What does the literature recommend regarding management of high blood pressure in hospitalized patients without acute organ damage?

Comment by InpharmD Researcher

The paucity of data on inpatient hypertension without evidence of end-organ damage precludes any definitive guidance for its management. Existing studies, which are retrospective in design, indicate a lack of clinical benefits in intensifying or routine blood pressure (BP) treatment, especially for older adults hospitalized for non-cardiac conditions.

Background

A systematic review of clinical practice guidelines for managing inpatient elevated BP was recently published in April 2024 to help address the paucity of evidence to guide a treatment approach for inpatient BP management. Among 14 guidelines developed by organizations in the US, other countries, and multinational organizations, no inpatient BP target or guidance on antihypertensive selection was found in managing asymptomatic elevated BP. Hypertensive urgency was consistently defined as an elevated BP > 180/120 mmHg without evidence of end-organ damage. Noting the lack of inpatient-specific guidance for elevated BP that is not considered an emergency, the authors stated many clinicians reference outpatient guidelines for treatment goals and prescribing decisions. Outpatient guidelines suggest a threshold of > 140-160/90-100 mmHg for immediate pharmacologic treatment with monotherapy for moderate elevations and consideration for combination therapy in those with stage 2 hypertension. Treatment decisions may also follow outpatient guidelines based on patient characteristics, comorbidities, and age. In the final discussions, the authors summarized the lack of robust data to guide non-emergent inpatient BP management with an observed wide pattern of treatment approaches and overall unknown risk versus benefit of intensive BP management. [1]

A 2022 narrative review on treating hypertension among non-cardiac hospitalized patients highlights the paucity of established guidance despite frequent encounters with inpatient hypertension. Existing data, although limited to retrospective studies, indicate that routine or intensified inpatient hypertension control in the absence of end-organ damage may potentially be harmful (see Tables 1-3). [2]

A 2020 review article discusses the available evidence for managing elevated inpatient blood pressure (BP). Despite the lack of evidence, a strong belief exists in controlling BP for hospitalized patients. No guidelines or recommendations are available for managing inpatient elevated BP. The authors’ literature review found that the limited studies and systematic reviews have failed to establish any benefits of anti-hypertensive medications for treating hypertensive urgency or emergency. Of note, this excludes settings like abdominal aortic aneurysms where treatment benefit is clearly represented. There is also a lack of evidence to inform the BP level that may warrant therapy. [3]

In light of these findings, the authors recommend that asymptomatic patients do not require immediate reduction at any BP level. Instead, clinicians should focus on underlying diagnosis for hospitalization and patient recovery. Asymptomatic patients may have their BP reduced over a period of days and withheld home anti-hypertensive regimens that can be resumed with increased dosage or intensity based on an individual basis. If titrated, oral medications should be done conservatively as they may require 2 to 3 days for an effect to be seen. [3]

A 2015 article presented a practical approach for elevated BP management in asymptomatic patients, firstly by assessing whether acute symptoms are contributing to elevated BP (e.g., anxiety, pain, nausea, etc.) prior to BP therapy initiation. Withdrawal from alcohol, benzodiazepines, or illicit drugs can also precipitate hypertension. If volume overload is present, treat accordingly to manage BP. Other inpatient medications may also contribute to hypertension. Unless contraindicated, home BP medications, if on hold, can be restarted. Despite addressing these factors, if BP remains elevated > 20 mmHg above recommended guidelines, then titration of existing BP medications or the addition of new agents can be considered; understanding that the effects may take days to weeks to manifest fully. Proper follow-up in the outpatient setting should be ensured. At the time of the article’s publication, there was no evidence for the efficacy or safety of intravenous (IV) hydralazine or asymptomatic elevated BP. [4]

A 2019 editorial discussed the frequent inappropriate use of IV antihypertensives in inpatient settings, which can lead to adverse events. The authors suggested limiting the use of inpatient IV antihypertensives and considering other underlying causes such as pain, anxiety, or withholding home medications. [5], [6], [7]

Retrospective cohort studies based on the National Veterans Health Administration database examined patients aged 65 years or over with hypertension hospitalized with non-cardiac conditions. Collected data showed approximately 14% of older adults hospitalized for non-cardiac issues had their antihypertensive treatment intensified upon discharge, predominantly those who had previously well-controlled outpatient BP. Most importantly, intensified antihypertensives at discharge neither reduced cardiac events nor improved BP control within 1 year but resulted in an increased risk of readmission and serious adverse events (e.g., first emergency department visit or hospitalization for injurious fall, syncope, hypotension, electrolyte abnormalities, or acute kidney injury) within 30 days. The authors noted the need for increased vigilance to mitigate the risk of over-treating BP in elderly patients transitioning from hospital to home. [8], [9]

