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Management of Hypertension in Patients with Diabetes Mellitus

Defining the Role of Lisinopril

  • Drugs in Disease Management
  • Published:
Disease Management and Health Outcomes

Abstract

Hypertension and diabetes mellitus are significant and independent risk factors for cardiovascular disease.

Antihypertensive therapy reduces cerebrovascular and cardiovascular morbidity and mortality in patients with hypertension. Tight blood pressure (BP) control [target diastolic BP (DBP) ≤80mm Hg] reduced the incidence of major cardiovascular events by 51% compared with less tight control (DBP ≤90mm Hg) in patients with diabetes mellitus in the Hypertension Optimal Treatment (HOT) study. Similarly, in the UK Prospective Diabetes Study (UKPDS), tight BP control [mean systolic BP (SBP)/DBP = 144/82mm Hg] with captopril or atenolol reduced diabetes mellitus-related morbidity and mortality by 24% compared with less tight control (mean SBP/DBP = 154/87mm Hg). Importantly, the frequency of microvascular disease (including retinopathy) was reduced by 37% among those randomised to tight BP control in the UKPDS.

In the diabetic subgroup in the Heart Outcomes Prevention Evaluation (HOPE) study, there was a 25% reduction in the composite end-point of death due to cardiovascular causes, or myocardial infarction or stroke during 5 years of treatment with ramipril 10 mg/day relative to placebo.

Lisinopril is an ACE inhibitor indicated for use in hypertension, heart failure and post-myocardial infarction. As an antihypertensive agent the drug is effective and generally well tolerated in patients with type 1 or 2 diabetes mellitus and in those with early or overt nephropathy.

In the Swedish Treatment of Old People (STOP) Hypertension 2 trial, there was no difference in the relative risk of cardiovascular death between those assigned to ACE inhibitors (lisinopril or enalapril), calcium channel blockers (felodipine or isradipine) or ‘conventional’ antihypertensive therapy (thiazide diuretics or β blockers); treatment effects did not differ significantly between diabetic and nondiabetic patients (10.9% of the 6614 patients had diabetes mellitus). Importantly, lower frequencies of nonfatal or fatal myocardial infarction [relative risk (RR) 0.77; 95% confidence interval (CI) 0.61 to 0.96] and congestive heart failure (RR 0.78; CI 0.83 to 0.97) were detected during 4 years’ treatment with lisinopril or enalapril than felodipine or isradipine in this study.

Lisinopril reduced albumin excretion rates in patients with type 1 or 2 diabetes mellitus. In the 2-year EURODIAB Controlled Trial of Lisinopril in IDDM (EUCLID) study, albumin excretion rates decreased by 49.7% relative to placebo in normotensive patients with type 1 diabetes mellitus and microalbuminuria during treatment with lisinopril 10 to 20 mg/day. Progression of retinopathy was attenuated in normotensive patients with type 1 diabetes mellitus during treatment with lisinopril in this study.

In conclusion, lisinopril, like other ACE inhibitors should be considered a first-line agent for reducing BP and attenuating nephropathy in patients with type 1 or 2 diabetes mellitus.

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Notes

  1. The doxazosin arm of the study was stopped in February 2000 after an independent data review by an advisory committee determined that recipients of doxazosin had 25% more cardiovascular events and were twice as likely to be hospitalised for congestive heart failure as were chlorthalidone recipients. Importantly, there was no difference in the risk of myocardial infarction or all-cause mortality between the 2 groups. The remaining arms of the study are continuing as scheduled.[191,192]

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    Blair Jarvis & Caroline M. Spencer

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Additional information

Various sections of the manuscript reviewed by: T. Baba, Department of Internal Medicine 3, Fukushima Medical University School of Medicine, Fukushima, Japan; T. Chowdhury, The Jeffrey Kelson Diabetic Centre, The North West London Hospitals NHS Trust, Central Middlesex Hospital, London, England; M.E. Cooper, Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, West Heidelberg, Victoria, Australia; P. Drury, Department of Medicine, University of Auckland, Auckland, New Zealand; E. Fineberg, Department of Medicine, Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana, USA; C. Fox, Diabetes Centre, Northampton General Hospital NHS Trust, Northampton, England; C. Hasslacher, St. Josefskrankenhaus Heidelberg, Akademisches Lehrkrankenhaus der Universitat Heidelberg, Heidelberg, Germany; D. Jones, University of Mississippi Medical Center, Jackson, Mississippi, USA; S.M. Marshall, Department of Diabetes and Metabolism, School of Clinical Medical Sciences, The Medical School, University of Newcastle, Newcastle upon Tyne, England; G. Zuanetti, Instituto di Ricerche Farmacologiche, Mario Negri, Milan, Italy.

Data Selection

Sources: Medical literature published in any language since 1989 on Lisinopril, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: AdisBase search terms were ‘Hypertension-in-diabetes’ and (‘guideline’ or ‘guideline-utilisation’ or ‘practice-guideline’ or ‘disease-management-programmes’ or ‘treatment-algorithms’ or ‘reviews-on-treatment’ or ‘drug-evaluations’ or ‘epidemiology’ or ‘cost-of-illness’ or ‘pathogenesis’), or ‘Lisinopril’ or ‘MK-521’ and (‘review’ or ‘clinical-study’). Searches were last updated 17, Apr 2000.

Selection: Studies in patients with diabetes mellitus and hypertension who received lisinopril. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic, pharmacokinetic, pharmacoeconomic and epidemiological data are also included.

Index terms: Diabetes mellitus, hypertension, lisinopril, disease management, review on treatment.

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Jarvis, B., Spencer, C.M. Management of Hypertension in Patients with Diabetes Mellitus. Dis-Manage-Health-Outcomes 7, 267–288 (2000). https://doi.org/10.2165/00115677-200007050-00004

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