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

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.

Pharmacokinetic and Safety Profiles of a Fixed‐Dose Combination of Amlodipine, Valsartan, and Atorvastatin: A 3‐Period Replicate Crossover Study

“…The most frequently reported TEAE was headache, followed by increased CK in this study. According to previous studies, headache was a common AE following administration of the amlodipine and valsartan combination, 27 and increased CK was one of the well-recognized AEs of atorvastatin. 28 There was no significant difference in terms of safety between the 2 interventions.…”