Meta-analysis of three observational studies of amlodipine/valsartan in hypertensive patients with additional risk factors

September 2013, Vol. 22, No. S1 , Pages 11-21 (doi:10.3109/08037051.2013.793891) Siegfried Eckert , Siegfried B. Freytag , Alfons Mller & Sven H. G. Klebs
1 2 3 3

Abstract
Objectives. In this study, the effectiveness of amlodipine/valsartan single-pill combination was assessed in hypertensive patients with diabetes, metabolic risk or overweight. Methods. Data from 12,265 patients treated with amlodipine/valsartan from three studies were analyzed in a meta-analysis. These studies focused on (i) non-diabetic hypertensive patients suffering from abdominal obesity; (ii) hypertensive patients with at least one metabolic risk factor; and (iii) hypertensive patients with type 2 diabetes mellitus. The observation periods were 16 weeks for the first two and 24 weeks for the latter cohort. Results. At start of observation, the mean blood pressure was 162.3 mmHg (systolic) and 93.5 mmHg (diastolic). A total of 7.4% of patients were aged 80 years. At end of the observation, a normalized blood pressure was present in 38.8% of patients. No appreciable differences in blood pressure reduction were evident between the study groups. In both age subgroups (< 80 years and 80 years) blood pressure reduction was comparable. Tolerability was assessed by treating physicians as very good (69.3%) and good (27.3%). Conclusions. In daily practice, treatment of hypertensive patients with additional risk factors with amlodipine/valsartan single-pill combinations is well tolerated and associated with effective reduction of blood pressure.

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension
August 2013, Vol. 29, No. 8 , Pages 901-910 (doi:10.1185/03007995.2013.803057)

Abstract
Objective:
To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320mg, and hydrochlorothiazide (HCTZ) 25mg 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 2 Hispanic/Latino), and body mass index (BMI, <30 vs. 30 kg/m ).

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 <140/90mmHg.

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 5.710.7mmHg more than Val/HCTZ, 3.48.3mmHg more than Aml/Val, and 4.4 9.4mmHg 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.

Efficacy and Safety of Angiotensin II Type 1 Receptor Blocker/Calcium Channel Blocker Combination Therapy for Hypertension: Focus on a Single-Pill Fixed-Dose Combination of Valsartan and Amlodipine
1. S Miura1,2 2. K Saku1

Abstract
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.

A Review of the Efficacy and Tolerability of Combination Amlodipine/Valsartan in Non-White Patients with Hypertension Keith C. Ferdinand, Samar A. Nasser

Abstract
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 angiotensinaldosterone 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.