Abstract
Hypertension affects approximately one‐third of the US adults. This study investigated antihypertensive utilization patterns among hypertensive patients who were prescribed treatment, yet still experienced uncontrolled hypertension. Data from the Decision Resources Group Real World Evidence Data Repository US database (2015‐2016) were used to construct a cohort of uncontrolled hypertension patients to observe antihypertensive utilization patterns. Results for 5059 patients, with an average age of 57.8 (SD = 13.7), who had, on average 2.4 agents prescribed. Approximately half (51.9%) were female, and most were White (86.8%). More than one‐third (N = 1877; 37.1%) of patients were diagnosed with diabetes mellitus (DM) or chronic kidney disease (CKD) that could independently contribute to increased cardiovascular complications. Overall, the most common treatments prescribed, as percent of agents and as percent of patients, respectively, were diuretics (24.9%; 59.6%), followed by angiotensin‐converting enzyme inhibitors (ACEIs) (23.8%; 56.9%), beta‐blockers (BBs) (18.7%; 44.8%), calcium channel blockers (CCBs) (15.4%; 36.8%), and angiotensin II receptor blockers (ARBs) (13.5%; 32.3%). Approximately one‐tenth (10.5%) of the prescriptions were written for fixed‐dose combination therapies. Among patients diagnosed with DM and CKD (N = 200), the order of the most common agents was the same as the overall cohort. Only 5.6% of prescriptions written for these patients were fixed‐dose combination therapy. Based on clinical guidelines, which suggest using ACEIs, ARBs, or CCBs as first‐line therapy, and fixed‐dose combination therapy to increase adherence, this indicates over‐prescribing of BBs and under‐prescribing of fixed‐dose combination therapy. These findings illustrate the need to further investigate challenges faced by patients and providers in treatment decision‐making.
Keywords: antihypertensive therapy, clinical management of high blood pressure, diabetes, renal disease, resistant hypertension
1. INTRODUCTION
Hypertension is a common and harmful chronic condition that affects approximately one out of every three adults and contributes to more than 1000 deaths a day in the United States. 1 , 2 Hypertension contributed $48.6 billion in annual US healthcare expenditures, including healthcare services, prescription medications, and missed days of work. 3
Hypertension is one of the most important preventable contributors to morbidity and mortality. 4 , 5 Left uncontrolled, hypertension independently increases the risk for cardiovascular disease, including myocardial infarction (MI) and stroke, as well as renal failure. 6 , 7 , 8 , 9
Diabetes mellitus (DM) and chronic kidney disease (CKD) independently contribute to an increased risk of cardiovascular complications in patients with hypertension. 10 , 11 , 12 , 13 , 14 , 15 Combined, patients with DM or CKD with comorbid uncontrolled hypertension have a further increased risk of MI, angina pectoris, stroke, and cardiovascular‐related death, compared to patients with hypertension, DM, or CKD alone. 16 , 17 , 18 , 19 , 20 While it is known that hypertension control reduces cardiovascular complications in patients with both hypertension and DM, only about 30% of these patients meet their blood pressure (BP) goal. 21 , 22 , 23 , 24
Evidence has shown the benefit of antihypertensive agent treatment in reducing important health outcomes in people with hypertension. 4 , 5 Evidence‐based clinical guidelines combine formal research evidence and pragmatic clinical actions to guide clinicians on how to improve patient outcomes. The American Heart Association (AHA) have developed evidence‐based statements and recommendations for hypertension treatment. These recommendations include advice on when patients should begin treatment based on clinical outcomes and how patients should be treated based on race, age, and comorbid conditions, such as DM and CKD. 25
The AHA recommends thiazide diuretics, angiotensin‐converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), or calcium channel blockers (CCBs) as a first‐line therapy. Furthermore, the AHA states that improved adherence can be achieved with once‐daily drug dosing and fixed‐dose combination therapy. 25
Prior studies have shown low adherence to the hypertension guidelines in the United States. 26 The number of treatment visits for hypertension in the United States increased from 56.9 million to 83.3 million between 1997 and 2008, but declined to 70.9 million visits by 2012. 27 , 28
The objective of this study was to examine the landscape of antihypertensive agents prescribed among patients with health insurance who have been diagnosed with hypertension, received pharmaceutical treatment, and still experienced uncontrolled hypertension. Through this investigation, we aim to contribute to the body of evidence that evaluates how prescribers are following the evidence‐based guidelines for hypertension management.
2. METHODS
This study took an observational retrospective approach using real‐world data. Data were obtained from the Decision Resources Group (DRG) Real World Evidence Data Repository US database, 29 which includes medical and pharmacy claims, and electronic health record data. These data provide a set of patient records with tests ordered, test results, diagnoses, comorbidities, medications, therapies, and patient demographics.
