Elsevier

Clinical Therapeutics

Volume 33, Issue 9, September 2011, Pages 1190-1203
Clinical Therapeutics

Pharmacotherapy
Original research
Retrospective Analysis of Real-World Efficacy of Angiotensin Receptor Blockers Versus Other Classes of Antihypertensive Agents in Blood Pressure Management

https://doi.org/10.1016/j.clinthera.2011.08.008Get rights and content

Abstract

Background

Efficacy of blood pressure (BP) lowering may differ between clinical trials and what is observed in clinical practice. These differences may contribute to poor BP control rates among those at risk.

Objective

We conducted an observational study to determine the BP-lowering efficacy of angiotensin receptor blocker (ARB) versus non–ARB-based antihypertensive treatments in a large Canadian primary care database.

Methods

We analyzed the South Western Ontario database of 170,000 adults (aged >18 years) with hypertension persisting with antihypertensive medication for ≥9 months. Routine standard of care office BP was measured using approved manual aneroid or automated devices. BP <140 mm Hg and/or <90 mm Hg ≤9 months after treatment initiation, persistence (presence of initial antihypertensive prescription at the first, second, third, and fourth year anniversary) with antihypertensive therapy, and the presence of a cardiovascular (CV) event (ie, myocardial infarction) were studied.

Results

After 9 months of monotherapy, 28% (978 of 3490) of patients on ARBs achieved target BP versus 27% (839 of 3110) on angiotensin-converting enzyme inhibitors (ACEIs) (P > 0.05), 26% (265 of 1020) on calcium channel blockers (CCBs) (P > 0.05), 21% (221 of 1050) on β-blockers (P = 0.002), and 19% (276 of 1450) on diuretics (P = 0.001). Attainment rates were significantly higher with irbesartan (38%; 332 of 873) versus losartan (32%; 335 of 1047; P = 0.01), valsartan (19%; 186 of 977; P = 0.001), and candesartan (25%; 148 of 593; P = 0.001). BP goal attainment rates were significantly higher when ARB was compared with non–ARB-based dual therapy (39%; 1007 of 2584 vs 31%; 1109 of 3576; P = 0.004); irbesartan + hydrochlorothiazide (HCTZ) was significantly higher than losartan + HCTZ (36%; 500 of 1390 vs 20%; 252 of 1261; P = 0.001). For patients receiving dual or tri-therapy, 48% (667 of 1390) of patients receiving irbesartan reached target BP versus 41% to 42% for losartan (517 of 1261), valsartan (194 of 462), and candesartan (168 of 401) (P = 0.001 for each). After 4 years, persistence rates were not statistically different among ARB, CCB, and diuretic monotherapies, but appeared somewhat higher with ACEIs and β-blockers (78%, 78%, 79%, 91%, and 84%, respectively). Persistence was not significantly different between irbesartan and losartan monotherapy (76% for both; P > 0.05), but was significantly higher with irbesartan + HCTZ versus losartan + HCTZ (96% vs 73%, respectively; P = 0.001). Patients treated with ARBs reported fewer CV events than those receiving ACEIs or CCBs (4.3% vs 7.0% and 11.0%, respectively; P < 0.001). Within the ARB class, the lowest rate was with irbesartan (3.0% vs 4.6%–5.0% for other ARBs; P < 0.02).

Conclusions

In this real-world setting, hypertensive adults treated with ARBs versus β-blockers or diuretics were more likely to have evidence-based target BP recorded. In addition, patients using ARBs versus ACEIs or CCBs had fewer reports of CV events.

