amlodipine--valsartan-drug-combination and Hypertension

The aim of this post-hoc analysis was to compare the results from randomized controlled trials (RCTs) and real-world evidence (RWE) studies of valsartan/amlodipine (Val/Aml) and valsartan/amlodipine/hydrochlorothiazide (Val/Aml/HCTZ) in patients with uncontrolled hypertension (>140/90 mmHg).. Data was pooled from 15 RCTs (N = 5542) and 8 RWE studies (N = 1397) for Val/Aml; and 2 RCTs (N = 804) and 5 RWE studies (N = 9380) for Val/Aml/HCTZ. Patients who received Val/Aml (80/5, 160/5, 160/10, 320/5, or 320/10 mg), Val/Aml/HCTZ (160/5/12.5, 160/5/25, 160/10/12.5, 160/10/25, or 320/10/25 mg) or placebo were considered for this analysis. Only patients with both baseline and follow-up assessment within 60-90 days after baseline had been included in the analysis. Patients with missing values were excluded from the analysis. Using fitted linear mixed-effects model and random factors, treatment interactions and study design with mean sitting systolic blood pressure (msSBP), diastolic BP (msDBP) and pulse pressure (msPP) reductions from baseline to Week 8-12 of treatment were compared.. Baseline demographics and patient characteristics were comparable between RCT and RWE datasets and within Val/Aml and Val/Aml/HCTZ treatment groups. In both RCT and RWE studies, least-squares mean (LSM) reduction in msSBP/msDBP and msPP from baseline were significant (p < .05) across all dosages. The efficacy of Val/Aml in RCTs was statistically significantly greater than in RWE studies for msSBP/msDBP (-23.1/-13.8 vs. -17.9/-9.1 mmHg) but the difference was non-significant for msPP (-8.6 vs. -9.3 mmHg; p = .77). For Val/Aml/HCTZ, no direct comparison was available but a similar trend was observed. The difference observed for msSBP and msDBP may be due to routine practice setting, larger populations may have more confounders and different behaviors towards treatment adherence.. These findings demonstrate that the efficacy of Val/Aml and Val/Aml/HCTZ in RCTs was more pronounced compared with their effectiveness in RWE studies in different ethnic populations although the overall benefit was not different.

Topics: Aged; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic

This study compared blood pressure (BP) changes after 8 weeks of therapy between a fixed-dose combination (FDC) of amlodipine/losartan and amlodipine/valsartan using a network meta-analysis because no trials directly compared amlodipine/losartan with other FDCs.. A systematic search identified six randomised controlled trials (amlodipine/losartan-3, amlodipine/valsartan-3) of FDCs and their component monotherapies. Conventional fixed-effects methods were used to conduct the comparisons. The primary and secondary effect measures were the changes in sitting diastolic and systolic blood pressure (sitDBP, sitSBP) at 8 weeks post-randomisation.. The estimated amlodipine/valsartan - amlodipine/losartan difference (95% confidence interval) in sitDBP reduction was -1.27 mmHg, (-5.7, 2.2) for lower dosages and -0.45 mmHg, (-3.7, 2.7) for higher dosages; for sitSBP, the values were -3.74 mmHg, (-9.0, 2.9) for lower dosages and 0.2 mmHg, (-6.2, 6.0) for higher dosages. The confidence of a greater reduction in BP (fixed difference = 0) on amlodipine/losartan 5/50 than on amlodipine/valsartan 5/80 was 77% for sitDBP and 89% for sitSBP. The corresponding confidence for the higher doses was 61% for sitDBP and 48% for sitSBP. The findings support asserting with (fixed) 95% confidence that the BP reduction on amlodipine/valsartan 5/80 exceeds the amlodipine/losartan 5/50 reduction by at most 1.6 mmHg for sitDBP, and at most 1.26 mmHg for sitSBP. The corresponding upper bounds for the higher dosages were 2.31 mmHg (sitDBP) and 5.38 mmHg (sitSBP).. The BP lowering effect with amlodipine/losartan and amlodipine/valsartan was comparable. Potential superiority of the reductions realised with amlodipine/valsartan relative to amlodipine/losartan, are unlikely to be clinically material.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Losartan; Male; Middle Aged; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Tetrazoles; Treatment Outcome

This article discusses racial/ethnic disparities in hypertension, with particular focus on non-white populations including blacks, Hispanics/Latinos, and Asians. Hypertension and its related morbidity and mortality affect a disproportionate number of black patients compared with white patients. Blacks, Hispanics/Latinos, and Asians have poor rates of hypertension awareness, treatment, and control. Given the high prevalence of comorbidities (e.g., obesity, diabetes, and metabolic syndrome) in these populations, renin-angiotensin-aldosterone system blockers are a good choice for foundation therapy. This review also discusses the importance of adherence and persistence with antihypertensive medication, which remain suboptimal in these non-white populations. Evidence suggests improvement with the use of single-pill combination therapy. Lastly, clinical trial data on the antihypertensive efficacy and safety of the combination of a dihydropyridine calcium channel blocker and an angiotensin receptor blocker, a widely utilized combination, in non-white populations are presented. PubMed was searched using the title/abstract key words (amlodipine AND valsartan AND [hypertension OR hypertensive] AND [black(s) OR African American(s) OR Hispanic(s) OR Latino(s) OR Mexican(s) OR Asian(s)]). In total, eight studies in patients with stage 1 or 2 hypertension were identified (n = 1,111 black, n = 389 Hispanic/Latino, and n = 3,094 Asian). Results showed that treatment with the combination of amlodipine plus valsartan is a reasonable choice for initial therapy or in patients who fail to respond to monotherapy. These drug classes have complementary mechanisms of action and, when used concomitantly, the magnitude of blood pressure lowering in these non-white populations is generally comparable with that seen in non-Hispanic white patients.

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asian People; Black or African American; Drug Combinations; Health Status Disparities; Hispanic or Latino; Humans; Hypertension; Medication Adherence; Tetrazoles; Treatment Outcome

Adequate lowering of blood pressure reduces the risk of hypertension-induced cardiovascular events. Worldwide, blood pressure is not optimally controlled and more effective management is needed. The efficacy and tolerability of angiotensin II type 1 receptor blockers (ARBs) have led to their widespread use. Calcium channel blockers (CCBs) are highly effective antihypertensives and amlodipine has a long half-life in the circulation. The combination of an ARB with a CCB as a single-pill, fixed-dose treatment is emerging as possibly the best therapy for preventing cardiovascular disease. Although many kinds of ARB are used in such combinations, amlodipine is mainly used as the CCB. Thus, differences in safety and efficacy among single-pill ARB/CCBs depend mainly on the ARB. Not all ARBs have the same effects and some of these may be molecular (or differential) rather than class (or common) effects. This review discusses the safety and efficacy of ARB/CCB combination therapy, with particular focus on a single-pill, fixed-dose combination of valsartan/amlodipine.

