is found to be well tolerated with minimal adverse event during the course of treatment. DOI: http://dx.doi.org/10.3329/cardio.v5i2.14323 Cardiovasc. j. 2013; 5(2): 182-189

Results of a 14-Week, Multicenter, Prospective, Randomized, Open-Label, Noninferiority Clinical Trial Comparing the Antihypertensive Effect and Edema Incidence of Lacidipine and Amlodipine in Older Korean Patients with Mild-to-Moderate Hypertension

BackgroundIt has been shown that administration of lacidipine markedly reduces systolic blood pressure in elderly patients with hypertension without increasing the incidence of cardiovascular events and total mortality. But in Korea, there were no available data about the effectiveness and safety of lacidipine. ObjectivesThe goal of our study was to compare the effect of lacidipine and amlodipine besylate on sitting systolic blood pressure (SBP) and edema regression time as primary parameters, and sitting diastolic blood pressure (DBP) and tolerability as a secondary parameter in patients with hypertension. MethodThis was a prospective, randomized, open-label, noninferiority study in which patients received 14 weeks of treatment with either lacidipine or amlodipine besylate. Patients aged 55 to 80 years having uncomplicated, mild-to-moderate essential hypertension (SBP 140 to <180 mm Hg or DBP ≥90 mm Hg) and receiving no antihypertensive medications during the 2 weeks before randomization were randomly assigned to receive lacidipine or amlodipine. The incidence of adverse events was also assessed. ResultsIn total, 315 patients (154 men, mean age 67.6 years) were included in the intent-to-treat analysis and randomly assigned to receive lacidipine (n = 162) or amlodipine besylate (n = 153); 286 patients were included in the per-protocol analysis (n = 150 for lacidipine, n = 136 for amlodipine) (12 in the lacidipine group and 17 in the amlodipine group were excluded from the per-protocol analysis due to consent withdrawal or protocol violation). There were no differences in demographic profiles between the 2 groups. Mean (SD) SBP changes at 14 weeks were −18.9 (12.7) mm Hg in the lacidipine group and −20.6 (12.4) mm Hg in the amlodipine group (P >0.05). Because the 1-sided 95% CI for the difference in mean SBP changes between groups (−4.18 to 0.72) was within the pre-specified lower limit (−5 mm Hg), lacidipine was considered noninferior to amlodipine. There were no differences in mean edema regression time and in mean DBP changes. These results were consistent in the isolated systolic hypertension subgroup analysis. The overall incidence of clinical adverse events was comparable between the 2 groups (ie, 7.4% in the lacidipine group and 11.1% in the amlodipine group [P >0.05]). The most common adverse events were headache and facial flushing (5 out of 162 patients [3.1%] in the lacidipine group and 11 out of 153 patients [7.2%] in the amlodipine group]. ConclusionsFourteen weeks of lacidipine treatment significantly reduced blood pressure in older Korean patients with mild-to-moderate hypertension. The efficacy of lacidipine was not inferior to that of amlodipine besylate and tolerability was comparable between the 2 treatment groups. ClinicalTrials.gov identifier: NCT00460915.

Titration of amlodipine to higher doses: a comparison of Asian and Western experience

In this retrospective analysis, data pooled from two Phase III/IV open-label Asian studies were used to quantify the additional blood pressure efficacy achieved when titrating amlodipine from 5 mg to 10 mg in mild/moderate hypertensive patients, and compared to data pooled from three Western studies. The primary efficacy end point was the change from baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) to the specified time point (4–8 weeks, depending on the trial). For the Asian analysis (n=174), both mean SBP and DBP were significantly decreased at the final visit (SBP −13.3 mmHg, 95% confidence interval [CI] −15.5 to −11.0; DBP −9.2 mmHg, 95% CI −10.6 to −7.8; both P<0.0001). These results were similar to the Western analysis (n=369; SBP −11.5 mmHg, 95% CI −13.1 to −10.0; DBP −6.3, 95% CI −7.1 to −5.5; both P<0.0001). In summary, titration of amlodipine from 5 mg to 10 mg significantly decreased both SBP and DBP in Asian patients with mild-to-moderate hypertension.

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...

Efficacy and safety of valsartan in reducing blood pressure and albuminuria in Chinese patients with essential hypertension: a multicenter prospective open-label observational study

