What literature exists comparing nicardipine and cleviprex in the management of hypertensive crisis?

Comment by InpharmD Researcher

Literature directly comparing clevidipine and nicardipine is scarce, with nearly all available studies being retrospective and observational in design, increasing the risk of bias. Nonetheless, available data suggest that both nicardipine and clevidipine are generally comparable, with few significant differences in measured outcomes (e.g., additional required antihypertensives). Data suggesting clevidipine’s efficacy in terms of cost and time in the therapeutic range are conflicting. Guidelines for the treatment of hypertensive emergencies and acute ischemic stroke generally refrain from identifying either of the two agents as superior (see Tables 1-3), though nicardipine may be preferred for the management of hypertensive encephalopathy, acute coronary syndromes, and eclampsia, while clevidipine may be preferred for acute pulmonary edema and pheochromocytoma.

Background

A 2024 systematic review and meta-analysis evaluated clevidipine administration in neurocritical patients, retrieving data from five retrospective cohort studies (N= 443) that utilized nicardipine as the comparator arm. Primary outcomes of interest included time to achieve target systolic blood pressure (SBP), as well as the amount of time spent within the therapeutic range. Length of intensive care unit (ICU) stay, hypotension, and tachycardia incidence were similar between groups. When assessing time to reach target SBP, there was no significant difference between clevidipine or nicardipine (standardized mean difference [SMD] -1.09; p= 0.33), but clevidipine did exhibit a greater amount of time spent within target range compared to nicardipine (SMD 0.33; p= 0.04); notably, moderate heterogeneity was observed, in part due to the dosing of clevidipine and the clinical settings in which it was used varied. Initial doses ranged from 1.5 mg/h to 10.8 mg/h, with different titration methods, up to doses as high as 32 mg/h. Patients’ diagnoses ranged from intracerebral hemorrhage (ICH) to subarachnoid hemorrhage (SAH), among many others. More robust data is required to substantiate clevidipine’s slight advantage over nicardipine in maintaining time in the therapeutic range. [1]

A 2023 systematic review and meta-analysis (N= 5 retrospective studies; 546 patients) evaluated the efficacy of clevidipine vs nicardipine in cerebrovascular diseases (CVD), including stroke, SAH, and ICH. Time to achieve SBP goal, total infusion volume, and LOS in both ICU and hospital were evaluated. Clevidipine was associated with a shorter mean time to SBP goal compared to nicardipine, but the difference was not significantly different (SMD -0.04; 95% confidence interval [CI] -0.66 to 0.58; p= 0.86; I2= 79.0%). Despite the removal of an outlier study to decrease heterogeneity, a significant difference in time to goal SBP was not achieved. Clevidipine was, however, associated with a significantly lower total volume of infusion compared to nicardipine (SMD -0.52; 95% CI -0.93 to -0.12; p= 0.03; I2= 0.0%). Pooled data indicated that overall hospital LOS was significantly shorter with clevidipine (SMD 0.15; 95% CI 0.03 to 0.27; p= 0.03; I2= 0.0%), but no significant differences were noted between the two agents for ICU length of stay (SMD 0.19; 95% CI -0.32 to 0.69; p= 0.25; I2= 0.0%). Adverse events were generally comparable between the two groups. While both clevidipine and nicardipine were found to be similar overall, clevidipine may still be an ideal choice in patients with volume overload due to decreased total infusion volume required. The quality of available evidence is hindered by the limited number of relevant studies and scarcity of evidence. [2]

Another 2023 review describes the treatment of hypertension in the emergency department. Nicardipine was recommended as a first-line agent for the treatment of hypertensive encephalopathy, while clevidipine may be considered as an alternative. The use of nicardipine was also suggested in intracerebral hemorrhage, as well as a second-line option for uncontrolled blood pressure in aortic dissection. Both nicardipine and clevidipine are listed as preferred agents for ischemic stroke, hemorrhagic stroke, and eclampsia. However, nicardipine is not listed as a preferred drug for pheochromocytoma, while clevidipine is. [3]

A 2022 systematic review was also conducted to compare the efficacy of intravenous (IV) antihypertensives for acute blood pressure control, with a focus on neurologic emergencies. The review assessed data from the same studies previously included in other literature, determining that very limited evidence was found to support the use of one IV antihypertensive over another for acute blood pressure management in this setting. Comparisons of nicardipine versus clevidipine, as presented in 3 observational studies (N= 386 patients), were considered to be based on suboptimal studies, with none evaluating functional outcome and all determined to have high risk of bias. Generally, no significant differences in primary outcomes, such as time within goal blood pressure, time to reach goal, or need for rescue therapy, were observed between the two drugs. [4]

References:

[1] Widiastuti M, Bisri DY, Rachman IA. The safety and efficacy of clevidipine for blood pressure management in neurocritical patients: a systematic review and meta-analysis. Sci Rep. 2024;14(1):6355. Published 2024 Mar 16. doi:10.1038/s41598-024-54667-9
[2] Seifi A, Azari Jafari A, Mirmoeeni S, et al. Comparison between clevidipine and nicardipine in cerebrovascular diseases: A systematic review and meta-analysis. Clin Neurol Neurosurg. 2023;227:107644. doi:10.1016/j.clineuro.2023.107644
[3] Manolis AJ, Kallistratos MS, Koutsaki M, et al. The diagnostic approach and management of hypertension in the emergency department. Eur J Intern Med. Published online December 11, 2023. doi:10.1016/j.ejim.2023.11.028
[4] Brown CS, Oliveira J E Silva L, Mattson AE, et al. Comparison of Intravenous Antihypertensives on Blood Pressure Control in Acute Neurovascular Emergencies: A Systematic Review. Neurocrit Care. 2022;37(2):435-446. doi:10.1007/s12028-021-01417-8
Literature Review

A search of the published medical literature revealed 11 studies investigating the researchable question:

What literature exists comparing nicardipine and cleviprex in the management of hypertensive crisis?

Level of evidence

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


Please see Tables 1-11 for your response.

 

Intravenous Antihypertensive Drugs for Treatment of Hypertensive Emergencies per ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guidelines
Class Drug(s) Usual Dose Range

Comments

CCB-dihydropyridines

Nicardipine

 Initial 5 mg/h, increasing every 5 min by 2.5 mg/h to maximum 15 mg/h.

Contraindicated in advanced aortic stenosis; no dose adjustment needed for elderly.

Clevidipine

 Initial 1–2 mg/h, doubling every 90 s until BP approaches target, then increasing by less than double every 5–10 min; maximum dose 32 mg/h; maximum duration 72 h.

Contraindicated in patients with soybean, soy product, egg, and egg product allergy and in patients with defective lipid metabolism (eg, pathological hyperlipidemia, lipoid nephrosis or acute pancreatitis). Use low-end dose range for elderly patients.

