This narrative review explores hypertensive emergencies, which account for 0.3%-0.5% of emergency department (ED) visits. We selected studies published between 2020 and 2025 through a focused search of PubMed and Google Scholar using keywords like ‘hypertensive emergency’, ‘pregnancy-induced hypertension’, and ‘IV antihypertensives’. Neuroimaging, ECG, and cardiac biomarkers are key diagnostic tools. IV agents such as labetalol, nicardipine, and hydralazine remain essential for rapid BP control. Trials in pregnancy settings highlight nicardipine’s advantage in respiratory outcomes and nifedipine’s BP-lowering efficacy. Adherence-focused interventions and pharmacogenetic studies underline challenges in chronic BP control. While mHealth has promise, clinical disparities persist. This review emphasizes integrated, evidence-informed approaches tailored to diverse clinical settings.
In pregnancy, an open-label randomized trial found that nicardipine was associated with fewer cases of respiratory distress syndrome (12.5%) compared to labetalol (42.9%, p=0.04), although differences in overall neonatal outcomes were not statistically significant (p=0.12). Another trial showed that nifedipine was most effective for single-dose BP reduction.
The Norwegian therapeutic drug monitoring (TDM) trial showed no significant BP difference between groups at 3 or 6 months, though adherence improved in both arms. A sub-study on amlodipine pharmacokinetics demonstrated that lower controlled dose ratios (CDRs) were associated with uncontrolled hypertension (HTN) (5.6 vs. 6.3 nmol/L/mg, p=0.014). The Reach Out trial in a U.S. safety-net ED showed a 6.6 mmHg systolic BP reduction at 12 months. However, no mHealth component significantly affected BP, and disparities in outcomes persisted among Black participants.

Hypertensive emergencies, Blood pressure management, Intravenous, Pregnancy-Induced hypertension, Antihypertensive therapy.

This review outlines the management of hypertensive emergencies and markedly elevated BP without end-organ damage in the ED, while also addressing the growing role of emergency medicine in managing non-markedly elevated BP. With nearly 145 million annual ED visits in the U.S. and elevated BP present in approximately 45% of cases, the ED offers a critical touchpoint for HTN intervention. Drawing on experience from Detroit, the review highlights the disproportionate cardiovascular burden in underserved urban populations, particularly among African Americans, and calls for a unified medical approach to reduce persistent disparities and improve long-term outcomes.[1-4]

Systemic HTN is the most prevalent non-communicable disease and the leading preventable cause of premature death worldwide, contributing to over half of myocardial infarction, heart failure, and stroke cases. Since 1990, the hypertensive population has doubled, with over 75% residing in low- and middle-income countries (LMICs). South Africa, with a 35% HTN prevalence, bears the highest burden of uncontrolled HTN in sub-Saharan Africa. Cardiac complications, acute heart failure, acute coronary syndrome, and acute aortic syndrome are the most common acute HTN-mediated organ damage in hypertensive emergencies. These emergencies are associated with elevated mortality, particularly among coronary care unit admissions. Elevated cardiac troponin levels are a significant prognostic marker for adverse cardiac and cerebrovascular events in these patients.[5-9]

Hypertensive emergencies represent a small proportion of ED visits, between 0.3% and 0.5% they are associated with high rates of hospitalization, in-hospital mortality, and long-term health deterioration. The diagnosis of hypertensive emergencies is primarily guided by clinical evaluation, focusing on symptoms and signs indicative of acute target organ damage. Diagnostic investigations commonly include comprehensive metabolic panels, urinalysis, B-type natriuretic peptide (BNP) levels, and cardiac biomarkers. In cases where cardiac involvement is suspected, an ECG is essential.[10,11]

Neuroimaging, particularly a head computed tomography (CT) scan, is indicated for patients presenting with acute neurological symptoms, while chest radiography is useful in evaluating dyspnea and potential pulmonary edema. Management of hypertensive emergencies typically involves the use of IV antihypertensive agents such as labetalol, esmolol, nicardipine, and NTG. These agents are effective in rapidly reducing BP while minimizing the risk of further organ injury. In the absence of target organ damage, BP reduction should be gradual, typically over 24 to 72 hours, to avoid ischemic complications.[12]