Objective:To evaluate the efficacy and safety of 80 or 160 mg/day valsartan in Chinese adult patients with essential hypertension and albuminuria.Methods:A multicenter prospective open-label observational study was conducted. Adult hypertensive patients with albuminuria were treated with 80 or 160 mg/day valsartan. Blood pressure (BP) was recorded at weeks 4, 8 and 12. Albuminuria was selectively measured at week 12.Results:The intent-to-treat (ITT) population included 1180 patients. Mean sitting systolic BP (MSSBP) and diastolic BP (MSDBP) at baseline was 153.5 [14.41] (mean [SD]) and 88.2 [11.99] (mean [SD]) mmHg. MSSBP and MSDBP at week 4 (mean [SD]: 139.1 [12.02] and 82.2 [8.54] mmHg), week 8 (mean [SD]: 135.3 [10.46] and 80.2 [7.55] mmHg) and week 12 (mean [SD]: 132.1 [9.80] and 78.1 [6.88] mmHg) were significantly lower than baseline (p < 0.001). The BP control rate of ITT patients at week 12 was 17.8%. Diabetic patients exhibited lower BP control rate than non-diabetic patients (14.0 vs. 22.4%, p < 0.001). A total of 904 patients had albuminuria assessed at week 12. UACR and UAER at week 12 were lower compared with baseline (p < 0.05). In all, 171 patients (18.9%) returned to normal albuminuria and albuminuria normalization percentage in diabetic patients exceeded that of non-diabetic patients (26.3 vs. 12.1%, p < 0.001). Albuminuria declined by more than 50% in 340 patients (37.6%) and more diabetic patients exhibited such decline in albuminuria than non-diabetic patients (41.7 vs. 33.8%, p < 0.05). No serious drug-related adverse effects (AEs) were observed.Limitations:Prior antihypertensive treatment before valsartan administration may interfere with the efficacy of subsequent treatment. The discrepancy between 80 and 160 mg may affect patient outcomes and occurrence of AEs.Conclusions:Valsartan can safely and effectively reduce BP and albuminuria in Chinese adult patients with essential hypertension and albuminuria. Valsartan has the more dramatic effect on albuminuria in diabetic patients than non-diabetic patients.

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.

Antihypertensive Response to Thiazide Diuretic or Angiotensin Receptor Blocker in Elderly Hypertensives Is Not Influenced by Pretreatment Plasma Renin Activity

Renin profiling has been proposed as a method to guide antihypertensive drug selection. This prespecified post-hoc analysis examined the influence of baseline plasma renin activity (PRA) on blood pressure (BP) responses. A 16-week, randomized, double-blind, prompted-titration trial evaluated initial valsartan (V)/hydrochlorothiazide (HCTZ) combination therapy versus initial HCTZ or V monotherapy in individuals aged ≥ 70 years with systolic hypertension. Sitting PRA was measured at baseline, Week 4, and Week 16. Subjects were stratified into 2 groups for analysis: low renin (baseline PRA < 0.65 ng/mL/h) or normal-high renin (baseline PRA ≥ 0.65 ng/mL/h). PRA data were available in 322/384 subjects: 178 had low PRA and 144 had normal-high PRA. At Week 4, V/HCTZ was more effective than HCTZ or V at reducing mean sitting systolic BP (MSSBP), independent of baseline PRA, with reductions of -16.9, -12.6, and -9.5 mmHg, respectively, in low-renin subjects and -19.4, -11.5, and -8.6 mmHg in normal-high renin subjects. Baseline PRA was similar in responders (subjects not uptitrated at Week 4) and nonresponders (subjects uptitrated at Week 4). In responders, the reactive rise in PRA at Week 4 was related to change in MSSBP, with the greatest increases in PRA observed in the V/HCTZ group. Higher baseline PRA was associated with a greater reactive rise in PRA. Baseline PRA is not a useful guide to the BP responses of initial combination V/HCTZ in elderly individuals with systolic hypertension.

Combination Angiotensin‐Receptor Blocker (ARB)/Calcium Channel Blocker With HCTZ vs the Maximal Recommended Dose of an ARB With HCTZ in Patients With Stage 2 Hypertension: The Exforge As Compared to Losartan Treatment in Stage 2 Systolic Hypertension (EXALT) Study

This study compared the efficacy and safety of combination angiotensin-receptor blocker (ARB)/calcium-channel blocker (CCB) with hydrochlorothiazide (valsartan/amlodipine/HCTZ 160/5/2mg) vs maximal available combination doses of an ARB with HCTZ (losartan/HCTZ 100/25 mg) in the management of stage 2 hypertension. After 1 to 2 weeks of antihypertensive drug washout, patients with a mean sitting systolic blood pressure (MSSBP) of ≥ 160 mm Hg and <200 mm Hg were randomized to valsartan/amlodipine 160/5 mg (n = 241) or losartan 100 mg (n = 247). At week 3, HCTZ 25 mg was added to both treatments. The primary end point, reduction in MSSBP from baseline to week 6, was significantly greater in the valsartan/amlodipine group than in the losartan group (least-squares [LS] mean change, -31.8 mm Hg vs -26.4 mm Hg; P<.001). Additional reductions occurred after titrating to 320/10/25 mg at week 6 in the valsartan/amlodipine group and switching from losartan/HCTZ to valsartan/amlodipine/HCTZ (week 6, 160/5/25 mg; week 9, 320/10/25 mg) in the losartan group. Achievement of blood pressure <140/90 mm Hg also favored the valsartan/amlodipine group. Dizziness was the only adverse event reported in >5% of patients (5.4% valsartan/amlodipine group, 3.6% losartan group). Moderate doses of an ARB/CCB combination with HCTZ reduced blood pressure more effectively than the maximal dose of an ARB with HCTZ.

Efficacy and safety of aliskiren-based dual and triple combination therapies in US minority patients with stage 2 hypertension

Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m 2, 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine ( P < .0001 between groups). At week 8, BP goal (<140/90 mm Hg) was achieved in 72.6% and 53.2% of patients in the two treatment groups, respectively ( P < .0001). Adverse events were experienced by 34.2% and 40.2%, respectively. Combination aliskiren/amlodipine therapy was effective in treating these high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated.

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.