Review Article
Review of blood pressure control rates and outcomes

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Abstract

Despite the high prevalence of hypertension and documented benefits of blood pressure (BP) control, >40% of patients with hypertension are not controlled. A majority of uncontrolled hypertensive patients receive two or more antihypertensive drugs. The current review examined the relationship between antihypertensive combination drug therapy, achievement of goal BP, and cardiovascular (CV) outcomes. Articles were selected from a PubMed search using a prespecified search strategy. Randomized, controlled clinical trials of adult human subjects published in English between January 1991 and January 2013 were included. From 2319 identified articles, 28 met inclusion criteria and contained a total of 226,877 subjects. There were seven placebo-controlled studies and 21 treatment comparator and combination therapy studies. The studies included in this review reported a positive association between the degree of BP lowering, number of medications, and CV outcomes. As combination therapy became available, it was increasingly utilized in clinical trials and enabled an increased proportion of patients to achieve a prespecified BP target. Adverse events with monotherapy and combination therapy were as anticipated for the specific classes of antihypertensive therapy. Although many patients reach BP goal, combination antihypertensive therapy is often needed to reach BP goal. Effective BP lowering has been shown to result in improvements in CV outcomes.

Introduction

The National Health and Nutritional Examination Survey (NHANES) 2007 through 2010 data show that an estimated 77.9 (33.0%) million adults ≥20 years of age in the US have hypertension; of these, 81.5% were aware of their condition, 74.9% were under current treatment, 52.5% had hypertension under control, and 47.5% did not have hypertension under control.1 By 2030, the prevalence of hypertension is estimated to reach 37.3% in the US.2 Effective blood pressure (BP) reduction has been associated with reductions in the risk of cardiovascular (CV) and/or cerebrovascular events and related morbidity and mortality.3 It has been estimated that approximately 75% of patients require combination therapy, and approximately 25% require three antihypertensive agents, to control BP.4, 5 Data from NHANES (2003 through 2008), showed that among United States adults with hypertension, 8.9% met criteria for resistant hypertension, which represented 12.8% of the antihypertensive drug-treated population. Adults with hypertension were classified as resistant if BP was ≥140/90 mm Hg and they reported using antihypertensive medications from three different drug classes or drugs from four or more antihypertensive drug classes regardless of BP.6

The results of the Cardiac Arrhythmia Suppression Trial (CAST) demonstrated the potential of biomarkers to generate incorrect assumptions in the absence of CV outcome data.7, 8 The CAST study was done to determine whether reduction of ventricular premature beats with United States Food and Drug Administration-approved agents (encainide and flecainide) in patients with recent myocardial infarction would decrease mortality.7 The results showed that the risk of death for the treated patients was higher than for patients receiving placebo.7 Due to this, the CAST study raised doubts regarding the strength of the biomarker concept and increased skepticism about the use of surrogate, biomarker end points to substitute for clinical, CV end points in phase III trials.8 As a result, many large randomized clinical trials and meta-analyses have instead examined the relationship between hypertension control and clinical outcomes.9, 10, 11 The purpose of the present review was to perform a literature search of published studies since CAST was published in 1991 to examine the percentage of patients treated for hypertension who achieved office BP goal/target in CV outcomes trials. Additional analyses included the average number of antihypertensive drugs administered during the study, outcomes and CV events in the overall patient populations, and the incidence of adverse events (AEs) with combination therapy compared with maximum-dose monotherapy.

Section snippets

Search Strategy

A literature search limited to clinical trials conducted in human adults and published in English between January 1, 1991 and January 23, 2013 was performed using PubMed. Both Medical Subject Heading (MeSH) terms and text word searches were used in the following two search strategies and Boolean operatives: (1) (hypertension OR blood pressure) AND (cardiovascular events OR mortality OR stroke OR heart failure) AND (angiotensin receptor blocker OR angiotensin converting enzyme OR calcium channel

Results

The initial two searches identified 1980 and 319 articles, respectively, for a total of 2299 potential articles (Figure 1). The UpToDate online resource yielded 67 additional publications. Duplicates were deleted, 2319 articles were screened, and 2049 were excluded based on title and abstract review. Two-hundred seventy articles were retrieved in full and assessed for eligibility; 28 studies that met all inclusion criteria were included in this review.10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,

Discussion

The objective of this review was to examine the percentage of patients treated for hypertension who achieved office BP goal/target in CV outcomes trials since 1991. Additional analyses included the average number of antihypertensive drugs administered during the study outcomes, CV events in the overall patient populations, and the incidence of AEs with combination therapy compared with maximum-dose monotherapy. Evidence from clinical trials and other studies in patients with diabetes and kidney

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    Research funds for preparation of the manuscript were provided by Daiichi Sankyo, Inc, Parsippany, New Jersey. Editorial support for this article was provided by Vrinda Mahajan, PharmD, of Peloton Advantage, LLC, Parsippany, New Jersey. The opinions expressed in the current article are those of the authors. The authors received no honoraria/fee for service or other form of financial support related to the development of this article. Moreover, the format and content of the entire manuscript was proposed by the authors, who edited every draft before approving the final manuscript.

    Conflict of interest: Dr Bakris has served as a consultant for Takeda, Abbott, Daiichi Sankyo, Boehringer Ingelheim, Roche, Bayer, and Lilly; has served as a principal investigator for trials sponsored by Medtronic and Relapsya; and has served on the executive committee of CVRx. Dr Sarafidis has served as a speaker for Astra-Zeneca, Bayer, Boehringer Ingelheim, and Novartis. Dr Agarwal has served as a consultant for Ardelyx, Roche, Merck, Takeda, Daiichi-Sankyo, Eli Lilly, Sigma Tau, and Abbvie; serves on the speaker bureau of Merck and Abbvie; serves on the steering committees of Abbvie, Celgene, Roche, Reata, and Sandoz; and has received research support from NIH, VA, and Daiichi Sankyo. Dr Ruilope has served as advisor/speaker for Astra-Zeneca, Bayer, BMS, Daiichi Sankyo, Esteve, GSK, Medtronic, Menarini, Novartis, Otsuka, Pfizer, Roche, Servier, and Takeda.

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