What updated literature is there to suggesting harm with using PRN blood pressure medications while patients are hospitalized and increased incidence of stroke/heart attack/kidney dysfunction?

Comment by InpharmD Researcher

Recent guidance generally recommends against routine as-needed (PRN) antihypertensive treatment for asymptomatic elevated blood pressure (BP) in hospitalized patients, favoring assessment of reversible causes and cautious management of chronic therapy. Available evidence, which primarily consists of retrospective and observational data, has associated PRN antihypertensive use with acute kidney injury (AKI), rapid BP reductions, increased length of hospital stay, and higher risk of myocardial infarction, stroke, or death. One study found that the risk of AKI was greater with IV versus oral antihypertensive agents when used PRN. Overall, the evidence suggests potential harm with routine PRN treatment, although causality has not been established. Further research is needed to determine optimal inpatient BP management and which patients may benefit from PRN therapy.
Background

The 2025 joint multisociety hypertension guideline from the American Heart Association (AHA), American College of Cardiology (ACC), and 11 other partnering organizations recommends avoiding as-needed (PRN) antihypertensive medications in hospitalized patients with asymptomatic severe hypertension. This recommendation is based on observational evidence associating the initiation or intermittent use of additional IV or oral antihypertensive medications in patients hospitalized for noncardiac conditions with increased risks of in-hospital mortality, acute kidney injury, and prolonged hospital stay. [1]

Recent reviews discussing PRN antihypertensive use in hospitalized patients highlight evidence of potential harm with routine treatment of asymptomatic elevated blood pressure (BP). The review cites observational studies associating PRN antihypertensive use with acute kidney injury, rapid BP reductions, and increased risk of myocardial infarction, stroke, or death, with greater AKI risk observed with IV agents. The reviews note that a 2024 scientific statement by the AHA recommends against routine pharmacologic treatment of markedly elevated and asymptomatic elevated BP, while emphasizing accurate BP measurement, correction of reversible factors, and cautious management of home antihypertensive therapy. Overall, the evidence supports avoiding routine PRN antihypertensive use in the absence of acute target-organ injury, while recognizing that further research is needed to define appropriate treatment thresholds. [2], [3]

A 2026 systematic review and meta-analysis evaluated the safety of intensified versus more conservative BP control strategies during non-cardiac hospital admissions and at discharge. The analysis included four retrospective studies comprising 77,448 patients, evenly split between intensified (newly initiated, increased dose, intravenous, or pro re nata antihypertensive regimens) and non-intensified BP control groups (continuation of preadmission regimens or no pro re nata therapy). Patients with hypertensive emergencies or acute cardiovascular events at admission were excluded. Outcomes of interest were incidence of stroke, acute kidney injury (AKI), myocardial infarction (MI), and length of hospital stay (LOS). The meta-analysis demonstrated that intensified BP control was associated with significantly increased odds of stroke (odds ratio [OR] 3.77; 95% confidence interval [CI] 1.38–10.27; p<0.01) and AKI (OR 1.23; 95% CI 1.13–1.33; p<0.00001), along with an extended LOS (mean difference 1.17 days; 95% CI 1.11–1.93; p<0.00001). Although the pooled estimate for MI showed a trend toward increased risk (OR 2.04; 95% CI 0.85–4.89; p= 0.11), it did not reach statistical significance; however, sensitivity analysis restricted to inpatient BP intensification revealed a significant association with MI (OR 3.08; 95% CI 1.46–6.30; p= 0.003). Heterogeneity was moderate to high across outcomes but was fully explained by mean age in meta-regression models, with older cohorts facing higher risks. The findings suggest that initiating or escalating antihypertensive therapy during hospitalization or at discharge in asymptomatic patients may confer increased risks of adverse events, underscoring the need for cautious BP management and prospective randomized trials to delineate optimal inpatient strategies. [4]