References:

[1] Wilson LM, Herzig SJ, Steinman MA, et al. Management of Inpatient Elevated Blood Pressures : A Systematic Review of Clinical Practice Guidelines. Ann Intern Med. 2024;177(4):497-506. doi:10.7326/M23-3251
[2] Chaganti B, Lange RA. Treatment of Hypertension Among Non-Cardiac Hospitalized Patients. Curr Cardiol Rep. 2022;24(7):801-805. doi:10.1007/s11886-022-01699-0
[3] Stanistreet B, Nicholas JA, Bisognano JD. An Evidence-Based Review of Elevated Blood Pressure for the Inpatient. Am J Med. 2020;133(2):165-169. doi:10.1016/j.amjmed.2019.10.004
[4] Axon RN, Turner M, Buckley R. An Update on Inpatient Hypertension Management. Curr Cardiol Rep. 2015;17(11):94. doi:10.1007/s11886-015-0648-y
[5] Anstey J, Lucas BP. Treatment of Inpatient Asymptomatic Hypertension: Not a Call to Act but to Think. J Hosp Med. 2019;14(3):190-191. doi:10.12788/jhm.3160
[6] Jacobs ZG, Najafi N, Fang MC, et al. Reducing Unnecessary Treatment of Asymptomatic Elevated Blood Pressure with Intravenous Medications on the General Internal Medicine Wards: A Quality Improvement Initiative. J Hosp Med. 2019;14(3):144-150. doi:10.12788/jhm.3087
[7] Pasik SD, Chiu S, Yang J, et al. Assess Before Rx: Reducing the Overtreatment of Asymptomatic Blood Pressure Elevation in the Inpatient Setting. J Hosp Med. 2019;14(3):151-156. doi:10.12788/jhm.3190
[8] Anderson TS, Wray CM, Jing B, et al. Intensification of older adults' outpatient blood pressure treatment at hospital discharge: national retrospective cohort study. BMJ. 2018;362:k3503. Published 2018 Sep 12. doi:10.1136/bmj.k3503
[9] Anderson TS, Jing B, Auerbach A, et al. Clinical Outcomes After Intensifying Antihypertensive Medication Regimens Among Older Adults at Hospital Discharge. JAMA Intern Med. 2019;179(11):1528-1536.
doi:10.1001/jamainternmed.2019.3007

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

What does the literature recommend regarding management of high blood pressure in hospitalized patients without acute organ damage?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-3 for your response.


 

Treatment and Outcomes of Inpatient Hypertension Among Adults With Noncardiac Admissions

Design

Retrospective cohort study

N= 9,040

Objective

To characterize clinician response to blood pressure (BP) in the hospital and at discharge and to compare short- and long-term outcomes associated with antihypertensive treatment intensification.

Study Groups

Propensity-matched cohort

No treatment (n= 4,520)

Treatment (n= 4,520)

Inclusion Criteria

Age > 18 years, admitted to a medical service

Exclusion Criteria

Admission for cardiovascular diagnosis or admission within the past 30 days from a cerebrovascular event or acute coronary syndrome, pregnancy, length of stay less than 2 or greater than 14 days, no outpatient medication data

Methods

Patient data along with their medication history were collected for analysis. For patients with multiple admissions, a single admission was chosen at random. Medications were classified based on the 2017 ACC/AHA BP guidelines. Spironolactone and loop diuretics were excluded for the analysis. A propensity model was built to match demographic, individual comorbities, and index BP characteristics between treatment and no treatment groups.

Duration

Data recruitment period: January 1 to December 31, 2017

Outcome Measures

Composite outcome defined as the occurrence of acute kidney injury, myocardial infarction, or stroke

Baseline Characteristics

 

No treatment (n= 4,520)

Treatment (n= 4,520)

 

Age, years

69.8 (16.0%) 69.7 (15.7%)  

Male

1,988 (44%) 1,955 (43.3%)  

Race/ethnicity

White

Black

Other

Unknown

 

3,109 (68.8%)

1,174 (26%)

82 (1.8%)

155 (3.4%)

 

3,052 (67.5%)

1,215 (26.9%)

90 (2%)

163 (3.6%)

 

Body mass index, kg/m(Standard deviation [SD])

29.8 (8.8)

29.9 (8.4)

 

Smoking status

Current smoker

Nonsmoker

Unknown

 

836 (18.5%)

3,538 (78.3%)

146 (3.2%)

 

802 (17.7%)

3,571 (79%)

147 (3.3%)

 

