Hypertension is a major modifiable risk factor for heart. Hypertension

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1 Hypertension Trends in Antihypertensive Medication Use and Blood Pressure Control Among United States Adults With Hypertension The National Health and Nutrition Examination Survey, 2001 to 2010 Qiuping Gu, MD, PhD, MPH; Vicki L. Burt, ScM, RN; Charles F. Dillon, MD, PhD, MPH; Sarah Yoon, PhD Background The monitoring of national trends in hypertension treatment and control can provide important insight into the effectiveness of primary prevention efforts for cardiovascular disease. The objective of this study was to examine recent trends in antihypertensive medication use and its impact on blood pressure control among US adults with hypertension. Methods and Results A total of 9320 hypertensive people aged 18 years from the National Health and Nutrition Examination Survey 2001 to 2010 were included in this study. The prevalence of antihypertensive medication use increased from 63.5% in 2001 to 2002 to 77.3% in 2009 to 2010 (P trend 0.01). Most notably, there was a large increase in the use of multiple antihypertensive agents (from 36.8% to 47.7%, P trend 0.01). Overall, the use of thiazide diuretics, -blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers increased by 23%, 57%, 31%, and 100%, respectively. In comparison with monotherapy, single-pill combinations and multiple-pill combinations were associated with 55% and 26% increased likelihoods of blood pressure control, respectively. By the 2009 to 2010 time period, 47% of all hypertensive people and 60% of treated hypertensive people had blood pressure controlled. However, higher treated but uncontrolled hypertension rates continued to persist among older Americans, non-hispanic blacks, diabetic people, and those with chronic kidney disease. Also, Mexican Americans with hypertension were still less likely to take antihypertensive medication than non-hispanic whites with hypertension. Conclusions Antihypertensive medication use and blood pressure control among US adults with hypertension significantly increased over the past 10 years. Combination therapy regimens can facilitate achievement of blood pressure goals. (Circulation. 2012;126: ) Key Words: hypertension population treatment trends NHANES Hypertension is a major modifiable risk factor for heart disease, stroke, end-stage renal failure, and peripheral vascular disease, and it affects nearly 1 in every 3 US adults. 1 Lowering blood pressure (BP) can reduce cardiovascular morbidity and mortality rates and slow the progression of renal disease and overall mortality, as well. 2,3 Although lifestyle modification is important in hypertension management, most hypertensive individuals require 2 antihypertensive drugs to reduce their BP and maintain it within acceptable ranges. 3,4 The effectiveness of at least 5 classes of drugs in treating hypertension and preventing cardiovascular events is well documented. 5 7 Major findings from the Antihypertensive and Lipid- Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) concluded that thiazide diuretics are equal or superior to other antihypertensive drugs in reducing cardiovascular events. 8 In 2003, the National High Blood Pressure Education Program Coordinating Committee published the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). 3 This national hypertension treatment guideline recommended the use of thiazide diuretics as initial drug therapy for most patients with uncomplicated hypertension, and the use of 2 antihypertensive agents from different drug classes to achieve the goal of BP control (a BP 130/80 mm Hg for patients with diabetes mellitus or chronic kidney disease; and a BP of 140/90 mm Hg for all other hypertensive people). Received January 26, 2012; accepted September 6, From the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Center for Health Statistics, Centers for Disease Control and Prevention. The online-only Data Supplement is available with this article at /-/DC1. Correspondence to Qiuping Gu, MD, PhD, MPH, Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, Center for Disease Control and Prevention, Room 4333, 3311 Toledo Rd, Hyattsville, MD qag3@cdc.gov 2012 American Heart Association, Inc. Circulation is available at DOI: /CIRCULATIONAHA

2 2106 Circulation October 23, 2012 Clinical Perspective on p 2114 Diuretics have long been recommended as the first-line agents for pharmacological antihypertensive therapy, but previously published data examining prescription or use patterns before the publication of the JNC 7 guidelines indicated an increasing use of more expensive calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors Several studies have recently evaluated changes in antihypertensive prescription patterns before and after the public release of the JNC 7 treatment guidelines Despite different study populations and methodologies, one of the common findings is an increase in the prescribing of thiazide diuretics. Because all of these studies are based on either pharmacy database or physician surveys and medical chart reviews, changes in actual therapy regimens being used by the US hypertensive population sampled on an individual person level are still unknown. The JNC 7 guidelines recommend initial combination therapy when BP is 20/10 mm Hg above goal BP. 3 Controlled clinical trials document that 2 antihypertensive drugs are required for most hypertensive patients to achieve BP control. 3,4 However, only 36% of hypertensive individuals were actually taking multiple antihypertensive drugs in 1999 to It is not known to what degree these important antihypertensive clinical trial results and evidencedbased clinical guidelines have been integrated into current clinical practice for hypertensive treatment and control. The National Health and Nutrition Examination Surveys (NHANES) data have been used to track the progress in preventing, treating, and controlling hypertension in the US population for 40 years. 16 Its nationally representative person-level data have recently shown an increased trend in the awareness, treatment, and control of hypertension among US adults with hypertension. 