Background References: [1] Writing Committee Members*, Jones DW, Ferdinand KC, et al. 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM 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 Joint Committee on Clinical Practice Guidelines. Hypertension. 2025;82(10):e212-e316. doi:10.1161/HYP.0000000000000249
[2] Kondrad E, Westling A, Harper M, Weldon S. Use of Intravenous Antihypertensives in Adults Hospitalized for Noncardiac Causes. Am Fam Physician. 2025;112(1):81-82.
[3] Popat A. PRN Antihypertensives in Hospitals: A Crisis of Precision or Pragmatism?. Clin Med Res. 2025;23(1):1-2. doi:10.3121/cmr.2025.2002
[4] Kushnir Y, Barrera N, Arias-Sanchez P, et al. Intensified blood pressure control during hospital admission and on discharge: a systematic review and meta-analysis of retrospective cohort studies. Front Cardiovasc Med. 2026;13:1691926. Published 2026 Feb 5. doi:10.3389/fcvm.2026.1691926
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What updated literature is there to suggesting harm with using PRN blood pressure medications while patients are hospitalized and increased incidence of stroke/heart attack/kidney dysfunction?

Level of evidence

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


Please see Tables 1-5 for your response.

As-Needed Blood Pressure Medication and Adverse Outcomes in VA Hospitals
Design

Retrospective cohort study

N= 51,356 (propensity score-matched population)
Objective To assess the risks of acute kidney injury (AKI) and other outcomes from as-needed (PRN) BP medication administration in a hospitalized veteran cohort
Study Groups

PRN BP medication (n= 25,678)

No PRN BP medication (n= 25,678)
Inclusion Criteria Adult veterans hospitalized ≥3 days in VA hospitals between October 1, 2015, and September 30, 2020, on a non-ICU medical or surgical floor, did not undergo surgery, received at least 1 scheduled BP medication in the first 24 hours, and had at least 1 SBP >140 mmHg during hospitalization
Exclusion Criteria Required surgery during admission, received BP medication PRN before first systolic BP <140 mm Hg, admission diagnoses that may require rapid lowering of BP, overlapping hospitalizations or readmitted within 24 hours, admitted from observation stay, ESKD on admission
Methods Data were obtained from the VA Informatics and Computing Infrastructure. Eligible veterans with inpatient hypertension (≥1 systolic BP >140 mm Hg) were classified into either a PRN BP medication group (defined as receipt of at least 1 recurring or 1-time PRN BP medication during hospitalization) or a control group with no PRN BP medication use.
Duration October 1, 2015, to September 30, 2020
Outcome Measures

Primary: Time to first AKI occurrence during hospitalization

Secondary: Rapid BP drop (>25% reduction in SBP within 3 hours), composite outcome of myocardial infarction (MI), stroke, or death during hospitalization
Baseline Characteristics   PRN BP medication (n= 25,678) No PRN BP medication (n= 25,678) p-value
Age, years 70.9 ± 11.9 71.2 ± 11.6 0.03
Male 96.6% 96.8% 0.01

Race

White

Black

Other

 

72.7%

23.8%

1.7%

 

73.1%

23.4%

1.7%

0.08

 

 

 
Current tobacco user 29.1% 28.4% 0.02

Comorbid conditions

Cerebrovascular disease

Chronic kidney disease

Congestive heart failure 

Coronary artery disease 

Diabetes

Hypertension 

Peripheral vascular disease

 

12.7%

25.2%

22.9%

28.0%

41.9%

76.5%

12.5%

 

12.7%

25.9%

26.4%

30.1%

42.6%

76.8%

13.1%

 