Introduction

Hypertension is a major modifiable risk factor for cardiovascular (CV) disease1, 2 and the most common risk factor for death, both worldwide3 and in Canada.4, 5 Numerous randomized controlled clinical trials have demonstrated that effective blood pressure (BP) control using any of the 5 conventional antihypertensive drug classes is associated with significant reductions in CV risk in people with hypertension.6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 Based largely on results from these and similar studies, hypertension treatment guidelines recommend lowering BP to <140/90 mm Hg in the general population and to <130/80 mm Hg in patients with diabetes and renal disease.4, 20, 21, 22, 23 According to these guidelines, the initial choice of antihypertensive treatment strategy depends largely on patients' comorbidities and degree of hypertension. For example, people with diabetes, chronic kidney disease, and/or BP ≥20 mm Hg above the systolic BP (SBP) goal or ≥10 mm Hg above the diastolic BP (DBP) goal should be initiated on ≥2 agents; those with CKD should receive at least 1 angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and most combination therapies should include a thiazide diuretic according to standard of care.4

Treatment guidelines are continuously updated to reflect the ever-increasing volume of data from clinical studies and published meta-analyses. However, clinical trial populations often do not represent those seen in real-life clinical practice.21, 24, 25, 26, 27 Factors such as persistence with treatment tend to be artificially high in clinical trials. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), for example, persistence with any antihypertensive agent was 96% at 1 year compared with 5% to 75% in observational studies.28, 29, 30, 31 Such differences may lead to over-exaggerated treatment efficacy in responsive patients who may not have persisted with treatment in a real-world setting or to under-exaggerated efficacy in unresponsive patients who may have switched to a more suitable drug in clinical practice.21 It is therefore important that guidelines should take into account results from observational real-world studies as well as those from clinical trials.29, 30, 31, 32

Like randomized clinical trials, observational studies are often designed to assess treatment efficacy and tolerability in specific patient populations, such as those with hypertension and diabetes or kidney disease.33, 34, 35, 36, 37, 38, 39 Few studies have captured treatment efficacy in the broad range of patients that are routinely seen in clinical practice. Recently, the observational The Health Improvement Network (THIN) study examined the BP-lowering efficacy of various antihypertensive drug classes in primary care in the United Kingdom.40, 41, 42 In this study, patients prescribed ARBs, either as monotherapy or as part of a combination therapy regimen, were more likely to achieve and maintain target BP than patients using other classes of antihypertensive agents.40, 41, 42 The aim of our study was to compare the BP-lowering efficacy and long-term persistence rates of ARB- versus non–ARB-based monotherapy, dual, and tri-therapies in a “real world” primary care population in Canada. The CV event rates associated with each treatment strategy were also assessed.

Section snippets

Data Source

This retrospective observational study utilized data collected from routine primary care practices in Canada, stored in the South Western Ontario (SWO) database. The longitudinal investigation was carried out in a geographically defined area comprising rural and urban clinical practices in London, Ontario, Canada, and surrounding counties with a catchment of 1.5 million inhabitants. This retrospective study began in 2000 and, at the time of this report in 2010, included information from 53

Blood Pressure Control With Monotherapy

Overall, 10,120 adult, nondiabetic patients with hypertension were initiated on monotherapy treatment in 2005 and continued with their prescribed treatment for at least 9 months. Over 90% of the patients were white. The mean age of the target population was 65 years; mean weight 81.3 kg; 41% were male; and mean BP at index date was 149/84 mm Hg (Table I). There were no significant differences across antihypertensive drug classes for age, sex, or baseline BP. After 9 months of treatment with

Discussion

In primary care practice in Canada, ARB, ACEI, and CCB monotherapies were significantly more effective than β-blockers and diuretics for the attainment of a BP target <140/90 mm Hg in nondiabetic patients with mild to moderate hypertension.45 Although the proportion of people reporting target BP was slightly higher with ARB monotherapy than with ACEI or CCB monotherapy, the between-group differences were not statistically significant. In a similar study, records of 158,995 adults with

Conclusions

In a real-world setting, hypertensive adults treated with ARBs versus β-blockers or diuretics were more likely to have evidence-based target BP recorded. In addition, patients using ARBs versus ACEIs or CCBs had fewer reports of CV events.

Acknowledgments

Both authors were sole contributors to the collection and interpretation of the data, the intellectual development, writing of the manuscript, extensive editing, and final approval of this article. The authors received no financial support or other compensation related to its development. This report was supported by an unrestricted grant from Bristol-Myers Squibb/Sanofi-Synthelabo. The authors do not have any conflict of interest with the sponsors of this report. The authors thank PPSI, a

References (90)

  • R.J. Ligthelm et al.

