Azilsartan medoxomil (Edarbi®; Ipreziv™) is an orally administered
angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with
essential hypertension. This article reviews data on the clinical efficacy and tolerability of
azilsartan medoxomil in adults with
essential hypertension and provides a summary of its pharmacological properties.
Azilsartan medoxomil is a
prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after
oral administration to the bioactive moiety
azilsartan, before systemic absorption.
Azilsartan medoxomil produces
antihypertensive effects by selectively blocking the binding of
angiotensin II to the
angiotensin type 1 (AT(1)) receptor, thereby antagonizing the pressor response activity of
angiotensin II. In vitro,
azilsartan produced greater and more sustained AT(1) receptor binding/blockade activity than several comparator
angiotensin II receptor antagonists.
Azilsartan medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the
drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1) receptor blockade). In adults with
essential hypertension,
azilsartan medoxomil 20, 40 or 80 mg effectively reduced BP over a 24-hour period with once-daily administration in three major, randomized, controlled trials in which the primary endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6 (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two 6-week trials,
azilsartan medoxomil showed dose-dependent efficacy over all evaluated dosages and was more effective than placebo in lowering SBP. At the maximum approved dosage of 80 mg once daily,
azilsartan medoxomil was significantly more effective than maximum dosages of
olmesartan medoxomil (40 mg once daily) or
valsartan (320 mg once daily), based on primary endpoint assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP) measurements were also generally greater with
azilsartan medoxomil 80 mg once daily than with the comparator drugs in these 6-week studies. Over a longer treatment period of 24 weeks,
azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with
azilsartan medoxomil 40 or 80 mg once daily than with
valsartan 320 mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with
azilsartan medoxomil 40 or 80 mg once daily than with
valsartan.
Azilsartan medoxomil was generally well tolerated, with a tolerability profile similar to that of placebo in the 6-week trials. Across the three major trials,
headache and
dizziness were among the most common adverse events. Overall, rates of treatment discontinuation as a result of adverse events were low in the 6-week and 24-week trials. In conclusion, once-daily
azilsartan medoxomil effectively lowers BP in adults with
essential hypertension and has shown better
antihypertensive efficacy than maximum therapeutic dosages of
olmesartan medoxomil or
valsartan in major trials of up to 24 weeks' duration.
Azilsartan medoxomil is generally well tolerated and the low rates of discontinuation due to adverse events suggest that patients are likely to persist with long-term treatment.
Azilsartan medoxomil is therefore a useful and attractive new option for lowering BP in patients with
essential hypertension, particularly for those not able to tolerate other
antihypertensive drugs. Further studies are required to evaluate the effects of
azilsartan medoxomil on cardiovascular morbidity and mortality.