Vasodilators—Nitric oxide dependent

 Sodium nitroprusside

Initial 0.3–0.5 mcg/kg/min; increase in increments of 0.5 mcg/kg/min to achieve BP target; maximum dose 10 mcg/ kg/min; duration of treatment as short as possible. For infusion rates ≥4–10 mcg/kg/min or duration >30 min, thiosulfate can be coadministered to prevent cyanide toxicity.

 Intra-arterial BP monitoring recommended to prevent “overshoot.” Lower dosing adjustment required for elderly. Tachyphylaxis common with extended use. Cyanide toxicity with prolonged use can result in irreversible neurological changes and cardiac arrest.
Nitroglycerin

Initial 5 mcg/min; increase in increments of 5 mcg/min every 3–5 min to a maximum of 20 mcg/min.

 Use only in patients with acute coronary syndrome and/ or acute pulmonary edema. Do not use in volume-depleted patients.
Vasodilators—direct Hydralazine

Initial 10 mg via slow IV infusion (maximum initial dose 20 mg); repeat every 4–6 h as needed.

BP begins to decrease within 10–30 min, and the fall lasts 2–4 h. Unpredictability of response and prolonged duration of action do not make hydralazine a desirable first-line agent for acute treatment in most patients.

Adrenergic blockers—beta1 receptor selective antagonist

 Esmolol Loading dose 500–1000 mcg/kg/min over 1 min followed by a 50-mcg/kg/min infusion. For additional dosing, the bolus dose is repeated and the infusion increased in 50-mcg/kg/min increments as needed to a maximum of 200 mcg/kg/min.

Contraindicated in patients with concurrent beta-blocker therapy, bradycardia, or decompensated HF.

Monitor for bradycardia.

May worsen HF.

Higher doses may block beta2 receptors and impact lung function in reactive airway disease.

Adrenergic blockers—combined alpha1 and nonselective beta receptor antagonist

 Labetalol Initial 0.3–1.0-mg/kg dose (maximum 20 mg) slow IV injection every 10 min or 0.4–1.0-mg/kg/h IV infusion up to 3 mg/kg/h. Adjust rate up to total cumulative dose of 300 mg. This dose can be repeated every 4–6 h.

Contraindicated in reactive airways disease or chronic obstructive pulmonary disease. Especially useful in hyperadrenergic syndromes. May worsen HF and should not be given in patients with second- or third-degree heart block or bradycardia.

Adrenergic blockers—nonselective alpha receptor antagonist

 Phentolamine IV bolus dose 5 mg. Additional bolus doses every 10 min as needed to lower BP to target.

Used in hypertensive emergencies induced by catecholamine excess (pheochromocytoma, interactions between monoamine oxidase inhibitors and other drugs or food, cocaine toxicity, amphetamine overdose, or clonidine withdrawal).

Dopamine1-receptor selective agonist

 Fenoldopam

Initial 0.1–0.3 mcg/kg/min; may be increased in increments of 0.05–0.1 mcg/kg/min every 15 min until target BP is reached. Maximum infusion rate 1.6 mcg/kg/min.

 Contraindicated in patients at risk of increased intraocular pressure (glaucoma) or intracranial pressure and those with sulfite allergy.
ACE inhibitor

Enalaprilat

Initial 1.25 mg over a 5-min period. Doses can be increased up to 5 mg every 6 h as needed to achieve BP target.

Contraindicated in pregnancy and should not be used in acute MI or bilateral renal artery stenosis.

Mainly useful in hypertensive emergencies associated with high plasma renin activity.

Dose not easily adjusted.

Relatively slow onset of action (15 min) and unpredictability of BP response.

ACE, angiotensin-converting enzyme; BP, blood pressure; CCB, calcium channel blocker; HF, heart failure; IV, intravenous; MI, myocardial infarction

 

References:

Adapted from:
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: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e426-e483. doi:10.1161/CIR.0000000000000597

 

Intravenous Antihypertensive Drugs for Treatment of Hypertensive Emergencies in Patients With Selected Comorbidities per ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guidelines

Comorbidity

 Preferred Drug(s)* Comments

Acute aortic dissection

 Esmolol, labetalol

Requires rapid lowering of SBP to ≤120 mm Hg.

Beta blockade should precede vasodilator (e.g., nicardipine or nitroprusside) administration, if needed for BP control or to prevent reflex tachycardia or inotropic effect; SBP ≤120 mm Hg should be achieved within 20 min.

Acute pulmonary edema

 Clevidipine, nitroglycerin, nitroprusside Beta blockers contraindicated.

Acute coronary syndromes

 Esmolol, labetalol, nicardipine, nitroglycerin

Nitrates given in the presence of PDE-5 inhibitors may induce profound hypotension. Contraindications to beta blockers include moderate-to-severe LV failure with pulmonary edema, bradycardia (​< 60 bpm), hypotension (SBP < 100 mm Hg), poor peripheral perfusion, second- or third-degree heart block, and reactive airway disease.

Acute renal failure

 Clevidipine, fenoldopam, nicardipine N/A

Eclampsia or preeclampsia

 Hydralazine, labetalol, nicardipine

Requires rapid BP lowering.

ACE inhibitors, ARBs, renin inhibitors, and nitroprusside contraindicated.

Perioperative hypertension (BP ≥160/90 mm Hg or SBP elevation ≥20% of the preoperative value that persists for >15 min)

 Clevidipine, esmolol, nicardipine, nitroglycerin Intraoperative hypertension is most frequently seen during anesthesia induction and airway manipulation.

Acute sympathetic discharge or catecholamine excess states (e.g., pheochromocytoma, postcarotid endarterectomy status)

 Clevidipine, nicardipine, phentolamine Requires rapid lowering of BP.

*Agents are listed in alphabetical order, not in order of preference.

ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; bpm, beats per minute; LV, left ventricular; PDE-5; phosphodiesterase type-5; SBP, systolic blood pressure

 

References:

Adapted from:
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: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e426-e483. doi:10.1161/CIR.0000000000000597
Options to Treat Arterial Hypertension in Patients With AIS Who Are Candidates for Emergency Reperfusion Therapy (COR IIb; LOE C-EO)*

Patient otherwise eligible for emergency reperfusion therapy except that BP is >185/110 mmHg:

  • Labetalol 10-20 mg IV over 1-2 min, may repeat 1 time; or
  • Nicardipine 5 mg/h IV, titrate up by 2.5 mg/h every 5-15 min, maximum 15 mg/h; when desired BP reached, adjust to maintain proper BP limits; or
  • Clevidipine 1-2 mg/h IV, titrate by doubling the dose every 2-5 min until desired BP reached; maximum 21 mg/h
  • Other agents (e.g., hydralazine, enalaprilat) may also be considered

If BP is not maintained ≤185/110 mmHg, do not administer alteplase

Management of BP during and after alteplase or other emergency reperfusion therapy to maintain BP ≤185/105 mmHg:

  • Monitor BP every 15 min for 2 h from the start of alteplase therapy, then every 30 min for 6 h, and then every hour for 16 h

If systolic BP >180-230 mmHg or diastolic BP >105-120 mmHg:

  • Labetalol 10 mg IV followed by continuous IV infusion 2-8 mg/min; or
  • Nicardipine 5 mg/h IV, titrate up to desired effect by 2.5 mg/h every 5-15 min, maximum 15 mg/h; or
  • Clevidipine 1-2 mg/h, titrate by doubling the dose every 2-5 min until desired BP reached; maximum 21 mg/h

If BP not controlled or diastolic BP >140 mmHg, consider IV sodium nitroprusside

Abbreviations: AIS= acute ischemic stroke; BP= blood pressure; COR= class of recommendation; IV= intravenous; LOE= level of evidence

* Different treatment options may be appropriate in patients who have comorbid conditions that may benefit from rapid reductions in BP such as acute coronary event, acute heart failure, aortic dissection, or preeclampsia/eclampsia.
References:

Adapted from:
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association [published correction appears in Stroke. 2019 Dec;50(12):e440-e441. doi: 10.1161/STR.0000000000000215]. Stroke. 2019;50(12):e344-e418. doi:10.1161/STR.0000000000000211
Summary of Select Trials Comparing Clevidipine and Nicardipine in Cerebrovascular Diseases
Study Patient Population Intervention Outcomes

Martini et al., 2022 1

Retrospective, observational study

Patients with acute cerebrovascular accident (CVA) who received nicardipine or clevidipine (N= 71)

Nicardipine (n= 37)

Clevidipine (n= 34)

Titration instructions for pharmacy-prepared nicardipine (0.2 mg/mL): to start at a rate of 2.5 mg/h and titrate by 0 to 2.5 mg/h every 5 to 15 minutes at nursing staff discretion, with a maximum rate of 15 mg/h.

Premade clevidipine (0.5 mg/ mL) titration instructions: start at a rate of 1 mg/h, then increase by doubling the dose every 90 seconds. Once a rate of 4 mg/h was reached, clevidipine was titrated by 0 to 2 mg/h every 5 minutes at the nursing staff's discretion to a maximum rate of 14 mg/h. At the provider's discretion, the maximum rate of clevidipine could be increased to 21 mg/h. 

Nicardipine group vs. clevidipine group:

Mean time to goal systolic blood pressure (SBP): 150.9 minutes vs. 69.3 minutes (p< 0.01)

Time from order to administration: 80.1 minutes vs. 35.2 minutes (p< 0.01)

Mean time from administration to goal SBP: 70.9 minutes vs. 42.3 minutes (p= 0.02)

No difference between groups in the percentage of SBP readings below goal, total volume administered, length of stay, or inpatient mortality

Adverse events: 35.1% vs. 50% (p=0.42)

The costs of available products per 12 hours of continuous infusion were $129, $540, and $59 for premade clevidipine 4 mg/h, premade nicardipine 7 mg/h, and pharmacy-prepared nicardipine 7 mg/h, respectively (at the time of formulary evaluation in March 2020)

Costs of a course of therapy (based on hospital contract costs and mean IV infusion volume received in this study): $61.25 vs. $304.68; the higher cost of premade clevidipine therapy is offset by improved patient outcomes, such as time to goal SBP

Author's conclusion: Compared to the use of pharmacy-prepared nicardipine, the use of premade clevidipine was associated with a shorter time to goal SBP in patients with acute CVA. There were no significant between-group differences in safety outcomes. Premade clevidipine should be considered over pharmacy-prepared nicardipine when rapid blood pressure lowering is warranted in acute CVA.

Saldana et al., 2022 2

Single-center, retrospective, observational cohort study

Adult hemorrhagic patients with stroke who received clevidipine or nicardipine (N= 89)

Nicardipine (n= 60)

Clevidipine (n= 29)

 The default nicardipine drip concentration was 0.1 mg/mL with a maximum rate of 15 mg/h, and the default clevidipine concentration was 0.5 mg/mL with a maximum rate of 32 mg/h. Nicardipine drips were initiated at 5 mg/h and titrated by 2.5 mg/h every 5 min until the goal SBP was achieved. Clevidipine drips were started at 1–2 mg/h, then doubled every 90 s until the SBP began to approach the goal, and then increased by less than double every 5–10 min until the goal SBP was achieved.

Nicardipine group vs. clevidipine group:

Time to goal SBP: 30 minutes vs. 45 minutes (p= 0.47)

Total volume from infusion: 1,410 vs. 330 mL (p< 0.0001)

Cost: standard concentrated nicardipine (25 mg/250 mL) costs $18.10 per bag, and double-concentrated nicardipine (50 mg/250 mL) costs $33.20 per bag. Clevidipine 25 mg/50 mL costs $62.18 per vial, and clevidipine 50 mg/100 mL costs $124.35 per vial.

Medication acquisition cost per infusion (median [IQR]): $99.6 [36.2–235.3] vs. $497.4 [217.6–1,057.0]; p< 0.0001

No significant differences in the need for additional antihypertensives, percentage of time at goal SBP, all-cause mortality, 30-day readmission, rebleeding, hematoma expansion, intensive care unit length of stay (LOS), and hospital LOS.

Adverse events: rebound hypertension (40% vs. 75.9%; p= 0.0017); bradycardia (23.3% vs. 44.8%; p= 0.05); no significant differences in hypotension, severe hypotension, tachycardia, and acute kidney injury

Author's conclusion: In patients with hemorrhagic stroke, nicardipine appeared to have similar efficacy as clevidipine in SBP reduction, with a more likely reduction of rebound hypertension and drug cost. This retrospective study was underpowered, which may limit these implications. Further prospective studies are warranted to confirm these results.

Allison et al., 2019 3

Retrospective, observational, cohort study

Patients with acute ischemic stroke (AIS) or spontaneous intracerebral hemorrhage (ICH) admitted to the emergency department who received clevidipine or nicardipine continuous infusion for acute blood pressure management (N= 210)

Nicardipine (n= 140)

Clevidipine (n= 70)

 Clevidipine titration used a starting rate of 2 mg/h, which was then increased by doubling the dose every 90 seconds until a rate of 12 mg/h was reached, and then increasing by 4 mg/h increments to a maximum dose of 32 mg/h. Nicardipine was initially started at 5 mg/h and titrated by nursing discretion every 15 minutes to a maximum dose of 15 mg/h. Both agents were continued until the patient no longer required continuous intravenous therapy. Patients may also have received labetalol 10 mg intravenous doses throughout the first 24 hours. 

Clevidipine group vs. nicardipine group:

Time to goal SBP: 50 ± 83 minutes vs. 74 ± 103 minutes (p= 0.101)

Adverse events: hypotension (7.1% vs. 10%, p= 0.003)

Percentage change at 2 hours: -20% ± 16% vs. -16% ± 16% (p= 0.058)

Time to alteplase administration from admission: 56 ± 22 minutes vs. 59 ± 25 minutes (p= 0.684)

Bottles and bags administered per patient during the first 24 hours: 1.46 ± 0.95 clevidipine 50 mg/100 mL bottles vs. 2.44 ± 1.48 nicardipine 40 mg/200 mL bags (p< 0.001). Based on hospital contract costs, this resulted in relatively equivalent costs per patient between groups.