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Calcium Channel Blockers; Dose-Response Relationship, Drug; Drug Combinations; Humans; Hypertension; Tetrazoles; Treatment Outcome

Early initiation of rational and effective combination therapy consisting of antihypertensive drugs with two different and complementary mechanisms of actions is increasingly becoming accepted in clinical practice and by guidelines as a first-line approach to control blood pressure (BP) and prevent cardiovascular outcomes in patients with hypertension. Once-daily combination therapy provides more rapid control of BP, which is important for preventing cardiovascular events, with similar or improved tolerability compared with the component monotherapies, and improved adherence because of regimen simplification. Combination therapy with a calcium channel antagonist (calcium channel blocker [CCB]) and an inhibitor of the renin-angiotensin-aldosterone system (RAAS) is a rational approach to achieve BP goals and provide protection against renal and cardiovascular morbidity and mortality. A number of CCB/RAAS inhibitor combinations, including CCB/angiotensin-converting enzyme (ACE) inhibitor and CCB/ angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]) combinations are available as fixed-dose formulations. There is substantial evidence for the BP-lowering efficacy of CCB/RAAS inhibitor combinations in diverse patient populations, and their use in combination is associated with favourable tolerability and fewer adverse metabolic effects than some other combination therapies. Recent evidence from large outcome trials supports the use of CCB/RAAS inhibitor combinations for reducing the risk of cardiovascular and renal events, particularly in high-risk patients, together with evidence that the benefits of CCB/RAAS inhibitor combinations may extend beyond their efficacy in lowering BP in terms of protecting against fatal and nonfatal stroke, myocardial infarction and cardiovascular-related deaths. The efficacy of the CCB amlodipine and the ARB valsartan in lowering BP and protecting against cardiovascular events and stroke across a range of hypertensive patient populations has been established over many years. Fixed-dose amlodipine/valsartan combinations are available in many countries and have shown greater BP reductions and better BP control than the respective monotherapies in diverse patient populations, together with a favourable tolerability profile. Once-daily amlodipine/valsartan is a rational and convenient treatment option for the effective management of patients with hypertension, improving adherence to antihypertensive medication

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Drug Combinations; Humans; Hypertension; Tetrazoles; Treatment Outcome

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists and blockers of the renin-angiotensin system are widely used today to initiate antihypertensive therapy but, when given as monotherapy, do not suffice in most patients to normalize blood pressure. Combining the two types of agents considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. This is exemplified by the experience accumulated with the recently developed fixed dose combination containing the AT(1)-receptor blocker valsartan (160 mg) and the dihydropyridine amlodipine (5 or 10 mg). In a randomized trial, an 8-week treatment normalized blood pressure (<140/90 mmHg) within 8 weeks in a large fraction of hypertensive patients (78.4% and 85.2% using the 5/160 [n = 371] and 10/160 mg [n = 377] dosage, respectively). Like all AT(1)-receptor blockers valsartan has a placebo-like tolerability. Valsartan prevents to a large extent the occurrence amlodipine-induced peripheral edema. Both amlodipine and valsartan have beneficial effects on cardiovascular morbidity and mortality, as well as protective effects on renal function. The co-administration of these two agents is therefore very attractive, as it enables a rapid and sustained blood pressure control in hypertensive patients. The availability of a fixed-dose combination based on amlodipine and valsartan is expected therefore to facilitate the management of hypertension, to improve long-term adherence with antihypertensive therapy and, ultimately, to have a positive impact on cardiovascular and renal outcomes.

Topics: Age Factors; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Combinations; Humans; Hypertension; Medication Adherence; Middle Aged; Tetrazoles; Treatment Outcome

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are established antihypertensive agents. Fixed-dose combinations of amlodipine/valsartan are available in several European countries and in the US. Individual dose titration with amlodipine and valsartan is generally recommended before changing to the fixed-dose combination. Amlodipine/valsartan, at approved dosage regimens, achieved significantly greater reductions in mean sitting diastolic and systolic blood pressure (BP) than amlodipine or valsartan monotherapy, or placebo in two randomized, double-blind, factorial trials in patients with mild to moderate hypertension. Approximately 80-90% of patients receiving approved dosages of amlodipine/valsartan achieved a response, defined as a mean sitting diastolic BP <90 mmHg or a >or= 10 mmHg reduction from baseline. Subgroup analyses of data from the two trials showed that the antihypertensive efficacy of amlodipine/valsartan in the elderly, Black patients and those with stage 2 hypertension was consistent with that observed in the overall study population. Marked reductions in BP were also observed in patients whose BP was previously uncontrolled on monotherapy (with various antihypertensives) who were switched (without washout) to amlodipine/valsartan in a phase IIIb-IV study. Amlodipine/valsartan was generally well tolerated in clinical trials. In particular, the incidence of peripheral oedema was significantly lower in patients receiving amlodipine/valsartan than in those treated with amlodipine monotherapy.

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Calcium Channel Blockers; Drug Combinations; Drug Synergism; Humans; Hypertension; Tetrazoles; Valine; Valsartan

In a pre-specified subgroup analysis of a 12-week randomized multicenter study, we investigated effects of valsartan/amlodipine 80/5 mg single-pill combination (n = 75) and nifedipine GITS 30 mg (n = 75) on ambulatory blood pressure (BP) and arterial stiffness assessed by brachial-ankle pulse wave velocity (PWV) in patients with uncontrolled hypertension. At week 12, the between-treatment mean differences in systolic/diastolic BP were smaller for 24-hour and daytime (-2.1/-1.7 and -2.0/-1.5 mm Hg, respectively, P ≥ 0.22) but greater (P < 0.01) for nighttime (-4.0/-2.8 mm Hg, P ≤ 0.09), especially in sustained uncontrolled hypertension (-5.0/-4.1 mm Hg, P ≤ 0.04) and non-dippers (-6.5/-3.7 mm Hg, P ≤ 0.07), in favor of valsartan/amlodipine. At week 12, PWV was significantly reduced from baseline by valsartan/amlodipine (n = 59, P < 0.0001) but not nifedipine (n = 59, P = 0.06). The changes in PWV were significantly associated with that in ambulatory systolic BP and pulse pressure in the nifedipine (P ≤ 0.0008) but not valsartan/amlodipine group (P ≥ 0.57), with a significant interaction (P ≤ 0.045). The valsartan/amlodipine combination was more efficacious than nifedipine GITS in lowering nighttime BP in sustained uncontrolled hypertension and non-dippers, and in lowering arterial stiffness independent of BP lowering.

Topics: Adult; Amlodipine, Valsartan Drug Combination; Ankle Brachial Index; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Circadian Rhythm; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Treatment Outcome; Vascular Stiffness

We aimed to assess the association of changes in brachial or central nocturnal systolic blood pressure (SBP) with change in urine albumin-creatinine ratio (UACR) by a valsartan/amlodipine combination (80/5 mg) therapy in hypertensive patients.. Twenty-three patients (age range, 47-78 years; mean, 68.0 years; 35% men, 65% with chronic kidney disease) with clinic brachial BP ≥140/90 mm Hg were treated with valsartan/amlodipine combination therapy for 16 weeks. At baseline and 16 weeks later, we measured brachial and central nocturnal SBP using an oscillometric Mobil-O-Graph device and UACR by spot urine in 23 patients.. The changes in brachial nocturnal SBP (r = 0.445, P = 0.033) and those in central nocturnal SBP (r = 0.616, P = 0.002) were significantly associated with change in UACR by intervention. In multivariable-adjusted multiple regression analyses including changes in both brachial and central nocturnal SBP jointly, only central nocturnal SBP change retained a statistically significant association with change in UACR (β = 0.919, P = 0.020).. Lowering central nocturnal SBP by a valsartan/amlodipine combination therapy was associated with reduction of UACR, independently of brachial nocturnal SBP reduction. Central nocturnal SBP may be a therapeutic target to protect the kidney. A larger scale interventional study will be needed to confirm the kidney protection conferred by lowering central nocturnal SBP.. Trial Number UMIN000013519.

