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

BACKGROUND: Rapid 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. METHODS: This 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. RESULTS: Of 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. CONCLUSIONS: In hypertensive AHF, clevidipine safely and rapidly reduces BP and improves dyspnea more effectively than SOC.

Clevidipine, an intravenous dihydropyridine calcium channel blocker, is safe and effective for the treatment of patients with acute severe hypertension.

STUDY OBJECTIVE: We 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. METHODS: Prospective, 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. RESULTS: Study 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. CONCLUSION: Clevidipine, 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.