Author's conclusion: There was no difference in the mean time from initiation of the infusion to the SBP goal between agents or in the secondary outcomes. Due to the lack of differences observed, each agent should be considered based on the patient care needs of the institution.

Rosenfeldt et al., 2018 4

Cross-sectional retrospective chart review

Acute stroke patients (N= 119)

Nicardipine (n= 60)

Clevidipine (n= 59)

 Doses and dose adjustment methods were not reviewed in this study.

Nicardipine group vs. clevidipine group:

Time to goal SBP: 65.5 ± 108.2 minutes vs. 65.8 ± 101 minutes (p= 0.83)

Average ICU LOS: 5.35 days vs. 7.71 days (p = 0.015)

Average length of hospital stay: 10.66 days vs. 11.95 days (p= 0.17)

Adverse events: hypotension (73% vs. 81%)

Author's conclusion: Both nicardipine and clevidipine are reasonable antihypertensive agents in stroke, although cost and volume restriction could differentiate preference.
References:

[1] Martini BE, Schalk AL. Comparison of premade clevidipine and pharmacy-prepared nicardipine in time to goal systolic blood pressure in acute cerebrovascular accident. Am J Health Syst Pharm. 2022;79(9):e110-e116. doi:10.1093/ajhp/zxab394
[2] Saldana S, Breslin J 2nd, Hanify J, et al. Comparison of Clevidipine and Nicardipine for Acute Blood Pressure Reduction in Hemorrhagic Stroke. Neurocrit Care. 2022;36(3):983-992. doi:10.1007/s12028-021-01407-w
[3] ​​Allison TA, Bowman S, Gulbis B, Hartman H, Schepcoff S, Lee K. Comparison of Clevidipine and Nicardipine for Acute Blood Pressure Reduction in Patients With Stroke. J Intensive Care Med. 2019;34(11-12):990-995. doi:10.1177/0885066617724340
[4] Rosenfeldt Z, Conklen K, Jones B, Ferrill D, Deshpande M, Siddiqui FM. Comparison of Nicardipine with Clevidipine in the Management of Hypertension in Acute Cerebrovascular Diseases. J Stroke Cerebrovasc Dis. 2018;27(8):2067-2073. doi:10.1016/j.jstrokecerebrovasdis.2018.03.001

Comparison of clevidipine vs nicardipine in the treatment of hypertensive urgency and emergency in critically ill patients
Design

Multicenter, retrospective cohort study

N= 182
Objective

To compare the treatment success of clevidipine and nicardipine in hypertensive crisis
Study Groups

Clevidipine (n= 79)

Nicardipine (n= 103)
Inclusion Criteria

Patients aged 18 or older, received clevidipine or nicardipine for more than 1 hour for hypertensive crisis, infusion initiated in ED or critical care service
Exclusion Criteria

Therapy initiated for other indications, acute CT surgery, hemorrhagic stroke, aortic aneurysm/dissection, pregnancy, received both drugs within 24 hours
Methods

Patients received either clevidipine or nicardipine; clevidipine was started at 1 mg/h, titrated by 1-3 mg/h every 2 minutes, while nicardipine was started at 2.5 mg/h and titrated by 2.5 mg/h every 15 minutes. At the time of the protocol, the criteria for use of clevidipine included short-term management (72 hours or less) with suspected or confirmed acute pulmonary edema, acute renal failure, perioperative hypertension, acute ischemic stroke, and intracranial hemorrhage; although these criteria overlapped with nicardipine usage, it did not encompass all indications for nicardipine.
Duration

Clevidipine infused for an average of 26 hours, nicardipine for 21 hours
Outcome Measures

Primary: Time from infusion start to attainment of goal BP

Secondary: Time to guideline-directed 25% reduction in BP, drug and total volume intake, time from order entry to BP goal attainment, number of BP and heart rate excursions, ICU length of stay, study medication cost
Baseline Characteristics   Clevidipine (n= 79)

Nicardipine (n= 103)

  

Age, years

 60.7 ± 1.8 58.1 ± 1.6  

Female

 44.3% 50.5%  

Initial weight, kg (IQR)

 83.4 (68.6-97.6) 80.3 (68.8-100.2)  

Race/ethnicity

African American/Black

Caucasian

Other

 

49.4%

38.0%

12.6%

 

63.1%

30.1%

6.8%

  

Admitting service

Medical critical care

Neurology critical care

Cardiology service

 

57.0%

27.8%

15.2%

 

62.1%

28.2%

8.7%

  

Past medical history

Hypertension

Chronic kidney disease

Heart failure

Cerebrovascular disease

Atrial fibrillation

Myocardial infarction

 

79.7%

43.0%

27.8%

25.3%

15.2%

8.9%

 

81.6%

44.7%

30.4%

29.4%

16.5%

12.7%

  

Charlson comorbidity score (IQR)

 4 (2-5.5) 4 (3-7)  

NT-proBNP, pg/mL (IQR)

 269 (97-1,564) 1,047 (243-3,536)  

Abbreviations: IQR= interquartile range

NT-proBNP was lower in the clevidipine group at baseline vs nicardipine (p= 0.04).
Results

Endpoint

 Clevidipine (n= 79) Nicardipine (n= 103) p-value
Time to goal BP, minutes (IQR) 35 (21-86)

33 (15-72)

 0.37

Achieved guideline 25% reduction within 1 hour

 65.8% 71.8% 0.42

Medication volume, mL (IQR)

 222 (81-624) 518 (190-1,215) 0.01

Total volume, mL (IQR)

 3,370 (1,888-7,036) 3,383 (1,428-6,083) 0.43

ICU length of stay, days (IQR)

 5.9 (3-14) 5.8 (3-10) 0.26

Fraction of time spent in targeted BP goal range, % (IQR)

 43.1 (18.8-65) 42.3 (22.2-56.8) 0.89

Additional parenteral antihypertensives

Antihypertensive medications at end of therapy (IQR)

36.7%

2 (1-3)

18.4%

2 (2-3)

0.01

0.99

Oral antihypertensives at infusion initiation

Additional oral antihypertensives or dose increase

25.3%

62.0%

24.3%

51.4%

0.99

0.18

The cost of clevidipine was $199.37 per vial (based on the average wholesale price as of June 2023). This cost was 682% higher than that for a bag of nicardipine.
Adverse Events

Similar rates of BP lability, HR excursions, and BP variability; no significant differences in tachycardia or bradycardia events
Study Author Conclusions

While our findings suggest that clevidipine may result in lower volume burden, clevidipine was of questionable clinical importance and time to goal BP was similar to that with nicardipine. The additional cost associated with clevidipine may not justify the minimal clinically relevant benefit seen in patients with hypertensive crisis, and its use should be restricted to patients where rapid BP control has been associated with improved outcomes.
Critique

