Lala Dunbar

Clevidipine, an Intravenous Dihydropyridine Calcium Channel Blocker, Is Safe and Effective for the Treatment of Patients With Acute Severe Hypertension

STUDY OBJECTIVEnWe assess the safety and efficacy of intravenous clevidipine for treating patients with acute severe increase in blood pressure by using prespecified, non-weight-based titration dosing, with continuous maintenance infusion for 18 hours or longer.nnnMETHODSnProspective, open-label, single-arm evaluation of patients aged 18 years or older and presenting in the emergency department or ICU with severe hypertension (systolic blood pressure >180 mm Hg and/or diastolic blood pressure >115 mm Hg) and treated with clevidipine to achieve a predetermined, patient-specific systolic blood pressure target range. Clevidipine was initiated at 2 mg per hour and titrated as needed in doubling increments every 3 minutes to a maximum of 32 mg per hour, during 30 minutes, and then continued for a total duration of 18 to 96 hours.nnnRESULTSnStudy patients commonly presented with both acute hypertension and end-organ injury; 81% (102/126) had demonstrable end-organ injury at baseline. Within 30 minutes of starting clevidipine, 88.9% (104/117) of patients achieved target range. Median time to target range was 10.9 minutes. No concomitant intravenous antihypertensives were needed in 92.3% (108/117) of patients receiving 18 hours or more of clevidipine infusion. Clevidipine was well tolerated with successful transition to oral antihypertensive therapy after infusion to a defined blood pressure target in 91.3% (115/126) of patients.nnnCONCLUSIONnClevidipine, dosed in a non-weight-based manner, was safe and effective in a cohort of patients with severe hypertension at a starting dose of 2 mg per hour, followed by simple titration during 18 hours or more of continuous infusion. Patients were effectively managed via simple blood pressure cuff monitoring throughout.

Clevidipine in acute heart failure: Results of the A Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)

BACKGROUNDnRapid blood pressure (BP) control improves dyspnea in hypertensive acute heart failure (AHF). Although effective antihypertensives, calcium-channel blockers are poorly studied in AHF. Clevidipine is a rapidly acting, arterial selective intravenous calcium-channel blocker. Our purpose was to determine the efficacy and safety of clevidipine vs standard-of-care intravenous antihypertensive therapy (SOC) in hypertensive AHF.nnnMETHODSnThis is a randomized, open-label, active control study of clevidipine vs SOC in emergency department patients with AHF having systolic BP ≥160 mm Hg and dyspnea ≥50 on a 100-mm visual analog scale (VAS). Coprimary end points were median time to, and percent attaining, a systolic BP within a prespecified target BP range (TBPR) at 30 minutes. Dyspnea reduction was the main secondary end point.nnnRESULTSnOf 104 patients (mean [SD] age 61 [14.9] years, 52% female, 80% African American), 51 received clevidipine and 53 received SOC. Baseline mean (SD) systolic BP and VAS dyspnea were 186.5 (23.4) mm Hg and 64.8 (19.6) mm. More clevidipine patients (71%) reached TBPR than did those receiving SOC (37%; P = .002), and clevidipine was faster to TBPR (P = .0006). At 45 minutes, clevidipine patients had greater mean (SD) VAS dyspnea improvement than did SOC patients (-37 [20.9] vs -28 mm [21.7], P = .02), a difference that remained significant up to 3 hours. Serious adverse events (24% vs 19%) and 30-day mortality (3 vs 2) were similar between clevedipine and SOC, respectively, and there were no deaths during study drug administration.nnnCONCLUSIONSnIn hypertensive AHF, clevidipine safely and rapidly reduces BP and improves dyspnea more effectively than SOC.