0.00

0.02

0.08

0.05

0.02

0.01

0.02

Baseline eGFR, mL/min/1.73m2

 74.7 ± 22.8 74.2 ± 22.7 0.03
SBP, mm Hg 156.4 ± 23.0 155.6 ± 21.7 0.04
DBP, mm Hg 83.9 ± 14.0 83.7 ± 13.2 0.02
No. of scheduled BP medications in the first 24 h 2.5 ± 1.5 2.5 ± 1.6 0.04
Results   PRN BP medication No PRN BP medication Hazard Ratio (95% CI)
AKI events 3,940 3,450 1.23 (1.18-1.29)
Rapid BP decrease >25% at 3h 1,644 1,125 1.50 (1.39-1.62)
Composite of MI, stroke, or death 848 340  1.69 (1.49-1.92)
Adverse Events In this cohort of veterans hospitalized to medical floors without indication for acute lowering of BP and without surgery during hospitalization, use of as-needed BP medications for asymptomatic BP elevation was associated with greater risk of AKI, rapid drop in BP, MI, stroke, and death.
Study Author Conclusions The results suggest that as-needed BP medication use among veterans is associated with increased AKI risk. The risks and benefits of this type of BP medication use would best be determined through a prospective trial, and these data suggest that there is the necessary equipoise to conduct such a trial.
Critique The study's strengths include its large sample size and use of target trial emulation to address confounding by indication. However, limitations include potential unmeasured confounding, missing baseline data, and limited generalizability to non-veteran populations and women. The retrospective design also limits causal inference.

 

Table 1 References:
[5] Canales MT, Yang S, Westanmo A, et al. As-Needed Blood Pressure Medication and Adverse Outcomes in VA Hospitals. JAMA Intern Med. 2025;185(1):52-60. doi:10.1001/jamainternmed.2024.6213
PRN Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity Matched Cohort Study
Design

Single-center, retrospective cohort study

N= 8,438 (propensity-matched population)
Objective To evaluate the association between the use of as-needed (PRN) antihypertensive medications and adverse outcomes in hospitalized patients without hypertensive emergencies
Study Groups

PRN BP MEDs (n= 4,219)

Scheduled BP MEDs (n= 4,219)
Inclusion Criteria Patients who received BP medications at any time during hospitalization
Exclusion Criteria Patients admitted to intensive care units, obstetric service, or who underwent any surgical procedure, and those with end-stage kidney disease, aortic dissection, stroke, or myocardial infarction (MI), or those who had insufficient data to ascertain the primary outcomes
Methods A retrospective analysis using hospital electronic medical records was conducted. Patients were divided into those receiving PRN and scheduled BP medications versus scheduled BP medications only.
Duration January 2012 to April 2016
Outcome Measures

Primary: Ischemic events (AKI and stroke), abrupt lowering in BP, in-hospital mortality, hospital length of stay

Secondary: Association between number of PRN doses and adverse outcomes
Baseline Characteristics   PRN BP MEDs (n= 4,219) Scheduled BP MEDs (n= 4,219) p-value
Age, years 62 ±16 63 ±15 0.049
Female 2,326 (55%)  2,316 (55%) 0.825

Race

White

African-American

Other

 

2,372 (56.2%)

1,705 (40.4%) 

142 (3.4%) 

 

2,399 (56.8%) 

1,670 (39.6%)

150 (3.6%)

0.379

 

 

 
Current smoker 982 (23%) 983 (23%) 0.979

Comorbid Conditions

Diabetes

Hypertension

Congestive Heart Failure

Myocardial Infarction

Peripheral Vascular Disease 

Cerebrovascular Disease 

Chronic Kidney Disease

 

1,968 (47%)

3,792 (90%)

1,375 (33%)

619 (15%)

1,020 (24%)

1,394 (33%) 

1,665 (40%) 

 

2,012 (48%)

3,755 (89%) 

1,364 (32%) 

613 (15%)

1,039 (25%) 

1,442 (34%)

1,718 (41%) 

 