Strengths of this study include a multicenter design and a focus on critically ill patients, while limitations include potential type 2 error due to not reaching projected sample size, retrospective design, and potential bias in BP goal determination. The study's findings may not be generalizable to all settings due to institutional practices.
References:

Johnson L, Erdman M, Ferreira J. Comparison of clevidipine vs nicardipine in the treatment of hypertensive urgency and emergency in critically ill patients. Am J Health Syst Pharm. 2024;81(21):e668-e676. doi:10.1093/ajhp/zxae156

Evaluation of the Efficacy and Safety of Nicardipine Versus Clevidipine for Blood Pressure Control in Hypertensive Crisis
Design

Single-center, retrospective cohort study with historical comparison

N= 156
Objective

To evaluate the efficacy and safety of nicardipine versus clevidipine for blood pressure control in hypertensive crisis
Study Groups

Nicardipine (n= 74)

Clevidipine (n= 82)
Inclusion Criteria

Patients with hypertensive crisis (initial BP ≥180/120 mm Hg) receiving nicardipine or clevidipine
Exclusion Criteria

Patients treated for conditions other than hypertensive crisis or transferred to another hospital before admission
Methods

Patients who received continuous IV antihypertensive treatment with nicardipine or clevidipine were included for analysis. Each agent was on formulary at the study site at different points in time, meaning there was no overlap between use of clevidipine or nicardipine.
Duration

January 2018 to June 2023
Outcome Measures

Primary: 25% reduction in MAP at 1 h

Secondary: SBP <160 mm Hg at 2-6 h, medication volume, additional antihypertensives, rebound hypertension, cost savings, length of stay
Baseline Characteristics  

Nicardipine (n= 74)

 Clevidipine (n= 82)  

Age, years

 64 ± 18 59 ± 17  

Weight, kg

 86.5 ± 29 88.5 ± 24.1  

Male

 31 (42%) 33 (40%)  

White

 54 (73%) 54 (66%)  

Coexisting conditions

Hypertension

Coronary artery disease

Hyperlipidemia

Atrial fibrillation

Diabetes 

 

59 (80%)

28 (38%)

23 (31%)

7 (10%)

18 (24%)

 

69 (84%)

31 (38%)

36 (44%)

8 (10%)

33 (40%)

  
No. of home BP medications

1.6 ± 1.6

 2.2 ± 1.6  

Hypertensive crisis type

Hypertensive urgency

Hypertensive emergency

 

15 (20%)

59 (80%)

 

15 (18%)

67 (82%)

  

Systolic blood pressure on admission, mmHg

 206 201  

Systolic blood pressure at start, mmHg

 201 201  

Mean arterial pressure at infusion start, mmHg

 131 135  
Results

Endpoint

 Nicardipine (n= 74) Clevidipine (n= 82) p-value

25% reduction in MAP at 1 h

 43 (58.1%) 39 (47.6%) 0.19

SBP goal ≤160 mm Hg at 2-6 h

 66 (89.2%) 61 (74.4%) 0.018

Volume administered per patient, mL

 939 186 <0.001
Total cost per patient, $ 191 359

0.002

Safety outcomes

Hypotension

Overcorrection of MAP at 1 h

 

32 (43.2%)

22 (29.7%)

 

30 (36.6%)

13 (15.9%)

 

0.40

0.04

Additional antihypertensive agents required, n

 2.1 2.3

0.59
Adverse Events

See Results
Study Author Conclusions

This single-center, retrospective cohort study found no difference between agents for initial blood pressure control based on MAP for the treatment of hypertensive crisis. Patients receiving nicardipine had more sustained blood pressure control with lessrebound hypertension, and there was a significant per vial cost savings compared with clevidipine.
Critique

Limitations include the small sample size and retrospective design, which may confound the findings. Reliance on nursing documentation and the lack of formal titration plan also limits generalizability and may introduce potential bias.
References:

Storey C, Pouliot J. Evaluation of the Efficacy and Safety of Nicardipine Versus Clevidipine for Blood Pressure Control in Hypertensive Crisis. J Emerg Med. 2024;67(4):e368-e374. doi:10.1016/j.jemermed.2024.04.006

 

Comparative Study of Clevidipine to Nicardipine for Perioperative Hypertension in Patients Undergoing Cardiac Surgery

Design

Single-center retrospective cohort study

N= 67

Objective

To compare the efficacy of clevidipine to nicardipine in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery

Study Groups

Clevidipine (n= 29)

Nicardipine (n= 38)

Inclusion Criteria

Adult patients undergoing cardiac surgery during the study period and required a continuous infusion of clevidipine or nicardipine for blood pressure management

Exclusion Criteria

Underwent cardiac surgery from February 1, 2019, to June 30, 2019, and included in the previous pilot study; had end-stage renal disease requiring dialysis; received both medications in a 24-hour time period; or received either medication before surgery

Methods

ACE inhibitors and angiotensin II receptor blockers (ARBs) were withheld for a minimum of 24 hours before the surgery. All patients were administered beta-blockers prior to surgery. Home medications indicated for blood pressure were held the morning of the surgery. Starting at 1-2 mg/hour, clevidipine was titrated in 1-2mg/hour increments every 2–5 minutes to a maximum of 21 mg/hour. The dosage of nicardipine was titrated by starting at 5 mg/hour and increasing by 2.5 mg every 15 minutes, up to a maximum of 15 mg/hour. While the premixed clevidipine vials had a 12-hour expiration date once opened, the compounded nicardipine bags had a 24-hour expiration date.

Duration

From August 2018 to January 2019 and from July 2019 to February 2020

Outcome Measures

Primary: Percentage of time spent within patient-specific systolic blood pressure (SBP) goal

Secondary: Time from start of infusion to goal SBP; incidence, length, and magnitude of hypertensive episodes; need for additional intravenous hypertension agents; infusion rates of each medication; and total volume infused from the study medication

Safety: Incidence, length, and magnitude of hypotensive episodes; incidence of atrial fibrillation; increase in SCr by ≥.3 mg/dl within 72 hours; incidence of tachycardia; and if vasopressors were required as a result of the study medication use

Baseline Characteristics

  

Clevidipine (n= 29)

Nicardipine (n= 38)

  

Age, years (IQR)

 61 (57.0 - 69.0) 68 (61.3 - 72.8)  

Male

21 (72.4%) 23 (60.5%)  

Weight, kg (IQR) 

 85.7 (65.8 - 96.6) 88.1 (76.1 - 99.5)  

Serum creatinine (SCr) before surgery, mg/dL (IQR)

 1.1 (1.0 - 1.4) 1.0 (0.9 - 1.2)  

Past medical history

Hypertension

Chronic heart failure

Reduced ejection fraction 

Preserved ejection fraction

Recovered ejection fraction

Atrial  fibrillation

Number of home anti-HTN medications (IQR)

Patients on calcium channel blockers

 

27 (93.1%)

7 (24.1%)

2 (6.9%)

3 (10.3%)

2 (6.9%)

1 (3.5%)

3 (2 - 3)

16 (55.2%)

 

36 (94.7%)

8 (21.1%)

2 (5.3%)

4 (10.5%)

2 (5.3%)

3 (7.9%)

2 (2 - 3)

15 (39.5%)

  

Surgery

Coronary artery bypass grafting (CABG)

Valve

Replacement

Repair

Both CABG and valve

Other

Procedure duration, hours (IQR)

Study medication started in O.R.