NTG is a potent vasodilator commonly employed for the rapid relief of angina in patients presenting with chest pain or suspected acute myocardial infarction (AMI). The vasodilatory mechanism of NTG involves NO-mediated activation of guanylyl cyclase in vascular smooth muscle cells. This activation increases intracellular levels of cyclic guanosine monophosphate (cGMP), which facilitates the dephosphorylation of myosin light chains. The result is smooth muscle relaxation, leading to reduced myocardial oxygen demand through decreased ventricular wall stress. NTG exhibits high bioavailability due to its rapid absorption across various routes, including transdermal, sublingual, oral, mucosal, and IV pathways.[13-17]

Epidemiology
Hypertensive emergencies constitute a relatively rare but clinically significant subset of hypertensive crises, with an estimated global prevalence of 0.3% to 0.5% of all ED visits. While overall HTN remains a major global health burden affecting over 1.28 billion adults, only a small proportion progress to hypertensive emergencies, which are distinguished by the presence of acute target organ damage (TOD) and a high risk of morbidity and mortality.

Multiple large-scale retrospective and prospective studies conducted between 2020 and 2025 indicate that hypertensive emergencies account for approximately 25-36% of all hypertensive crises. Data from high-income countries such as the United States, Italy, and Japan reveal a consistent prevalence of hypertensive emergencies in EDs ranging between 0.2-0.6%, whereas in low- and middle-income countries, the proportion is often higher due to delayed diagnosis, poor access to antihypertensive therapy, and low adherence to treatment.[18-21]

Hospitalization rates for hypertensive emergencies are consistently high, reported at 80%-90% in most studies. The in-hospital mortality ranges from 5% to 15%, depending on the type of organ damage, comorbid conditions, and timeliness of intervention. Readmission and recurrence rates within 6-12 months can reach 20-30%, particularly in those with poor outpatient follow-up or medication noncompliance.[22-25]

This article is a narrative review that synthesizes recent evidence on hypertensive emergencies from a variety of clinical contexts, including pregnancy, pharmacologic interventions, and underserved populations. A structured but non-systematic search was conducted across PubMed and Google Scholar for peer-reviewed articles published between January 2020 and June 2025. Search terms included: “hypertensive emergency,” “acute hypertension,” “IV antihypertensives,” “pregnancy-induced hypertension,” “mHealth hypertension,” and “pharmacogenetics in hypertension.”

Articles were selected based on clinical relevance, study quality, and their contribution to understanding diagnosis, treatment, and outcome disparities in hypertensive emergencies. Included studies spanned randomized controlled trials, observational studies, and pharmacokinetic/pharmacogenetic evaluations.

Efficacy and safety outcomes of labetalol versus nicardipine in severe HTN during pregnancy
In the study by Bij Weg et al., an open-label randomized controlled trial was conducted from August 2018 to April 2022 at two Dutch hospitals. Pregnant women (≥24 weeks) with a first episode of severe HTN (systolic ≥160 mmHg and/or diastolic ≥110 mmHg) requiring IV antihypertensives were included. Exclusion criteria were age <18, language barriers, major fetal anomalies, pulmonary edema, or contraindications to labetalol or nicardipine. Participants gave written informed consent and were randomized (1:1) to receive either drug using stratified web-based randomization. Labetalol began at 20 mg/hr with 20 mg/hr increases every 30 minutes (max 2400 mg/day); nicardipine at 1 mg/hr with 1 mg/hr increases every 15 minutes (max 10 mg/hr). BP targets were systolic 130-155 mmHg and diastolic 85-105 mmHg. If targets were not reached, treatment switched to the alternate drug. Fetal monitoring was continuous until stabilization, then daily.

