BACKGROUND: Intravenous antihypertensive agents are used when immediate control of blood pressure (BP) is required, including during the perioperative cardiac surgery period. Controlling postoperative BP is challenging because of the need to adequately reduce BP while maintaining appropriate end-organ perfusion. Clevidipine is an intravenous, ultra-short-acting, third-generation dihydropyridine calcium channel antagonist with selectivity for arteriolar vasodilatation. It is approved by the US Food and Drug Administration for the treatment of severe hypertension. OBJECTIVE: This paper reviews the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of clevidipine. METHODS: To minimize selection bias, each author conducted an independent search for English-language publications indexed on MEDLINE and International Pharmaceutical Abstracts through January 2010 using the term clevidipine. All identified prospective, randomized and nonrandomized Phase III trials were included in the review. RESULTS: Seven Phase III trials were identified in which clevidipine was compared with baseline, placebo, or other intravenous antihypertensive agents in the settings of severe hypertension (1 study), preoperative cardiac surgery (1), perioperative cardiac surgery (1), and postoperative cardiac surgery (4). In a multicenter, randomized, double-blind, placebo-controlled study of the efficacy of clevidipine in treating preoperative hypertension, the mean reduction from baseline in mean arterial pressure was 31.2% with clevidipine and 11.2% with placebo (P < 0.001). In a randomized, open-label, prospective study involving separate comparisons of clevidipine with nitroglycerin, sodium nitroprusside, and nicardipine, the median total AUC for digression in systolic BP from the predetermined target range differed significantly between clevidipine and nitroglycerin (4.14 vs 8.87 mm Hg . min/h; respectively, P < 0.001) and between clevidipine and sodium nitroprusside (4.37 vs 10.5 mm Hg . min/h; P = 0.003), but not between clevidipine and nicardipine (1.76 and 1.69 mm Hg . min/h). Another study found no significant difference in efficacy in controlling BP during the 3-hour study period between clevidipine and sodium nitroprusside (AUC for mean [SD] arterial pressure, 106 [25] and 101 [28] mm Hg . min/h, respectively). Adverse events in these studies included atrial fibrillation (13.0%-36.1% clevidipine vs 12.0% placebo), nausea (5.0%-21.0% vs 12.0%, respectively), fever (19.0% vs 13.7%), insomnia (12.0% vs 6.1%), and acute renal failure (9.0% vs 2.0%). In the studies reviewed, only 1 case of chest discomfort in the setting of severe hypertension was considered a serious adverse event related to clevidipine therapy. CONCLUSION: In the Phase III trials reviewed, clevidipine was effective in controlling BP in the settings of perioperative cardiac surgery and severe hypertension and was associated with minimal adverse effects.
BACKGROUND: Intravenous antihypertensive agents are used when immediate control of blood pressure (BP) is required, including during the perioperative cardiac surgery period. Controlling postoperative BP is challenging because of the need to adequately reduce BP while maintaining appropriate end-organ perfusion. Clevidipine is an intravenous, ultra-short-acting, third-generation dihydropyridine calcium channel antagonist with selectivity for arteriolar vasodilatation. It is approved by the US Food and Drug Administration for the treatment of severe hypertension. OBJECTIVE: This paper reviews the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of clevidipine. METHODS: To minimize selection bias, each author conducted an independent search for English-language publications indexed on MEDLINE and International Pharmaceutical Abstracts through January 2010 using the term clevidipine. All identified prospective, randomized and nonrandomized Phase III trials were included in the review. RESULTS: Seven Phase III trials were identified in which clevidipine was compared with baseline, placebo, or other intravenous antihypertensive agents in the settings of severe hypertension (1 study), preoperative cardiac surgery (1), perioperative cardiac surgery (1), and postoperative cardiac surgery (4). In a multicenter, randomized, double-blind, placebo-controlled study of the efficacy of clevidipine in treating preoperative hypertension, the mean reduction from baseline in mean arterial pressure was 31.2% with clevidipine and 11.2% with placebo (P < 0.001). In a randomized, open-label, prospective study involving separate comparisons of clevidipine with nitroglycerin, sodium nitroprusside, and nicardipine, the median total AUC for digression in systolic BP from the predetermined target range differed significantly between clevidipine and nitroglycerin (4.14 vs 8.87 mm Hg . min/h; respectively, P < 0.001) and between clevidipine and sodium nitroprusside (4.37 vs 10.5 mm Hg . min/h; P = 0.003), but not between clevidipine and nicardipine (1.76 and 1.69 mm Hg . min/h). Another study found no significant difference in efficacy in controlling BP during the 3-hour study period between clevidipine and sodium nitroprusside (AUC for mean [SD] arterial pressure, 106 [25] and 101 [28] mm Hg . min/h, respectively). Adverse events in these studies included atrial fibrillation (13.0%-36.1% clevidipine vs 12.0% placebo), nausea (5.0%-21.0% vs 12.0%, respectively), fever (19.0% vs 13.7%), insomnia (12.0% vs 6.1%), and acute renal failure (9.0% vs 2.0%). In the studies reviewed, only 1 case of chest discomfort in the setting of severe hypertension was considered a serious adverse event related to clevidipine therapy. CONCLUSION: In the Phase III trials reviewed, clevidipine was effective in controlling BP in the settings of perioperative cardiac surgery and severe hypertension and was associated with minimal adverse effects.