17,18 However, national hypertension treatment patterns and JNC 7 recommended BP control rates have not yet been examined with the latest available data. In this study, we use the NHANES 2001 to 2010 data to examine recent trends in antihypertensive medication use, changes in drug use patterns, and rates for BP goals among US adults with hypertension during the periods both before and after publication of the JNC 7 guidelines. Methods The NHANES is a nationally representative, multistage probability sample of the US civilian, noninstitutionalized population conducted by the National Center for Health Statistics. 19 Since 1999, NHANES has been implemented as a continuous, annual survey, and data are publicly released in 2-year cycles. Each 2-year NHANES cycle is a nationally representative cross-sectional sample of the US population. Survey participants receive detailed in-person home interviews, followed by standardized physical examinations conducted in mobile examination centers, and laboratory tests using blood and urine specimens provided by participants during the physical examination. Informed consent was obtained from all participants, and the protocol was approved by the ethics review board of the National Center for Health Statistics. During the home interview, participants were asked if they had used or taken a prescription drug in the past month. Those who answered yes were further asked to report the name, duration, and main reason for each product used. An interviewer recorded the exact product name from the medication container label. If the container was unavailable, the participant verbally reported this information. Approximately 84% of all reported prescription drugs were obtained from container data. Antihypertensive agents reported by participants in NHANES 2001 to 2010 were identified and categorized into the following classes 3,11 : (1) diuretics, (2) -blockers, (3) CCBs, (4) ACE inhibitors, (5) angiotensin receptor blockers, and (6) other antihypertensive agents (including 1 - blockers, central 2 -agonists, direct vasodilators, renin inhibitors, and other centrally acting drugs). Monotherapy was defined as a person who reported using only 1 antihypertensive agent. Polytherapy (combination therapy) was defined as a person who reported using 1 antihypertensive drug. Single-pill antihypertensive combination users were also considered to be receiving polytherapy. Participants age, sex, race/ethnicity, health insurance status, and medical conditions including a history of physician-diagnosed diabetes mellitus, cardiovascular disease including stroke, congestive heart failure, angina pectoris, heart attack, or coronary heart disease were also obtained by questionnaire. Serum creatinine concentration, and urine albumin and creatinine concentrations, as well, were measured according to standard methods. Serum creatinine values for NHANES 2005 to 2006 data 20 were corrected according to the recommended standards. Glomerular filtration rate was estimated with the use of the Modification of Diet in Renal Disease equation, 21 and chronic kidney disease was defined as either an estimated glomerular filtration rate 60 ml/min per 1.73 m 2 or a urinary albumin concentration of 200 mg/g urinary creatinine. 3 BP was measured with the participant in the sitting position after 5 minutes of rest by trained physicians at the mobile examination centers following a standard protocol. Appropriate cuff sizes were used for participants based on the measurement of midarm circumference. Up to 3 BP readings were obtained and used to calculate a mean systolic BP and a mean diastolic BP for each individual. Hypertension was defined as a mean systolic BP 140 mm Hg, a mean diastolic BP 90 mm Hg, or an affirmative response to the question Because of your hypertension/high BP, are you now taking prescribed medicine? Among the subset of hypertensive people, those who reported taking at least 1 antihypertensive agent identified in the NHANES prescription medication data were considered to be antihypertensive medication users. BP control was defined as a mean systolic BP 130 mm Hg and a mean diastolic BP 80 mm Hg for patients with diabetes mellitus or chronic kidney disease or a mean systolic BP 140 mm Hg and a mean diastolic BP 90 mm Hg for other hypertensive people. Data from the last 5 NHANES cycles, 2001 to 2002, 2003 to 2004, 2005 to 2006, 2007 to 2008, and 2009 to 2010, were included in this analysis. The overall response rate for completion of the interview and health examination was 77%. Of those who completed the interview and health examination, a total of 9421 adults aged 18 years were identified as hypertensive. One hundred one of these adults were excluded because of either lack of prescription medication data (n 85) or pregnancy (n 16). The final analytic sample was Online-only Data Supplement Table I lists the sex and race/ethnicity stratified numbers of hypertensive participants in each cycle. Statistical analyses were conducted with the use of SAS version 9.2 (SAS Institute, NC) and SUDAAN version 10.0 (Research Triangle Institute). 22 Appropriate sampling weights were used to account for differential probabilities of selection and the complex multistage sample survey design. Variance estimates were computed with the Taylor series linearization approximation. 23 An estimate with a relative standard error 30% was considered statistically unreliable, and this was noted in the tables. Statistical tests for linear trends across survey cycles were performed with the use of orthogonal polynomial contrasts, and probability values of 0.05 were considered statistically significant. Examination of the hypertensive sample people included in our study indicated that age distributions were similar across the 5 survey cycles (P 0.63). Hence, we present the estimates for the prevalence of antihypertensive medication use and for BP control among US adults with hypertension without age standardization. To further examine the major demographics and clinical factors associated with antihypertensive medication use and BP control, the 2005 to 2006, 2007 to 2008, and 2009 to 2010 NHANES data were combined, and prevalence ratios and 95% confidence intervals (CIs) were calculated by using multivariate