Adult patients (18 years or older at the time of baseline record) were included in the study cohort if the patient, at any time in 2015, had: (a) a new diagnosis of hypertension with no prior diagnosis in 2014, and blood pressure (BP) defined as systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg for hypertension; or (b) SBP > 130 mm Hg or DBP > 80 mm Hg for patients with a diabetes mellitus (DM) or chronic kidney disease (CKD) diagnosis (Figure 1).
Figure 1.
Patient inclusion diagram. 1Hypertension (ICD‐9: 401*, ICD‐10: I10). 2Overlapping EHR, medical, and pharmacy claims data. 3Uncontrolled Blood Pressure defined as (1) SBP 140 mm Hg or diastolic BP (DBP) 90 mm Hg for uncomplicated hypertension or (2) SBP 130 mm Hg or DBP 80 mm Hg for patients with diabetes or chronic kidney disease (CKD) for complicated hypertension
Because of the open network nature of the databases used in the current analysis, patients’ continuous eligibility cannot be ascertained. Some medical or pharmacy claims may be outside of the claims network for which we have data access. To mitigate the risk of this resulting in missing data, all eligible patients had available medical claims, pharmacy claims, and electronic health record (EHR) data with at least one medical and pharmacy claim in the year pre‐diagnosis (2014), at least one medical and pharmacy claim and at least three documented visits where BP was recorded in the EHR data over the one‐year post‐diagnosis in the study observation period between January 2015 and December 2016.
Patients BP records were observed in each of the follow‐up visits in the EHR data over the one‐year post‐diagnosis observation period to verify continuing uncontrolled hypertension status. Antihypertensive medication was identified through pharmacy claims. A patient is considered to have use of an antihypertensive if a prescription was filled and transaction completed any time in the post‐index observation period in the pharmacy claims. Patient use of a given class was determined by at least one filled pharmacy claim for a therapy in that class.
Patients were excluded from the study cohort if, at time of diagnosis, (a) the patient had current signs of hypertensive emergency, including acute angina, stroke, or renal failure; (b) the patient's SBP was greater than 200 mm Hg or DBP was greater than 114 mm Hg; (c) the patient experienced systolic dysfunction with a left ventricular ejection fraction < 35% documented by echocardiography, nuclear medicine study, or ventriculography; (d) the patient's glomerular filtration rate was <20 mL/min or proteinuria > 1 g/d; (e) the patient was pregnant; (f) the patient experienced pulmonary hypertension or sleep apnea, unless treated by continuous positive airway pressure ventilation or bilevel positive airway pressure ventilation; or (g) the patient resided at a nursing home or had a diagnosis of dementia. Additionally, patients were excluded if, in the 6 months prior to diagnosis, (h) the patient had a history of MI, or unstable angina; (i) the patient had a diagnosis of cirrhosis or hepatitis B or C infection; or (j) patient had no antihypertensive prescription claims in the 1‐year post‐diagnosis observation period.
Univariate distributions were inspected for normality, outliers, skewness, or other abnormalities within the distribution. Univariate descriptive statistics, including means, standard deviations, and proportions, were calculated for study variables. Data were analyzed using the standard statistical packages of StataCorp. 2017. Stata Statistical Software: Release 15. StataCorp LLC.
3. RESULTS
In total, 5059 patients met inclusion and exclusion criteria (Figure 1). Of the 5059 patients in the study cohort, the average age was 57.8 (standard deviation (SD) = 13.7) and 68.7% were aged under 65 years. Approximately half of patients were female (51.9%), and the majority were White (86.8%). About 11% of the patients were African American and 1.3% Latino. Less than 1% of the patients were Asian/Pacific Islander or other, respectively; 87.7% of the patients identified as non‐Hispanic.
With respect to geographic distribution, 36.3% of the cohort lived in the South, 31.6% in the Midwest, 11.4% in the Northeast, and 5.9% in the West, with a few additional patients living in either Puerto Rico or the US Virgin Islands. Geographic location was not classified in the data for approximately 15% of patients.
Patients were largely covered by commercial insurance (44.8%), with 21.1% covered under Medicare, 7.8% covered under Medicaid, and 26.3% classified under another payer source.
One thousand eight hundred and seventy‐seven (37.1%) patients had been diagnosed with at least one comorbid condition that could independently contribute to an increased risk of cardiovascular complications; 28.9% (N = 1462) were diagnosed with DM; 4.2% (N = 215) were diagnosed with CKD; and 3.9% (N = 200) were diagnosed with both DM and CKD (Table 1).
Table 1.