Length of stay, days (SD)

5.01 (2.6)

4.98 (2.6)

 

Comorbidities

Atrial fibrillation

Diabetes

Heart failure

Hypertension

Hyperlipidemia

 

558 (12.3%)

1,208 (26.7%)

420 (9.3%)

2394 (53%)

1455 (32.2%)

 

533 (11.8%)

1,204 (26.6%)

436 (9.6%)

2,369 (52.4%)

1,443 (31.9%)

 

Results

Endpoint

No treatment (n= 4,520)

Treatment (n= 4,520)

p-Value

Occurrence of the composite outcome

Stroke

Acute kidney injury

Myocardial injury

371 (8.2%)

4 (0.1%)

357 (7.9%)

26 (0.6%)

499 (11%)

4 (0.1%)

466 (10.3%)

53 (1.2%)

<0.001

>0.99

<0.001

0.003

Length of stay after index BP, days (SD)

3.56 (2.55) 3.60 (2.27) 0.36

When analyzing separate BP intervals, none of the treated patients had better outcomes than the no-treatment group. Medication intensification was not associated with better BP control in the following year.

Adverse Events

N/A

Study Author Conclusions

This cohort study found that 78% of adult patients admitted for noncardiovascular diagnoses had at least 1 hypertensive BP measurement, but fewer than 1 in 3 had their medication intensified. More surprisingly, only 8% of hypertensive BP readings prompted medication intensification, and even readings over 220 mm Hg systolic were treated less than half of the time. Paradoxically, treatment, which presumably was meant to prevent end-organ damage, was associated with higher rates of AKI and myocardial injury. In fact, we found no benefit associated with any treatment route or at any BP interval. Our findings suggest that hypertension among medical inpatients should be managed conservatively. Intensification of treatment on discharge also does not appear to be helpful.

InpharmD Researcher Critique

Patients with a recent diagnosis of acute coronary syndrome or cerebrovascular accident were excluded as they typically require specific blood pressure management. It is possible there were unmeasured differences between the treated and untreated groups, which may influence the clinician to treat those at higher risk of organ damage. 

 

 
References:

Rastogi R, Sheehan MM, Hu B, Shaker V, Kojima L, Rothberg MB. Treatment and Outcomes of Inpatient Hypertension Among Adults With Noncardiac Admissions. JAMA Intern Med. 2021;181(3):345-352. doi:10.1001/jamainternmed.2020.7501

 

Impact of Intravenous Antihypertensives on Outcomes Among Hospitalized Patients

Design

Retrospective cohort study 

N= 5,680

Objective

To investigate the effects of intravenous (IV) as-needed (PRN) antihypertensives on blood pressure (BP), hospital length of stay (LoS), and mortality

Study Groups

No IV med (n= 3,896)

Received IV med (n= 1,784)

Inclusion Criteria

Patients admitted to Largo Medical Center between January 1st, and December 31st, 2017, with an order for an IV PRN antihypertensive medications (labetalol, hydralazine, or enalapril)

Exclusion Criteria

Patients with symptoms, including headaches, changes in vision, chest pain, shortness of breath, and diaphoresis; patients with aortic dissection and acute stroke

Methods

The closest BP values were obtained before the order was placed and before and after administering the drugs if given. Multivariate analysis assessed whether the medication was independently associated with specified outcomes. 

Duration

Data collection: January 1, 2017 to December 31, 2017

Outcome Measures

Primary: hospital length of stay (LoS), mortality

Baseline Characteristics

 

No IV med (n= 3,896)

Received IV med (n= 1,784)

p-Value  

Age, years

66 ± 13 69 ± 14 <0.001  

Female

1,962 (50%) 984 (55%) <0.001  

Race

White

Black 

Other

 

3,457 (89%)

257 (7%)

182 (4%)

 

1,521 (85%)

146 (8%)

117 (7%)

0.05

 

 

 

 

Comorbidities

Hypertension

Diabetes

Chronic kidney disease

Stroke

Coronary artery disease

Hyperlipidemia

Atrial fibrillation

Tobacco use

Obesity

 

2,828 (73%)

1,177 (30%)

559 (14%)

366 (9%)

1,040 (27%)

1,993 (51%)

731 (19%)

131 (3%)

738 (19%) 

 

1,007 (56%)

724 (41%)

465 (26%)

300 (17%)

616 (34%)

1,108 (62%)

403 (23%)

62 (3.5%)

300 (17%) 

 

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

<0.001

Not significant (NS)

NS 

 

 

Baseline systolic BP, mmHg

151

168

<0.001  

Antihypertensive

Hydralazine

Enalapril

Labetalol

-

 