3 Gu et al Hypertension Treatment and Control 2107 logistic regression models. Variables included in the model are age, sex, race/ethnicity, health insurance status, and diabetes mellitus, chronic kidney disease, and cardiovascular disease. Results The percentage of hypertensive adults who reported taking any antihypertensive drug increased from 63.5% in NHANES 2001 to 2002 to 77.3% in NHANES 2009 to 2010 (P trend 0.01; Table 1). An increased trend in the use of any antihypertensive medication was observed in almost all stratified groups, with the exception of the youngest age group and the subgroup with a history of cardiovascular disease. Here, the prevalence of antihypertensive medication use was unchanged. The percentage of hypertensive adults who reported taking multiple antihypertensive drugs increased from 36.8% in NHANES 2001 to 2002 to 47.7% in NHANES 2009 to 2010 (P trend 0.01). An upward trend in the use of multiple antihypertensive medications was observed in almost all stratified groups, with the exception of youngest age group and the subgroup with diabetes mellitus. Overall, diuretics remained the most commonly used antihypertensive drug class during the 10-year period (Table 2). By NHANES 2009 to 2010, more than one third of hypertensive adults reported taking diuretics, an increase of 19% from NHANES 2001 to 2002 (P trend 0.01). Use of thiazide diuretics, one of the major diuretic subclasses, accounted for three fourths of all diuretic use. The prevalence of thiazide diuretic use increased from 22.4% in NHANES 2001 to 2002 to 27.6% in 2009 to 2010 (P trend 0.02), primarily because of its increased use in polytherapy. The overall prevalence of use of -blockers increased from 20.3% in NHANES 2001 to 2002 to 31.9% in NHANES 2009 to This was mainly driven by a 65% increase in the use of -blockers used in polytherapy regimens to treat hypertension. Approximately 20% of hypertensive adults reported taking CCBs in each survey period, and the use of CCBs remained relatively constant. ACE inhibitors were the second most commonly used antihypertensive drug class during the past 10 years. The use of ACE inhibitors increased significantly overall and also in polytherapy regimens. The use of angiotensin receptor blockers increased significantly in both monotherapy and polytherapy hypertension drug treatment regimens. The potential interactions between trend and sex or race/ethnicity for the use of each specific antihypertensive drug class were tested. There were no significant interactions, with the exception of -blocker use by sex (P 0.04) and angiotensin receptor blocker use across racial/ethnic groups (P 0.01). Online-only Data Supplement Table II shows sex and race/ethnicity stratified proportions for the use of specific antihypertensive drug classes in each survey. Table 3 shows the prevalence of commonly used individual antihypertensive drugs in the US hypertensive population. Lisinopril (an ACE inhibitor) was the most commonly used antihypertensive drug. By NHANES 2009 to 2010, 20.1% of the hypertensive population was taking lisinopril, almost double the rate in NHANES 2001 to In addition, the use of a fixed-dose lisinopril and hydrochlorothiazide combination drug increased substantially. Metoprolol (a -blocker) and hydrochlorothiazide (a thiazide diuretic) were the second and third most frequently used antihypertensive drugs in NHANES 2009 to 2010, and their corresponding use increased by 145% and 47%, respectively, from NHANES 2001 to 2002 to NHANES 2009 to The proportion using amlodipine (a CCB) also significantly increased, whereas the proportions using CCB agents such as diltiazem and verapamil (the seventh and ninth most frequently used antihypertensive drugs, respectively, in NHANES ) decreased significantly in the same period. The use of valsartan and losartan each doubled over the 10-year time period, making them the seventh and ninth most frequently used antihypertensive medications, respectively, in NHANES 2009 to Olmesartan was not in general clinical use before NHANES 2003 to 2004, but 2.0% of hypertensive people reported taking this drug in NHANES 2009 to In concert with the upward trends in antihypertensive drug use, BP control rates improved substantially over the 10-year time period 2001 to 2010 (Table 4). The overall hypertension control rate in the US hypertensive population increased from 28.7% in NHANES 2001 to 2002 to 47.2% in NHANES 2009 to 2010 (P trend 0.01). These increased trends in hypertension control rates were observed across all examined subgroups, with the exception of the youngest age group. Hypertension control rates specifically in the subgroup of hypertensive people taking drug treatment increased significantly from 44.6% to 60.3% in the same period (P trend 0.01). By NHANES 2009 to 2010, 69.5% of people without comorbidity had met the JNC 7 therapeutic goal. The JNC 7 therapeutic goal achievement rate was 43.7% for hypertensive people with chronic kidney disease and 44.6% for hypertensive people with diabetes mellitus. With the use of a less stringent criterion of 140/90 mm Hg as a therapeutic goal, the treated BP control rates were 61.7% for hypertensive people with chronic kidney disease and 67.0% for hypertensive people with diabetes mellitus, respectively (data not shown). A further logistic regression analysis was used to examine disparities in hypertension treatment and control in the most recent 2005 to 2010 time period. As shown in Table 5, age was positively associated with antihypertensive medication use but negatively associated with BP control. Women and insured people were more likely to use antihypertensive medications but were no different in their rates of BP control than their respective counterparts. In comparison with non- Hispanic white people, non-hispanic black people had higher odds of using multiple antihypertensive drugs and thiazide diuretics, but lower odds of BP control; Mexican-American people had lower odds of using antihypertensive drugs, multiple antihypertensive drugs, and thiazide diuretics or of achieving BP control. People with diabetes mellitus or chronic kidney disease were more likely to use antihypertensive medications but less likely to have BP control than their respective reference group. People with cardiovascular disease were more likely to use antihypertensive drugs and multiple antihypertensive drugs, but they were no different in BP control than those without cardiovascular disease. Among treated hypertensive people, those who received single-pill combination and multiple-pill combinations were 55% and 26% more likely to meet JNC 7 BP goals than those who received only monotherapy.