Patient demographics and characteristics
| All patients | Patients without diabetes or CKD | Diabetes patients a | CKD patients b | Patients with diabetes and CKD | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| N = 5059 | N = 3182 (62.9%) | N = 1462 (28.9%) | N = 215 (4.2%) | N = 200 (3.9%) | ||||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | Mean | SD | |
| Age | 57.8 | 13.7 | 56.6 | 12.9 | 61.9 | 12.5 | 67.2 | 13.7 | 66.8 | 12.4 |
| Antihypertensive agents prescribed over the 1‐y follow‐up | 2.4 | 1.3 | 2.3 | 1.3 | 2.5 | 1.3 | 2.7 | 1.4 | 3.2 | 1.5 |
| N | % | N | % | N | % | N | % | N | % | |
|---|---|---|---|---|---|---|---|---|---|---|
| Age class | ||||||||||
| Aged under 65 | 3475 | 68.7 | 2440 | 76.7 | 877 | 60.0 | 83 | 38.6 | 75 | 37.5 |
| Aged 65 or older | 1584 | 31.3 | 742 | 23.3 | 585 | 40.0 | 132 | 61.4 | 125 | 62.5 |
| Gender | ||||||||||
| Female | 2626 | 51.9 | 1668 | 52.4 | 767 | 52.5 | 103 | 47.9 | 88 | 44.0 |
| Male | 2433 | 48.1 | 1514 | 47.6 | 695 | 47.5 | 112 | 52.1 | 112 | 56.0 |
| Race | ||||||||||
| White | 4392 | 86.8 | 2842 | 89.3 | 1223 | 83.7 | 171 | 79.5 | 156 | 78.0 |
| African American/Black | 559 | 11.1 | 284 | 8.9 | 197 | 13.5 | 40 | 18.6 | 38 | 19.0 |
| Latino | 63 | 1.3 | 36 | 1.1 | 21 | 1.4 | 2 | 0.9 | 4 | 2.0 |
| Asian/Pacific Islander | 45 | 0.9 | 20 | 0.6 | 21 | 1.4 | 2 | 0.9 | 2 | 1.0 |
| Ethnicity | ||||||||||
| Non‐Hispanic | 4437 | 87.7 | 2803 | 88.1 | 1281 | 87.6 | 179 | 83.3 | 174 | 87.0 |
| Hispanic | 179 | 3.5 | 101 | 3.2 | 64 | 4.4 | 3 | 1.4 | 11 | 5.5 |
| Other | 33 | 0.7 | 17 | 0.5 | 8 | 0.6 | 4 | 1.9 | 4 | 2.0 |
| Unknown | 410 | 8.1 | 261 | 8.2 | 109 | 7.5 | 29 | 13.5 | 11 | 5.5 |
| Geographic region | ||||||||||
| South | 1834 | 36.3 | 1071 | 33.7 | 585 | 40.0 | 89 | 41.4 | 89 | 44.5 |
| Midwest | 1596 | 31.6 | 1123 | 35.3 | 398 | 27.2 | 38 | 17.7 | 37 | 18.5 |
| Northeast | 576 | 11.4 | 348 | 10.9 | 171 | 11.7 | 29 | 13.5 | 28 | 14.0 |
| West | 299 | 5.9 | 184 | 5.8 | 84 | 5.8 | 18 | 8.4 | 13 | 6.5 |
| US Virgin Islands or Puerto Rico | 3 | 0.1 | 3 | 0.1 | – | – | – | – | – | – |
| Unknown | 751 | 14.8 | 453 | 14.2 | 224 | 15.3 | 41 | 19.1 | 33 | 16.5 |
| Antihypertensive agents prescribed | ||||||||||
| 1 | 2138 | 42.3 | 1482 | 46.6 | 526 | 36.0 | 81 | 37.7 | 49 | 24.5 |
| 2 | 1483 | 29.3 | 936 | 29.4 | 449 | 30.7 | 46 | 21.4 | 52 | 26.0 |
| 3 or more | 1438 | 28.4 | 764 | 24.0 | 487 | 33.3 | 88 | 40.9 | 99 | 49.5 |
| Prescriptions written c | ||||||||||
| Single‐drug monotherapy | 9796 | 89.5 | 5263 | 87.7 | 3656 | 91.6 | 1056 | 94.8 | 551 | 94.4 |
| Fixed‐dose combination therapy d , e | 1151 | 10.5 | 726 | 12.3 | 334 | 8.4 | 58 | 5.2 | 33 | 5.6 |
Patients with diabetes without CKD.
Patients with CKD without diabetes.
Antihypertensive agent prescriptions, patients can have multiple agents prescribed over course of observation period.
Antihypertensive agents that contain ≥2 different medication within one tablet/capsule/dose.
10 947 prescriptions yielded 12 101 agents.
3.1. Antihypertensive agent utilization patterns
Because some of the prescriptions contained two antihypertensives (fixed‐dose combination therapy), a total of 10 947 prescriptions yielded 12 101 agents. Overall, the mean number of antihypertensive agents per patient over the observation period was 2.4 (SD = 1.3), with 42.3% of patients receiving one agent, 29.3% of patients receiving two agents, and 28.4% receiving three or more agents. If a patient had more than one antihypertensive reported, it could be either due to therapy switching, multiple concurrent prescriptions, or fixed‐dose combination therapy. Among the 10 947 prescriptions, we found that 1151 (10.5%) were for fixed‐dose combination therapies (Table 2).
