Clevidipine Shows Promise for Acute HF with High BP

Marlene Busko

February 10, 2014

HOUSTON, TX — In a small study of patients presenting to the ER with hypertensive acute heart failure (HF), the IV calcium-channel blocker clevidipine (Cleviprex, the Medicines Company) was safe and more effective than standard IV drugs to rapidly reduce BP and improve dyspnea[1].

These promising early findings from A Study of Blood Pressure Control in Acute Heart Failure-A Pilot Study (PRONTO) were published online January 15, 2014, in the American Heart Journal.

Further studies are needed to confirm whether clevidipine may have a role in treating patients with acute heart failure, hypertension and dyspnea,  Dr W Frank Peacock (Baylor College of Medicine, Houston, TX) told heartwire .

In PRONTO, among patients who received clevidipine, shortness of breath was completely gone in three hours, whereas in patients who received usual care—mainly IV nitroglycerin or IV nicardipine—dyspnea resolved in 12 hours.

"The question then becomes, 'does clevidipine have a unique effect in this population?' If it does, and we can validate that, then it clearly would be a drug that gives a tremendous amount of hope in HF, because nobody has a drug that cures you in three hours," Peacock said. PRONTO 2, which is about to start enrolling patients, is designed to answer that question.

Clevidipine for Acute AF

Nearly half of patients with acute heart failure present with systolic blood pressure above 140 mm Hg, but few trials have compared the safety and effectiveness of available agents. Nitrates, hydralazine, and nicardipine are used most often, but each has limitations.

Animal studies and an analysis of a subgroup of hypertensive patients with acute HF in the VELOCITY study suggested that clevidipine may be beneficial in such patients, Peacock said.

PRONTO is an international 13-center, prospective, randomized, open-label trial of patients with HF who presented at the ER with systolic BP >160 mm Hg and had dyspnea that was >50 mm on a 100-mm visual-analog scale.

The trial enrolled 104 patients who were randomized within one hour of presentation to clevidipine or standard care IV antihypertensives. The patients had a mean age of 61 and a mean baseline systolic BP of 186.5 mm Hg. About half were female, and 80% were African American.

Eighty-five patients met the criteria of "confirmed acute HF." Of the 53 patients who received standard care, most received nitroglycerin (30 patients) or nicardipine (16), and the rest received nitroprusside (one), hydralazine (one), diltiazem (one), and isosorbide dinitrate (four).

Patients assigned to clevidipine achieved a target blood-pressure range more often than patients assigned to standard care (71% vs 37%; p=0.002), and they reached this end point sooner.

At 45 minutes after treatment initiation, patients who had received clevidipine had a greater improvement in their dyspnea than patients who received standard care.

The rates of serious adverse events (24% vs 19%) and of 30-day mortality (three vs two) were similar in the patients who received clevidipine and those who received standard care, respectively, and no deaths occurred during administration of the drug.

Pure Pulmonary Artery Vasodilation?

"Clevidipine's effects on dyspnea appear . . . to be partially independent of blood-pressure reduction and may indicate a unique mechanism of action that warrants further study," the researchers write.

"Our data add to the existing body of literature and further support the hypothesis that these patients have an underlying 'vascular-redistribution' phenotype, in contradistinction to volume overload, as the underlying pathologic precipitant for their symptoms," they continue.

"We think it's a pure pulmonary-artery vasodilation that is the benefit of clevidipine," Peacock said. "It's a unique drug. It's very short acting: if you get into trouble, you turn it off."

PRONTO was sponsored by the Medicines Company.

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