Clevidipine for the treatment of severe hypertension in adults.

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.

Effect of nesiritide on renal function: a retrospective review.

OBJECTIVES: Recent meta-analysis has demonstrated that nesiritide may worsen renal function (RF) in patients with acute decompensated heart failure (ADHF). A nesiritide utilization evaluation (NUE) performed in our institution reflected that belief of RF preservation was one reason leading to nesiritide overuse. This study examined the effect of nesiritide on RF in patients evaluated in this NUE. RESEARCH DESIGN AND METHODS: Nesiritide patient records from October 1, 2003 to March 31, 2004 were reviewed (n = 162). Pertinent demographics, laboratory and medication utilization data were obtained. MAIN OUTCOME MEASURES: Changes in creatinine clearance (CrCl) and percentage of patients demonstrating worsening RF (decrease in CrCl > or = 25%) during diuretics therapy before nesiritide initiation and during nesiritide initiation and during nesiritide therapy were compared using Wilcoxon Signed-Ranks test and Chi-Square respectively. RESULTS: Overall, the addition of nesiritide to IV furosemide did not clinically change RF as compared to the use of IV furosemide alone (% change in CrCl: 0 vs. -2.13 mL/min, p = 0.023), although the difference was statistically significant. When categorized into different RF, there is no different in CrCl changes between the nesiritide group and the IV furosemide alone group. There is also no difference in terms of number of patients experiencing > or = 25% reduction in CrCl overall. Changes in RF were also not correlated to dose or duration of therapy. CONCLUSION: Nesiritide did not demonstrate significant impact in RF. Larger studies that examine RF in a more systematic and controlled manner and relate changes in RF to clinical outcomes are necessary to further elucidate the risk versus benefit profile of nesiritide.