Topics: Aged; Albuminuria; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; Blood Pressure; Calcium Channel Blockers; Circadian Rhythm; Creatinine; Drug Administration Schedule; Female; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Time Factors; Treatment Outcome

Although hypertensive drugs may have the same effect on peripheral blood pressure, they vary in their effect on central blood pressure and its indices.. To evaluate efficacy of fixed-dose combination of amlodipine 10 mg/valsartan 160 mg versus nebivolol 5 mg/valsartan 160 mg in grade 2 or more hypertensive patients assessed by peripheral and central blood pressure.. A prospective, open label, randomized study done in the outpatient cardiology clinic at Beni-Suef University Hospital. A total of 137 patients continued the study; group I (n = 75) received Amlodipine 10 mg/Valsartan 160 mg (A/V) and group II (n = 62) received Nebivolol 5 mg/Valsartan 160 mg (N/V). Peripheral, central blood pressure and its indices were measured at baseline, after 6 and 12 weeks.. The two combinations reduced peripheral and central BP (P < 0.0001) after 6 and 12 weeks. A/V combination significantly reduces central Pulse Pressure (PP) after 6 and 12 weeks (- 8.53 ± 13.80 and - 10.17 ± 11.29 (P < 0.0001) respectively), while N/V showed its efficacy in reducing central PP after 12 weeks (- 7.03 ± 13.10, P = 0.005). A/V combination was more effective in reducing Pulse Wave Velocity (PWV) after 6 and 12 weeks; P < 0.0001 vs P = 0.004. After 6 weeks, N/V was more effective in reducing Augmentation Index (AIx) (- 6.00 ± 10.94 (P = 0.002) vs. - 3.44 ± 9.80 (P = 0.026)) while after 12 weeks A/V did not show any significance (P = 0.085).. Both treatment groups lowered patients' peripheral, central blood pressure after 6 and 12 week of treatment, but Amlodipine/Valsartan combination was more effective. Both treatments exerted different effects on central indices.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Egypt; Female; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome

The aim of this study was to compare the effect of morning and bedtime administration of valsartan/amlodipine combination therapy (80/5 mg) on nocturnal brachial and central blood pressure (BP) measured by ambulatory BP monitoring in patients with hypertension. This was a 16-week prospective, multicenter, randomized, open-label, crossover, noninferiority clinical trial. Patients underwent 24-hour ambulatory BP monitoring at randomization, at switching, and at the end of the study. Twenty-three patients (mean age, 68.0 years) were studied. The difference in nocturnal brachial systolic BP between the morning and bedtime administrations of combination valsartan/amlodipine was -3.2 mm Hg, and the two-sided 95% confidence interval ranged from -6.8 to 0.4 mm Hg. The difference in nocturnal central systolic BP was -4.0 mm Hg (95% confidence interval, -7.6 to -0.4 mm Hg). The upper limit of the 95% confidence interval was below the margin of 3.0 mm Hg in both nocturnal brachial and central systolic BP, confirming the noninferiority of morning administration to the bedtime administration of valsartan/amlodipine combination therapy.

Topics: Aged; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cross-Over Studies; Drug Chronotherapy; Drug Monitoring; Female; Humans; Hypertension; Male; Treatment Outcome

An international double-blind, parallel-group, randomized controlled trial was performed to determine the efficacy and safety of a new first-line strategy in mild to moderate hypertension based on a single-pill combination of perindopril/amlodipine versus a validated stepped-care strategy (initiation with valsartan monotherapy, up-titrating to valsartan/amlodipine after 2 months).. At inclusion, patients received perindopril/amlodipine 3.5/2.5 mg or valsartan 80 mg. At 1, 2, and 3 months, patients were up-titrated if they had uncontrolled hypertension (≥140/90 mmHg). The up-titration steps were: perindopril/amlodipine 7/5 mg, 14/10 mg, and 14/10 mg + indapamide sustained release 1.5 mg; or valsartan 160 mg, valsartan/amlodipine 160/5 mg, and 160/10 mg. The two groups were similar at baseline (55.5 years, 53% men, blood pressure 163.5/100.2 mmHg); 881 perindopril/amlodipine and 876 valsartan/amlodipine patients were analyzed for efficacy.. After 1 month, the rate of controlled hypertension was 33% with perindopril/amlodipine versus 27% with valsartan/amlodipine (estimate of difference, +6.1%; P = 0.005); this between-strategy difference remained significant at every visit (P < 0.05). After 3 months, blood pressure was 137.8 ± 12.4/83.3 ± 8.7 and 139.7 ± 13.3/84.8 ± 9.0 mmHg, respectively, with greater reductions from baseline with perindopril/amlodipine (primary endpoint -2.0/-1.5 mmHg; both P < 0.001). Similar results were observed at all other visits (all P ≤ 0.001). The safety of the two strategies was equivalent.. The three-step strategy of initiation with single-pill perindopril/amlodipine produces greater reductions in blood pressure, and better and quicker rates of control of hypertension. This can be expected to be associated with benefits beyond blood pressure control, notably improved compliance and better cardioprotection.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Valsartan

It is unclear whether thiazide diuretics (TZs) or calcium channel blockers (CCBs) are more effective as add-on therapy to angiotensin receptor blockers (ARBs) in controlling hypertension. Because TZs are a rational choice in salt-sensitive hypertension, patients with high salt intake might preferentially benefit from ARB/TZ over ARB/CCB combination therapy.. Hypertensive patients who failed to reach blood pressure goals despite treatment with ARBs alone were randomly assigned to receive either ARB/TZ or ARB/CCB combination therapy. Estimated daily sodium intake was calculated from spot urine values of sodium and creatinine.. Blood pressure was measured at baseline, and at 4, 8 and 12 weeks after starting combination therapy. For all study patients (n = 87), diastolic blood pressure reduction was greater in patients receiving ARB/CCB treatment. However, in the 37 patients with a baseline estimated daily salt intake greater than 10 g and baseline systolic blood pressure (SBP) ranging from 150 to 200 mm Hg, SBP was lower (P < 0.05) and SBP reduction was greater (P < 0.05) 4 weeks after starting combination therapy in those receiving ARB/TZ treatment. In the 31 patients whose estimated daily salt intake increased at 12 weeks compared with baseline, SBP at 12 weeks was lower in those receiving ARB/TZ treatment (P < 0.05).. Estimated daily salt intake is a useful tool for guiding antihypertensive therapy and should be measured repeatedly during the therapeutic course.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Diuretics; Drug Combinations; Female; Heart Rate; Humans; Hydrochlorothiazide; Hypertension; Male; Metabolic Syndrome; Middle Aged; Potassium; Prospective Studies; Sodium; Sodium Chloride, Dietary; Tetrazoles; Treatment Outcome; Valine; Valsartan

Obesity is a major global health concern and is associated with hypertension. However, there is a lack of studies evaluating the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy. To evaluate this effectiveness and its association with obese categories, we performed a prespecified subanalysis and a post hoc analysis of patients from China status II study. In this subanalysis, 11,289 and 11,182 patients stratified by body mass index (BMI) and waist circumference (WC), respectively, were included. Significant mean sitting systolic and diastolic blood pressure (BP) reductions from baseline were observed at week 8 across all BMI and WC subgroups (P < 0.001). The percentages of patients achieving BP control were 65.2%, 62.8%, and 64.5% (men 64.5% and women 64.4%) in the overweight, obesity, and abdominal obesity subgroups, respectively. The positive association between BP control and obese categories could only be found in subgroups stratified by BMI other than WC. Our study demonstrated the effectiveness of valsartan/amlodipine single-pill combination in Chinese hypertensive patients with excess body weight uncontrolled by monotherapy, and its effectiveness was better associated with BMI than WC.

