Antihypertensive prescribing patterns and hypertension control in females of childbearing age
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Antihypertensive prescribing patterns and hypertension
control in females of childbearing age
Blaire M. White, PharmD, Billings
Clinic; Billings, MT, USA Purpose. The use of angiotensin-converting enzyme (ACE) inhibitors
Sarah L. Anderson, PharmD, or angiotensin receptor blockers (ARBs) to treat hypertension (HTN)
University of Colorado Skaggs School of during pregnancy presents well-established risks to a developing fetus.
Pharmacy & Pharmaceutical Sciences,
Aurora, CO, USA A cross-sectional study was conducted to evaluate the current state of
Joel C. Marrs, PharmD, MPH,
antihypertensive prescribing and contraceptive use in females of child-
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University of Colorado Skaggs School of bearing age within a large safety-net health system.
Pharmacy & Pharmaceutical Sciences,
Aurora, CO, USA Methods. The retrospective cross-sectional study focused on females
aged 18-49 years with a documented diagnosis of HTN. The proportion of
patients prescribed an ACE inhibitor or ARB and using a documented form
of contraception was calculated. Documented forms of contraception in-
cluded oral contraceptives, intrauterine devices, injections, implants, and
surgical intervention.
Results. A total of 4,187 patients were identified from the HTN registry;
after application of exclusion criteria 3,045 patients were included in the
study population. The mean age was 39 years (range, 18-49 years). The
most frequently prescribed classes of antihypertensive medications were
ACE inhibitors and ARBs (one or the other was used by 1,146 patients
[37.6%]), followed by thiazide diuretics (n = 710, 23.3%) and calcium
channel blockers (n = 599, 19.7%). Of the 1,146 patients prescribed an
ACE inhibitor or ARB, 553 (48%) were using a documented form of contra-
ception.
Conclusion. Rates of ACE inhibitor or ARB prescribing to females of
childbearing age were high despite the teratogenic risks, and fewer than
half of patients had documented protection from pregnancy. Provider and
patient education and potential creation of best practice alerts in the elec-
tronic medical record regarding the risks of using ACE inhibitors and ARBs
in females of childbearing age are warranted.
Keywords: angiotensin converting enzyme inhibitor, angiotensin receptor
blocker, contraception, hypertension, reproductive-aged women
Am J Health-Syst Pharm. 2021;78:1317-1322
H ypertension (HTN) affects one-
third of all females in the United
States, and the prevalence of HTN in fe-
indication such as proteinuric renal
disease.3 If use of these medications
is unavoidable or strongly indicated,
males of childbearing age continues to then females should be counseled re-
rise.1 The use of angiotensin-converting garding teratogenic and other risks,
enzyme (ACE) inhibitors or angiotensin and effective contraception is recom-
receptor blockers (ARBs) during preg- mended.3 The ACOG recommenda-
Address correspondence to Dr. Marrs nancy presents well-established risks tion differs from the 2017 American
(Joel.Marrs@cuanschutz.edu). to a developing fetus.2 Therefore, the College of Cardiology/American Heart
American College of Obstetricians and Association (ACC/AHA) guideline for
© American Society of Health-System Gynecologists (ACOG) recommends management of high blood pressure
Pharmacists 2021. All rights reserved.
For permissions, please e-mail: journals. against the use of ACE inhibitors, ARBs, (BP) in adults, which recommends
permissions@oup.com. and renin inhibitors in females of child- ACE inhibitors and ARBs as first-line
DOI 10.1093/ajhp/zxab162 bearing age unless there is a compelling options for most patients with HTN
AM J HEALTH-SYST PHARM | VOLUME 78 | NUMBER 14 | July 15, 2021 1317Note ANTIHYPERTENSIVE PRESCRIBING IN FEMALES OF CHILDBEARING AGE
regardless of age or gender.4 The ACC/ other safety-net institutions across the
AHA guideline further states that for KEY POINTS nation. Denver Health provides care
females with HTN who become preg- • Angiotensin-converting for one-third of Denver’s population
nant or are planning to become preg- enzyme (ACE) inhibitors on an annual basis. Twenty-one per-
nant, antihypertensive therapy should and angiotensin receptor cent of Denver Health’s patients are
be changed to methyldopa, nifedi- blockers (ARBs) are fre- uninsured, compared to 10% of those
pine, and/or labetalol, given the safety quently prescribed to females at other Colorado hospitals. Further,
profile of these medications during of childbearing age despite the institution cares for the needs of
pregnancy.4 teratogenic risks. special populations such as the poor,
Despite the prevalence of HTN the uninsured, pregnant teens, per-
• In a large sample of younger
in females of childbearing age and sons addicted to alcohol and/or other
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female patients within a
the common use of ACE inhibitors substances, victims of violence, and
safety-net health system, less
and ARBs to manage HTN, there the homeless. The electronic med-
than 50% of patients pre-
is a limited body of published data ical record (EMR) was used to obtain
scribed an ACE inhibitor or
describing use of these agents in this a list of female patients 18 to 49 years
ARB had documented protec-
population. Another area of interest of age with a diagnosis of HTN as de-
tion from pregnancy.