 

27 (74.1%)

7 (24.1%)

7 (24.1%)

0

0

1 (3.5%)

4.1 (3.7 - 4.7)

4 (13.8%)

 

24 (63.2%)

10 (26.3%)

9 (23.7%)

1 (2.6%)

2 (5.3%)

2 (5.3%)

3.7 (2.2 - 4.7)

7 (18.4%)

  

IQR: interquartile range; ACE: Angiotensin-converting-enzyme; ARB: Angiotensin receptor blocker; O.R.: Operating room; HTN: hypertension

Results

Endpoint

Clevidipine (n= 29)

Nicardipine (n= 38)

p-value

Median percentage of time spent within patient-specific SBP goal

 55.2% 36.4% 0.036

Time from medication start of infusion to goal SBP, minutes (IQR)

 15 (0 - 55.2) 30 (0 - 117.0) 0.303

Hypertension episodes per patient (IQR)

 3 (2 - 6) 2 (1 - 4) 0.211

Length of hypertensive episode, hours (IQR)

 1 (5 - 2) 1.25 (0.7 - 4) 0.006

Magnitude of hypertensive episode above goal SBP, mmHg (IQR)

 10 (5 - 21) 18 (8 - 30) 0.003

Need for additional IV anti-hypertensive medications

Hydralazine

Nitrates

Other

 

6 (20.7%)

1 (3.5%)

1 (3.5%)

 

6 (15.8%)

1 (2.6%)

1 (2.6%)

 

0.75

1.0

1.0

Amount of volume infused, mL (IQR)

 68.7 (10.0 - 128.8) 488.6 (155.4 - 1,039.6) 0.001

Infusion rate during therapy, mg/hour (IQR)

 2.7 (1.5 - 4.3) 4.7 (3.7 - 6.2) N/A

Safety*

Incidence of hypotension

Incidence of vasopressor use

SCr elevation ≥.3 mg/dL in 72 hours

Incidence of tachycardia

Incidence of atrial fibrillation

 

8 (27.6%)

1 (3.5%)

8 (27.6%)

3 (10.3%)

0

 

9 (23.7%)

7 (18.4%)

15 (39.5%)

1 (2.6%)

1 (2.6%)

  

* All p-values >0.05

The median cost of treatment required for the observed 48-hour period with clevidipine was $128.58 compared to $55.74 for nicardipine (p< 0.001).

Adverse Events

See above

Study Author Conclusions

Our findings suggest that patients undergoing cardiac surgery on clevidipine had better perioperative blood pressure control compared to nicardipine, with a negligible increase in cost, and no observed difference in safety. Despite clevidipine being more expensive per patient, we found this to be a negligible increase in cost to our program. Clevidipine may be a better option in volume overloaded patients or patients who cannot tolerate large amounts of intravenous fluids, such as patients with chronic heart failure and chronic kidney disease

InpharmD Researcher Critique

This was a observational retrospective study with a small sample. The nicardipine group's results with regard to pressure response may have been unintentionally skewed due to receiving a noticeably higher volume of fluids. Furthermore, most patients had CABG, which limits the relevance of these findings for other cardiac procedures. Impact of SBP management on clinical outcomes, including death, length of stay in the intensive care unit, time to extubation, and bleeding rate, could not be ascertained.
References:

Colomy VV, Reinaker TS. Comparative Study of Clevidipine to Nicardipine for Perioperative Hypertension in Patients Undergoing Cardiac Surgery. J Pharm Pract. 2023;36(3):501-507. doi:10.1177/08971900211053291

 

The ECLIPSE Trials: Comparative Studies of Clevidipine to Nitroglycerin, Sodium Nitroprusside, and Nicardipine for Acute Hypertension Treatment in Cardiac Surgery Patients

Design

Pooled data from 3 randomized, controlled, open-label, parallel-group, clinical trials

N= 1,506

Objective

To compare the safety and efficacy of clevidipine (CLV) with nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery

Study Groups

Clevidipine (n= 752)

Nitroglycerin (n= 278)

Sodium nitroprusside (n= 283)

Nicardipine (n= 193)

Inclusion Criteria

>18 years old, scheduled to undergo cardiac surgery (including on- or off-pump coronary artery bypass grafting [CABG], minimally invasive CABG, and/or valve replacement or repair surgery)

Exclusion Criteria

Cerebrovascular accident <3 months before randomization, intolerance or hypersensitivity to any study medication, permanent ventricular pacing, any condition or disease deemed by the investigator to place the patient at risk for participating

Methods

The patients were randomized 1:1 for each of the three parallel comparator treatment groups. Treatment was titrated to achieve a BP level deemed appropriate by the study physician and continued until discharge from the intensive care unit.

Clevidipine was initiated at an infusion rate of 0.4 µg/kg/min and was titrated as tolerated in doubling increments every 90 s up to 3.2 µg/kg/min. There were no protocol-specified limitations for administering sodium nitroprusside, nitroglycerin, or nicardipine and investigators were given the freedom to use these drugs as they normally would in clinical practice for the treatment of perioperative hypertension.

Duration

 30 days

Outcome Measures

 Pooled adverse events after 30 days

Baseline Characteristics

  

Clevidipine (n= 752)

Nitroglycerin (n= 278)

Sodium nitroprusside (n= 283)

Nicardipine (n= 193)

Age, years

 64.8 63.9 65.3 66.1

Male

 544 (72.3%) 207 (74.5%) 216 (76.3%) 138 (71.5%)

Procedure duration, h

 3.45 3.35 3.62 3.56

Results

  

Clevidipine (n=752)

Nitroglycerin (n=278)

Sodium nitroprusside (n=283)

Nicardipine (n=193)

Death

 20/719 (2.8%) 9/266 (3.4%)* 13/274 (4.7%) 6/189 (3.2%)

Myocardial infarction

 16/700 (2.3%) 9/260 (3.5%) 6/264 (2.3%) 2/183 (1.1%)

Stoke

 8/700 (1.1%) 6/260 (2.3%) 4/262 (1.5%) 2/183 (1.1%)

Renal dysfunction

 56/712 (7.9%) 21/260 (8.1%) 24/265 (9.1%) 11/185 (5.9%)

*p=0.04; all other data were non-significant when compared individually and pooled clevidipine vs pooled comparators

Clevidipine was equivalent to nicardipine in keeping patients within a prespecified BP range; however, when BP range was narrowed, clevidipine was associated with fewer BP excursions beyond these BP limits compared with nicardipine.