The primary outcome was a composite of severe neonatal complications or perinatal death. Secondary maternal outcomes included eclampsia, organ complications, ICU admission, or treatment resistance; neonatal outcomes included preterm birth, bradycardia, asphyxia, and hypoglycemia. The study required 472 participants but was terminated early due to slow inclusion, with only 30 women randomized (14 to labetalol, 16 to nicardipine). Baseline characteristics were similar, except for chronic HTN (44% nicardipine vs. 28.6% labetalol). Composite neonatal outcomes favoured nicardipine (25% vs. 43%, p=0.12). Respiratory Distress Syndrome (RDS) occurred more in the labetalol group (42.9% vs. 12.5%, p=0.04), particularly under 34 weeks gestation.[26]

Randomization, BP outcomes, and adherence trends
In a study by Halvorsen LV et al., from 2017 to 2022, a total of 1,156 hypertensive patients were screened for eligibility across four Norwegian university hospitals: Oslo (629 patients, 54%), Bergen (218, 19%), Tromsø (149, 13%), and Trondheim (160, 14%). Referrals came from primary care (662 patients, 57%), specialist centers (176, 15%), and self-referrals (313, 27%) via media outreach. Patients were instructed not to alter their medication prior to the initial visit to avoid biasing adherence data.

Inclusion ended in March 2022 (extended 16 months due to Coronavirus disease (COVID-19)), with all follow-ups completed by August 2022 and data queries resolved by January 2023. Patients ≥18 years, on ≥2 antihypertensive drugs (or ≥1 fixed-dose combination) with ≥4 weeks of stable treatment, were included. For baseline eligibility, systolic daytime ambulatory blood pressure measurement (ABPM) ≥135 mm Hg was required; those with ABPM ≥170 mm Hg or exclusion criteria were not invited further.

Out of 1,156 patients screened, 52 had uncontrolled hypertension due to nonadherence; 46 were randomized (26 to TDM, 20 to control). Six were excluded due to high BP. Baseline characteristics were similar. Four control patients were excluded from 3-month analysis. At 6 months, mean systolic ABPM was 136 ± 16 mm Hg (TDM) and 135 ± 14 mm Hg (control, p=0.79), with no significant BP reduction difference. Adherence improved in both groups: at 3 months, 73% (TDM) vs. 59% (control), and by 6 months, 87% vs. 62% (p=0.11). Complete nonadherence dropped from 17% to 6.5%, with varying individuals across time points.[27]

Amlodipine pharmacokinetics, genetic variability, and clinical correlates in hypertensive patients
This study by Rognstad S et al. utilized data from a national multicenter HTN project in Norway (2017–2022), involving 1,156 patients from four university hospitals. Of these, 495 adults using amlodipine were included based on systolic daytime ABPM ≥135 mmHg, use of ≥2 antihypertensives, and stable treatment for ≥4 weeks. Daily pill counts were averaged weekly. Blood samples were collected for serum amlodipine, routine labs, and cytochrome P (CYP) genotyping. Patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² were excluded from the main study but included in this sub-study. After excluding 24 with missing or undetectable data, 471 patients (319 men, 152 women) were analysed. Of these, 48% had uncontrolled HTN (mean ABPM 145.0 ± 8.7 mmHg), and 52% had controlled HTN (125.3 ± 6.8 mmHg). Mean age was 62 ± 11 years; 94% were Caucasian. Most were overweight (BMI ≥25), with 47% classified as obese.

The majority took either 5 mg (40%) or 10 mg (58%) of amlodipine daily. Median serum concentration significantly differed by dose (28 nmol/L for 5 mg vs. 52 nmol/L for 10 mg, p < 0.001). Dose explained 25% of serum concentration variance. Genotyping (n=258) revealed CYP3A4 *22 carriers had significantly higher dose-adjusted serum concentrations than *1/*1 (β = 1.94, p=0.006), while CYP3A5 variants showed no significant association. Nine clinical covariates explained 24% of CDR variability and 41% of serum concentration variability.

Patients with uncontrolled HTN had significantly lower mean CDR (5.6 vs. 6.3 nmol/L/mg, p=0.014), though serum concentrations did not differ (p=0.14). Female sex was linked to 50% reduced odds of uncontrolled HTN (odds ratio (OR) 0.504, p=0.003). Women had lower doses (7.3 vs. 8.3 mg, p<0.001), yet higher serum concentrations (51 vs. 44 nmol/L, p<0.022) and higher median CDR (6.7 vs. 4.9 nmol/L/mg, p<0.001).