4 2108 Circulation October 23, 2012 Table 1. Prevalence of Antihypertensive Medication Use Among Hypertensive Adults Over Time by Age, Sex, Race/Ethnicity, Health Insurance Status, and Comorbid Conditions: United States 2001 to 2010 Characteristics (n 1669) (n 1750) (n 1564) (n 2169) (n 2168) Any antihypertensive drug use, Overall 63.5 (1.7) 67.5 (2.3) 69.8 (2.4) 72.6 (0.9) 77.3 (1.5) 0.01 Age, y (4.4) 37.3 (7.7) 31.2 (4.8) 44.9 (4.9) 43.5 (4.6) (2.5) 63.8 (3.9) 64.8 (2.4) 67.7 (2.1) 75.7 (2.6) (2.0) 76.2 (1.9) 81.2 (1.9) 81.7 (1.3) 83.6 (1.6) 0.01 Sex Men 57.2 (1.8) 63.9 (2.9) 61.5 (3.1) 68.5 (1.8) 71.7 (1.3) 0.01 Women 68.6 (2.9) 70.7 (2.1) 77.5 (2.1) 76.3 (1.2) 82.5 (2.1) 0.01 Race/ethnicity* Non-Hispanic white 65.1 (2.0) 68.4 (2.4) 71.9 (3.2) 74.9 (1.0) 78.5 (2.0) 0.01 Non-Hispanic black 64.5 (1.6) 66.8 (3.3) 72.8 (2.4) 70.2 (2.3) 75.3 (2.0) 0.01 Mexican American 42.8 (3.8) 57.9 (4.9) 44.9 (5.1) 62.2 (2.0) 68.1 (2.8) 0.01 Health insurance status Insured 66.0 (1.9) 70.5 (2.2) 73.3 (2.7) 76.8 (1.0) 80.2 (1.4) 0.01 Uninsured 33.7 (2.8) 43.9 (5.0) 39.4 (5.6) 40.8 (3.6) 54.8 (2.5) With comorbidities Diabetes mellitus 86.6 (2.4) 88.2 (1.9) 87.5 (2.4) 91.3 (1.8) 93.4 (1.1) 0.01 Chronic kidney disease 79.0 (2.8) 83.9 (1.8) 85.6 (1.6) 87.2 (2.1) 88.3 (1.4) 0.01 Cardiovascular disease 90.3 (1.9) 88.9 (1.2) 89.8 (2.7) 90.6 (1.9) 94.0 (1.8) 0.11 Without comorbidities 50.8 (2.6) 55.0 (3.0) 60.8 (3.0) 62.2 (1.6) 67.8 (2.1) 0.01 Multiple antihypertensive drug use, Overall 36.8 (2.1) 42.8 (2.1) 42.7 (2.2) 45.2 (2.0) 47.7 (1.1) 0.01 Age, ye (4.9) 20.5 (4.5) 12.2 (2.6) 21.8 (3.8) 19.2 (3.7) (3.2) 36.0 (3.8) 36.2 (2.5) 36.7 (3.4) 42.1 (1.9) (2.2) 52.8 (2.0) 53.7 (1.8) 56.5 (2.1) 56.1 (1.7) 0.01 Sex Men 33.2 (2.9) 40.1 (2.6) 36.5 (2.9) 41.3 (2.8) 45.8 (1.9) 0.01 Women 39.7 (2.5) 45.3 (2.2) 48.4 (2.7) 48.8 (2.0) 49.5 (1.8) 0.01 Race/ethnicity* Non-Hispanic white 38.8 (2.3) 43.4 (2.2) 44.1 (2.8) 46.4 (2.3) 48.2 (1.4) 0.01 Non-Hispanic black 41.3 (2.9) 43.5 (3.8) 48.5 (2.5) 49.4 (3.6) 51.7 (1.9) 0.01 Mexican American 18.6 (3.1) 32.8 (3.9) 20.3 (4.1) 34.2 (2.5) 43.0 (3.0) 0.01 Health insurance status Insured 66.0 (1.9) 70.5 (2.2) 73.3 (2.7) 76.8 (1.0) 80.2 (1.4) 0.01 Uninsured 33.7 (2.8) 43.9 (5.0) 39.4 (5.6) 40.8 (3.6) 54.8 (2.5) With comorbidities Diabetes mellitus 56.3 (4.9) 59.5 (2.0) 58.2 (4.5) 66.4 (3.4) 63.9 (2.5) 0.06 Chronic kidney disease 54.2 (3.5) 65.5 (3.0) 62.0 (2.9) 65.0 (3.1) 65.6 (3.0) 0.03 Cardiovascular disease 64.2 (3.1) 70.5 (2.3) 69.5 (2.8) 71.7 (2.6) 75.1 (2.5) 0.01 Without comorbidities 24.8 (2.5) 30.0 (2.5) 32.5 (1.5) 33.2 (2.1) 35.5 (2.2) 0.01 NHANES indicates National Health and Nutrition Examination Surveys. *Data shown only for major race/ethnic groups in NHANES sample design, other race/ethnic groups not shown, but included in total estimate. P trend

5 Gu et al Hypertension Treatment and Control 2109 Table 2. Prevalence of Antihypertensive Medication Use Among Hypertensive Adults Over Time by Drug Classes: United States 2001 to 2010 Drug Classes and Therapy Discussion This is the first large-scale national person-level study to document the trends of antihypertensive medication use, drug use patterns, and disease-specific BP control rates both before and after the publication of the JNC 7 hypertension treatment guidelines. Our data show that, in the United States, the prevalence of antihypertensive medication use continues to significantly increase among adults with hypertension. These recent increases appear to be almost exclusively driven by a significant increase in the proportion of hypertensive people who were taking multiple antihypertensive agents, and hypertensive people on polytherapy regimens were the most