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| | | | | ACC 2005 | | | | | | The American College of Cardiology
54th Annual Scientific Session
March 6-9, 2005
Orlando, Florida |
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| | | |  | Perioperative Bridging Therapy With Unfractionated Heparin or Low-Molecular-Weight Heparin in Patients With Mechanical Heart Valves on Long-Term Oral Anticoagulants: Results From the REGIMEN Registry
Alex Spyropoulos and A.G.G. Turpie et al.
Dr Turpie presented this poster on behalf of Dr Spyropoulos et al, comparing the use of low-molecular-weight heparin (LMWH) with that of unfractionated heparin (UFH) as a temporary anticoagulant in patients with mechanical heart valves. Patients with mechanical heart valves frequently receive long-term anticoagulation with warfarin due to their increased risk of thrombosis. However, if these patients need to undergo an invasive or surgical procedure, warfarin therapy is temporarily interrupted to reduce the risk of bleeding. Commonly, IV UFH or SC LMWH is used as a short-acting anticoagulant to “bridge” the patient and reduce the risk of thrombosis. The REGIMEN registry was developed to evaluate the use of these 2 compounds as bridging therapy in a prospective manner.
Patients were included in the REGIMEN registry if they had been receiving warfarin for at least 3 months. Warfarin therapy was interrupted for at least 2 days in the pre- and postoperative periods and replaced by treatment or prophylaxis dose UFH or LMWH. In total, 1077 patients were included in this observational registry study; 246 of these patients had mechanical heart valves. LMWH was used in 174 patients, while UFH was used in 72 patients. The adverse events reported were similar with both treatment options – 22.9% of patients reported an adverse event with LMWH vs 20.9% with UFH (P = NS). One incidence of thrombosis occurred in the UFH group (a cardiac valvular or mural thrombus) and major bleeding occurred in 7.5% of patients treated with UFH compared with 4.2% of patients receiving LMWH (P = NS). Length of hospital stay was reported to be reduced with LMWH (4.3 days vs 10.4 days, P < 0.001), which seems to indicate that LMWH reduces costs while appearing to be as safe as IV UFH when utilized as a perioperative anticoagulant bridging strategy.
Reference
Spyropoulos AC, et al. Perioperative bridging therapy with unfractionated heparin or low-molecular-weight heparin in patients with mechanical heart valves on long-term oral anticoagulants: results from the REGIMEN registry. J Am Coll Cardiol. 2005;45(suppl A). Abstract 1016-47.Back to top
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| | | | | Undertreatment of Atherothrombotic Patients Worldwide: Baseline Data From the REACH REGISTRY
Philippe Gabriel Steg et al.
The REACH (Reduction of Atherothrombosis for Continued Health) registry is a prospective, observational, worldwide registry of outpatients at risk of atherothrombotic events or with symptomatic atherothrombosis (either documented coronary artery, cerebrovascular, or peripheral arterial disease). In total, between December 2003 and June 2004, more than 60,000 patients were included in the REACH registry, from over 5000 sites in 43 countries. The registry has a global span, with data being collected in all major regions except Africa. The poster presented at ACC aimed to address the management characteristics of patients with atherothrombotic disease, and included data on patients from North America (27,809), Latin America (1927), Western Europe (17,829), Eastern Europe (5659), the Middle East (848), Asia (5931), and Australia (2869).
For all classes of atherothrombotic disease studied, there was a reported under-usage of appropriate guideline-recommended therapy. This problem appeared to be endemic, and was observed in all regions studied. However, the severity of under-use of medications varied per region, with antihypertensives being most adequately prescribed and statins being least used in patients who would benefit from them.
In addition, the poster revealed that many patients were not within commonly accepted therapeutic goals for their conditions. For example, as many as 31.9% to 53.0% of patients with diabetes had glucose levels above the “target” level of 110 mg/dL. Similar data were obtained for cholesterol and blood pressure targets, with the ranges of patients above the target ranges varying from 24.4% to 64.4% and 39.9% to 65.0%, respectively.
Reference
Steg PG, et al. Undertreatment of atherothrombotic patients worldwide: baseline data from the REACH REGISTRY. J Am Coll Cardiol. 2005;45(suppl A). Abstract 1070-121.Back to top
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| | | | | Enoxaparin Is Consistently More Effective Than Unfractionated Heparin Across the Spectrum of Risk in Non-ST Elevation Acute Coronary Syndrome Patients: Insights From the INTERACT Trial
Andrew T. Yan et al.