0.331

0.179

0.797

0.852

0.633

0.267

0.237
Charlson Comorbidity Index, median (IQR)  5 (3–8) 6 (4–9) <0.001
SBP, mmHg 157 ±29 156 ±28  <0.001
DBP, mmHg 84 ±21 83 ±18  <0.001
Results   PRN BP MEDs (n= 4,219) Scheduled BP MEDs (n= 4,219) p-value
Ischemic events - AKI 538 (15.5%) 444 (12.8%) 0.002
Ischemic events - Stroke 17 (0.40%) 2 (0.05%) <0.001
Abrupt lowering of BP 350 (11.1%) 103 (5.9%) <0.001
In-Hospital mortality 33 (0.78%) 14 (0.33%) 0.006
Length of stay, median (IQR), days 4.7 (2.9–7.9) 2.9 (1.8–5.0) <0.001
Adverse Events The use of PRN antihypertensive medications was associated with an increased risk of acute kidney injury (AKI), ischemic stroke, abrupt lowering of blood pressure, and in-hospital mortality. The risk of these adverse events increased with the number of PRN doses administered.
Study Author Conclusions The routine use of PRN antihypertensive medications in hospitalized patients without hypertensive emergencies is associated with adverse outcomes and should be discouraged.
Critique The study effectively used propensity score matching to minimize confounding, providing robust evidence of the risks associated with PRN antihypertensive use. However, as a retrospective study, it is subject to selection bias and residual confounding. The single-center design may limit generalizability, and the lack of data on prescription patterns and clinical scenarios limits understanding of the context of PRN medication use.

 

Table 2 References:
[6] Mohandas R, Chamarthi G, Bozorgmehri S, et al. Pro Re Nata Antihypertensive Medications and Adverse Outcomes in Hospitalized Patients: A Propensity-Matched Cohort Study. Hypertension. 2021;78(2):516-524. doi:10.1161/HYPERTENSIONAHA.121.17279
Use Of Intravenous Antihypertensives In Hospitalized Patients
Design

Retrospective cohort study

N= 5,680
Objective To investigate the effects of IV as-needed (PRN) antihypertensives on blood pressure, hospital length of stay, and mortality
Study Groups

Recieved PRN medication (PRN) (n= 1,784)

Did not receive PRN (No PRN) (n= 3,896)
Inclusion Criteria Hospitalized patients with an order for an IV PRN antihypertensive medication
Exclusion Criteria Patients with evidence of target organ damage
Methods A multivariate analysis was performed to assess the association of IV PRN antihypertensive medication with outcomes. The study compared outcomes between patients who received the medication and those who did not. Intravenous hydralazine, enalapril, and labetalol were the medications analyzed.
Duration Not specified
Outcome Measures

Primary: Length of hospital stay

Secondary: In-hospital mortality, blood pressure reduction
Baseline Characteristics   PRN (n= 1,784) No PRN (n= 3,896)
Patient characteristics Not specified Not specified
Results   PRN (n= 1,784) No PRN (n= 3,896) p-value
Length of hospital stay, days 4.9 ± 6.1 3.1 ± 4.1 <0.001
In-hospital mortality 3.3% 1.6% <0.001

The difference in length of hospital stay remained statistically significant after adjusting for covariates, whereas the difference in in-hospital mortality did not.

Intravenous hydralazine was associated with a longer length of stay and caused the most significant reduction in blood pressure compared to enalapril and labetalol.
Adverse Events Not specified
Study Author Conclusions Treating hypertension in the in-patient setting is complex and multifactorial. Rapid lowering of blood pressure can harm patients, and antihypertensive medication increased hospital length of stay. A strategic approach should be used to treat modifiable factors and gradually reduce blood pressure.
Critique The study highlights the potential harm of rapid blood pressure reduction in hospitalized patients without target organ damage. However, the retrospective design may limit the ability to establish causality. The abstract design of the study does not specify the patient baseline characteristics, duration of follow-up, or other detailed characteristics of the study, and the exclusion of patients with target organ damage may limit the generalizability of the findings to all hypertensive patients in a hospital setting.

