Montalescot G: SafeTy and Efficacy of Intravenous Enoxaparin in Elective Percutaneous Coronary Intervention: An InternationaL Randomized Evaluation (STEEPLE) (Abstract 2574)
A bright but still indirect light was thrown on the subject of enoxaparin dosing by a later Hot Line session. The STEEPLE trial compared enoxaparin and UFH in patients undergoing elective PCI. The important difference between the use of enoxaparin in both OASIS 5 and SYNERGY and in STEEPLE was that STEEPLE incorporated an intravenous (IV) rather than a subcutaneous route of administration, with a single injection, with a shorter half-life (1.7 hours vs. 4.4 hours). No crossovers to UFH were permitted, according to the lead investigator, professor Gilles Montalescot, MD, at the Hopital Pitie-Salpetriere in Paris, France.
The goal of the STEEPLE trial was to demonstrate the superior safety of IV enoxaparin (0.5 or 0.75 mg/kg) up to 48 hours after the procedure, compared with IV UFH in patients undergoing non-emergent PCI. IV UFH was dosed at 70-100 IU without glycoprotein (GP) IIb/IIIa inhibitors (activated clotting time, 300-350 seconds) or 50-70 IU with GP IIb/IIIa inhibitors (activated clotting time, 200-300 seconds). The primary endpoint, which excluded patients going to bypass surgery, was the occurrence of major and minor bleeding. canada pharmacy mall
The mean age of the 3,528 patients was 64 years (75% men). About 56% had three or more risk factors; 37% had undergone prior PCI. This study population was a “real-world” one because patients were not restricted by age, weight, or renal function.
About 41% of the participants received GPIIb/IIIa inhibitors, and 23% received a clopidogrel loading dose of more than 300 mg; about 47% received chronic thienopyridine therapy.
Major bleeding was reduced significantly with both enoxa-parin doses (1.2% for each dose vs. 2.8% for UFH, a reduction of 57%). Combined major and minor bleeding was reduced significantly (P = .014) in those taking enoxaparin 0.5 mg/kg, with a trend favoring enoxaparin 0.75 mg/kg (P = .052). Minor bleeding was similar between the patient arms. A secondary endpoint of attaining target anti-factor Xa and target activated clotting time strongly favored enoxaparin (0.5 mg/kg, 78.8% of patients; 0.75 mg/kg, 91.7°%; and UFH, 19.7°%).
Clinical endpoints were similar among the patient groups. Dr. Montalescot concluded that IV enoxaparin in patients scheduled to have elective PCI was associated with “significantly less bleeding and similar efficacy compared with UFH.”
Discussant professor Jean-Pierre Bassand, MD, from University Hospital Jean Minjoz in Besangon, France, added: “It is no longer necessary to switch from enoxaparin to UFH in patients with non-ST ACS [acute coronary syndrome] at the time of PCI. That was significantly associated with increased risk of bleeding in SYNERGY and OASIS 5.”
Montalescot G: Clopidogrel as Adjunctive Reperfusion Ther-apy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI 28) (Abstract 755)
Turning to the opposite challenge, keeping platelet activation from precipitating major cardiac events in patients being treated for ST-elevation MI (STEMI), the CLARITY trial investigators sought to examine the issue of pretreatment with clopidogrel (Bristol-Myers Squibb/Sanofi). These investigators, also led by Dr. Montalescot, hypothesized that after initial pharmacological (fibrinolytic, aspirin, heparin) therapy, clopido-grel pretreatment, hours to days before angioplasty, was superior to clopidogrel therapy in preventing major adverse cardiovascular events when it was initiated at the time of a PCI.
An earlier CLARITY-TIMI 28 analysis among 3,491 STEMI patients had shown that helped to open blocked arteries and decreased the odds of a second heart attack by 31%. For this analysis, investigators compared 933 patients who were randomly assigned to receive a pre-angioplasty loading dose of clopidogrel 300 mg for two to eight days, followed by 75 mg once daily for those given placebo (n = 930). Following angioplasty, open-label clopidogrel was given in both groups, in accordance with the physician’s recommendation. The patients, whose mean age was 57.5 years, reported to the hospital less than 12 hours from symptom onset. Stents were implanted in 95% of the patients.
The time from randomization to a PCI was significantly longer for the clopidogrel pretreatment group (3.2 days) than the placebo group (2.9 days) (P = .003). Overall, for patients receiving clopidogrel, the risk of having a closed artery or an MI or dying was reduced by 36% before angiography. Infarct-related artery patency occurred in 87% of patients receiving clopidogrel pretreatment and in 81% of those receiving placebo (P < .001). The odds of MI, urgent revascularization, or dying of cardiovascular disease within 30 days was also reduced by 20% in the pretreatment patients (P= .026).
Among PCI patients receiving canadian clopidogrel pretreatment, the risk of MI, stroke, or cardiovascular death was reduced by 46% (3.6% with clopidogrel vs. 6.2% with placebo; P = .008).
No excess in major bleeding or intracranial hemorrhage was reported with clopidogrel pretreatment.
Dr. Montalescot concluded that pretreatment with clopido-grel before a PCI resulted in a consistent benefit for all subgroups. For every 100 patients undergoing PCI, four major cardiovascular events were prevented.