Fixed-dose Combination Therapy in Hypertension: Focus on Fixed-dose combination of Amlodipine and Valsartan (Exforge®)

Shakil Aslam

doi:10.4137/cmt.s1982

Abstract

Hypertension is the leading cause of disability and cardiovascular mortality world-wide. Approximately one-third of the US adult population and over a billion people world-wide have hypertension. Despite increased awareness of hypertension and availability of many effective antihypertensive agents, only one third of patients achieve their target blood pressure (BP). All expert panels now recommend use of combination therapy for stage 2 and higher hypertension and for individuals who are at increased risk of cardiovascular disease (CVD). Amlodipine, a dihydropyridine calcium channel blocker and Valsartan, an angiotensin II receptor (AT1-R) antagonist are widely used antihypertensive agents. Their efficacy in lowering systolic and diastolic BP and reducing CVD events has been demonstrated in several randomized trials. Fixed-dose combination of amlodipine and valsartan (A/V) has been shown to be more effective in lowering BP than monotherapy with either of these agents alone in randomized trials with comparable side effect profile. Approximately 80%-90% of patients with stage 1-2 hypertension receiving A/V fixed-dose combination achieve significant response, defined as a mean sitting diastolic BP < 90 mmHg or > 10 mmHg reduction from the baseline. Subgroup analyses show that A/V fixed-dose combination is equally effective in older individuals (>65), Blacks, in patients with isolated systolic hypertension, and in those who fail monotherapy. Furthermore, A/V fixed-dose combination is well tolerated and simplifies antihypertensive regimen enhancing patient adherence and a better BP control compared to monotherapy.

Highlights

Hypertension is a major health problem world-wide and exceeds smoking as a causal factor in attributable mortality, accounting for 12.8% of all deaths
In diabetics and in patients with chronic kidney disease (CKD) the control rates were 72.5% and 70.8%, respectively. These results demonstrate that monotherapy is ineffective in achieving the target blood pressure (BP) in majority of the hypertensive individuals
The peripheral edema rates were higher in older patients (9.9% vs. 4.3%) in this study. These findings demonstrate that the fixed-dose combination of A/V is effective in achieving predefined target BP control in patients 65 years of age, and is generally well tolerated

Summary

Introduction

Hypertension is a major health problem world-wide and exceeds smoking as a causal factor in attributable mortality, accounting for 12.8% of all deaths. The peripheral edema rates were higher in older patients (9.9% vs 4.3%) in this study These findings demonstrate that the fixed-dose combination of A/V is effective in achieving predefined target BP control in patients 65 years of age, and is generally well tolerated. Blacks have an earlier onset of hypertension, higher levels of BP once hypertensive, greater end-organ damage, and excess morbid and fatal CVD events including stroke, coronary heart disease, heart failure and CKD from hypertension.[6] the prevalence of resistant and poorly controlled hypertension is high among Blacks due to concurrent obesity, diabetes, salt sensitivity, and impaired renal function.[50] Combination therapy in Blacks has been shown to be more effective in achieving target BP than monotherapy.

Summary

Findings

44. Summary of product characteristics