A New Intravenous Calcium Channel Blocker Option to Treat Acute Elevations in Blood Pressure

Abstract

Intravenous (IV) agents are needed to treat acute elevations in blood pressure (BP) in a number of different clinical settings including in the emergency department, perioperatively, and during hypertensive crises in the intensive care unit. IV agents are often needed to maintain BP within a narrow target range and many of the existing agents have a prolonged half-life, with overshooting of BP goals occurring frequently. IV agents available up to now have included a number of different agents with various advantages and adverse effects. For more than a decade, only one IV dihydropyridine calcium channel blocker (CCB), nicardipine, has been available for IV use for treatment of hypertension. Issues with IV dihydropyridine CCB delivery in the past include poor water solubility of this class and the reduction of pH in the 3.7 to 4.7 range with IV nicardipine, which may be part of the reason why changing the peripheral IV site every 12 hours is recommended in the package insert. Nicardipine is a second-generation IV dihydropyridine CCB. It is an effective antihypertensive; however, its major limitation is a longer half-life that precludes rapid titration. Its onset of action is within 10 to 15 minutes and its duration of action is 15 to 30 minutes but may exceed 4 hours. Clevidipine is a new third-generation IV dihydropyridine CCB that was recently approved by the US Food and Drug Administration in 2008 for treatment of severe hypertension. It reduces BP without affecting cardiac filling pressures or causing reflex tachycardia.1,2 The main advantage of this drug is that it has an ultra-short half-life of <1 minute.3 It exerts a rapid and titratable arterial BP reduction with fast termination of effect. It is an arterial selective vasodilator that reduces peripheral vascular resistance directly without causing venous capacitance dilation.4 BP reductions occur within 6 to 10 minutes and BP and heart rate return to baseline within 10 to 15 minutes after discontinuation of the drug. Rapid elimination of the drug is maintained after stopping either a long (24-hour) or short infusion.5 Clevidipine incorporates an easily hydrolyzable ester group into its chemical structure and, as a result, clevidipine is rapidly metabolized by the blood and tissue esterases independent of liver and kidney function.6 Esterase-based metabolism may also partially account for the lack of drug toxicity and little to no risk of cytochrome P450–associated drug toxicity.7 Clevidipine does result in a modest increase in heart rate from baseline, as has been shown with other IV CCB agents. Heart rate increases within the first 30 minutes of administration, but this appears to decrease back to baseline.8 The drug has been shown to be well tolerated without an increase in adverse side effects compared with placebo. Initial studies showed a slight increase in atrial fibrillation, but this has not been reproduced in subsequent studies. Clevidipine represents a new IV option for acute reduction in BP with an ultrashort half-life, therefore reducing the risk of overshooting BP targets.9 It has been shown in various studies to be effective in producing acute reductions in BP in the emergency department9 and perioperatively in cardiac surgery where maintenance of a narrow range of BP is required.1,10