is the frequency of contraceptive use fined by the health system’s HTN
in females with HTN who are treated • Provider and patient education registry. According to the US Centers
with an ACE inhibitor or ARB. The au- and creation of best practice for Disease Control and Prevention,
thors identified 3 previous studies in alerts in the electronic medical childbearing age can be defined as
this area, with the most recent pub- record regarding the risks of 16 to 49 years of age. Patients 16 or
lished more than 10 years ago.5-7 Two ACE inhibitor and ARB use in 17 years of age (pediatric patients)
retrospective studies evaluated the females of childbearing age are are considered to be a vulnerable
incidence of contraceptive use in fe- proposed solutions to help miti- population and were excluded from
males of childbearing age who were gate risk. the study. To be included in the HTN
taking an ACE inhibitor or ARB; the registry, patients must have had
study populations comprised 101 and HTN on their current problem list or
6,467 females, respectively.5,6 One of documentation of an International
those studies found that of the patients Classification of Diseases code (ICD-9
taking an ACE inhibitor or ARB, 66% the current state of antihypertensive or ICD-10) for HTN documented in
were using a form of contraception.5 In prescribing and contraceptive use for the EMR at least twice within the last
the other retrospective study, contra- females of childbearing age within a 5 years. Patients must also have been
ceptive use was remarkably lower, at large safety-net health system, a prac- seen by their primary care provider
only 11.7%.6 The third study we iden- tice setting not included in previous within the last 18 months. From this
tified aimed to quantify ACE inhibitor, studies. The findings will be used to list, the proportion of patients pre-
ARB, and statin prescribing to female identify potential safety issues that war- scribed an ACE inhibitor or ARB and
patients of childbearing age and rates rant further educational approaches using a documented form of contra-
of documented discussions of terato- to prescribers, particularly those who ception was calculated. Oral contra-
genic risk before and after educational provide care to an underserved patient ceptives, vaginal contraceptive rings,
intervention.7 Risk documentation oc- population. and contraceptive patches were
curred for 20% of patients, indicating identified from a patient’s medica-
that physicians’ baseline awareness of Methods tion list. Injections were identified
teratogenic risks and risk documenta- Study design. The retrospective from the medication list and Current
tion was lacking.7 After the interven- cross-sectional study was approved Procedural Terminology (CPT) codes.
tion (n = 131), the frequency of risk by the Denver Health Sponsored Insertion and removal of intrauterine
documentation was 2.4 times greater Programs and Research Office and devices (IUDs), contraceptive im-
than before intervention. the Colorado Multiple Institutional plants, and fallopian tube inserts
These studies showed that ACE in- Review Board. The study was con- were identified using the medica-
hibitors and ARBs are commonly pre- ducted at Denver Health, which is a tion list and documented ICD-10 and
scribed antihypertensive medications large, urban safety-net health system CPT codes. Surgical interventions,
for females of childbearing age and located in Denver, CO. Denver Health including tubal ligation and hyster-
that many patients do not have a docu- is Colorado’s primary safety-net insti- ectomy, were identified using ICD-
mented form of contraception despite tution and has provided $2.8 billion 10 codes. Exclusion criteria were
the teratogenic risks. The purpose of the in uncompensated care over the last as follows: age ofANTIHYPERTENSIVE PRESCRIBING IN FEMALES OF CHILDBEARING AGE Note
eclampsia or preeclampsia, and cur- the study (Figure 1). Baseline charac- of antihypertensive agent, 944 of 3,039
rent incarceration. teristics are listed in Table 1. The mean patients (31%) had controlled BP.
Primary and secondary out- age was 39 years (range, 18-49 years). Rates of BP control were not different
comes. The primary outcome was The most frequently patient-reported between patients prescribed ACE in-
the percentage of patients prescribed race/ethnicity was Hispanic (45.5%), hibitor or ARB therapy and those in
an ACE inhibitor or ARB and using a followed by Black (25.3%) and white other antihypertensive medication
documented form of contraception. (22.1%). Twenty percent of patients categories (data not shown). BP data
Secondary outcomes were controlled were current smokers, and 22% had were missing for 6 patients.