    Importance of observational studies in clinical practice

    Clin Ther

    (2007)
  • B.M. Psaty et al.

    Hypertension and outcomes researchFrom clinical trials to clinical epidemiology

    Am J Hypertens

    (1996)
  • F.J. Morales-Olivas et al.

    The KARTAN study: a postmarketing assessment of irbesartan in patients with hypertension

    Clin Ther

    (2004)
  • N.R. Robles et al.

    Effectiveness of eprosartan in diabetic hypertensive patients

    Eur J Intern Med

    (2008)
  • K. Kassler-Taub et al.

    Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertensionIrbesartan/Losartan Study Investigators

    Am J Hypertens

    (1998)
  • G. Bobrie et al.

    A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

    Am J Hypertens

    (2005)
  • B.S. Bloom

    Continuation of initial antihypertensive medication after 1 year of therapy

    Clin Ther

    (1998)
  • J. Lachaine et al.

    Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data

    Can J Cardiol

    (2008)
  • A. Patel et al.

    Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial

    Lancet

    (2007)
  • A.I. Goldberg et al.

    Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension

    Am J Cardiol

    (1995)
  • T.A. Simon et al.

    Safety of irbesartan in the treatment of mild to moderate systemic hypertension

    Am J Cardiol

    (1998)
  • J. McMurray et al.

    The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

    J Am Coll Cardiol

    (2006)
  • J.J. McMurray et al.

    Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial

    Lancet

    (2003)
  • B.J. Materson et al.

    Department of Veterans Affairs single-drug therapy of hypertension studyRevised figures and new data. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

    Am J Hypertens

    (1995)
  • S. Lewington et al.

    Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies

    Lancet

    (2002)
  • W. Rosamond et al.

    Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee

    Circulation

    (2007)
  • J.A. Whitworth

    2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension

    J Hypertens

    (2003)
  • R.J. Petrella et al.

    Awareness and misconception of hypertension in Canada: results of a national survey

    Can J Cardiol

    (2005)
  • The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialMajor outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

    JAMA

    (2002)
  • S.E. Kjeldsen et al.

    Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy

    JAMA

    (2002)
  • M.R. Law et al.

    Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials

    BMJ

    (2003)
  • E.J. Lewis et al.

    Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes

    N Engl J Med

    (2001)
  • H. Lithell et al.

    The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial

    J Hypertens

    (2003)
  • A.P. Maggioni et al.

    VALIANT (VALsartan In Acute myocardial iNfarcTion) trial

    Expert Opin Pharmacother

    (2005)
  • S. Yusuf et al.

    Telmisartan, ramipril, or both in patients at high risk for vascular events

    N Engl J Med

    (2008)
  • A.V. Chobanian et al.

    The Seventh Report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report

    JAMA

    (2003)
  • G. Mancia et al.

    2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

    J Hypertens

    (2007)
  • G. Mancia et al.

    Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document

    J Hypertens

    (2009)
  • C. Rosendorff et al.

    Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention

    Circulation

    (2007)
  • M.R. Chassin

    Is health care ready for Six Sigma quality?

    Milbank Q

    (1998)
  • S.H. Woolf et al.

    Clinical guidelines: potential benefits, limitations, and harms of clinical guidelines

    BMJ

    (1999)
  • A. Zanchetti

    Evidence-based medicine in hypertension: what type of evidence?

    J Hypertens

    (2005)
  • H. Cardinal et al.

    A comparison between persistence to therapy in ALLHAT and in everyday clinical practice: a generalizability issue

    Can J Cardiol

    (2004)
  • P. Craig et al.

    Developing and evaluating complex interventions: the new Medical Research Council guidance

    BMJ

    (2008)
  • P. Bramlage et al.

    The effect of irbesartan in reducing cardiovascular risk in hypertensive type 2 diabetic patients: an observational study in 16,600 patients in primary care

    Curr Med Res Opin

    (2004)
  • Cited by (0)

    View full text