 

 

 

72%

20%

8%

-

 

 

 

 

Results

Endpoint

No IV med (n= 3,896)

Received IV med (n= 1,784)

multivariate odds ratio (OR) (95% confidence interval [CI])

p-Value*

Hospital LoS, days*

3.1 ± 4.1 4.9 ± 6.1  1.525 (1.424 – 1.634) <0.001

In-hospital mortality**

1.6% 3.3% 1.286 (0.863 – 1.916) 

0.217

*Multivariate negative binomial regression

IV hydralazine had the largest effect on systolic BP (−22 vs. −18 mmHg for enalapril vs. −10 mmHg for labetalol, p< 0.001) and shortest LoS (p< 0.05). 

A total of 62% of patients who received the medication for a systolic BP lower than 180 mm Hg had a longer length of stay (5.3 vs. 4.4 days p= 0.001) than those with systolic BP before receiving the drug was >180 mm Hg.

Adverse Events

Not disclosed

Study Author Conclusions

Treating hypertension in the in-patient setting remains complex. Rapid lowering of BP can cause harm to patients, and this study showed that antihypertensive medication increased hospital length of stay. Once assuring no target organ damage, a strategic approach should be to treat modifiable factors and gradually reduce BP.

InpharmD Researcher Critique

The presented data only represents a single institution's retrospective experience. The data collected through ICD code analysis might not encompass all patients and could contain inaccuracies, including potential misidentification of target organ damage or other exclusion diagnoses.



References:

Bean-Thompson K, Exposito J, Fowler O, Mhaskar R, Chen L, Codolosa JN. Impact of Intravenous Antihypertensives on Outcomes Among Hospitalized Patients. Am J Hypertens. 2021;34(8):867-873. doi:10.1093/ajh/hpab060

 

Clinical Outcomes of Intensive Inpatient Blood Pressure Management in Hospitalized Older Adults

Design

Retrospective cohort study

N= 66,140

Objective

To examine the association of intensive treatment of elevated inpatient BPs with in-hospital clinical outcomes of older adults hospitalized for noncardiac conditions

Study Groups

Not intensively treated (n = 52,076)

Intensively treated (n = 14,064)

Inclusion Criteria

Patients aged ≥65 years; hospitalized in Veterans Health Administration (VHA); ≥2 elevated blood pressure (BP) measurements (systolic BP ≥140 mmHg) in the first 48 hours of hospitalization for noncardiovascular diagnoses

Exclusion Criteria

Patients hospitalized for cardiovascular disease, cerebrovascular conditions, renal failure, or symptoms of hypertensive emergencies such as chest pain; patients admitted to intensive care, surgical, psychiatric, or inpatient rehabilitation units; end-stage renal disease prior to hospitalization; experienced a study outcome in the first 48 hours of hospitalization; discharged in the first 48 hours of hospitalization. Additionally patients receiving < 80% of their outpatient visits in the HVA system, enrolled in Medicare Advantage, or did not receive medications from the VHA pharmacy in the prior year, or admitted from a nursing home or acute care hospital were excluded.

Methods

Data was retrospectively collected to identify two cohorts of patients experiencing elevated inpatient BPs: those who received intensive treatment in the first 48 hours of hospitalization and those who did not. The exposure window began at the time of the first recorded vital sign measurement, which could occur in the emergency department or hospital ward. 

Patients were classified as exposed to early intensive treatment if they received one or more intravenous (IV) antihypertensive doses of any class or oral doses of antihypertensive classes not being filled prior to hospitalization. Loop diuretics or alpha blockers were exluded due to use in other indications other than blood pressure. Preadmission antihypertensive use was defined as having a pharmacy fill that provided a supply lasting until at least 60 days before admission.

Duration

Admissions between October 1, 2015, and December 31, 2017

Data analysis between October 1, 2021 and January 10, 2023

Outcome Measures

Primary: Composite of inpatient mortality, intensive care unit transfer, stroke, acute kidney injury, B-type natriuretic peptide elevation, and troponin elevation

Secondary: Each component of the composite outcome as well as hypotensive episodes (systolic BP <100 mmHg), length of stay, and discharge disposition 

Baseline Characteristics

 

Not intensively treated

(n= 52,076)

Intensively treated

(n= 14,064)

 

Age, years

74.5 ± 8.1 74.1 ± 7.9  

Male

97.4%  97.6%  

Race

Black

Hispanic

White

Other

 

16.7%

1.7%

76.6%

1.8% 

 

19.9%

1.4%

73.4% 

1.6%

 

Preadmission health

SBP, mmHg

DBP, mmHg

Creatinine, mg/dL

 