BP (BP ofNote ANTIHYPERTENSIVE PRESCRIBING IN FEMALES OF CHILDBEARING AGE
Discussion
Table 1. Baseline Characteristics of Patients in Study Population
(n = 3,045) The results of the study highlight
the fact that ACE inhibitors and ARBs
Characteristic No. (%)a
are frequently prescribed to females of
Age range, y childbearing age despite teratogenic
risks. Less than half of patients pre-
18 to 40 1,502 (49.3)
scribed an ACE inhibitor or ARB had
41 to 44 571 (18.8) documented protection from preg-
45 to 49 972 (31.9) nancy. This rate of contraception use
is lower than that reflected in the most
Race/ethnicity
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recent data (for 2015-2017) from the
Hispanic 1,386 (45.5) National Survey of Family Growth,
Black 769 (25.3) which indicated that 64.9% of females
White 674 (22.1) 15 to 49 years of age were currently
using contraception.8 Documented
Other 216 (7.1)
forms of contraception included oral
Primary language contraceptives, vaginal rings, patches,
English 2,231 (73.3) IUDs, injections, implants, and surgical
intervention. The ACOG guidelines
Spanish 648 (21.3)
recommend against the use of ACE
Other 166 (5.4) inhibitors, ARBs, and renin inhibitors
Medical history in women of childbearing age unless
Current smoking 600 (19.7) there is a compelling indication such as
proteinuric renal disease.3 Heart failure
Diabetes mellitus 675 (22.2)
is another compelling reason to use an
Chronic kidney disease 97 (3.2) ACE inhibitor or ARB. However, very
Heart failure 79 (2.6) few patients in our study had either of
these compelling indications.
Selected clinical/laboratory data
The study included a patient popula-
Systolic BP, mean (SD), mm Hg 131.7 (16.4) tion larger than those in previous studies
Diastolic BP, mean (SD), mm Hg 84.2 (10.7) evaluating similar outcomes. Overall,
Pulse, mean (SD), beats/min 83.8 (13.2) our findings were similar to findings in
previous studies. Compared to the study
BMI (kg/m ), mean (SD)
2
33.8 (9.0)
of Martin et al,5 our study found a lower
Serum potassium, mean (SD), mEq/L 3.8 (0.4) rate of ACE inhibitor or ARB prescribing
Serum creatinine, mean (SD), mg/dL 0.8 (0.6) amongst females of childbearing age
Antihypertensive use b (37.6% vs 47%); however, documented
contraceptive use was lower in our study
ACE inhibitor or ARB 1,146 (37.6)
(48% vs 66%). Further, when comparing
Thiazide diuretic 710 (23.3) contraception use in patients 40 years of
Calcium channel blocker 599 (19.7) age or younger, the rate of documented
contraception was 44.7% in our study
Beta-blocker 267 (8.8)
versus 30.8% in the study by Martin
Alpha/beta-blocker 119 (3.9) et al. One key finding in our explora-
Loop diuretic 118 (3.9) tory analysis was a doubling of the rate
Potassium-sparing diuretic 93 (3.1)
of ACE inhibitor or ARB prescribing to
those 41 to 49 years of age versus 18 to
Other c
80 (2.6)
40 years of age, meaning there were po-
Abbreviations: ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; BMI, tentially more discussions with patients
body mass index; BP, blood pressure; SD, standard deviation.
a
All data are number (percentage) of patients unless specified otherwise.
about the safe use of ACE inhibitors or
b
Some patients were using more than 1 agent. ARBs in the younger female population
c
Included clonidine, guanfacine, hydralazine, methyldopa, minoxidil, and reserpine.
with HTN.
1320 AM J HEALTH-SYST PHARM | VOLUME 78 | NUMBER 14 | July 15, 2021ANTIHYPERTENSIVE PRESCRIBING IN FEMALES OF CHILDBEARING AGE Note
females with HTN who become preg-
Table 2. Forms of Contraception Used by Study Population (n = 553)
nant or are planning to become preg-
Type of Contraception No. (%) nant, antihypertensive therapy should
be changed to methyldopa, nifedipine,
Surgical intervention 308 (55.7) and/or labetalol.
IUD 99 (17.9)
Conclusion
Implant 70 (12.7)
Rates of ACE inhibitor or ARB pre-
Combination pill 36 (6.5)
scribing to females of childbearing
Progestin-only pill 25 (4.5) age were high despite the teratogenic
Injection 15 (2.7) risk, and less than half of patients had
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documented protection from preg-
Patch 0 (0)
nancy. Therefore, additional provider
Ring 0 (0) education, patient education, and po-
Abbreviation: IUD, intrauterine device. tential creation of best practice alerts
in the EMR are warranted for appro-
priate antihypertensive selection in this
Because the study was conducted appropriate care; without this informa- population and to inform counseling
in a large, urban safety-net health tion, the analysis may have underesti- on and prescribing of effective forms of
system, it highlights an opportunity for mated the proportion of patients who contraception when ACE inhibitor or
pharmacists to address health dispar- received appropriate care. Moreover, ARB use is necessary.