Topics: Adolescent; Adult; Aged; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Body Mass Index; Calcium Channel Blockers; China; Female; Humans; Hypertension; Male; Middle Aged; Overweight; Prospective Studies; Time Factors; Treatment Outcome; Waist Circumference; Young Adult

To compare the effect of adding canrenone or hydrochlorothiazide (HCTZ) to valsartan/amlodipine combination on urinary albumin excretion (UAE) in microalbuminuric type 2 diabetic hypertensives.. After a 2-week placebo period and after 4 weeks of valsartan 160 mg plus amlodipine 5 mg combination, 120 patients whose blood pressure (BP) was not controlled (> 130/80 mmHg) were randomized to canrenone 25 mg or HCTZ 12.5 mg in addition to the previous therapy for 24 weeks. After the first 6 weeks of triple therapy, canrenone or HCTZ doses were doubled in the patients whose BP was yet uncontrolled. At the end of each period (placebo, dual combination and triple combination therapy), clinic and ambulatory BP measurements were recorded and 24 h UAE was evaluated.. Both triple combinations produced greater clinical and ambulatory BP reduction than dual therapy, with no difference between the two groups. UAE was reduced by both regimens, but the decrease associated with canrenone add-on therapy was more pronounced. At week 24, UAE decreased by 45.3% in the canrenone group and by 20.3% in the HCTZ group (p < 0.01).. These findings indicate that, despite similar BP-lowering effect, the addition of canrenone to valsartan/amlodipine combination was more effective in reducing UAE than HCTZ addition.

Topics: Adult; Aged; Albuminuria; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Canrenone; Diabetes Mellitus, Type 2; Diuretics; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Prospective Studies; Tetrazoles

Current hypertension guidelines recommend single-pill combinations because they not only improve convenience and compliance to therapy and thus blood pressure (BP) control, but also reduce health-care costs. This study compared the efficacy and safety of valsartan/amlodipine single-pill combination with nifedipine gastrointestinal therapeutic system (GITS) in Chinese patients with hypertension who were inadequately controlled with monotherapy.. In this multicenter, open-label, active-controlled, parallel-group study, 564 patients with hypertension not adequately controlled by prior monotherapy were randomized to receive valsartan/amlodipine 80/5 mg or nifedipine GITS 30 mg once daily for 12 weeks.. In the intention-to-treat analysis (n = 540), valsartan/amlodipine (n = 272) showed a least-square mean reduction of -16.6 versus -10.8 mmHg by nifedipine GITS (n = 268; mean between-treatment difference: -5.8 mmHg; P < 0.0001) from baseline to week 12. The corresponding results for mean sitting diastolic BP were -8.6 and -4.6 mmHg, respectively (difference: -4.0 mmHg; P < 0.0001). The percentage of patients achieving the BP target (<140/90 or <130/80 mmHg in the absence or presence of diabetes mellitus, respectively) was significantly higher with valsartan/amlodipine (79.0%) versus nifedipine GITS (57.4%; P < 0.0001). The overall incidence rate of adverse events was lower with valsartan/amlodipine (19.2%) than with nifedipine GITS (29.4%; P = 0.004).. The valsartan/amlodipine 80/5 mg single-pill combination is well tolerated and more effective than nifedipine GITS 30 mg for BP control in Chinese patients with hypertension.

Topics: Adult; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asian People; Delayed-Action Preparations; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Tetrazoles; Treatment Outcome

A 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 5/160 mg SPC for the treatment of hypertension in predominantly Chinese patients not adequately controlled on valsartan 160 mg alone.. In 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 5/160 mg SPC or valsartan 160 mg once daily for 8 weeks.. The 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<140/90 mm Hg) with combination therapy (61.3%) versus monotherapy (39.3%; p<0.0001). Both treatments were well tolerated.. Amlodipine/valsartan 5/160 mg 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 160 mg monotherapy.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asian People; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Valine; Valsartan

A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p <0.05). The adjusted hazard ratio for the primary end point in the highest in-trial HR heart rate quintile versus the lowest quintile was 1.53 (95% confidence interval 1.26 to 1.85). The incidence of primary end points in the highest in-trial HR group compared to the pooled 4 lower quintiles was 53% greater in patients with well-controlled blood pressure (p <0.001) and 34% greater in those with uncontrolled blood pressure (p = 0.002). In conclusion, an increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension. This effect was not modified by good blood pressure control. It is not yet known whether a therapeutic reduction of HR would improve cardiovascular prognosis.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Hypertension; Incidence; Male; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Factors; Survival Rate; Tachycardia; Tetrazoles; Time Factors; Treatment Outcome

The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.. Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E). To attain blood pressure <140/<90 mmHg during six months, the doses of bisoprolol and amlodipine should be increased to 10 mg/day with the possible addition of up to 2 g/day α-methyldopa.. At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg, 19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n = 49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory. Only two patients dropped out of the study.. NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents. NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa are feasible.

Topics: Administration, Oral; Adult; Africa South of the Sahara; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Bisoprolol; Black People; Blood Pressure; Diuretics; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Patient Dropouts; Patient Selection; Risk Factors; Tablets; Tetrazoles; Time Factors; Treatment Outcome

The steady-state pharmacokinetic (PK) interaction potential between amlodipine (10 mg), valsartan (320 mg), and hydrochlorothiazide (HCTZ; 25 mg) was evaluated in patients with hypertension in a multicenter, multiple-dose, open-label, 4-cohort, parallel-group study. Eligible patients were randomly allocated to the dual combination of valsartan + HCTZ, amlodipine + valsartan, or amlodipine + HCTZ and nonrandomly allotted to amlodipine + valsartan + HCTZ triple combination treatment. After 6 days of treatment with a half-maximal dose of different combinations, patients were up-titrated to the maximal drug doses from day 7 through day 17. PK parameters of corresponding analytes from the triple- and dual-treatment groups were estimated on day 17 and compared. Safety and tolerability of all treatments was assessed. The C ( ssmax ) and AUC(0-τ) values of amlodipine or HCTZ remained unaffected when administered with valsartan + HCTZ or valsartan + amlodipine, respectively. On the other hand, valsartan exposure increased by 10% to 25% when coadministered with HCTZ and amlodipine, which is not considered clinically relevant. In conclusion, there were no clinically relevant PK interactions with amlodipine, valsartan, and HCTZ triple combination compared with the corresponding dual combinations. All treatments were safe and well tolerated.