 

Table 3 References:
[7] Thompson K, Exposito J, Fowler O, Codolosa J. Use of intravenous antihypertensives in hospitalized patients. J Am Coll Cardiol. 2021;77(18 Suppl 1):1548. doi:10.1016/S0735-1097(21)02906-5
Retrospective Review Of The Use Of As-Needed Hydralazine And Labetalol For The Treatment Of Acute Hypertension In Hospitalized Medicine Patients
Design

Single-center, retrospective study

N= 250
Objective To evaluate the use of as-needed (PRN) labetalol and hydralazine in hospitalized medicine patients for the treatment of severe asymptomatic hypertension and to examine the potential negative outcomes associated with their use
Study Groups All patients (N= 250)
Inclusion Criteria Patients aged 18–89, admitted to a UCH internal medicine service, and had at least one documented administered dose of PRN IV or oral hydralazine or labetalol
Exclusion Criteria Patients admitted to the intensive care unit, pregnant, had a cerebrovascular accident within the last 6 months, admitted for hypertensive emergency or conditions associated with hypertensive emergency (e.g., cerebral hemorrhage, hypertensive encephalopathy, and aortic dissection or aneurysm)
Methods A retrospective review of patient electronic health records was conducted. Data collected included demographics, comorbidities, antihypertensive regimen prior to admission, changes during admission, detailed information on the PRN antihypertensive medication order, and outcomes associated with PRN antihypertensive therapy.
Duration November 2014 to April 2016
Outcome Measures

Primary: Description of the use of PRN antihypertensive medications

Secondary: Potential harm associated with acute treatment, changes to antihypertensive regimens during hospitalization and at discharge
Baseline Characteristics   N= 250
Age, years 55.6 ± 15.5
Female 123 (49.2%)

Race

White

Black

 

147 (58.8%)

84 (33.6%)

Past medical history

Hypertension

Diabetes

Chronic kidney disease

Coronary artery disease

 

216 (86.4%)

128 (51.2%)

75 (30.0%)

46 (18.4%)
No. BP medications prior to admission 1.8 ± 1.3
Results   All patients (N= 250)
Total number of doses of PRN IV or oral hydralazine or labetalol 573

Distribution of 573 PRN IV or oral doses by agent

Oral hydralazine

IV hydralazine

Oral labetalol

IV labetalol

 

90.9%

5.4%

3.0%

0.7%

PRN Dosing frequency

Q6h

Q8h

 

44.3%

48.3%

Number of doses received per patient

1

2

3

>3

 

46.4%

23.6%

12.4%

17.6%
BP readings prior to administration, mmHg Number of administrations out of 573
SBP <150 4
SBP 150–159 17
SBP 160–169 56
SBP 170–179 127
SBP 180–189 156
SBP 190–199 116
SBP ⩾200 60
SBP <180, but DBP ⩾110 37
No. BP medications at discharge 2.0 ± 1.2
Adverse Events

No serious adverse events related to PRN antihypertensive administration. A greater than 25% reduction in blood pressure within 6 h was observed in 21.5% of administrations.

One patient experienced a headache, one experienced dizziness, and one fell post-administration.
Study Author Conclusions As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering with administration thresholds often less than what are used to define acute severe hypertension. Many patients are prescribed PRN antihypertensive medication instead of being continued on their home regimens, and most patients do not have the intensity of their home regimens increased. Providers need to be educated about the use of PRN antihypertensive medication for the management of severe asymptomatic hypertension in the hospital setting.
Critique The study highlights the common use of PRN antihypertensive medications in hospitalized patients, revealing inconsistencies in prescription practices. However, it is limited by its single-center, retrospective design, which may affect the generalizability of the findings. The study did not evaluate other short-acting antihypertensives and lacked long-term outcome data, which could provide a more comprehensive understanding of the impact of PRN antihypertensive use.