Clevidipine for Severe Hypertension in Acute Heart Failure: A VELOCITY Trial Analysis

Acute severe hypertension occurs in approximately 50% of patients with acute heart failure (AHF). Clevidipine, the latest-generation dihydropyridine calcium channel blocker, may be useful in the treatment of this patient population. The Evaluation of the Effect of Ultra-Short-Acting Clevidipine in the Treatment of Patients With Severe Hypertension (VELOCITY) trial enrolled 126 patients with systolic blood pressure (SBP) >180 mm Hg for treatment with clevidipine to a patient-specific prespecified initial target range (ITR) of SBP to be achieved within 30 minutes. Of the enrolled patients, 19 had AHF on presentation. Primary end points were the percentage in whom ITR was achieved within 30 minutes and the number whose SBP was below the ITR after 3 minutes of clevidipine infusion. Among the 19 AHF patients in VELOCITY, median time to ITR was 11.3 minutes (95% confidence interval, 7-19). ITR was reached in most patients (94%) within 30 minutes. No patient had hypotension below the ITR, and heart rate remained stable. At 18 hours, 16 of 19 patients had received continuous clevidipine infusion, and their SBP was reduced by mean of 50 mm Hg (25%) from baseline. There were no treatment-related adverse events or adverse events that led to clevidipine discontinuation. Clevidipine safely decreases SBP in AHF and does not cause unexpected hypotension. The results of this post hoc subgroup analysis suggest that clevidipine is safe, well tolerated, and efficacious in AHF patients with hypertension.

Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension : a multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial

This study was a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of oral nicardipine for the treatment of urgent hypertension in the emergency department. Of 57 patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women, 43 black and 10 white, age range 48 +/- 11 years, and diastolic blood pressure 128 +/- 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or placebo in blind fashion followed by 30 mg open-label nicardipine in nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg nicardipine three times a day for 1 week after discharge from the emergency department. Adequate blood pressure reduction, defined as a reduction of diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo (p = 0.002). Adequate blood pressure reduction after administration of open-label nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure reductions were maintained at 1 week after discharge. The drug was well tolerated, and no significant adverse events occurred. We conclude that oral nicardipine is a safe and effective drug for the initial treatment of urgent hypertension.

Clevidipine for severe hypertension in patients with renal dysfunction: a VELOCITY trial analysis.

Abstract Introduction. Acute and severe hypertension is common, especially in patients with renal dysfunction (RD). Clevidipine is a rapidly acting (t½∼1 min) intravenous (IV) dihydropyridine calcium-channel blocker metabolized by blood and tissue esterases and may be useful in patients with RD. The purpose of this analysis was to assess the safety and efficacy of clevidipine in patients with RD. Methods. VELOCITY, a multicenter open-label study of severe hypertension, enrolled 126 patients with persistent systolic blood pressure (SBP) >180 mmHg. Investigators pre-specified a SBP initial target range (ITR) for each patient to be achieved within 30 min. Blood pressure monitoring was by cuff. Clevidipine was infused via peripheral IV at 2 mg/h for at least 3 min, then doubled every 3 min as needed to a maximum of 32 mg/h (non-weight-based treat-to-target protocol). Per protocol, clevidipine was continued for at least 18 h (96 h maximum). RD was diagnosed and reported as an end-organ injury by the investigator and was defined as requiring dialysis or an initial creatinine >2.0 mg/dl. Primary endpoints were the percentage of patients within the ITR by 30 min and the percentage below the ITR after 3 min of clevidipine infusion. Results. Of the 24 patients with moderate to severe RD, most (13/24) were dialysis dependent. Forty-six percent were male, with mean age 51±14 years; 63% were black and 96% had a hypertension history. Median time to achieve the ITR was 8.5 min. Almost 90% of patients reached the ITR in 30 min without evidence of overshoot and were maintained on clevidipine through 18 h. Most patients (88%) transitioned to oral antihypertensive therapy within 6 h of clevidipine termination. Conclusions. This report is the first demonstrating that clevidipine is safe and effective in RD complicated by severe hypertension. Prolonged infusion maintained blood pressure within a target range and allowed successful transition to oral therapy.