Table 2.
Overall antihypertensive utilization patterns among observed patients by agent
| N a , b | % Prescribed agents N = 12 101 b | % Patients, N = 5059 | |
|---|---|---|---|
| Antihypertensive agent | |||
| Diuretic | 3018 | 24.9 | 59.6 |
| [Thiazide] | [2131] | [17.6] | [42.1] |
| [Loop] | [753] | [6.2] | [14.9] |
| [Potassium‐sparing] | [134] | [1.1] | [2.6] |
| Angiotensin‐converting enzyme inhibitor (ACEI) | 2880 | 23.8 | 56.9 |
| Beta‐blocker (BB) | 2264 | 18.7 | 44.8 |
| Calcium channel blocker (CCB) | 1864 | 15.4 | 36.8 |
| Angiotensin receptor blocker (ARB) | 1632 | 13.5 | 32.3 |
| Centrally acting antihypertensive | 252 | 2.1 | 5.0 |
| Aldosterone antagonist | 185 | 1.5 | 3.7 |
| Direct renin inhibitor | 6 | 0.1 | 0.1 |
Antihypertensive agent prescriptions, patients can have multiple agents prescribed over course of observation period.
Fixed‐dose combination therapies were divided into their individual compound agent.
Because some of the prescription contained two or more antihypertensives, a total of 1151 combination products yielded 2305 agents. Overall, the most common treatment class prescribed in this cohort by percent of agents and percent of patients, respectively, was diuretics (24.9%; 59.6%) (17.6%; 42.1% thiazide, 6.2%; 14.9% loop, and 1.1%; 2.6% potassium‐sparing diuretics), followed by angiotensin‐converting enzyme (ACE) inhibitors (23.8%; 56.9%), beta‐blockers (18.7%; 44.8%), calcium channel blockers (CCB) (15.4%; 36.8%), angiotensin receptor blockers (ARB) (13.5%; 32.3%), centrally acting antihypertensives (2.1%; 5.0%), and aldosterone antagonists (1.5%; 3.7%). Direct renin inhibitors were prescribed <1% of the time.
3.2. Antihypertensive agent utilization patterns by comorbidity (CKD and/or DM)
We examined utilization patterns among patients with a diagnosis of both DM and CKD as well as those patients with no diagnosis of DM nor CKD.
Among patients with no diagnosis of either DM or CKD (N = 3182), the most common treatment prescribed by percent of agents and percent of patients, respectively, was diuretics (25.4%; 57.0%) (20.4%; 45.8% thiazide, 3.8%; 8.6% loop, and 1.2%; 2.6 potassium‐sparing diuretics), followed by ACE inhibitors (24.6%; 55.3%), beta‐blockers (17.9%; 40.4%), CCBs (15.1%; 33.8%), ARBs (13.7%; 30.8%), centrally acting antihypertensives (2.0%; 4.5%), aldosterone antagonists (1.2%; 2.7%), and direct renin inhibitors (<1.0) (Table 3).
Table 3.
Antihypertensive utilization patterns among observed patients by agent and comorbidity
| Patients without diabetes or CKD | Diabetes patients a | CKD patients b | Patients with diabetes and CKD | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N = 3182 patients (62.9%) | N = 1462 patients (28.9%) | N = 215 patients (4.2%) | N = 200 patients (3.9%) | |||||||||
| N = 7150 prescribed agents (59.0%) | N = 3718 prescribed agents (31.2%) | N = 589 prescribed agents (4.9%) | N = 644 prescribed agents (5.3%) | |||||||||
| N c , d | % Prescribed agents | % Patients | N c , d | % Prescribed agents | % Patients | N c , d | % Prescribed agents | % Patients | N c , d | % Prescribed agents | % Patients | |
| Antihypertensive agent | ||||||||||||
| Diuretic | 1814 | 25.4 | 57.0 | 892 | 24.0 | 61.0 | 140 | 23.8 | 65.1 | 172 | 26.7 | 86.0 |
| [Thiazide] | [1456] | [20.4] | [45.8] | [537] | [14.4] | [36.7] | 59 | [10.0] | [27.4] | 79 | [12.3] | [39.5] |
| [Loop] | [274] | [3.8] | [8.6] | [313] | [8.4] | [21.4] | 77 | [13.1] | [35.8] | 89 | [13.8] | [44.5] |
| [Potassium‐sparing] | [84] | [1.2] | [2.6] | [42] | [1.1] | [2.9] | 4 | [0.7] | [1.9] | 4 | [0.6] | [2.0] |
| Angiotensin‐converting enzyme inhibitor (ACEI) | 1761 | 24.6 | 55.3 | 911 | 24.5 | 62.3 | 98 | 16.6 | 45.6 | 110 | 17.1 | 55.0 |
| Beta‐blocker (BB) | 1285 | 18.0 | 40.4 | 711 | 19.1 | 48.6 | 121 | 20.5 | 56.3 | 147 | 22.8 | 73.5 |
| Calcium channel blocker (CCB) | 1076 | 15.0 | 33.8 | 555 | 14.9 | 38.0 | 125 | 21.2 | 58.1 | 108 | 16.8 | 54.0 |
| Angiotensin receptor blocker (ARB) | 981 | 13.7 | 30.8 | 512 | 13.8 | 35.0 | 70 | 11.9 | 32.6 | 69 | 10.7 | 34.5 |
| Centrally acting antihypertensive | 143 | 2.0 | 4.5 | 69 | 1.9 | 4.7 | 21 | 3.6 | 9.8 | 19 | 3.0 | 9.5 |
| Aldosterone antagonist | 87 | 1.2 | 2.7 | 66 | 1.8 | 4.5 | 13 | 2.2 | 6.0 | 19 | 3.0 | 9.5 |
| Direct renin inhibitor | 3 | 0.0 | 0.1 | 2 | 0.1 | 0.1 | 1 | 0.2 | 0.5 | ⎼ | ⎼ | ⎼ |
Patients with diabetes without CKD.