 

Table 4 References:
[8] Gaynor MF, Wright GC, Vondracek S. Retrospective review of the use of as-needed hydralazine and labetalol for the treatment of acute hypertension in hospitalized medicine patients. Ther Adv Cardiovasc Dis. 2018;12(1):7-15. doi:10.1177/1753944717746613
As-Needed Intravenous Antihypertensive Therapy and Blood Pressure Control
Design

Retrospective study

N= 246
Objective To determine the frequency of prescribing and administering episodic IV antihypertensives and outcomes
Study Groups

No IV antihypertensive (n= 74)

IV antihypertensive (n= 172)
Inclusion Criteria Non–critically ill, hospitalized patients aged 18-89 years, with an IV antihypertensive order for enalaprilat, labetalol, hydralazine, or metoprolol
Exclusion Criteria Admitted to intensive care or coronary care unit, receiving nothing by mouth, pregnant, received a renal transplant in the past 3 months, or with clinical manifestation of new or worsening target-organ injury
Methods A retrospective review of patient medical charts from November 1, 2010 to January 31, 2011 was conducted. Patients were identified through the hospital electronic medical record system. Data collected included demographics, antihypertensive regimen, BP changes, and adverse events. Therapeutic intensity score (TIS) was calculated for oral antihypertensive regimen on admission and discharge.
Duration November 1, 2010 to January 31, 2011
Outcome Measures

Primary: Frequency of prescribing and administering episodic IV antihypertensives

Secondary: BP change during hospitalization, adverse outcomes
Baseline Characteristics   No IV Antihypertensive (n= 74) IV Antihypertensive (n= 172) p-value
Age, years 61.6 ± 13.9 60.6 ± 13.7 -
Male 51% 47% -
Weight, kg 94.6 ± 33.2 88.5 ± 27.7 -
African American 74% 87% 0.008
Systolic BP 148 ± 23 163 ± 32 <0.0001
Diastolic BP 82 ± 13 87 ± 18 0.009
Heart rate 87 ± 18 82 ± 20 0.069
Admit TIS 0.84 ± 0.72 1.08 ± 0.88 0.026
SCr 1.78 ± 2.00 2.74 ± 3.30 0.006
AST 26.5 ± 12.5 65 ± 126.2 0.046
1-time-only order 5% 19% -
As-needed order 95% 81% -
Results   No IV Antihypertensive (n= 74) IV Antihypertensive (n= 172) p-value
BP reduction >25% within 6 hours - 32.6% -
Oral regimen intensified - 52% -

Hydralazine was the preferred antihypertensive agent (80.1%), with IV beta-blockers prescribed less frequently (labetalol 15.6% and metoprolol 4.4%).

172 received 458 doses, with 48% receiving a single dose, 26% receiving 2 doses, and 11% receiving 3 doses. Over 98% of episodic IV antihypertensive doses were administered for systolic blood pressure (SBP) <200 mmHg and 84.5% for SBP <180 mmHg.
Adverse Events

Out of the patients who experienced a BP reduction >25% within 6 hours, 2 patients received IV fluids, and 6 had a scheduled oral BP medication held.

13 patients had an increase in heart rate >20 bpm, with 7 having a heart rate >100 bpm. One patient experienced bradycardia.
Study Author Conclusions IV antihypertensive drugs are ordered and administered in patients with asymptomatic, uncontrolled BP for levels unassociated with substantive immediate cardiovascular risk, which may cause adverse effects.
Critique The study highlights the frequent use of IV antihypertensives in non-critical settings without clear evidence of benefit, potentially leading to adverse effects. However, it is limited by its retrospective design, single-center setting, and lack of long-term outcome data.

 

Table 5 References:
[9] Lipari M, Moser LR, Petrovitch EA, Farber M, Flack JM. As-needed intravenous antihypertensive therapy and blood pressure control. J Hosp Med. 2016;11(3):193-198. doi:10.1002/jhm.2510