Adverse Events

 N/A

Study Author Conclusions

Clevidipine is a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery.

InpharmD Researcher Critique

Limitations of this study include the open-label designs and the pooled aspect of the analysis since each study population differed slightly.

Additionally, by protocol, clevidipine was dosed in a standard fashion at all study sites, whereas comparator drugs were administered according to institutional practice. This limitation enabled a real-world analysis that was more applicable to actual clinical practice.



References:

Aronson S, Dyke CM, Stierer KA, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008;107(4):1110-1121.

 

Impact of Clevidipine Versus Nicardipine on Time in Range when Lowering Blood Pressure

Design

Multi-center, retrospective chart review

N= 391

Objective

To evaluate efficacy and safety outcomes associated with current use of these medications across a variety of indications in a hospital system

Study Groups

Nicardipine (n= 216)

Clevidipine (n= 175)

Inclusion Criteria

Age ≥ 18 years and < 90 years old, treated with nicardipine or clevidipine intravenous (IV) infusion at an acute care facility within the health system

Exclusion Criteria

Pregnant, experiencing eclampsia post-partum, no documented blood pressure goal, initiated on a nicardipine and/or clevidipine drip prior to transfer from one acute care facility to another within 24 hours of infusion initiation, transferred from an internal acute care facility to an external acute care facility prior to discharge, in-hospital mortality or discharged within 24 hours of nicardipine and/or clevidipine infusion initiation

Methods

Patient data were compiled via review of electronic medical records. For patients receiving both treatments, classification was based on the medication given first, and data were collected only during the first infusion. Patients were matched 1:1 based on indication for blood pressure control and similar pre-intervention systolic blood pressure (SBP); a total of 100 matched pairs were created. 

Institutional protocols dictated clevidipine dosing starting at 2 mg/hour, with a maximum dose of 16 mg/hour, titrated by 2 mg every 2 minutes or every 5 minutes when within 20 mmHg of the SBP goal. Nicardipine was initiated at a starting dose of 2.5 mg/hour with a maximum dose of 15 mg/hour, titrated by 2.5 mg every 15 minutes. 

Duration

 Treated between June 1, 2020 and June 30, 2021

Outcome Measures

Primary: timing within range (% of time within target SBP range)

Secondary: time to blood pressure goal, incidence of hypotension during infusion, use of rescue medications during infusion

Baseline Characteristics

  

Nicardipine (n= 100)

Clevidipine (n= 100)

  

Age, years

 62.1 ± 15.5 63.9 ± 16.6  

Male

 56% 58%  

Race

Asian

Black

White

Other

 

0% 

19.4%

66.3%

14.3%

 

2.0%

19.4%

53.1%

25.5%

  

Body mass index, kg/m2*

 30.0 ± 8.2 27.2 ± 6.6  

Intubated during infusion*

 43% 24%  

Indications

Acute ischemic stroke

Aortic emergency

Hypertensive emergency

Intracranial hemorrhage

Peri-op for cardiothoracic surgery

Peri-op for neurosurgery

 

16%

9%

22%

42%

10%

1%

 

16%

9%

22%

42%

10%

1%

  

Data above presented for matched sample 

*p< 0.05

Results

Endpoint

Nicardipine (n= 100)

Clevidipine (n= 100)

p-Value

Percent of time in target BP range

Overall

Emergency department

Intensive care unit

Step down unit

Perioperative care

 

59.0 ± 27.9

51.5 ± 28.9

68.1 ± 25.2

39.2 ± 26.5

60.7 ± 6.7

 

55.2 ± 29.2

51.7 ± 29.1

68.8 ± 25.4

N/A

64.5 ± 46.0

 

-

-

-

-

- 

Time to target BP goal, min (IQR)

Overall

Emergency department

Intensive care unit

Step down unit

Perioperative care

 

34.0 (14.5 to 57.0)

34.0 (18.0 to 59.0)

32.5 (7.5 to 56.0)

N/A

6.0 (0.0 to 89.0)

 

20.0 (7.0 to 43.0)

22.0 (11.0 to 48.3)

13.0 (0.0 to 29.0)

41.0 (36.5 to 225.5)

21.5 (0.0 to 43.0)

 

0.013

-

0.022

-

-

Incidence of hypotension

Overall

Emergency department

Intensive care unit

Step down unit

Perioperative care

 

17% (17 of 100)

11.1% (5 of 45)

21.3% (10 of 47)

0% (0 of 5)

66.7% (2 of 3)

 

10% (10 of 100)

6.3% (5 of 79)

10.5% (2 of 19)

0% (0 of 0)

100% (2 of 2)

 

-

-

-

-

-

Rescue medications required

Overall

Total boluses given

Total infusions given

Emergency department

Intensive care unit

Step down unit

Perioperative care

 

29% (29 of 100)

62

10

28.9% (13 of 45)

29.8% (14 of 47)

0% (0 of 5)

66.7% (2 of 3)

 

33% (33 of 100)

48

19

29.1% (23 of 79)

52.6% (10 of 19)

0% (0 of 0)

0% (0 of 2)

 

-

-

-

-

-

-

-

Both interventions received

6% (6 of 100)

32% (32 of 100)

 < 0.001

Hospital length of stay, days (IQR)

 7.6 (4.0 to 14.7)

6.3 (4.0 to 13.1)

 -

Intensive care unit length of stay, days (IQR)

2.4 (0.9 to 6.9)

 2.1 (0.9 to 5.5) -

Only p-values < 0.05 are shown. 

Adverse Events

 While numerically higher rates of hypotension were observed with nicardipine, the difference was not statistically significant (p= 0.093). 

Study Author Conclusions

This study suggests that while clevidipine and nicardipine produce similar percentages of time in range, blood pressure control can be attained faster using clevidipine with similar rates of hypotension and rescue medication requirements. These findings remain consistent across diverse patient populations and various settings of care in a large health system. These findings reflect the pharmacokinetic differences in these medications and demonstrate that clevidipine is as safe and potentially more effective than nicardipine for rapid blood pressure control.

InpharmD Researcher Critique

This present study was underpowered for the primary endpoint, as 1,870 patients were required to detect a difference of ±5% between the two groups.