Patients with CKD without diabetes.
Antihypertensive agent prescriptions, patients can have multiple agents prescribed over course of observation period.
Fixed‐dose combination therapies were divided into their individual compound agent.
Among patients with a diagnosis of DM without CKD (N = 1462), the most common treatment prescribed was ACE inhibitors (24.5%; 62.3%), diuretics (24.0%; 61.0%) (14.4%; 36.7%, thiazide, 8.4%; 21.4% loop, and 1.1%; 2.9% potassium‐sparing diuretics), followed by beta‐blockers (19.1%; 48.6%), CCBs (14.9%; 38.0%), ARBs (13.8%; 35.0%), centrally acting antihypertensives (1.9%; 4.7%), aldosterone antagonists (1.8%; 4.5%), and direct renin inhibitors (<1.0%).
Among patients with a diagnosis of CKD without DM (N = 215), the most common treatment prescribed by agent and patient was diuretics (23.8%; 65.1%) (10.0%; 27.4% thiazide, 13.1%; 35.8% loop, and 0.7%; 1.9% potassium‐sparing diuretics), followed by beta‐blockers (21.5%; 58.1%), CCBs (20.5%; 56.3%), ACE inhibitors (16.6%; 45.6%), ARBs (11.9%; 32.6%), centrally acting antihypertensives (3.6%; 9.8%), aldosterone antagonists (2.2%; 6.0%), and direct renin inhibitors (<1.0%).
Among patients with a diagnosis of both DM and CKD (N = 200), the most common treatment prescribed by agent and patient was diuretics (26.7%; 86.0%) (12.3%; 39.5% thiazide, 13.8%; 44.5% loop, and 0.6%; 2.0% potassium‐sparing diuretics), followed by beta‐blockers (22.8%; 73.5%), ACE inhibitors (17.1%; 55.0%), CCBs (16.8%; 54.0%), ARBs (10.7%; 34.5%), and both centrally acting antihypertensives and aldosterone antagonists (3.0%; 9.5%), respectively.
3.3. Antihypertensive agent utilization patterns by race
We also explored differences in antihypertensive utilization patterns by patient race.
Among Caucasians, by percent of agents and percent of patients, respectively, diuretics (24.9%; 58.3%) (17.5%; 41.4% thiazide, 6.2%; 14.4% loop, and 1.0%; 2.5% potassium‐sparing diuretics), ACE inhibitors (24.3%; 57.0%), and beta‐blockers (19.0%; 44.6%) were the most prescribed agents. However, among African Americans, diuretics (25.7%; 71.5%) (16.9%; 47.0% thiazide, 7.1%; 19.9% loop, and 1.7%; 4.7% potassium‐sparing diuretics), ACE inhibitors (19.7%; 54.7%), and CCBs (19.3%; 53.7%) made up the majority of the agents prescribed. Among Latinos, we observed ACE inhibitors (27.0%; 63.5%), diuretics (23.0%; 54.0%) (18.9%; 44.4% thiazide, 4.1%; 9.5% loop, and no potassium‐sparing diuretics), and beta‐blockers (20.3%; 47.6%), and among Asian/Pacific Islanders, we observed ACE inhibitors (28.2%; 68.9%), ARBs (21.8%; 53.3%), and diuretics (20.0%; 48.9%) (18.2%; 44.4% thiazide, 1.8%; 4.4% loop, and no potassium‐sparing diuretics) made up the majority of the prescribed agents (Table 4).
Table 4.
