Physician’s Weekly: online CME courses, articles on hypertension, arthritis

Perioperative acute hypertension is an unacceptable increase in blood pressure (BP) that occurs just before, during, or after surgery. If the condition is not addressed in an appropriate (eg, establishment of optimal BP conditions) and timely manner—minutes—it could result in devastating complications. These include cerebral dysfunction, myocardial dysfunction, renal dysfunction, and/or bleeding at the surgical site.

Clevidipine is an intravenous short-acting dihydropyridine calcium channel antagonist that was recently approved by the FDA for the treatment of perioperative hypertension. The agent selectively relaxes the smooth muscle cells that line small arteries. The pharmacodynamic and pharmacokinetic clinical effects of clevidipine allow for a rapid onset and offset of action. The agent can be titrated for precise BP control, allowing acute care specialists to take a tailored approach to treating hypertension. The FDA’s approval of clevidipine for perioperative hypertension was based on the results of the two phase III efficacy trials: ECLIPSE (Evaluation of Clevidipine In the Postoperative Treatment of Hypertension Assessing Safety Events) and ESCAPE (Efficacy Study of Clevidipine Assessing the Pre/Postoperative Antihypertensive Effect in Cardiac Surgery).

ECLIPSE Findings

The ECLIPSE trials were published in the October 2008 issue of Anesthesia & Analgesia. They compared clevidipine to current intravenous antihypertensive agents for perioperative hypertension control during cardiac surgery. Primary findings from ECLIPSE demonstrated that clevidipine was safe and effective in treating acute hypertension in patients undergoing cardiac surgery and provided comparable outcomes versus comparators in the domains of death, myocardial infarction, stroke, and renal dysfunction. Furthermore, a secondary objective in ECLIPSE which compared clevidipine to nitroglycerin and sodium nitroprusside for BP control demonstrated that clevidipine controlled BP significantly better, with approximately half the blood pressure excursion outside a pre-specified target BP range. A secondary analysis from ECLIPSE revealed that a protocol-specified index of BP control and area under the curve (AUC) was significantly linked to 30-day mortality. AUC was significantly greater in the comparator groups when compared with the clevidipine treatment arm.

These data suggest the need for clinicians to help patients reach the “sweet spot” of BP in order to mitigate adverse outcomes. Subtle perioperative BP changes can trigger hypercoagulable and hyperinflammatory reactions that concurrently decrease microvascular blood flow to organs. These events can lead to adverse outcomes within weeks following surgery. Prior to these data, the concept of strict BP control was underappreciated, so the findings represent a substantial paradigm shift in the way clinicians manage BP in acute care settings.

Pearls From ESCAPE

The ESCAPE trials, published in the July 2008 issue of Anesthesia & Analgesia, were two double-blinded, placebo-controlled trials that evaluated the ability of clevidipine to control BP preoperatively (ESCAPE-1) and postoperatively (ESCAPE-2) in high-risk cardiovascular surgery patients. Data from both trials demonstrated that the drug significantly decreased mean arterial BP when compared with placebo at the 5-minute time point. Both ESCAPE-1 and ESCAPE-2 concluded that clevidipine had the ability to precisely achieve target BP reductions in high-risk patients in a short period of time (ie, within 1 to 2 minutes).

Findings from both ECLIPSE and ESCAPE indicate that clevidipine, a novel dihydropyridine calcium channel blocker, will provide added value in controlling perioperative BP. The data for BP control suggest that we have entered a new era of knowledge in this area. Future inquires that address the role of BP control should be considered similar to the role of heart rate and blood glucose control so that clinicians can further optimize postoperative outcomes.

Solomon Aronson, MD, FACC, FCCP, FAHA, has indicated to Physician’s Weekly that he has received grants/research support from Abbott and has served as a consultant for The Medicines Company. He has also served on the speaker’s bureau for Baxter and is a major shareholder for Medwave.