References:

Armstrong KJ, Shepard K, Horsfield M, Levine AR, O'Sullivan DM, Zeiner AL. Impact of Clevidipine Versus Nicardipine on Time in Range when Lowering Blood Pressure. J Pharm Pract. Published online September 10, 2024. doi:10.1177/08971900241279638
Clevidipine Versus Nicardipine for Acute Blood Pressure Reduction in a Neuroscience Intensive Care Population
Design

Retrospective study

N= 57 
Objective To compare the difference in time to achieve target systolic blood pressure (SBP) goals with clevidipine versus nicardipine infusions in patients admitted to the neuroscience intensive care unit (NSICU)
Study Groups

Clevidipine group (n= 19)

Nicardipine group (n= 38)
Inclusion Criteria Patients 18 years or older, receiving clevidipine or nicardipine infusions, diagnosed with a primary neurological injury dictating specific blood pressure goals while in the NSICU
Exclusion Criteria Pregnant patients, prisoners, concurrent use of other continuous intravenous (IV) antihypertensive agents, and patients switched between clevidipine and nicardipine without a 24-hour washout period.
Methods Patients were matched based on indication for BP lowering and target SBP. Data were retrieved from electronic medical records. 
Duration Between July 1, 2011 and June 30, 2014
Outcome Measures

Primary: Time to target SBP, percentage of time within target BP range

Secondary: Infusion duration, median SBP readings, median and maximum rate used, volumes infused, cardiac and metabolic adverse effects
Baseline Characteristics   Clevidipine (n= 19) Nicardipine (n= 38)
Age, yrs [median (IQR)] 61 (57–73) 56 (47–66)
Male 12 (63.2) 20 (52.6)
Weight, kg [median (IQR)] 93 (77–106) 90 (76–101)

Indication 

ICH

Ischemic stroke

Other

 

8 (42.1%)

2 (10.5%)

9 (47.4%)

 

16 (42.1%)

4 (10.5%)

18 (47.4%)

Target SBP, mmHg

<180

<160

<150

<140

 

2 (10.5%)

11 (57.9%)

2 (10.5%)

4 (21.1%)

 

4 (10.5%)

22 (57.9%)

4 (10.5%)

8 (21.1%)

Ordering physician service

Neurosurgery

Neurology

Intensivist

Emergency department

 

6 (31.6%)

4 (21.1%)

9 (47.4%)

0

 

23 (60.5%)

8 (21.1%)

2 (5.3%)

5 (13.2%)
Results Endpoint Clevidipine (n= 19) Nicardipine (n= 38) p-Value

Primary endpoints

Time to target SBP, min [median (IQR)]

Percentage of time in target SBP range [median (IQR)]

 

30 (21–65)

79 (67–92)

 

46 (30–126)

78 (61–92)

 

0.13

0.64

Secondary endpoints

SBP, mmHg [median (IQR)]

Dose, mg/h [median (IQR)]

Max dose, mg/h [median (IQR)]

Infusion time, h [median (IQR)]

Rescue antihypertensive medications given infusion

Total volume of administration, mL [mean (SD)]

 

145 (141–151)

3 (1.5–8)

5.3 (3–10)

23 (9.7–67)

8 (42.1%)

530 (750)

 

146 (138–153)

5 (4–7)

8.5 (5–10.3)

13.5 (6.3–26.1)

15 (39.5%)

1254 (1803)

 

0.92

0.13

0.18

0.07

0.8

0.02

Safety endpoints

SBP <100 mmHg

HR >120 bpm

 

3 (15.8)

4 (21.1)

 

3 (7.9)

4 (10.5)

 

0.4

0.4
Adverse Events

See Results
Study Author Conclusions There were no statistically significant differences in acute BP management between the two agents; however, there was a trend toward shorter time to target and significantly less volume administered in the clevidipine group. Either agent should be considered a viable option in a NSICU population.
InpharmD Researcher Critique The study's retrospective design and small sample size limit its power and may introduce bias. The reliance on manual charting for blood pressure readings could lead to inaccuracies. 
 
References:

Finger JR, Kurczewski LM, Brophy GM. Clevidipine Versus Nicardipine for Acute Blood Pressure Reduction in a Neuroscience Intensive Care Population. Neurocrit Care. 2017;26(2):167-173. doi:10.1007/s12028-016-0349-4

Clevidipine Use After First-Line Treatment Failure for Perioperative Hypertension in Neurosurgical Patients: A Single-Center Experience

Design

Retrospective, observational study

N= 12

Objective

To assess the effectiveness of the administration of clevidipine after nicardipine treatment failure in neurosurgical patients

Study Groups

All (N= 12)

Inclusion Criteria

Adults neurosurgical patients

Exclusion Criteria

Age <18 years old, non-neurosurgical patients, prisoners, pregnancy

Methods

Retrospectively reviewed the medical charts of adult patients admitted to the neurosurgical department during the study period. 

Per institutional guidelines, nicardipine was administered as a first-line single agent for perioperative hypertension therapy with an individually targeted SBP goal of <140 mm Hg for ICH, <160 mm Hg for SAH, and <180 mm Hg for IS. Clevidipine was used if failed to achieve BP control with nicardipine therapy according to the corresponding critical care team criteria.

Duration

Between October 1, 2015 and October 31, 2018

Outcome Measures

Primary endpoint: Comparison of the percentage of time spent at targeted SBP goals during nicardipine and clevidipine administration, respectively

Baseline Characteristics

  

All (N= 12)

 

  

Age, years

 52.5 (48.0, 57.5)    

Female

 8 (67%)    

BMI, kg/m2

 33.4 (25.0, 39.2)     

American Society of Anesthesiology (ASA) score

I

II

III

IV

 

0 (0%)

0 (0%)

4 (33%)

8 (67%)

    

Race

Asian

Black

White

 

1 (8%)

2 (17%)

9 (75%)

    

Diagnosis at admission

Intracranial Abscess

Intracranial Hemorrhage

Ischemic Stroke

Subarachnoid Hmoerrhage

 

1 (8%)

7 (58%)

1 (8%)

3 (25%)

    

Baseline BP

SBP, mmHg

DBP, mmHg

 

173.5 (159.0 to 202.5)

98.5 (85.0 to 112.0)

    

Length of stay, days

 25.9 (25.9 to 34.1)    

Data presented in median (IQR) or percentage.

Results

Endpoint

Nicardipine (n= 12)

Clevidipine (n= 12)

p-Value

Total time of Infusion, hours

 52.9 (22.0 to 79.8) 32.4 (7 to 43.3) 0.007

Drug-titration events, n

 20.5 (12.0 to 25.5) 17 (5 to 29.5)  0.534 

Percentage time spent in targeted SBP, %

 76.2 (51.0 to 93.3) 93.4 (73 to 100) 0.123 

Percentage of time spent with tachycardia %

 13.1 (2.0 to 35.7) 2.2 (0 to 22.1) 0.250 

Data presented in median (IQR) or percentage.

Adverse Events

See Results

Study Author Conclusions

Our study suggests that clevidipine could be an alternative effective drug with an acceptable benefit/risk ratio in the neurosurgical population that fails to achieve BP control with nicardipine treatment.

InpharmD Researcher Critique

The present data only represents a single institution's retrospective experience which may not be reflective of settings with dissimilar population characteristics. However, this small-scale data provide some insight in using clevidipine as the second-line treatment after the failed attempt with nicardipine in a neurosurgical setting. 
References:

Borrell-Vega J, Uribe AA, Palettas M, et al. Clevidipine use after first-line treatment failure for perioperative hypertension in neurosurgical patients: A single-center experience. Medicine (Baltimore). 2020;99(1):e18541. doi:10.1097/MD.0000000000018541