Antihypertensive utilization patterns among observed patients by agent and race
| White | African American/Black | Latino | Asian/Pacific Islander | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N = 4392 patients (86.8%) | N = 559 patients (11.0%) | N = 63 patients (1.2%) | N = 45 patients (0.9%) | |||||||||
| N =10 289 prescribed agents (85.0%) | N = 1554 prescribed agents (12.8%) | N = 148 prescribed agents (1.2%) | N = 110 prescribed agents (0.9%) | |||||||||
| N a , b | % Prescribed agents | % Patients | N a , b | % Prescribed agents | % Patients | N a , b | % Prescribed agents | % Patients | N a , b | % Prescribed agents | % Patients | |
| Antihypertensive agent | ||||||||||||
| Diuretic | 2562 | 24.9 | 58.3 | 400 | 25.7 | 71.6 | 34 | 23.0 | 54.0 | 22 | 20.0 | 48.9 |
| [Thiazide] | [1820] | [17.7] | [41.4] | 263 | [16.9] | [47.0] | [28] | [18.9] | [44.4] | 20 | [18.2] | [44.4] |
| [Loop] | [634] | [6.2] | [14.4] | 111 | [7.1] | [19.9] | [6] | [4.1] | [9.5] | 2 | [1.8] | [4.4] |
| [Potassium‐sparing] | [108] | [1.0] | [2.5] | 26 | [1.7] | [4.7] | [⎼] | [⎼] | [⎼] | ⎼ | [⎼] | [⎼] |
| Angiotensin‐converting enzyme inhibitor (ACEI) | 2503 | 24.3 | 57.0 | 306 | 19.7 | 54.7 | 40 | 27.0 | 63.5 | 31 | 28.2 | 68.9 |
| Beta‐blocker (BB) | 1960 | 19.0 | 44.6 | 258 | 16.6 | 46.2 | 30 | 20.3 | 47.6 | 16 | 14.5 | 35.6 |
| Calcium channel blocker (CCB) | 1525 | 14.8 | 34.7 | 300 | 19.3 | 53.7 | 23 | 15.5 | 36.5 | 16 | 14.5 | 35.6 |
| Angiotensin receptor blocker (ARB) | 1386 | 13.5 | 31.6 | 206 | 13.3 | 36.9 | 16 | 10.8 | 25.4 | 24 | 21.8 | 53.3 |
| Centrally acting antihypertensive | 193 | 1.9 | 4.4 | 56 | 3.6 | 10.0 | 3 | 2.0 | 4.8 | ⎼ | ⎼ | ⎼ |
| Aldosterone antagonist | 155 | 1.5 | 3.5 | 28 | 1.8 | 5.0 | 2 | 1.4 | 3.2 | ⎼ | ⎼ | ⎼ |
| Direct renin inhibitor | 5 | 0.0 | 0.1 | ⎼ | ⎼ | ⎼ | ⎼ | ⎼ | ⎼ | 1 | 0.9 | 2.2 |
Antihypertensive agent prescriptions, patients can have multiple agents prescribed over course of observation period.
Fixed‐dose combination therapies were divided into their individual compound agent.
4. DISCUSSION
Data on utilization patterns among patients with uncontrolled hypertension are limited. This analysis assessed utilization patterns in a real‐world setting using longitudinal patient‐level data from around the United States. The results highlight the difference between clinical utilization patterns and evidence‐based guidelines.
Because data from 2015 to 2016 were used in the analyses, trends were compared with JNC 8 guidelines 5 which were current in that time frame. Newer guidelines are now available (2017 AHA). 25 All inferences hold for this population under either set of guidelines.
It should be noted that of the patients with hypertension (N = 37 815), about 23% had uncontrolled hypertension (N = 8713; Figure 1), which is much lower than national estimates for uncontrolled hypertension of treated patients which is about 55%, or 17 million patients of the 31 million treated patients in the United States. 30
For 5059 patients who met all criteria for the analyses, we found that approximately one‐tenth of the prescriptions were for a fixed‐dose combination therapy. However, guidelines advise initial use of two antihypertensive drugs in most hypertensive patients. 5 , 31 It has been shown that use of fixed‐dose combination therapies improves rates of blood pressure control and requires less time to achieve target blood pressure, with equivalent or better tolerability than monotherapy. 31 , 32 , 33 , 34 Depending on the combination used, fixed‐dose combination therapies could provide cost savings and improved patient adherence. Further, guidelines do not advise beta‐blockers as an initial treatment of hypertension because evidence suggests that use of beta‐blockers can lead to increased rates of the myocardial infarction, stroke, or cardiovascular death. 35 In our study, we observed that approximately 19% of prescriptions written for about 45% of the patients included beta‐blockers.