Older age (β=0.064, p<0.001) and reduced kidney function (eGFR <60 mL/min) were also associated with higher CDR. Lower eGFR predicted higher CDR (β=−0.043, R²=0.125, p<0.001), with no sex differences in this effect.[28]

Comparative effectiveness of nifedipine, labetalol, and hydralazine in managing severe preeclampsia
This double-blind, randomized clinical trial by S D. Novri DA. Compared oral nifedipine, IV labetalol, and IV hydralazine in managing hypertensive emergency in severe preeclampsia. Conducted at four hospitals in Riau Province, Indonesia (May 2021-April 2022), the study enrolled 60 patients (20 per group) with 28-34 weeks of gestation and sustained severe hypertension. Inclusion required a live fetus, upper arm circumference of 23.5-33 cm, and haemoglobin ≥10.5 g/dL; key exclusions included eclampsia, haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, kidney failure, and ongoing labor. Patients received up to three doses every 20 minutes, with BP measured at baseline and six time points over six hours. Physicians were trained and blinded, and BP was measured using the Omron 7600T after 10 minutes of rest. Those not achieving target mean arterial pressure (MAP) after three doses were excluded. Data analysis included Kolmogorov-Smirnov, analysis of variance (ANOVA), Kruskal-Wallis, Friedmann, N-Gain, Cohen’s d, and Kaplan-Meier, using Statistical Package for the Social Sciences (SPSS) version 22.

This study included 60 patients with severe preeclampsia, randomized equally into three groups to receive oral nifedipine, IV labetalol, or IV hydralazine. Eleven patients who failed to achieve the target MAP reduction after three doses were excluded from effectiveness analysis: 3 from the nifedipine group, 7 from labetalol, and 1 from hydralazine. Baseline characteristics (age, gestational age, BP, pulse, etc.) were uniform across groups.

Regarding dose response, 4 patients (nifedipine), 1 (labetalol), and 3 (hydralazine) achieved target MAP with only one dose. Nifedipine significantly reduced systolic BP by 13.41 mmHg and diastolic BP by 16.71 mmHg at 20 minutes post-first dose (p < 0.001), with a MAP reduction of 15.61 mmHg. Subsequent doses showed lesser and non-significant effects.

Labetalol significantly reduced systolic BP after the first and third doses (13.38 mmHg and 12.00 mmHg) and diastolic BP similarly (9.69 mmHg and 8.30 mmHg), with MAP reductions paralleling diastolic changes. Hydralazine significantly lowered systolic BP up to 20 minutes post-third dose (p < 0.001), with a mild rebound at 1 hour; diastolic BP and MAP also declined significantly. N-gain analysis showed nifedipine was most effective (0.575, 58%), followed by labetalol (0.421, 42%) and hydralazine (0.408, 41%). MAP reduction differed significantly among drugs (p=0.037), with a significant difference between nifedipine and hydralazine (p=0.048).[29]

BP reduction and engagement outcomes of the reach out trial
The Reach Out trial by Skolarus LE et al. was a randomized, controlled 2×2×2 factorial study using the MOST framework to evaluate mHealth components for BP control. Conducted in Flint, Michigan (2017–2020), it enrolled safety-net ED patients with elevated BP (SBP ≥160 or DBP ≥100 mmHg) who were being discharged and owned a mobile phone. After a 3-week run-in phase with weekly BP texts, participants with at least one elevated reading were randomized into eight groups combining text messaging, BP monitoring frequency, and facilitated PCP scheduling/transport. All received wrist BP monitors and culturally tailored education. Outcomes were assessed at 6 and 12 months.

Sample size calculations estimated that 196 participants were needed for 80% power. Analyses included complete case linear modelling, longitudinal mixed-effects models, and multiple imputation for missing data. Statistical methods included ANOVA, logistic regression, Cox models, and Kaplan-Meier curves using SAS and R software.

During a 12-month enrolment (March 2019-March 2020), 20,819 ED patients with elevated BP were flagged; 1,373 were approached, 833 enrolled, 488 randomized, and 211 (43%) completed 12-month follow-up. Participants averaged 45.5 years; 22% lacked a primary care physician (PCP), 10% were uninsured, and 44% hadn’t used antihypertensives in 6 months. Follow-up completers were older, female, Black, had lower baseline BP, and were more likely to have a PCP or HTN history. SBP declined by 9.2 mmHg at 6 months and 6.6 mmHg at 12 months. No mHealth component showed significant BP reduction. Prior antihypertensive use and existing PCP strongly predicted visit attendance.[30]

Limitations
This review includes studies with varied designs (RCTs, pharmacokinetic, implementation), introducing heterogeneity. Absence of a systematic methodology may introduce selection bias. Evidence strength across studies varies; findings should be interpreted within their specific contexts.

