Phase III results with Investigational Drug Show Better Cardiac
Peri-Operative Blood Pressure Control

Clevidipine, an intravenous antihypertensive agent, was shown to reduce the number of “blood pressure excursions”, how much and how long systolic blood pressure (SBP) went above or below predefined perioperative blood pressure ranges), compared to the currently used intravenous agents.  The results of the ECLIPSE program were presented by Dr. Solomon Aronson, Duke University Medical Center, at the 56th Scientific Sessions of the American College of Cardiology, held in New Orleans from March 24 to 27, 2007. The ECLIPSE program is the largest safety program to date comparing intravenous antihypertensive agents.

“This analysis from ECLIPSE showed tight perioperative blood pressure control” with clevidipine, and “if approved, may provide a potentially important new treatment option for acute hypertension, a condition which affects nearly 3 million people in the US each year,” stated Aronson.

In the ECLIPSE program, 1,964 cardiac surgery patients were enrolled in one of three randomized, open-label trials comparing clevidipine to nitroglycerin (ECLIPSE-NTG), sodium nitroprusside (ECLIPSE-SNP), and nicardipine (ECLIPSE-NIC). Just prior to cardiac surgery, blood pressure was monitored and the assigned intravenous antihypertensive agent administered at the physician’s discretion if blood pressure was too elevated. Investigators determined “blood pressure excursions” based on the patient’s blood pressure response during the 24-hour period after initiating therapy. The acceptable blood pressure range for the pre-operative and post-operative periods was 85-145 mmHg and 75-135 mmHg during surgery.

The data from all the trials together and separately were evaluated. The number of blood pressure excursions was nearly halved for the widest blood pressure range (75-145 mmHg) with clevidipine compared to the other agents in the pooled analysis (3.8 mmHg vs 7.8 mmHg x min/h; p=0.0004). For the narrowest range (105-145 mmHg pre- and post-operative, 95-135 mmHg during surgery), clevidipine was also associated with fewer excursions (87.7 mmHg vs 111.5 mmHg x min/h; p=0.0002).

Further, with clevidipine, for the widest blood pressure range, about one-half fewer blood pressure excursions occurred in the ECLIPSE-NTG (4.14 mmHg vs 8.87 mmHg x min/h; p=0.0006) and ECLIPSE-SNP (4.37 vs 10.50 mmHg x min/h; p=0.0027) studies. No difference was seen in ECLIPSE-NIC (1.76 vs 1.79 mmHg x min/h; p=0.8508), but this was for the post-operative period only.

For the narrowest blood pressure range, there were also fewer excursions in the ECLIPSE-NTG (83.74 vs 108.57 mmHg x min/h; p=0.0556), ECLIPSE-SNP (100.17 vs 127.87 mmHg x min/h; p=0.0068), and ECLIPSE-NIC (76.5 vs 101.59 mmHg x min/h; p=0.0231).

Significantly lower mortality was seen in the ECLIPSE-SNP trial with clevidipine (1.7% vs 4.7% with sodium nitroprusside; p=0.045). The results for the primary endpoints of mortality rate, stroke, myocardial infarction, and kidney dysfunction were similar for clevidipine and the comparative drug.

The analysis showed a significant association between blood pressure excursions and 30-day mortality risk, with a 20% increase in mortality with an average blood pressure excursion of 1 mmHg/min for 60 minutes, and increased rapidly with each 1 mmHg/min increase; a 5 mmHg/min for 60 minutes increase in blood pressure was associated with about a 150% increased risk of mortality.