Abstract

This review aimed to assess the efficacy and safety of once- versus twice-daily administration of angiotensin-converting enzyme (ACE) inhibitors for the management of hypertension. A literature search on PubMed and Google Scholar was performed (January 1980 to June 2020) using the following search terms: ACE inhibitors, lisinopril, enalapril, fosinopril, trandolapril, ramipril, perindopril, captopril, benazepril, ambulatory blood pressure, hypertension, twice-daily dosing, once-daily dosing. Reference lists from retrieved articles were examined for additional reports. Relevant English-language studies or those conducted in humans were considered. Overall, six studies were included that compared the efficacy of once-daily to twice-daily dosing of ACE inhibitors. Similar blood pressure-lowering effects, and, in some studies, greater blood pressure lowering has been noted in the twice-daily administration arm than once-daily administration of ACE inhibitors. ACE inhibitors' pharmacokinetic and pharmacodynamic properties play an integral role in determining the expected blood pressure-lowering outcome. It is noteworthy that adherence issues may arise when transitioning from a once-daily regimen to a twice-daily regimen. There appear to be no added safety concerns between twice-daily and once-daily administration of ACE inhibitors regarding safety outcomes. After reviewing the available literature, twice-daily dosing of ACE inhibitors may promote added blood pressure-lowering effects, with the advantages of reducing cost, reducing the risk of drug-drug interactions, reducing polypharmacy, and reducing patient confusion about their medications. Recommendations for twice-daily administration of ACE -inhibitors should be made via shared decision-making with the patient, and clinician judgment, to drive treatment selection.

Highlights

  • BackgroundHypertension remains a significant public health challenge in the United States due to the substantial increase in cardiovascular disease (CVD) [1]

  • This review aims to provide a concise overview of the current literature to elucidate any difference in efficacy and safety of once-daily compared to twice-daily dosing of angiotensin-converting enzyme (ACE) inhibitors

  • The evidence may suggest this to be a class effect given that twice-daily dosing with lisinopril, enalapril, trandolapril, perindopril, captopril, and ramipril all demonstrated greater or similar blood pressure-lowering effects than once-daily administration of these agents [18,19,20,21,22,23]

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Summary

Introduction

BackgroundHypertension remains a significant public health challenge in the United States due to the substantial increase in cardiovascular disease (CVD) [1]. As one of the major modifiable risk factors for CVD, optimizing blood pressure control is critical in reducing heart disease and, healthcare costs [2]. Many individuals newly diagnosed with hypertension are often started on a single antihypertensive agent and titrated to the maximum effective dose. ACE inhibitors are one of the most commonly prescribed antihypertensive agents. With less angiotensin II circulating in the system, the effects observed are decreased blood pressure, increased natriuresis, and the prevention of smooth muscle and cardiac myocytes remodeling [4]. The pharmacokinetics of ACE inhibitors are essential in determining the plasma concentration profile and the agent's duration of effect [5]. Understanding ACE inhibitor pharmacokinetic data is vital to optimizing the dose and dose frequency best. ACE inhibitor doses commonly seen in the clinical setting are on the upper linear plateau of the concentration-effect curve. ACE inhibitors are typically dosed once daily, this suggests some ACE inhibitors' optimal frequency may be twice-daily administration [5,6,7]

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