likely to meet their BP goals. By the 2009 to 2010 time period 77.3% of US adults with hypertension used at least 1 antihypertensive medication, nearly two thirds of them were taking multiple antihypertensive agents, and 60.3% of treated hypertensive people had controlled their BP to the JNC 7 goal. Adequate BP control is considered to be paramount in reducing the risk of adverse cardiovascular events, and the benefits of more aggressive therapeutic approaches to hypertension are especially pronounced in high-risk groups such as P trend Diuretics Overall 30.0 (2.2) 32.1 (1.7) 34.0 (2.2) 34.7 (2.0) 35.8 (1.2) 0.01 Monotherapy 2.7 (0.6) 2.5 (0.4) 4.8 (0.6) 2.7 (0.5) 3.3 (0.6) 0.46 Polytherapy 27.3 (2.1) 29.6 (1.7) 29.2 (2.0) 32.0 (1.9) 32.5 (1.3) 0.02 Thiazide diuretics Overall 22.4 (2.1) 24.2 (1.4) 26.3 (1.9) 26.7 (1.8) 27.6 (1.3) 0.02 Monotherapy 1.6* 1.6 (0.4) 4.1 (0.6) 2.1 (0.5) 2.5 (0.4) 0.09 Polytherapy 20.8 (1.9) 22.5 (1.4) 22.2 (1.7) 24.5 (1.6) 25.1 (1.3) blockers Overall 20.3 (1.3) 25.4 (1.4) 30.1 (2.2) 27.7 (1.0) 31.9 (1.6) 0.01 Monotherapy 4.6 (0.7) 5.9 (0.9) 8.5 (0.9) 5.6 (0.8) 5.9 (0.5) 0.28 Polytherapy 15.7 (1.1) 19.6 (1.4) 21.6 (2.0) 22.0 (1.1) 25.9 (1.5) 0.01 Calcium channel blockers Overall 19.2 (1.7) 20.7 (1.4) 21.7 (1.7) 19.4 (1.3) 20.9 (1.4) 0.65 Monotherapy 5.5 (0.8) 3.8 (0.5) 3.1 (0.5) 3.2 (0.8) 3.7 (0.5) 0.05 Polytherapy 13.7 (1.2) 16.9 (1.3) 18.6 (1.4) 16.2 (1.2) 17.2 (1.5) 0.14 Angiotensin-converting enzyme inhibitors Overall 25.5 (1.2) 29.8 (2.0) 29.4 (1.7) 29.3 (1.7) 33.3 (1.1) 0.01 Monotherapy 9.7 (1.3) 8.8 (0.9) 6.9 (0.8) 9.3 (1.1) 11.2 (0.8) 0.33 Polytherapy 15.8 (1.0) 21.0 (1.6) 22.5 (1.7) 20.0 (1.6) 22.2 (0.6) 0.01 Angiotensin receptor blockers Overall 10.5 (1.0) 14.5 (1.2) 14.5 (1.3) 20.3 (1.3) 22.2 (1.6) 0.01 Monotherapy 3.0 (0.4) 2.9 (0.8) 3.2 (0.7) 5.9 (0.7) 4.9 (0.7) 0.01 Polytherapy 7.6 (0.9) 11.6 (0.8) 11.3 (1.3) 14.4 (1.2) 16.1 (1.1) 0.01 People who reported taking a single-pill antihypertensive combination drug or 1 antihypertensive drug were counted once within each drug class. *Estimate is unstable: the relative standard error is 30%. patients with diabetes mellitus or chronic kidney disease. 3,24,25 In an analysis of a retrospective time series data from 27 provider groups and managed-care organizations between 1998 and 2006, Jackson et al 26 reported that the proportion of all hypertensive patients with disease-specific BP control rates rose from 40.8% before JNC 7 to 49.3% after JNC 7. Another managed-care organization study recently showed that JNC 7 BP control goals were not achieved among most hypertensive patients with diabetes mellitus. 27 However, despite the fact that reported levels of BP control may vary greatly between recent publications depending on the particular study population, the time frame, and the specific definitions of hypertension, treatment, and control, most studies find a substantial increase in the attainment of BP control after the publication of the JNC 7 treatment guidelines. Because of the high prevalence of hypertension and the serious cardiovascular consequences of untreated, inadequately treated, and uncontrolled hypertension, hypertension control continues to be an important public health concern. Thus, the selection of drugs for initial and continuing longterm therapy of hypertension has large-scale public health and economic implications. Previous data on national hypertension treatment patterns showed an increased trend in