Topics: Adolescent; Adult; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Tetrazoles; Valine; Valsartan

This study compared the effects of morning and evening dosing of amlodipine/valsartan combination on 24-h blood pressure (BP) in patients uncontrolled by amlodipine (5 mg).. This was a multicenter study that used a prospective, randomized, open-label, blinded endpoint design. Patients with essential hypertension, who's ambulatory BP was uncontrolled after 4 weeks on amlodipine (5 mg) were randomized to receive amlodipine/valsartan (5/160 mg) for 8 weeks in the morning or evening (n=231, 232, respectively), with optional uptitration up to 10/160 mg after 4 weeks if the office BP was uncontrolled. A 30-h ambulatory BP measurement was taken at randomization and at the end of the study.. Morning and evening dosing with amlodipine/valsartan had equivalent effects on systolic BP (mean 24 h, daytime, night-time, and 24-30 h) and diastolic BP (mean 24 h, daytime, night-time, and 24-30 h). There was a small difference in the night-time diastolic BP (-4.92 vs.-6.20 mmHg; P=0.02) and a slight but nonsignificant trend for higher BP reduction during daytime for morning intake and during night-time for evening intake. BP control rates based on 24-h ambulatory BP measurement values (<120/80 mmHg) were similar between morning and evening dosing (47 vs. 45%).. These results indicate that, in patients with BP uncontrolled by amlodipine (5 mg), morning and evening treatment with amlodipine/valsartan combination have similar effects on circadian BP, especially when 24-h mean values are considered.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Chronotherapy; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles

Ambulatory blood pressure monitoring (ABPM) has greater predictive value than office blood pressure (BP) with respect to hypertension-related target-organ damage and morbidity. ABPM in a subset of 80 patients from the Exforge Target Achievement trial (N=728) was used to compare the efficacy of intensive-treatment and moderate-treatment regimens of amlodipine/valsartan, and to determine whether treatment differences could be better assessed with ABPM than with office or home BP. Home BP was measured on the morning of clinic visits to minimize differences that timing might have on home versus office BP measures.. A 12-week randomized, double-blind study in which hypertensive patients earlier uncontrolled (mean sitting systolic BP≥150 and <200 mmHg) on angiotensin receptor blocker monotherapy (other than valsartan) after 28 days or more (N=728) were randomized to amlodipine/valsartan treatment [10/320 mg (intensive) or 5/160 mg (moderate)]. Treatment-naive patients (in previous 28 days) or patients who failed on a nonangiotensin receptor blocker agent underwent a 28-day run-in period with a 20-mg or 40-mg dose of olmesartan, respectively.. Significantly greater 24-h ABP reductions from baseline to week 4 (primary time point) were observed with intensive versus moderate treatment (least-square mean systolic/diastolic BP reduction of -16.2/-10.1 vs. -9.5/-6.5 mmHg; P=0.0024/P=0.010 for least-square mean difference). Similarly, a significantly greater proportion of patients receiving an intensive treatment achieved ambulatory BP goal (<130/80 mmHg) at week 4 than did those receiving a moderate treatment (P=0.040). Treatment-group differences did not reach statistical significance for these end points when measured by office and home BP.. In this first randomized trial evaluating the effects of intensive versus moderate dosing of the combination of amlodipine/valsartan, our data suggest that ABPM was a better method for assessing between-treatment differences than clinic or home BP recordings, although measurement of home BP as a single recording was a limitation of our trial.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Self Care; Tetrazoles

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.

Topics: Adolescent; Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Treatment Outcome; Young Adult

The strategy of initiating hypertension treatment with combination versus single-drug therapy was formally tested in a prospective, double-blind, parallel-group trial in blacks with stage 2 hypertension (mean sitting systolic BP (MSSBP) >or=160 and <200 mm Hg). Participants were randomized equally to amlodipine/valsartan (A/V) (n=286) or amlodipine (A) monotherapy (n=286). After 2 weeks, there was forced titration of A/V 5/160 mg to A/V 10/160 mg and of A 5 to A 10 mg followed by 10 additional weeks of treatment. If SBP was >or=130 mm Hg at week 4, the protocol allowed optional titration of A/V to the 10/320 mg dose and, at week 8, hydrochlorothiazide 12.5 mg was optionally added to both A/V and A if SBP >or=130 mm Hg. Amlodipine/valsartan at week 8 lowered MSSBP last observation carried forward significantly>A (33.3 vs 26.6 mm Hg, P<0.0001). Lowering of MSSBP with A/V significantly exceeded that of A in several specified subgroups-the elderly (>or=65 years), isolated systolic hypertension, and those with body mass index (BMI) >or=30 kg/m(2). More patients treated with A/V than A achieved BP control (<140/90 mm Hg) both at weeks 8 (49.8 vs 30.2%; P<0.0001) and 12 (57.2 vs 35.9%; P<0.0001). Both treatment regimens were well tolerated. In conclusion, the strategy of initiating combination antihypertensive drug therapy in blacks with stage 2 hypertension with amlodipine /valsartan achieves greater and quicker reductions in BP as well as significantly higher BP control rates than starting treatment with amlodipine monotherapy.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Black People; Double-Blind Method; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Tetrazoles

Both diastolic dysfunction and increased vascular stiffness represent important measures of target-organ damage in hypertension. Whether intensive blood pressure (BP) control can further improve these measures remains unknown.. EXCEED is a prospective, randomized open-label blinded endpoint trial (PROBE) design, aiming to test the hypothesis that more aggressive BP lowering would result in greater improvement in diastolic function among patients with stage II hypertension, evidence of diastolic dysfunction and preserved systolic function (EF > or = 50%). Patients were randomized to one of two treatment strategies, targeting systolic blood pressure (SBP) <140 mmHg or <130 mmHg using a combination of amlodipine/valsartan with additional antihypertensive medications as needed to achieve the prescribed targets. Diastolic function was assessed using Doppler tissue imaging of early diastolic velocity of lateral mitral annulus (E'), while vascular stiffness was assessed using radial augmentation index (RAI) derived from radial artery tonometry. The study primary endpoint will be the change in lateral E' velocity between baseline and 24 weeks.. Two hundred and twenty eight patients (50% female) with mean age of (59.6+/-9.7) years and mean BP of (162+/-14/92+/-13 mmHg) were randomized equally to either treatment strategies. Left ventricular hypertrophy was present among <4% of the enrolled patients. Inspite diastolic function was impaired, baseline lateral E' velocity (7.6+/-1.2 cm/s) was not related to baseline SBP while baseline RAI was weakly related (r = 0.2, p <0.01) to SBP even after adjustment to age, gender and heart rate.. EXCEED will determine whether intensive BP lowering will further improve diastolic dysfunction and vascular stiffness among patients with uncontrolled hypertension.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Diastole; Drug Combinations; Echocardiography, Doppler; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Manometry; Middle Aged; Prospective Studies; Radial Artery; Severity of Illness Index; Tetrazoles

This study aimed to compare the Hamilton anxiety rating/Hamilton depression rating (HAMA/HAMD) scale scores and blood pressure (BP) goal achievement associated with the use of valsartan-amlodipine single-pill combinations (SPCs) versus valsartan and amlodipine combination in adult hypertensive patients.A total of 476 hypertensive patients were randomly assigned into the SPC (valsartan-amlodipine) and control (valsartan and amlodipine combination) groups. All patients had an uncontrolled BP (160-179/100-109 mm Hg). BP goal was <140/90 mm Hg. Cox proportional hazards regression analysis was used to analyze the likelihood of HAMA/HAMD scales, SPCs, control group, and daily dosage number. Kaplan-Meier analysis was used to estimate the rates of BP goal achievement over time among the 2 groups.A total of 476 patients were included in the study, and 439 patients completed the follow-up and received the index drug therapy. There was a significant difference in BP between the 2 groups on days 28, 42, and 56. Patients who received SPCs had a significantly higher rate of BP goal achievement over time (P = .000). The average HAMD scores in the SPC and control groups were 5.54 and 5.49 and 6.06 and 6.21 on days 28 and 56, respectively. The average HAMA scores in the SPC and control groups were 7.41 and 7.13 and 7.90 and 8.01 on days 28 and 56, respectively. The means of HAMD and HAMA scores were 5.826 and 7.614, respectively. The higher the HAMA/HAMD scores, the lower was the BP goal achievement. The number of drugs taken by the patients was associated with the HAMA and HAMD scores. There was no significant difference between HAMA scores of patients taking 1 tablet daily (7.22 ± 1.885) and those taking two-tablets daily (7.38 ± 1.953) (P = .408). However, when these scores were compared to those of patients taking 4 tablets daily (8.08 ± 2.285), a significant difference was observed (P = .000, P = .000).Hypertensive patients treated with valsartan-amlodipine SPCs were significantly more likely to achieve BP goal and have lesser HAMA/HAMD scores compared to patients treated with valsartan and amlodipine combination.