In the INTERACT (Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment) study, 746 patients with acute coronary syndromes (ACS) were randomized to receive enoxaparin or UFH, while being simultaneously treated with aspirin and eptifibatide. This study showed that enoxaparin was more effective than UFH. However, in order to investigate if therapeutic benefit was linked to the baseline risk of the patient, Dr Yan and colleagues used a published and validated mortality risk assessment model, the GRACE risk score, to divide the patients into 2 different “risk categories” — those with a higher than median risk score (n = 353) and those with a median or lower risk score (n = 358).
Forty-eight hour Holter ECG monitoring revealed that ischemia occurred in 12.6% of the lower-risk group and in 26.2% of the higher-risk group (P < 0.001). In both groups, the effect of enoxaparin therapy was reported to be uniform (pooled OR = 0.43, 95% CI, 0.29-0.64).
The endpoints of death and MI at 30 days were also studied. These were significantly lower in the lower-risk group (4.5% vs 9.9%, P = 0.006), with enoxaparin therapy being consistently more effective than UFH (pooled OR = 0.49, 95% CI, 0.27-0.90).
Reference
Yan AT, et al. Enoxaparin is consistently more effective than unfractionated heparin across the spectrum of risk in non-ST elevation acute coronary syndrome patients: insights from the INTERACT trial. J Am Coll Cardiol. 2005;45(suppl A). Abstract 1118-215. Back to top
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| | | | | The Safety of Antithrombin Therapy in Non-ST-Segment Elevation Acute Coronary Syndrome Patients: Results From the CRUSADE Initiative
Kanwar P. Singh et al.
The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines?) initiative evaluates care patterns and outcomes in high-risk non-ST-segment elevation (NSTE) ACS patients hospitalized throughout the United States. This poster reported a substudy of CRUSADE investigating the safety of LMWH or UFH in more than 38,000 patients treated at 311 revascularization-capable hospitals.
In this patient group, 38.4% of patients received LMWH alone, 54.4% received UFH alone, and 7.3% received both medications within 24 hours of admission. Although the groups had similar clinical characteristics, transfusion rates were lowest in the LMWH only group (13.8% vs 15.2% in the UFH group). In the group of patients receiving both medications, the transfusion rate was higher (17.0%). An analysis was also performed to adjust for different clinical factors and revascularization. This analysis revealed transfusion rates to be lower in LMWH-treated patients compared with those receiving UFH (OR = 0.81; 95% CI, 0.76-0.87). The authors concluded that these data indicate that the safety profiles of antithrombins differ in clinical practice from those observed in a controlled clinical trial.
Reference
Singh KP, et al. The safety of antithrombin therapy in non-ST-segment elevation acute coronary syndrome patients: results from the CRUSADE initiative. J Am Coll Cardiol. 2005;45(suppl A). Abstract 1119-201.Back to top
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| | | | | Late-Breaking Clinical Trial: Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY): Thrombolysis in Myocardial Infarction (TIMI) 28
Marc S. Sabatine et al.
The CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) study was presented as part of this year’s late-breaking clinical trials series. This study, conducted by the TIMI study group, aimed to elucidate if clopidogrel provides a benefit when added to fibrinolytic therapy and aspirin in ST-elevation myocardial infarction (STEMI) patients.
In total, 3491 patients aged 18 to 75 with STEMI of less than 12 hours who were being treated with a lytic, aspirin, and possibly heparin, were randomized to receive either clopidogrel (300 mg loading dose and 75 mg once daily) or matching placebo. Patients underwent angiography at 48 to 192 hours after first treatment, at which time clopidogrel or placebo was stopped. Dr Sabatine reported that the therapy was effective at reducing the incidence of the angiographic endpoint of TIMI 0 and 1 flow and reinfarction, without significantly increasing bleeding (see Table). The mortality rate was not reduced, although the study was most likely not powered to show a difference in this endpoint. Overall, the study suggests that, in STEMI patients aged less than 75, clopidogrel may be an effective addition to standard lytic therapy.