Previous studies have shown that patients with hypertension and DM have lower rates of blood pressure control compared to patients without DM. DM and hypertension are the two leading causes of end‐stage renal disease. 36 Hypertension can be a result of CKD but can also lead to CKD and worsen existing CKD. Combination therapy is often needed to effectively lower blood pressure to goal levels in patients with CKD. With monotherapy, patients do not often attain the level of blood pressure reduction required to slow the decline in glomerular filtration rate. 36 , 37 However, only 5.6% of the prescriptions written for patients with DM and CKD in this database were for fixed‐dose combination therapy. Guidelines also recommend that antihypertensive treatment should include an ACE inhibitor or ARB to improve kidney outcomes. In our study, we only observed that only about 17% of agents for 45% patients with CKD and 17% of agents for 55% patients with both CKD and DM were ACE inhibitors. Only approximately 12% of agents for 33% patients with CKD and about 11% of agents for 35% patients with both CKD and DM were ARBs.
In common with all investigations of this type, this study has a number of limitations. Real‐world databases collate data from routine practice and, although there are systems in place to ensure data quality, there will be missing and erroneous data, coding imperfections, lack of standardization of clinical measures, variations between clinical testing centers, and measurements that are taken with varying periodicity. Certain covariates of interest may not be recorded consistently within the database. Furthermore, due to the open network data, there may periodically be patient treatment records that fall out of the network without the investigator's knowledge.
5. CONCLUSION
Hypertension is one of the most common forms of treatable disease in the United States, and, left uncontrolled, patients with hypertension experience increased risk of cardiovascular disease, stroke, and renal failure. 1 , 6 , 7 , 8 , 9 Patients with uncontrolled hypertension along with DM and CKD have an even further elevated risk of cardiovascular complications than patients with hypertension alone. 10 , 11 , 12 , 13 , 14 These finding show that there are some regular deviations from the published evidence‐based guidelines for hypertension management from the both the JNC 8 and American Heart Association (AHA). 5 , 25 Of particular, concern is the overall low prescription rate of fixed‐dose combination therapies, the apparent over‐prescribing of beta‐blockers as initial therapy, and the under‐prescribing of ACE inhibitors and ARBs in patients with CKD. However, further research is needed to understand the barriers that may affect treatment choices for uncontrolled hypertension for both patients and providers.
CONFLICT OF INTEREST
None.
AUTHOR CONTRIBUTIONS
Chris LaVallee was responsible for the design of the research, analysis, interpretation of the data, writing the manuscript, and final approval. Karen L. Rascati was responsible for intellectual content, critical revisions of the manuscript, and final approval. Tyler H. Gums was responsible for the conception and design of the research, interpretation of the data, intellectual content, critical revisions of the manuscript, and final approval.
ACKNOWLEDGMENTS
Data for this study were provided by Decision Resources Group (DRG).
LaVallee C, Rascati KL, Gums TH. Antihypertensive agent utilization patterns among patients with uncontrolled hypertension in the United States. J Clin Hypertens. 2020;22:2084–2092. 10.1111/jch.14041
REFERENCES
- 1. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29‐e322. [DOI] [PubMed] [Google Scholar]
- 2. Health. United States , 2015: With Special Feature on Racial and Ethnic Health Disparities. Hyattsville, MD: National Center for Health Statistics; 2016. http://www.cdc.gov/nchs/hus.htm. Accessed November 10, 2019. [PubMed] [Google Scholar]
- 3. Wofford MR, Minor DS. Hypertension: issues in control and resistance. Curr Hypertens Rep. 2009;11(5):323‐328. [DOI] [PubMed] [Google Scholar]
- 4. Merai R, Siegel C, Rakotz M, et al. CDC grand rounds: a public health approach to detect and control hypertension. MMWR Morb Mortal Wkly Rep. 2016;65(45):1261‐1264. [DOI] [PubMed] [Google Scholar]
- 5. James PA, Oparil S, Carter BL, et al. 2014 evidence‐based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507‐520. [DOI] [PubMed] [Google Scholar]
- 6. Muntner P, Halanych JH, Reynolds K, et al. Low medication adherence and the incidence of stroke symptoms among individuals with hypertension: the REGARDS study. J Clin Hypertens. 2011;13(7):479‐486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Bailey JE, Wan JY, Tang J, Ghani MA, Cushman WC. Antihypertensive medication adherence, ambulatory visits, and risk of stroke and death. J Gen Intern Med. 2010;25(6):495‐503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Ovbiagele B, Campbell S, Faiz A, Chambless LE. Relationship between non‐specific prescription pill adherence and ischemic stroke outcomes. Cerebrovasc Dis. 2010;29(2):146‐153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Gehi AK, Ali S, Na B, Whooley MA. Self‐reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study. Arch Intern Med. 2007;167(16):1798‐1803. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Vinik A, Flemmer M. Diabetes and macrovascular disease. J Diabetes Complicat. 2002;16(3):235‐245. [DOI] [PubMed] [Google Scholar]