6 2110 Circulation October 23, 2012 Table 3. Prevalence of Commonly Used Antihypertensive Agents Among Hypertensive Adults Over Time: United States 2001 to 2010 Drug Classes and Generic Drug Name , , , , , P trend Diuretics Hydrochlorothiazide 7.3 (0.9) 9.5 (1.0) 12.5 (1.4) 9.8 (0.9) 10.7 (1.0) 0.02 Furosemide 6.2 (0.7) 6.4 (0.7) 6.7 (0.7) 6.8 (0.6) 7.0 (0.6) 0.37 Hydrochlorothiazide; triamterene 4.4 (0.8) 4.4 (0.7) 4.0 (0.6) 4.0 (0.6) 3.1 (0.5) blockers Metoprolol 6.2 (0.7) 10.7 (1.1) 15.0 (2.1) 12.0 (0.8) 15.1 (0.8) 0.01 Atenolol 7.9 (1.0) 8.8 (0.9) 9.9 (1.0) 8.9 (1.0) 8.5 (0.8) 0.64 Carvedilol 0.4* 1.5 (0.4) 1.4 (0.3) 1.8 (0.3) 4.3 (0.6) 0.01 Calcium channel blockers Amlodipine 5.0 (0.7) 7.4 (0.8) 8.2 (0.9) 8.4 (0.6) 10.4 (0.9) 0.01 Diltiazem 4.7 (0.6) 3.8 (0.5) 3.9 (0.6) 2.6 (0.5) 2.5 (0.4) 0.01 Nifedipine 2.6 (0.6) 2.2 (0.5) 2.2 (0.5) 1.9 (0.3) 1.8 (0.4) 0.16 Verapamil 3.9 (0.5) 2.3 (0.5) 2.2 (0.4) 1.3 (0.3) 1.8 (0.3) 0.01 Angiotensin-converting enzyme inhibitors Lisinopril 10.4 (1.4) 11.2 (1.3) 14.7 (1.7) 14.6 (1.0) 20.1 (1.5) 0.01 Lisinopril; hydrochlorothiazide 1.5 (0.3) 1.2 (0.2) 1.8 (0.6) 2.5 (0.3) 3.9 (0.6) 0.01 Angiotensin receptor blockers Valsartan 2.6 (0.3) 3.7 (0.7) 3.8 (0.6) 4.7 (0.5) 5.2 (0.5) 0.01 Losartan 2.1 (0.5) 2.1 (0.3) 1.8 (0.4) 3.5 (0.6) 4.1 (0.6) 0.01 Olmesartan 0.2* 0.9* 2.4 (0.4) 2.0 (0.5) 0.01 *Estimate is unstable: the relative standard error is 30%. polytherapy with CCBs, -blockers, or ACE inhibitors, but a decreased trend in monotherapy with diuretics or -blockers from 1988 to Clinically, the largest controlled clinical trial of antihypertensive drugs demonstrated that the thiazide diuretics were as effective as the more expensive ACE inhibitors and CCBs in lowering BP and cardiovascular outcomes. 8 The JNC 7 guideline specifically emphasizes the use of thiazide diuretics as first-line therapy agents for most hypertensive patients and the use of multiple antihypertensive agents from different classes to achieve BP control goals. 3 As observed in our data, the use of multiple antihypertensive agents containing thiazide diuretics, -blockers, or ACE inhibitors increased by 20%, 65%, or 41% from 2001 to The use of multiple antihypertensive agents containing angiotensin receptor blockers doubled. However, the use of thiazide diuretics was still comparatively low. Only 1 in every 4 hypertensive people received treatment regimens that contained a thiazide diuretic. Other studies from pharmacy database or physician-based surveys also found an increased prescribing of thiazide diuretics shortly after the publication of the JNC 7 hypertension treatment guidelines ,28 Importantly, at the same time that there was an upward trend in antihypertensive medication use, our data also showed a significant increase in BP control rates overall and across almost all examined subgroups. This general improvement in BP control observed in the US hypertensive population may be associated with an increased use of combination therapy, because hypertensive people who received polytherapy were more likely to meet BP goals than those who only received monotherapy regimens. A retrospective analysis of the medical records of patients with newly diagnosed hypertension suggests that reliance on monotherapy was the single most important factor contributing to the low rate of BP control in that study. 29 Large clinical trials demonstrated that most patients with hypertension can achieve and sustain adequate BP control only with the use of multiple antihypertensive drugs. 3,4 The value of using multiple antihypertensive drugs improves the overall efficacy of drugs, reduces dosedependent side effects, and increases patient s adherence to medication regimens. 