135.2 ± 15.6

73.8 ± 9.3

1.1 ± 0.6

 

140.4 ± 17.4

75.9 ± 10.1

1.1 ± 0.7

 

Comorbidities

Hypertension

Atrial fibrillation

Alzheimer disease

Acute myocardial infarction

CKD

COPD

Diabetes

Heart failure

Ischemic heart disease

Stroke or TIA 

 

87.0% 

21.2%

20.4%

4.4%

47.4%

43.9%

49.8%

24.3%

40.0%

13.7%

 

89.0% 

21.8%

20.7%

4.7%

47.2%

38.6%

50.1%

23.7%

39.8%

13.9%

 

Admission medications

ACEI

Alpha-blockers

ARBs

Beta-blockers

CCBs

Clonidine

Hydralazine

Potassium-sparing diuretic

Thiazide-type diuretics

Loop diuretics

 

35.7%

35.9%

12.1%

47.8%

33.9%

1.6%

4.1%

5.7%

16.1%

22.5%

 

21.9%

24.2%

7.6%

26.9%

19.6%

1.6%

3%

3.1%

10.4%

13.7%

 

First 48 hours of hospitalization

≥1 SBP reading ≥180 

≥2 SBP readings 140-159/90-99

≥2 SBP readings 160-179

≥2 SBP readings ≥180

 

15.2%

63.8%

30.6%

5.6%

 

37.9%

39.6%

37%

23.4%

 

Abbreviations: ACEI= angiotensin-converting enzyme inhibitors; ARBs= angiotensin II receptor blockers; CCBs= calcium channel blockers; CKD- chronic kidney disease; COPD= chronic obstructive pulmonary disease; DBP= diastolic blood pressure; SBP= systolic blood pressure; TIA= transient ischemic attack 

Baseline characteristic values are prior to propensity score overlap weighting

Patients who received intensive BP treatment within the first 48 hours received a greater number of additional antihypertensives throughout their hospitalization

Results

Endpoint

Not intensively treated

(n= 52,076)

Intensively treated

(n= 14,064)

OR (95% CI)

Composite outcome* 

3,570 (6.9%) 1,220 (8.7%) 1.28 (1.18 to 1.39) 

Clinical outcome

Death

ICU transfer

Any stage AKI

Stroke

BNP elevation

Troponin elevation 

Hypotension

 

573 (1.1))

1,322 (2.5)

2,031 (3.9%)

43 (0.1%)

95 (0.2%)

710 (1.4%)

7,283 (14.0%)

 

156 (1.1%)

408 (2.9%)

769 (5.5%)

21 (0.2%)

38 (0.3%)

227 (1.6%)

2,078 (12.5%) 

 

1.11 (0.91 to 1.37)

1.20 (1.05 to 1.37)

1.43 (1.29 to 1.58)

1.46 (0.77 to 2.78)

1.81 (1.16 to 2.82)

1.20 (1.00 to 1.43)

1.22 (1.15 to 1.30)

Disposition

SNF discharge

Home

 

5,239 (10.1%)

45,372 (87.1%)

 

1,714 (12.2%)

11,936 (84.9%)

 

1.12 (1.04 to 1.20) 

0.89 (0.83 to 0.94) 

Abbreviations: AKI= acute kidney injury; BNP= b-type natriuretic peptide; CI= confidence interval; ICU= intensive care unit; OR= odds ratio; SNF= skilled nursing facility 

*Number needed to harm of 56 (95% CI 37 to 75)

Event rates are unadjusted while ORs are after overlap weighting

17.8% of patients who received intensive BP treatment received intravenous antihypertensives

Adverse Events

See results 

Study Author Conclusions

The study’s findings indicate that among hospitalized older adults with elevated BPs, intensive pharmacologic antihypertensive treatment was associated with a greater risk of adverse events. These findings do not support the treatment of elevated inpatient BPs without evidence of end-organ damage, and they highlight the need for randomized clinical trials of inpatient BP treatment targets

InpharmD Researcher Critique

Although the results suggest that intensive pharmacologic antihypertensive treatment in hospitalized older adults with elevated BPs is associated with a greater risk of adverse events, there are several limitations. The retrospective design carries inherent biases, and the study's focus on older adults within the VHA system, where patients are predominantly male and have higher rates of multimorbidity, may limit the generalizability of the findings to other populations.



References:

Anderson TS, Herzig SJ, Jing B, et al. Clinical Outcomes of Intensive Inpatient Blood Pressure Management in Hospitalized Older Adults. JAMA Intern Med. 2023;183(7):715-723. doi:10.1001/jamainternmed.2023.1667