Topics: Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Anxiety; Blood Pressure; Depression; Female; Humans; Hypertension; Male; Middle Aged; Retrospective Studies

Clinical researchers found that Amlodipine besylate and Valsartan (ABVS) can effectively treat mild to moderate hypertension (MMH). However, no study has systematically investigated its efficacy and safety for patients with MMH. Thus, present study will systematically assess the efficacy and safety of ABVS for patients with MMH.. MEDICINE, Cochrane Library, EMBASE, Ovid, PsycINFO, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure will be searched for literatures related to the topic from inception to the present without language limitations. All randomized controlled trials that assess the efficacy and safety of ABVS for patients with MMH will be considered for inclusion. Two researchers will independently select study, extract data, and assess risk of bias for all eligible studies.. The primary outcome includes the change of seated diastolic blood pressure. The secondary outcomes consist of the change of seated systolic blood pressure, health-related quality of life, and the tolerability.. The results of this study will summarize the latest evidence on ABVS for the treatment of MMH.. This study does not need ethical approval, because it will not use individual data. The results of this study are expected to be published at peer-reviewed journals.. PROSPERO CRD42019133123.

Topics: Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Humans; Hypertension; Randomized Controlled Trials as Topic; Research Design; Severity of Illness Index; Systematic Reviews as Topic

High blood pressure (BP) is a major risk factor associated with stroke in China. This is a subanalysis of patients from the China Status II study, aimed to evaluate the effectiveness and safety of valsartan/amlodipine (Val/Aml) single-pill combination (SPC) in hypertensive patients with different stroke subtypes (hemorrhagic, ischemic, or mixed).China Status II was a multicenter, postmarketing, prospective observational study in hypertensive patients uncontrolled on monotherapy. The study was an 8-week open-label treatment period with 2 4-week follow-ups. Change in BP from baseline to weeks 4 and 8, BP control rate, and response rate at weeks 4 and 8, and safety of 8-week treatment with Val/Aml (80/5 mg) were assessed.A total of 565 hypertensive patients with different types of stroke were analyzed in this China Status II substudy. Significant mean sitting systolic/diastolic BP (MSSBP/MSDBP) reductions from baseline to week 8 were observed across all stroke subtypes (P < .0001). At week 8, percentages of patients achieving MSSBP response (≥20 mm Hg reduction from baseline) were 76.3%, 74.4%, and 85.7%, MSDBP response (≥10 mm Hg reduction from baseline) were 67.8%, 65.9%, and 64.3%, and BP control (<140/90 mm Hg) were 74.6%, 80.5%, and 92.9%, in the hemorrhagic, ischemic, and mixed stroke subgroups, respectively. Adverse events (AEs) and serious AEs were reported in 5 patients (1%) and 1 patient (0.2%), respectively, in the ischemic stroke subgroup, while no AEs were reported in hemorrhagic and mixed stroke subgroups.Val/Aml SPC was effective in hypertensive patients with different stroke subtypes and was well tolerated.

Topics: Aged; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; China; Comorbidity; Female; Follow-Up Studies; Humans; Hypertension; Male; Prospective Studies; Stroke; Treatment Outcome

This retrospective claims database analysis compared two strategies of hypertension treatment in outpatient, emergency, and inpatient departments: a fixed-dose combination (FDC) of amlodipine/valsartan vs free combinations of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) (ARB+CCB group). After a mean follow-up of 15.2 months, the FDC group had significantly lower total healthcare costs (US $1844 vs US $2158; P<.001) and hospitalization rates (14.57% vs 18.43%; P<.001), a higher proportion of days covered (80.35% vs 72.57%; P<.001), and better persistence (266 vs 225 days; P<.001) compared with the ARB+CCB group. The FDC group also had a better major adverse cardiovascular event (MACE)-free survival (hazard ratio, 0.83; 95% confidence interval, 0.73-0.94; P=.003) and decreased rates of heart failure (2.12% vs 3.26%; P<.001), malignant dysrhythmia (0.18% vs 0.42%; P=.021), and percutaneous coronary intervention (0.76% vs 1.26%; P=.015). Compared with free combinations of ARB+CCB, an FDC of amlodipine/valsartan improved MACE-free survival and medication compliance and decreased total healthcare costs and hospitalization rates in hypertensive patients.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin Receptor Antagonists; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Cohort Studies; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Health Care Costs; Hospitalization; Humans; Hypertension; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Retrospective Studies; Tetrazoles; Treatment Outcome

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Female; Humans; Hypertension; Male; Perindopril

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Female; Humans; Hypertension; Male; Perindopril

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Medication Adherence; Tetrazoles; Valine

The aim of the work was to study dynamics of daily arterial pressure profile during combined antihypertensive therapy starting from calcium and angiotensin II antagonists (amlodipine-valsartan) in Far North employees suffering arterial hypertension engaged on different working schedules. A total of 137 patients with grade I-III AH were divided into 2 groups. Those in group 1 worked day shifts (n=70) and the remaining ones worked night shifts (group 2). 129 patients completed the course of therapy. The final mean daily doses of amlodipine-valsartan were 8.2 ± 1.1/144.8 1.8 and 9.4 ± 1.6/197.8 ± 3.5 mg in groups I and 2 respectively. AP monitoring was performed before, 4 weeks and 6 months after therapy. Six months after the onset of amlodipine-valsartan therapy 97.2 and 97.6% of the patients in groups 1 and 2 respectively showed the target AP level and normalization of daily AP profile. Daily variability of AP in group 2 (excepting night-time variability) was also normal. Morning AP dynamics markedly improved in both groups. Most patients demonstrated excellent compliance with therapy due to its high efficacy and good tolerability.

Topics: Adult; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Arctic Regions; Blood Pressure; Circadian Rhythm; Drug Combinations; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Work Schedule Tolerance

