16 Jun 10
Posted in Hypertension at 0:46 by Laci
By U Ndefo, G Erowele, R Ebiasah and W Green
Am J Health Syst Pharm.2010; 67: 351-360
The pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, and place in therapy of clevidipine are reviewed.
Summary
Clevidipine is a new lipophilic, short-acting, third-generation dihydropyridine calcium channel blocker (CCB) approved for use in the management of acute hypertension when oral agents are not feasible. It exerts its hemodynamic effects through selective arterial vasodilation without effects on the venous circulation. Clevidipine has a half-life of approximately two minutes after i.v. administration, resulting in very rapid onset and offset of antihypertensive action. Unlike many current i.v. antihypertensive agents that are metabolized by the kidneys or liver, clevidipine is metabolized in the blood and tissues and does not accumulate in the body. Clevidipine does not appear to inhibit or induce cytochrome P-450 isoenzymes. Several Phase III clinical trials have reported the clinical efficacy and safety of clevidipine in patients with severe hypertension and in cardiac surgical patients with perioperative hypertension. The most frequent adverse events reported in clinical trials of clevidipine were headache, nausea, and vomiting. Risk of rebound hypertension, especially in patients not transitioned from clevidipine to oral antihypertensive therapy after prolonged infusions, should be monitored for at least eight hours after the drug is discontinued.
Conclusion
Clevidipine, a novel third-generation dihydropyridine CCB, has demonstrated efficacy and safety in patients with acute hypertension and preoperative, perioperative, and postoperative hypertension. While its short duration of action and short half-life are appropriate for use in acute settings, more information on its safety is needed to assess its appropriate use in therapy.
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04 Jun 10
Posted in Antiplatelet therapy, Coronary artery disease at 0:36 by Laci
By G Stone, A Rizvi, W Newman, K Mastali, J Wang, R Caputo, J Doostzadeh, S Cao, C Simonton, K Sudhir, A Lansky, D Cutlip, D Kereiakes for the SPIRIT IV Investigators
NEJM 2010;362:1663-1674
Previous studies have established the superiority of coronary everolimus-eluting stents over paclitaxel-eluting stents with respect to angiographic findings. However, these trials were not powered for superiority in clinical end points.
Methods
We randomly assigned 3687 patients at 66 U.S. sites to receive everolimus-eluting stents or paclitaxel-eluting stents without routine follow-up angiography. The primary end point was the 1-year composite rate of target-lesion failure (defined as cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization).
Results
Everolimus-eluting stents were superior to paclitaxel-eluting stents with respect to the primary end point of target-lesion failure (4.2% vs. 6.8%; relative risk, 0.62; 95% confidence interval, 0.46 to 0.82; P=0.001). Everolimus-eluting stents were also superior with respect to the major secondary end point of the 1-year rate of ischemia-driven target-lesion revascularization (P=0.001) and were noninferior with respect to the major secondary end point of the 1-year composite rate of cardiac death or target-vessel myocardial infarction (P<0.001 for noninferiority; P=0.09 for superiority). The 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%, P=0.02 for myocardial infarction; 0.17% vs. 0.85%, P=0.004 for stent thrombosis). Target-lesion failure was consistently reduced with everolimus-eluting stents as compared with paclitaxel-eluting stents in 12 prespecified subgroups, except in the subgroup of patients with diabetes (6.4% vs. 6.9%, P=0.80).
Conclusions
Everolimus-eluting stents, as compared with paclitaxel-eluting stents, resulted in reduced rates of target-lesion failure at 1 year, results that were consistent in all patients except those with diabetes, in whom the results were nonsignificantly different.
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