30,31 Although hypertensive individuals from the general population usually have less complicated medical condition profiles than those who participate in antihypertensive drug clinical trials, the data reported here support the important role of antihypertensive polytherapy for achieving BP goals. Although there is a general upward trend in antihypertensive medication use and BP control in the US adult hypertensive population and in most demographic subgroups, important disparities in antihypertensive medication use and therapeutic goal achievement continue to exist. In particular, the suboptimal use of antihypertensive medication and poor hypertension control among Mexican Americans has been recognized for a long time. In our data, Mexican- American hypertensive people were less likely to take antihypertensive medication and less likely to use multiple antihypertensive agents in comparison with their non-hispanic white counter-

7 Gu et al Hypertension Treatment and Control 2111 Table 4. Blood Pressure Control Rates Among Hypertensive Adults Over Time by Age, Sex, Race/Ethnicity, Health Insurance Status, and Comorbid Conditions: United States 2001 to 2010 Characteristics , , , , , P trend Among all hypertensive people Overall 28.7 (1.5) 33.5 (2.2) 38.0 (1.8) 41.9 (1.9) 47.2 (1.6) 0.01 Age, y (3.8) 27.5 (6.9) 21.7 (4.4) 38.6 (6.4) 28.6 (4.9) (2.3) 37.3 (3.8) 44.0 (2.7) 44.4 (3.0) 51.5 (2.2) (1.2) 31.4 (2.1) 36.1 (2.2) 40.6 (1.9) 47.0 (1.8) 0.01 Sex Men 28.0 (2.2) 36.8 (3.4) 37.1 (2.5) 39.6 (2.3) 43.3 (2.4)) 0.01 Women 29.2 (2.0) 30.3 (2.5) 38.8 (2.0) 43.9 (1.9) 50.8 (2.0) 0.01 Race/ethnicity* Non-Hispanic white 30.0 (1.8) 35.3 (2.7) 39.1 (1.9) 43.8 (2.3) 50.3 (1.7) 0.01 Non-Hispanic black 24.8 (1.9) 31.7 (3.0) 36.7 (1.6) 38.7 (2.3) 41.4 (2.7) 0.01 Mexican American 25.3 (3.9) 24.7 (3.7) 26.6 (3.8) 35.2 (2.2) 33.8 (2.0) 0.01 Health insurance status Insured 29.7 (1.5) 34.9 (2.4) 39.3 (2.0) 49.3 (2.1) 49.6 (1.5) 0.01 Uninsured 17.8 (3.4) 22.6 (3.8) 26.7 (5.3) 27.0 (3.3) 28.7 (2.1) 0.01 With comorbidity Diabetes mellitus 30.8 (3.2) 33.4 (3.8) 29.4 (3.3) 38.0 (3.3) 42.1 (2.2) 0.01 Chronic kidney disease 24.1 (2.6) 25.2 (3.3) 26.6 (3.2) 32.3 (3.7) 38.8 (2.9) 0.01 Cardiovascular disease 35.0 (2.9) 33.5 (2.8) 41.5 (3.6) 43.4 (2.7) 54.6 (2.4) 0.01 Without comorbidity 28.4 (2.1) 34.7 (2.8) 41.7 (2.6) 44.0 (1.9) 47.8 (2.3) 0.01 Among treated hypertensive people Overall 44.6 (1.5) 48.9 (2.5) 53.0 (2.0) 56.1 (2.0) 60.3 (1.3) 0.01 Age, y (8.3) 71.8 (6.6) 73.4 (8.7) 76.3 (6.1) 62.3 (6.7) (2.6) 59.0 (4.0) 64.6 (3.8) 64.5 (2.9) 67.0 (2.8) (1.2) 39.7 (2.9) 44.1 (2.4) 48.5 (1.9) 55.8 (1.6) 0.01 Sex Men 49.3 (3.3) 55.7 (3.1) 58.0 (3.0) 56.5 (2.7) 60.0 (2.8) 0.02 Women 41.3 (1.6) 42.9 (3.8) 49.2 (2.5) 55.8 (2.1) 60.6 (1.3) 0.01 Race/ethnicity* Non-Hispanic white 46.1 (2.0) 51.3 (2.8) 52.9 (2.3) 57.3 (2.4) 63.7 (1.3) 0.01 Non-Hispanic black 38.6 (2.5) 46.6 (4.4) 49.9 (2.9) 52.8 (2.5) 52.6 (2.6) 0.01 Mexican American 45.8 (8.4) 38.0 (4.7) 55.0 (4.8) 51.2 (2.2) 48.0 (3.1) 0.35 Health insurance status Insured 44.3 (1.5) 48.9 (2.7) 52.6 (2.2) 55.8 (2.0) 61.0 (1.2) 0.01 Uninsured 51.5 (7.7) 48.0 (8.3) 58.7 (9.0) 61.3 (5.2) 52.5 (3.9) 0.45 With comorbidity Diabetes mellitus 35.6 (4.0) 32.5 (4.1) 33.5 (3.7) 40.5 (3.0) 44.6 (2.4) 0.02 Chronic kidney disease 29.6 (3.0) 29.1 (3.6) 31.1 (3.6) 36.1 (4.1) 43.7 (3.0) 0.01 Cardiovascular disease 39.0 (3.3) 36.8 (3.0) 44.5 (3.5) 47.0 (2.7) 57.4 (2.3) 0.01 Without comorbidity 54.7 (2.4) 63.3 (2.9) 66.7 (2.7) 68.4 (1.9) 69.5 (2.0) 0.01 Polytherapy Single-pill combination 44.2 (5.6) 58.8 (6.0) 61.6 (5.9) 68.6 (3.6) 68.8 (4.0) Multiple-pill combination 44.9 (3.1) 45.3 (4.0) 52.1 (2.3) 51.4 (2.4) 59.3 (1.6) NHANES indicates National Health and Nutrition Examination Surveys. *Data shown only for major race/ethnic groups in NHANES sample design; other race/ethnic groups not shown, but included in total estimate.