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Clopidogrel (300 mg loading dose plus 75 mg od)
(n = 1752)
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Placebo
(n = 1739)
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OR (95% CI)
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P value
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Composite of Death/MI or TIMI 0 or 1 flow
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15.0%
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21.7%
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0.64 (0.53-0.76)
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< 0.001
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Death prior to angiography
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2.6%
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2.2%
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1.17 (0.75-1.82)
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0.49
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MI prior to angiography
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2.5%
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3.6%
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0.70 (0.47-1.04)
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0.08
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TIMI 0 or 1 flow
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11.7%
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18.4%
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0.59 (0.48-0.72)
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< 0.001
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TIMI major bleeding
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1.3%
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1.1%
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0.64
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Reference
Sabatine MS, Cannon CP, Gibson CM, et al, for the CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med [serial online]. 2005. Available at: http://content.nejm.org/cgi/content/abstract/NEJMoa050522v1. Accessed March 17, 2005.
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| | | | | Late-Breaking Clinical Trials: COMMIT/CCS-2: Randomized, Placebo-Controlled Trial of Adding Clopidogrel to Aspirin in 46,000 Acute Myocardial Infarction Patients
Zhengming Chen and Rory Collins et al.
The COMMIT-CCS2 (Clopidogrel and Metoprolol in Myocardial Infarction Trial) study also formed part of the late-breaking session at ACC this year. In 2 separate presentations, the effects of clopidogrel and the beta-blocker metoprolol in MI patients were discussed, with both medications being compared to placebo through independent randomization. The trial was conducted in China, and included nearly 46,000 patients. Patients undergoing percutaneous coronary intervention or at high risk of bleeding were excluded. Only 49% of patients included in the trial received lytic therapy.
In the clopidogrel part of the study, patients were randomized to receive either clopidogrel 75 mg or placebo. All patients received aspirin. The event curve for the combined primary endpoint of death, MI, and stroke showed an early benefit of clopidogrel treatment, which by 28 days led to an event rate of 9.3% with clopidogrel compared with 10.1% with placebo, a 9% relative risk reduction (P = 0.002). In addition, death alone was significantly reduced by clopidogrel treatment (7.5% vs 8.1%, a 7% relative risk reduction; P = 0.03). This benefit in efficacy was observed with no increase in major bleeding. Any major bleed occurred in 0.6% of clopidogrel patients and 0.5% of placebo patients (P = NS).
In contrast, the metoprolol comparison from the same study showed surprising results. Patients were randomized to receive metoprolol 15 mg IV over 15 minutes, then 200 mg oral once daily or placebo. No significant differences were observed between the groups for the primary trial endpoint of death/reinfarction/cardiac arrest (9.5% vs 9.9% for metoprolol and placebo, respectively, P = NS) or the coprimary endpoint of all-cause mortality by discharge (7.7% vs 7.8% for metoprolol and placebo, respectively, P = NS). Death due to arrhythmia was reduced in the metoprolol group (1.7% vs 2.2% with placebo); however, this effect was cancelled out by an increase in shock-related deaths (2.2% vs 1.7%). This led the authors to conclude that it may be advisable to start beta-blockers later, when MI patients are stable.
References
CLARITY and COMMIT: advancing knowledge for the benefit of your STEMI patient. Available at: http://www.theheart.org/viewArticle.do?primaryKey=395865. Accessed March 17, 2005.
Stiles S. COMMIT/CCS-2 shows early hazard from IV beta blockade in higher-risk acute-MI patients. Available at: http://www.theheart.org/viewArticle.do?primaryKey=401951. Accessed March 17, 2005.
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| | | | | Superior Responder Rate for Inhibition of Platelet Aggregation With a 60 mg Loading Dose of Prasugrel (CS-747, LY640315) Compared With a 300 mg Loading Dose of Clopidogrel
John T. Brandt et al.
This presentation reported on the inhibition of platelet aggregation achieved in healthy subjects with a novel thienopyridine P2Y12 receptor antagonist. Sixty-eight subjects were randomized to receive either 60 mg prasugrel or 300 mg of clopidogrel, both administered as loading doses.
Response (defined as > 25% inhibition of platelet aggregation, or as > 10% decrease in maximum platelet aggregation) was significantly higher with prasugrel than with clopidogrel. This phenomenon was observed at both 4 and 24 hours after dosing.
Further studies are now required to determine how this platelet aggregation response translates to patient outcomes in the clinical setting.
Reference
Brandt JT, et al. Superior responder rate for inhibition of platelet aggregation with a 60 mg loading dose of prasugrel (CS-747, LY640315) compared with a 300 mg loading dose of clopidogrel. J Am Coll Cardiol. 2005;45(suppl A). Abstract 868-5.Back to top
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