This comprehensive review and collection of clinical trials underscore the critical complexity of hypertensive emergencies, and the diverse strategies needed to manage both emergent and chronic HTN in emergency and outpatient settings. Although hypertensive emergencies represent a small fraction (0.3%-0.5%) of ED visits, they are linked with high rates of hospitalization and mortality, particularly when organ damage is evident. Prompt diagnosis using biomarkers, ECG, neuroimaging, and appropriate pharmacologic intervention such as IV labetalol, nicardipine, and NTG is vital.

Management nuances in pregnancy-related hypertensive emergencies were illustrated in two randomized trials. In the trial by Bij Weg et al., nicardipine showed a trend toward better neonatal outcomes and significantly lower rates of respiratory distress syndrome compared to labetalol (12.5% vs. 42.9%, p=0.04), though the overall composite outcome difference was not statistically significant (p=0.12).[26] Another study from Indonesia revealed that oral nifedipine, while most effective in single-dose BP reduction, required careful monitoring due to differential efficacy profiles among agents.

Adherence and pharmacogenetic variability were emphasized in Norwegian multicenter studies. In Halvorsen et al.’s trial, improved adherence did not translate into significant BP differences between groups, but overall adherence rates rose, notably in the TDM group (87% vs. 62% at 6 months).[27] Rognstad et al. further linked pharmacokinetic variability of amlodipine to serum concentrations, with female sex and reduced eGFR correlating with higher drug levels.[28]

Finally, the Reach Out trial highlighted systemic barriers and demographic disparities in BP control, noting limited BP reduction in Black participants and suboptimal follow-up rates. Despite widespread mHealth integration, no individual intervention significantly affected 12-month SBP.[30] These findings underscore the need for tailored, multifaceted strategies addressing pharmacologic, behavioural, and social determinants to mitigate the burden of hypertensive crises.

This review highlights the multifactorial nature of hypertensive emergencies and underscores the importance of individualized, evidence-based strategies for their management. Despite representing only 0.3%-0.5% of ED visits, hypertensive emergencies are associated with substantial morbidity, mortality, and long-term cardiovascular risks due to acute target organ damage. Prompt clinical assessment supported by diagnostic imaging and laboratory evaluation is critical. Clinical trials suggest nicardipine may offer respiratory benefits in pregnancy, while nifedipine is effective for rapid BP reduction. In non-pregnant adults, adherence support and understanding pharmacogenetic factors are vital. Clinicians should prioritize rapid stabilization with IV agents, address adherence barriers, and consider patient-specific variables for optimal outcomes.

Clinical trials in pregnant populations reveal the complexity of treating severe HTN in preeclampsia. Nicardipine may offer neonatal respiratory advantages over labetalol, while nifedipine demonstrated superior efficacy in single-dose BP reduction.

In non-pregnant populations, medication adherence remains a cornerstone of effective BP control. Overall, improving hypertensive emergency outcomes requires personalized pharmacotherapy, enhanced patient adherence, and health system-level reforms.

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No funding

Corresponding Author:
Samatha Ampeti
Department of Pharmacology
Kakatiya University, University College of Pharmaceutical Sciences, Warangal, TS, India
Email: ampetisamatha9@gmail.com

Co-Authors:
Shubham Ravindra Sali, Mansi Srivastava, Raziya Begum Sheikh, Sonam Shashikala B V, Patel Nirali Kirankumar
Independent Researcher
Department of Content, medtigo India Pvt Ltd, Pune, India

All authors contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles. They were collectively involved in the writing – original draft preparation and writing-review & editing to refine the manuscript. Additionally, all authors participated in the supervision of the work, ensuring accuracy and completeness. The final manuscript was approved by all named authors for submission to the journal.

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None

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https://doi.org/10.63096/medtigo3092237