8 2112 Circulation October 23, 2012 Table 5. Multivariable-Adjusted Prevalence Ratios of Antihypertensive Medication Use and Blood Pressure Control: United States 2005 to 2010 Prevalence Ratio (95% CI) Use of Any Use of Multiple Antihypertensive Antihypertensive Use of Thiazide Treated Blood Parameter Drugs Drugs Diuretics Pressure Control Age, y (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) ( )* 2.30 ( )* 2.12 ( )* 0.76 ( ) ( )* 3.22 ( )* 2.34 ( )* 0.46 ( )* Sex Men 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Women 1.57 ( )* 1.22 ( ) 1.50 ( )* 0.98 ( ) Race/ethnicity Non-Hispanic white 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Non-Hispanic black 0.97 ( ) 1.34 ( )* 1.50 ( )* 0.71 ( )* Mexican American 0.61 ( )* 0.73 ( )* 0.69 ( )* 0.77 ( )* Health insurance status Uninsured 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Insured 2.97 ( )* 2.16 ( )* 1.77 ( )* 1.18 ( ) Diabetes mellitus Absent 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Present 3.80 ( )* 1.87 ( )* 1.08 ( ) 0.47 ( )* Chronic kidney disease Absent 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Present 1.61 ( )* 1.67 ( )* 1.14 ( ) 0.41 ( )* Cardiovascular disease Absent 1.00 (ref) 1.00 (ref) 1.00 (ref) 1.00 (ref) Present 3.21 ( )* 2.90 ( )* 0.89 ( ) 0.97 ( ) Treatment regimen Monotherapy 1.00 (ref) Single-pill combination 1.55 ( )* Multiple-pill combination 1.26 ( ) Multivariable adjusted for all variables listed in the table. CI indicates confidence interval. *Significantly different from reference, P Significantly different from reference, P Other race/ethnic people included in the regression model but did not show in the table. parts. In addition, nonpersistence with prescribed medication was 49% higher in Hispanics than in other racial groups. 32 So, their being less likely to be prescribed medicine when hypertension is present, their higher reliance on monotherapy when medicine is prescribed, and their nonpersistence with prescribed medication regimens may all contribute to the inadequate BP control seen among Mexican Americans. Other factors, including education, income, and financial strain may also contribute to variations across race/ethnicity groups in treated but uncontrolled hypertension. 33 Previous national data documented that hypertensive women were more likely to receive antihypertensive treatment but less likely to have BP controlled in comparison with hypertensive men. 34 The data presented here indicate that the sex difference in antihypertensive treatment prevalence continues to exist; however, in the 3 most recent NHANES cycles, BP control rates among treated hypertensive people are now essentially the same between men and women. There is still a gap between treatment and control in key US subpopulations. Older hypertensive people are more likely to use antihypertensive medications but less likely to meet BP goals than younger hypertensive people. Treated but uncontrolled hypertension is common among non-hispanic black people, and among those with diabetes mellitus or chronic kidney disease, even though they may be treated more aggressively than their counterparts. Lower control rates observed in patients with diabetes mellitus or chronic kidney disease were also related to the use of the condition-specific JNC 7 goals. Approximately 20% of the uncontrolled hypertension for those with diabetes mellitus or chronic kidney disease is attributable to the use of this more stringent 130/80 mm Hg threshold. The major strength of the present study is that the NHANES data provide a large, nationally representative sample of the noninstitutionalized US population. This in-

9 Gu et al Hypertension Treatment and Control 2113 cludes oversampling of key demographic subsamples such as older people, non-hispanic blacks, and Mexican Americans, resulting in increased precision of estimates for these groups, which are often underrepresented in published studies on hypertension. In addition, the NHANES prescription medication data were collected by trained interviewers by the use of a standardized in-person, household interview protocol, with verification of reported medications with drug containers. This helps to eliminate known biases associated with selfreported of medication use. However, several potential limitations of our study should be noted when interpreting our findings. First, survey participants were asked to recall medications used in the past month to minimize recall bias. Thus, hypertensive subjects who used an antihypertensive drug at any time before the 1-month recall period are classified as nonusers. Hence, our prevalence estimates could be affected to some extent by the particular choice for the study recall period. Second, the data collected also do not allow us to determine whether the drug reported was the initial hypertension drug that was prescribed for and used by the person or whether other drugs may have been prescribed and used at an earlier time. This limits our ability to address adherence to JNC 7 recommendations regarding drug classes for initial treatment of uncomplicated hypertension. Third, although the auscultatory method of BP measurement in NHANES is fully consistent with national standards, NHANES measurements are performed only at a single point in time, rather than on 2 separate occasions. It is therefore possible that some subjects were misclassified with regard to hypertension or hypertension control status. This potential problem was minimized to some extent by taking the average of 3 separate measurements obtained under the same standardized conditions at the time of the NHANES examination. In summary, antihypertensive medication use and BP control among US adults with hypertension continues to increase. More hypertensive patients are receiving combination therapy now than a decade ago. The increased use of multiple antihypertensive drugs apparently has contributed to substantial improvement in BP control in the treated hypertensive population. However, disparities in hypertension treatment and control still exist among specific subpopulations. More efforts are needed to close the gap between treatment and control and to maximize the public health and clinical benefits among those high-risk subpopulations. Sources of Funding This study was funded by the National Center for Health Statistics, Centers for Disease Control and Prevention and the National Heart, Lung, and Blood Institute, National Institutes of Health. None. Disclosures References 1. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, William B. Borden, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics 2012 update: a report from the American Heart Association. 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Gender differences in hypertension treatment, drug utilization patterns, and blood pressure control among US adults with hypertension: data from the National Health and Nutrition Examination Survey Am J Hypertens. 2008;21: CLINICAL PERSPECTIVE Trends in antihypertensive medication use and blood pressure control for US adults were examined at a population level during the decade 2001 to 2010 with the use of National Health and Nutrition Examination Survey data. The decade showed significant increases in the percentage of people with hypertension who are treated with medication (from 64% to 77%). Blood pressure control rates have improved from 29% to 47%, and treated control rates have improved from 45% to 60%. Consistent with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, significantly more patients with hypertension are on combination therapy now than a decade ago. In addition, the current data indicate that those receiving antihypertensive polytherapy were significantly more likely to meet their blood pressure goals than those who were on monotherapy regimens. Increased usage of multiple antihypertensive drugs has made substantial contributions to the overall control of blood pressure in the general population. This underscores the important role of antihypertensive polytherapy for achieving blood pressure control previously demonstrated in clinical drug trials. Patients whose hypertension is not controlled with monotherapy could benefit from more effective polytherapy regimens. The data also identify key population subgroups that apparently continue to lag behind. Younger adults and Mexican-American people appeared to be undertreated, as did those without health insurance. Older adults and non-hispanic black people were more likely to be treated, but their hypertension was less likely to be controlled once they were on treatment. The same was true for those with chronic kidney disease and diabetes mellitus. Continued efforts are needed to close these gaps in treatment and to control rates and maximize the public health and clinical benefits of hypertensive therapy.