ities in an underserved population as the patients’ originally prescribed HTN
they relate to the safe prescribing and regimens were not known. It may be Disclosures
monitoring of ACE inhibitors or ARBs that ACE inhibitors and ARBs were The authors have declared no potential con-
flicts of interest.
in females of childbearing age with being used as second- or third-line
HTN. Pharmacists could play a role in agents for BP control after other agents
Previous affiliations
developing best practice alerts within were not tolerated, in which case their
At the time of project completion Dr. White
the EMR and provide patient and pro- use would be reasonable. Finally, the was affiliated with Denver Health Medical
vider education on the risks of ACE in- study evaluated prescribing patterns Center, Denver, CO.
hibitor and ARB use during pregnancy. only and not patient adherence to
An opportunity for pharmacists to medications. Additional information
manage the HTN population through Of the 6.1 million pregnancies in Deidentified study data are available upon
collaborative practice agreements the United States in 2011, nearly half request.
could allow for improvement in the safe (45%, or 2.8 million) were unintended.9
management and monitoring of pa- Although ACOG and 2017 ACC/AHA References
tients with HTN. Additionally, this vul- guidelines have conflicting recom- 1. Fryar CD, Ostchega Y, Hales CM, et al.
nerable population could benefit from mendations for HTN management in Hypertension prevalence and control
among adults: United States, 2015-2016.
telephonic outreach by a pharmacist to females of childbearing age, ACE in- NCHS Data Brief. 2017;(289):1-8.
improve the safe prescribing and moni- hibitors and ARBs should be avoided 2. Fitton CA, Steiner MFC, Aucott L, et al.
toring of medications and evaluate BP whenever possible due to teratogenic In-utero exposure to antihypertensive
control in patients able to self-monitor risks, regardless of whether patients medication and neonatal and child
BP at home. are actively trying to become pregnant. health outcomes: a systematic review. J
Hypertens. 2017;35(11):2123-2137.
There were several limitations to The findings of our study highlight the 3. Roberts JM, August PA, Bakris G, et al.
our study, including the inability to need for additional provider education Hypertension in pregnancy. Report of
identify patients for whom contracep- and potential creation of best prac- the American College of Obstetricians
tive use was not necessary (eg, patients tice alerts in the EMR regarding the and Gynecologists’ Task Force on
with same-sex partners or male part- risk of ACE inhibitors and ARBs in this Hypertension in Pregnancy. Obstet
Gynecol. 2013;122(5):1122-1131.
ners with a vasectomy, patients prac- population. These next steps are im- 4. Whelton PK, Carey RM, Aronow WS,
ticing abstinence). Additionally, it was portant to prevent the continued pre- et al. 2017 ACC/AHA/AAPA/ABC/
not possible to identify condom (or scribing of ACE inhibitors and ARBs in ACPM/AGS/APhA/ASH/ASPC/
other barrier method) use or proper this population. If these medications NAMA/PCNA guideline for the pre-
contraception counseling with the data are unavoidable or strongly indicated, vention, detection, evaluation, and
management of high blood pressure
extraction methodology. Provision of then females should be counseled re- in adults: a report of the American
adequate contraception counseling garding risks, and effective contra- College of Cardiology/American Heart
should be considered to indicate ception should be recommended. For Association Task Force on Clinical
AM J HEALTH-SYST PHARM | VOLUME 78 | NUMBER 14 | July 15, 2021 1321Note ANTIHYPERTENSIVE PRESCRIBING IN FEMALES OF CHILDBEARING AGE
Practice Guidelines. Hypertension. August 24, 2020. https://www. 8. Daniels K, Abma JC. Current contra-
2018;71(6):e13. forwardhealth.wi.gov/WIPortal/ ceptive status among women aged
5. Martin U, Foreman MA, Travis JC, Subsystem/SW/StaticContent/ 15–49: United States, 2015–2017.
et al. Use of ACE inhibitors and ARBs Provider/medicaid/pharmacy/dur/ Published December 2018. NCHS
in hypertensive women of child- minutes/090209ACEARBStatinInterve Data Brief. Accessed August 24, 2020.
bearing age. J Clin Pharm Ther. ntion.pdf.spage https://www.cdc.gov/nchs/data/
2008;33(5):507-511. 7. Morrical-Kline KA, Walton AM, databriefs/db327-h.pdf
6. Targeted Intervention: ACEI/ARB Guildenbecher TM. Teratogen use in 9. Finer LB, Zolna MR. Declines in un-
and statin use in women of child- women of childbearing potential: an intended pregnancy in the United
bearing age without contraceptives. intervention study. J Am Board Fam States, 2008-2011. N Engl J Med.
ForwardHealth portal. Accessed Med. 2011;24(3):262-271. 2016;374(9):843-852.
Downloaded from https://academic.oup.com/ajhp/article/78/14/1317/6225093 by BINASSS user on 15 July 2021
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