- 11. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med. 1996;124(1 Pt 2):90‐96. [DOI] [PubMed] [Google Scholar]
- 12. Daly C. Is early chronic kidney disease an important risk factor for cardiovascular disease?: A Background Paper prepared for the UK Consensus Conference on Early Chronic Kidney Disease. Nephrol Dial Transplant. 2007;22(Suppl 9):ix19‐ix25. [DOI] [PubMed] [Google Scholar]
- 13. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow‐up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164(6):659‐663. [DOI] [PubMed] [Google Scholar]
- 14. Hypertension in Diabetes Study (HDS): II. Increased risk of cardiovascular complications in hypertensive type 2 diabetic patients. J Hypertens. 1993;11(3):319‐325. [DOI] [PubMed] [Google Scholar]
- 15. Suh DC, Kim CM, Choi IS, Plauschinat CA, Barone JA. Trends in blood pressure control and treatment among type 2 diabetes with comorbid hypertension in the United States: 1988–2004. J Hypertens. 2009;27(9):1908‐1916. [DOI] [PubMed] [Google Scholar]
- 16. Shulman NB, Ford CE, Hall WD, et al. Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the hypertension detection and follow‐up program. The Hypertension Detection and Follow‐up Program Cooperative Group. Hypertension. 1989;13(5 Suppl):I80‐I93. [DOI] [PubMed] [Google Scholar]
- 17. Yoon SS, Carroll MD, Fryar CD. Hypertension prevalence and control among adults: United States, 2011–2014. NCHS Data Brief. 2015;220:1‐8. [PubMed] [Google Scholar]
- 18. Snyder JJ, Collins AJ. KDOQI hypertension, dyslipidemia, and diabetes care guidelines and current care patterns in the United States CKD population: National Health and Nutrition Examination Survey 1999–2004. Am J Nephrol. 2009;30(1):44‐54. [DOI] [PubMed] [Google Scholar]
- 19. Sarafidis PA, Li S, Chen S‐C, et al. Hypertension awareness, treatment, and control in chronic kidney disease. Am J Med. 2008;121(4):332‐340. [DOI] [PubMed] [Google Scholar]
- 20. Manze M, Rose AJ, Orner MB, Berlowitz DR, Kressin NR. Understanding racial disparities in treatment intensification for hypertension management. J Gen Intern Med. 2010;25(8):819‐825. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703‐713. [PMC free article] [PubMed] [Google Scholar]
- 22. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):713‐720. [PMC free article] [PubMed] [Google Scholar]
- 23. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO‐HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355(9200):253‐259. [PubMed] [Google Scholar]
- 24. Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008;52(5):818‐827. [DOI] [PubMed] [Google Scholar]
- 25. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127‐e248. [DOI] [PubMed] [Google Scholar]
- 26. Milchak JL, Carter BL, James PA, Ardery G. Measuring adherence to practice guidelines for the management of hypertension: an evaluation of the literature. Hypertension. 2004;44(5):602‐608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27. Zhou M, Daubresse M, Stafford RS, Alexander GC. National trends in the ambulatory treatment of hypertension in the United States, 1997–2012. PLoS One. 2015;10(3):e0119292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Yoon SS, Gu Q, Nwankwo T, Wright JD, Hong Y, Burt V. Trends in blood pressure among adults with hypertension: United States, 2003 to 2012. Hypertension. 2015;65(1):54‐61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. DRG . Decision Resources Group (DRG) Real World Evidence US Data Repository.
- 30. Estimated Hypertension Prevalence, Treatment, and Control Among U.S. Adults. https://millionhearts.hhs.gov/data‐reports/hypertension‐prevalence.html. Published 2020. Updated February 5, 2020
- 31. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206‐1252. [DOI] [PubMed] [Google Scholar]
- 32. Bakris GL, Weir MR, Black HR. Improving blood pressure control rates: is there more we can do? J Clin Hypertens. 2007;9(2):134‐142. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Jamerson KA, Nwose O, Jean‐Louis L, Schofield L, Purkayastha D, Baron M. Initial angiotensin‐converting enzyme inhibitor/calcium channel blocker combination therapy achieves superior blood pressure control compared with calcium channel blocker monotherapy in patients with stage 2 hypertension. Am J Hypertens. 2004;17(6):495‐501. [DOI] [PubMed] [Google Scholar]
- 34. Elliott WJ. Is fixed combination therapy appropriate for initial hypertension treatment? Curr Hypertens Rep. 2002;4(4):278‐285. [DOI] [PubMed] [Google Scholar]
- 35. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995‐1003. [DOI] [PubMed] [Google Scholar]
- 36. Flack JM, Peters R, Mehra VC, Nasser SA. Hypertension in special populations. Cardiol Clin. 2002;20(2):303‐319, vii. [DOI] [PubMed] [Google Scholar]
- 37. Law MR, Wald NJ, Morris JK, Jordan RE. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326(7404):1427. [DOI] [PMC free article] [PubMed] [Google Scholar]