Imidapril and Candesartan Cilexetil in Patients with Hypertension

Abstract and Introduction

Abstract

Background: Twenty-four-hour ambulatory blood pressure monitoring (ABPM) provides the most accurate efficacy assessment of an antihypertensive agent throughout a 24-hour dosing interval. The objective of this prospective, randomised, double-blind, parallel-group, multicentre study was to compare the antihypertensive efficacy of imidapril versus candesartan cilexetil using ABPM.
Methods: After screening and a single-blind, placebo run-in phase, ambulatory adult patients with mild to moderate hypertension (defined as a mean office sitting diastolic BP [DBP] and systolic BP [SBP], respectively, of 90109mm Hg and 140179mm Hg, and a mean ABPM DBP and SBP, respectively, of =80mm Hg and =125mm Hg) were randomised to once-daily treatment with imidapril or candesartan cilexetil for 12 weeks. ABPM was performed at baseline and at the end of the 12-week treatment period in 112 patients (imidapril group, n = 55; candesartan cilexetil group, n = 57). To achieve the target BP of =140/90mm Hg, imidapril was titrated from 5 mg/day to 20 mg/day and candesartan cilexetil was titrated from 4 mg/day to 16 mg/day.
Results: Significant (p < 0.001) and similar decreases from baseline in clinic mean DBP and SBP, in mean 24-hour ABPM, DBP and SBP awake and asleep, and in mean BP (MBP) were observed in both treatment groups. In addition, significant and similar reductions in DBP and SBP were observed during the early morning acceleration period in both treatments. The reduction in BP load was higher with imidapril than with candesartan cilexetil: 44.6% versus 34.5% reduction in DBP load and 38.0% versus 32.9% reduction in SBP load, respectively. With respect to the average deviation index expressing a load index, the reduction with imidapril was 41.0% versus 33.6% with candesartan cilexetil. The percentage of DBP dipper patients remained identical before and after treatment in both groups. With regard to SBP, the percentage of dippers increased from 38.2% to 45.5% in the imidapril group and decreased from 54.4% to 42.1% in the candesartan cilexetil group. The incidence of adverse events was similar between the treatment groups and no cases of dry cough were reported.
Conclusion: Imidapril in once-daily doses of up to 20mg was shown to be at least as effective as candesartan cilexetil given in once-daily doses of up to 16mg in reducing BP throughout the entire 24-hour dosing interval. Both drugs were well tolerated.

Introduction

The renin-angiotensin system (RAS) plays an important role in regulating BP,^[1] and modulation of the RAS is considered to be the most complete way to manage high-risk cardiovascular risk patients, including those with hypertension.^[2] Both ACE inhibitors and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) inhibit the RAS and have been shown to be effective treatments in hypertension,^[3] but there remain important concerns regarding the distinct pharmacological profiles and modes of action of these two classes of drugs.^[2] Data from recent large-scale trials have suggested that, unlike ACE inhibitors, ARBs are either neutral or may actually increase rates of myocardial infarction despite similar levels of BP reduction.^[2]

Following captopril and losartan, which were respectively the first ACE inhibitor and the first ARB to become clinically available, several other ACE inhibitors and ARBs have been synthesised and developed. Of these, imidapril is one of the most recent ACE inhibitors to achieve marketing approval. Imidapril is a prodrug that is converted to its active metabolite, imidaprilat, by esterase activity. In contrast with captopril and enalapril, imidapril has a prolonged antihypertensive action.^[4,5] Furthermore, in the appropriate rat model, imidapril exhibited a four times higher stroke-preventive potency than enalapril.^[6] In clinical trials, imidapril has demonstrated a clinically relevant antihypertensive effect compared with reference treatments from the same or other drug classes.^[7,8,9,10] This effect lasts over a 24-hour dosing period, the reduction in BP after 24 hours is at least 80% of the peak effect, and the total incidence of adverse events with imidapril in placebo-controlled studies is comparable to that of placebo.^[11,12] Imidapril is indicated for the first-line treatment of all degrees of essential hypertension and a once-daily dosage regimen is recommended.

There is an abundance of clinical outcome data demonstrating that 24-hour ambulatory BP monitoring (ABPM) is a better predictor of clinical outcome than office BP.^[13] Mean 24-hour, awake and sleeping BP predict the likelihood of a patient experiencing a cardiovascular event better than office BP, even when office readings are obtained rigorously.^[13] To date, no comparative trial between imidapril and an ARB using ABPM has been available. The aim of this study was to compare the time-effect profile of imidapril and candesartan cilexetil in mild to moderate hypertensive patients, as measured by ABPM. Candesartan cilexetil was chosen as the comparator because it is an ARB that has demonstrated clinical efficacy superior to that of losartan,^[14] has a sustained duration of action over 24 hours, and is well tolerated in patients with essential hypertension.^[15]

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.