EXCITE (clinical EXperienCe of amlodIpine and valsarTan in hypErtension) evaluated the real-life effectiveness, safety, and tolerability of single-pill combinations (SPCs) of amlodipine/valsartan (Aml/Val) and amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) in patients with hypertension from 13 countries in the Middle East and Asia. Here, we present data from Pakistan.. This was a 26-week observational, multicenter, prospective, open-label study. At week 26, change from baseline in mean sitting systolic (msSBP) and diastolic blood pressure (msDBP) and the proportion of patients achieving BP goal (SBP/DBP <140/90 mmHg; <130/80 mmHg in patients with diabetes) and response rates (SBP <140 mmHg [130 mmHg for patients with diabetes] or reduction of ≥20 mmHg; DBP <90 mmHg [80 mmHg for patients with diabetes] or reduction of ≥10 mmHg), were evaluated. Incidence of adverse events (AEs) and serious AEs (SAEs) was recorded as safety variables. Subjective assessment of effectiveness, compliance and tolerability was done by the physician.. A total of 500 patients with hypertension (mean age of 48 years) were prescribed Aml/Val (n = 471, 94%) or Aml/Val/HCTZ (n = 29, 6%); 439 (87.8%) patients completed the study. At week 26, the mean BP decreased from 153.4/91.1 mmHg at baseline to 128.9/78.4 mmHg in the Aml/Val cohort (-24.5/-12.7 mmHg; p < 0.0001) and from 171.6/99.3 mmHg at baseline to 127.7/77.4 mmHg (-43.9/-21.9 mmHg; p < 0.0001) in the Aml/Val/HCTZ cohort. BP goals were achieved by 57% and 55.2% of patients in the Aml/Val and Aml/Val/HCTZ cohorts, respectively. A total of 40 (8%) patients reported at least one AE during the study period. Most common AEs included nausea (1.6%), headache (1.2%), vomiting (1.2%), and edema (1.2%). Most patients in Aml/Val cohort and all patients in Aml/Val/HCTZ cohort rated the effectiveness, compliance and tolerability as 'good' or 'very good'.. Aml/Val with or without HCTZ in a SPC was effective and well-tolerated for BP reduction in this cohort of patients with hypertension from Pakistan.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Drug Combinations; Female; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Prospective Studies; Tetrazoles

Single-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.. This 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.. A 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.. This 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.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asian People; Blood Pressure; China; Double-Blind Method; Drug Combinations; Edema; Female; Headache; Humans; Hypertension; Male; Middle Aged; Prospective Studies

The EXCITE (clinical EXperienCe of amlodIpine and valsarTan in hypErtension) study was designed to evaluate the effectiveness, tolerability and adherence of amlodipine/valsartan (Aml/Val) and amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCT) single-pill combination therapies in patients with hypertension from the Middle East and Asia studied in routine clinical practice.. This was a prospective, multinational, non-interventional real-world study in which adult patients with hypertension receiving treatment with Aml/Val or Aml/Val/HCT as part of routine clinical practice were observed for a period of 26 ± 8 weeks. Dosages in milligrams (prescribed in accordance with local prescribing information) were Aml/Val: 5/80, 5/160, 10/160, 5/320 or 10/320; Aml/Val/HCT: 5/160/12.5, 10/160/12.5, 5/160/25, 10/160/25 or 10/320/25.. Treatment effectiveness was assessed by change from baseline in mean sitting systolic blood pressure (BP)/diastolic BP (msSBP/msDBP), and the proportion of patients achieving therapeutic goal and BP response. Safety and tolerability were also assessed.. Of 9794 patients analyzed (mean age 53.2 years), 8603 received Aml/Val and 1191 Aml/Val/HCT. At study end (26 ± 8 weeks), overall msSBP (95% confidence interval [CI]) reductions from baseline were -31.0 (-31.42, -30.67) mmHg for Aml/Val and -36.6 (-37.61, -35.50) mmHg for Aml/Val/HCT; msDBP reductions from baseline were -16.6 (-16.79, -16.34) mmHg for Aml/Val and -17.8 (-18.41, -17.22) mmHg for Aml/Val/HCT. Meaningful reductions in BP from baseline were also consistently observed across all Aml/Val dosages and severities of hypertension. Adverse events (AEs) were reported in 11.2% and 6.1% of patients in the Aml/Val and Aml/Val/HCT groups, respectively. Most frequently reported AEs in the Aml/Val and Aml/Val/HCT groups were edema and peripheral edema. While the observational design of the study has inherent limitations, it enables collection of real-world data from a more naturalistic clinical setting, and the large size of the study increases the robustness of the study, as indicated by the narrow confidence intervals for the main study outcomes.. The EXCITE study provides evidence that Aml/Val and Aml/Val/HCT provide clinically meaningful BP reductions and are well tolerated in a large multi-ethnic hypertensive population studied in routine clinical practice.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Asia; Blood Pressure; Double-Blind Method; Drug Combinations; Drug Monitoring; Female; Heart Failure; Humans; Hydrochlorothiazide; Hypertension; Male; Middle Aged; Prospective Studies; Research Design; Tetrazoles; Treatment Outcome

Fixed-dose combination therapy reduces pill burden and may, therefore, improve medication adherence and health outcomes. This study compared adherence to and persistence with single-, double-, and triple-pill treatment regimens among hypertensive patients in a US clinical practice setting.. Adults with hypertension treated with three anti-hypertensive medications were identified. Index date was the first occurrence of a single-, double-, or triple-pill regimen with olmesartan or valsartan plus amlodipine and hydrochlorothiazide from July 2010 to September 2011. Patients were followed for 12 months to assess adherence (proportion of days covered [PDC] ≥ 80%) and time to discontinuation (medication gap ≥ 60 days) of the index regimen. Multivariate regression models were used to compare adjusted outcomes.. The number of prescribed pills in the index regimen was monotonically related to adherence with 55.3%, 40.4% and 32.6% of patients having PDC ≥ 80% in the single-, double- and triple-pill cohorts, respectively. In adjusted analysis, patients in the double- (odds ratio [OR]: 0.45; 95% confidence interval [CI]: 0.42-0.48) and triple-pill (OR: 0.26; 95% CI: 0.22-0.30) cohorts were less likely to be adherent to their index regimens than those in the single-pill cohort. Double-pill (hazard ratio [HR]: 1.89; 95% CI: 1.74-2.06) and triple-pill patients (HR: 2.49; 95% CI: 2.14-2.88) were more likely to discontinue treatment than single-pill patients.. Greater pill burden was directly and significantly associated with decreased adherence and persistence with antihypertensive therapies in real-practice settings. Use of fixed-dose combinations that reduce pill burden could help patients to continue treatment and may result in improved clinical outcomes. Typical of observational studies, the potential for residual confounding of adherence estimates remains due to lack of randomization of treatment groups.

Topics: Adult; Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Hypertension; Imidazoles; Male; Medication Adherence; Middle Aged; Odds Ratio; Olmesartan Medoxomil; Retrospective Studies; Tetrazoles

To collect information on the efficiency and safety of a fixed-dose combination of amlodipine/valsartan in patients who failed to achieve blood pressure (BP) control in the use of the combination of an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and a thiazide/thiazide-like diuretic.. During routine clinical practice, the 12-week observation program covered 8594 hypertensive patients receiving a fixed-dose combination of amlodipine/valsartan 5/160, 10/160 mg (exforge, Novartis Pharma) with/without a diuretic. The inclusion criteria were 18 years of age or older; systolic BP > OR = 140 mm Hg and/or diastolic BP > or = 90 mm Hg) at the first visit; failure to achieve BP (> or = 140/90 mm Hg) control in the use of the combination of an ACE inhibitor or an ARB and a thiazide/ thiazide-like diuretic; a patient's consent to participate in the program. The exclusion criteria were, besides the contraindications given in the drug use instruction, absent. Amlodipine/valsartan 5/160 or 10/160 mg were used after the previous ineffective therapy was discontinued. The patients visited their physician's office every 4 weeks.. The patients' baseline BP was 169.3/99.9 mm Hg. The risk of cardiovascular events was assessed as high in 38% of the patients and as very high in 43.1%. The previous therapy included thiazide or thiazide-like diuretics (92%), an ACE inhibitor (78.5%), an ARB (23.2%), beta-adrenoblockers (38.6%), calcium antagonists (23.1%), and other medications (25.5%). In the entire group, BP decreased from 169.3 +/- 15.6/99.9 +/- 9.3 to 129.1 +/- 9.1/80.3 +/- 6.4 mm Hg at the fourth visit. BP reductions at 12 weeks were 40.1 +/- 14.9/19.6 +/- 9.5 mm Hg. The therapy was effective in different treatment subgroups. At baseline, the majority of patients had grades 2 (53.1%) and 3 (35.4%) hypertension. At 12 weeks, 74% of the patients were found to have normal or high normal BP. Grade 3 hypertension was preserved only in 0.2% of the patients by the end of the program. BP goals were achieved in 79.5% of the patients. The therapy was well tolerated by the patients. Adverse reactions were observed in 3.1% of the patients and required treatment discontinuation in 0.5%. The most common side effect was peripheral edemas (1.4%).. In the observation program AESCULAP using the fixed-dose combination of amlodipine/valsartan as different dosage regimens (5/160 and 10/160 mg) and/or a diuretic, there was a marked antihypertensive effect in different subgroups of patients with previously uncontrolled hypertension and the BP goals being achieved in 79.5% of cases. Most patients tolerated amlodipine/ valsartan well and showed high compliance with the prescribed therapy. The rate of side effects in the AECULAP program was not greater than that (3.1%) in the earlier trials.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Diuretics; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Observational Studies as Topic; Tetrazoles; Treatment Outcome

