Clevidipine in the Management of Hypertensive Emergency

By: Neal Shah

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Defined by the Joint National Committee, hypertension (HTN) is a systolic blood pressure (SBP) greater than or equal to 140 mmHg and a diastolic blood pressure (DBP) greater than or equal to 90 mmHg.  Patients with Stage 1 HTN have a SBP between 140 and 159 mmHg and DBP between 90 and 99 mmHg.  Stage 2 HTN occurs when a patient’s SBP is between 160 and 179 mmHg and DBP is between 100 and 109 mmHg.  Stage 3 HTN is the most severe form, with a SBP of over 180 mmHg and DBP over 110 mmHg.  Pressures of this magnitude have detrimental effects on organs, such as the eyes, kidneys, heart, and brain.

The diffuse pathological effects of HTN can be gauged by an eye exam, especially since retinopathy occurs with increased blood pressure – eventually causing leakage and obstruction of vision.¹  Both, hypertensive urgency and hypertensive emergency, feature Stage 3 HTN.  However, unlike hypertensive urgency, hypertensive emergency has targeted organ damage to the aforementioned areas.  It is for this reason that hypertensive urgency is treatable with oral medications over a prolonged period, but hypertensive emergency requires immediate intravenous medication to lower blood pressure.  To prevent stroke due to decreased cranial perfusion, the goal in hypertensive emergency is to gradually reduce blood pressure to 160/110 mmHg within 6 hours.  Oral medications for hypertensive urgency include labetalol, carvedilol, and clonidine.¹  Medications used to treat hypertensive emergency include esmolol, fenoldopam, labetalol, nicardipine, nitroglycerin, nitroprusside, and a recently-approved dihydropyridine (DHP) known as clevidipine.²

Clevidipine is a third generation DHP with a rapid onset, ultra-short action, and easy titrations.  It is a racemic mixture, and inhibits L-type calcium channels in the arteries rather than the heart; thus, it does not affect contractility or conductivity.²  Since it is contained in an emulsion of phospholipids and other fats derived from soy and eggs, it is contraindicated in patients with: allergies to soy or eggs, hypertriglyceridemia, and severe arterial stenosis.  Advantages of clevidipine are that there is no weight-based dosing or need to adjust the dose in renal or hepatic dysfunction (as it is metabolized by esterases). In the open-labeled, non-placebo, non-controlled, VELOCITY trial, clevidipine was administered at a rate of 2 mg/hour (and doubled in dose every 3 minutes to a maximum of 32 mg/hour) to Stage 3 HTN patients.  Within 6 hours, 91% of these patients transitioned successfully to oral therapy following the goal of a 25% decrease in arterial blood pressure.³

Clevidipine is not indicated for use outside of an institutional setting; it should be used to stabilize patients so they can begin an oral regimen to manage their hypertension.  Major side effects of clevidipine include reflex tachycardia, atrial fibrillation, and acute renal failure.⁴

SOURCES:

1. AV, Bakris GL, Black HR, et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252
2. Ngyuen H, Ma K, Pham D. Clevidipine for the Treatment of Severe Hypertension in Adults. Clinical Therapeutics/Volume 32, Number 1, 2010.
3. Cleviprex [clevidipine] package insert.
4. Erickson AL, DeGrado JR, Fanikos JR et al. Clevidipine: a short-acting intravenous dihydropyridine calcium channel blocker for the management of hypertension. Pharmacotherapy. 2010 May;30(5):515-28.