As several international guidelines on hypertension have now recommended, single-pill/fixed-dose combination antihypertensive therapies may be particularly beneficial as first-line therapy in high-risk patients, in whom more rapid and pronounced blood pressure (BP) control is desired. Upon the single-pill combination of amlodipine and valsartan becoming available, the authors conducted this international, observational study to evaluate its efficacy and safety in a real-life practice setting.. This prospective, open-label, postmarketing surveillance study enrolled adults with arterial hypertension (systolic BP >140 mmHg and/or diastolic BP >90 mmHg) who were prescribed antihypertensive therapy with single-pill combination amlodipine/valsartan 5/80, 5/160, or 10/160 mg once daily. Patients were observed over a 3-month period (12 weeks) with approximately monthly intervals between clinic visits.. A total of 8336 patients completed all study visits and were included in the efficacy analysis. Mean age was 54.7 years and 83.4% of patients had received prior antihypertensive therapy. BP reductions were dose related. Overall, mean BP was reduced from 165.0/99.3 mmHg at baseline to 128.7/80.4 mmHg at 12 weeks (36.3/18.9 mmHg; P<0.0001). The magnitude of BP reduction rose with increasing severity of baseline BP. Control of BP (<140/90 mmHg) was achieved in 77.7% of patients. Efficacy was consistent in subgroups of patients with comorbidities and regardless of whether patients were previously treated with monotherapy or combination therapy. Adverse events were reported in 5.3% of patients. The incidence of edema declined from 10.4% at baseline to 8.5% at study end.. Single-pill combination amlodipine/valsartan safely and effectively reduced BP across all hypertension grades and allowed the vast majority of patients to achieve BP goals.

Topics: Adult; Aged; Aged, 80 and over; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Drug Combinations; Edema; Female; Humans; Hypertension; Male; Middle Aged; Prospective Studies; Tetrazoles; Treatment Outcome

In addition to high blood pressure (BP), BP variability has recently also been shown to increase cardiovascular events. The purpose of this study was to compare the effect of a fixed-dose combinations (FDCs) of valsartan/amlodipine and a valsartan- and amlodipine-free drug combination on 24-h BPV. A total of 85 patients aged 18 or older and with no exclusion criteria were enrolled; of the 85 patients, 43 used the FDCs valsartan/amlodipine (160/10 mg) and 42 used a free drug combination of valsartan 160 mg and amlodipine 10 mg. Twenty-four hour ambulatory BP monitoring (ABPM) was performed after office BP measurements. Mean hourly BP, all-day BP reduction, trough/peak (T/P) ratio and Smoothness Index (SI) were calculated from the 24-h ABPM data. These were calculated separately for all-day, daytime, nighttime and early morning periods. The hourly mean diastolic BP (DBP) at 0800 hours in the FDCs group was significantly higher compared with the free drug combination group in the 24-h BP chronogram (P=0.041). Decreases in the all-day, daytime, nighttime and early morning systolic BP (SBP) and DBP in patients using a free drug combination were significantly greater compared with the FDC group. The SI and T/P ratio of the all-day, daytime and nighttime systolic and diastolic were also significantly higher compared with the FDC group. In addition, nighttime DBP reduction and the SI of DBP were lower in the diabetic patients. A free drug combination of amlodipine and valsartan provides more effective and smooth SBP and DSP control compared with FDCs.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Circadian Rhythm; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hypertension; Male; Middle Aged; Tetrazoles; Time Factors; Valine; Valsartan

Both patient- and physician-related factors have been shown to explain variability in the outcomes of antihypertensive treatment. Total cardiovascular risk (TCVR) is increasingly used as a determinant of treatment effectiveness but has also been proposed as a treatment outcome. To our knowledge, no studies have reported how antihypertensive treatment impacts blood pressure and TCVR outcomes.. To examine in patients treated with a regimen including single-pill combinations (SPCs) of amlodipine/valsartan (1) blood pressure (BP) reduction and control, total cardiovascular risk (TCVR) change, and TCVR reduction of 1 class or more; (2) hierarchical patient- and physician-level determinants of these outcomes; and (3) predictors of uncontrolled BP and improved TCVR classification.. A prospective (90 days), multicenter, multilevel pharmacoepidemiologic study was conducted in 3546 patients with hypertension treated with SPC amlodipine/valsartan by 698 general practitioners. Statistical analysis included hierarchical linear and logistic modeling of BP and TCVR outcomes.. Mean (SD) systolic BP (SBP) reductions were 20.1 (15.5) mm Hg and diastolic BP (DBP) reductions were 9.8 (10.3) mm Hg, with higher reductions among high-risk patients. SBP, DBP, and SBP/DBP control rates were 33.3%, 45.3%, and 25.5%, respectively, with lower rates among high-risk patients. Mean TCVR improvement was a reduction of 0.73 (0.96) classes (-4 [best] to +4 [worst]), with higher reductions for high-risk patients; 58.2% of patients achieved a TCVR reduction of 1 or more classes, with lower percentages for high-risk patients. Twenty-two percent of systolic variability and 26% of diastolic variability in 90-day BP values were attributable to a physician class effect, as was 16% of TCVR change.. Regimens that include SPC amlodipine/valsartan formulations are effective in reducing BP and TCVR in a real-world observational setting. Hierarchical modeling identified patient- and physician-related determinants of BP values and TCVR change, as well as independent predictors of uncontrolled BP and reduced TCVR. TCVR is a scientifically feasible and clinically relevant effectiveness outcome of antihypertensive treatment.

Topics: Aged; Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Blood Pressure; Cardiovascular Diseases; Drug Combinations; Female; Humans; Hypertension; Linear Models; Logistic Models; Male; Middle Aged; Pharmacoepidemiology; Prospective Studies; Risk Factors; Tetrazoles

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Antihypertensive Agents; Drug Combinations; Humans; Hydrochlorothiazide; Hypertension; Medication Adherence; Myocardial Infarction; Stroke; Tetrazoles; Valine

Topics: Amlodipine; Amlodipine, Valsartan Drug Combination; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Calcium Channel Blockers; Clinical Trials as Topic; Diuretics; Drug Combinations; Drug Costs; Humans; Hydrochlorothiazide; Hypertension; Tetrazoles; Valine; Valsartan