Immediate Pharmacology in the Current Era of Reperfusion Therapy

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The relative reduction in death and MI with enoxaparin in the elderly was reduced to attenuated (6%), but because of the substantially higher risk in elderly patients, the absolute risk reduction was similar to that seen in younger patients. Importantly, bleeding rates, including intracranial hemorrhage rates, were similar in patients randomized to unfractionated heparin or to enoxaparin. In EXTRACT a once-daily regimen was also used in patients with a creatinine clearance of <30 ml/minute. Interestingly, no benefit with enoxaparin was seen among patients not undergoing reperfusion therapy in a well-powered randomised trial.10 Evidence of a benefit of enoxaparin among patients receiving catheter-based reperfusion is currently limited to uncontrolled studies though these appear to suggest that the practice is feasible and provides reasonable anti-Xa levels.11

Data with fondaparinux, a long-acting factor Xa inhibitor, also demonstrate advantages among patients presenting with STEMI. This agent was studied in the Organization for the Assessment of Strategies for Ischemic Syndromes (OASIS)-6 study in patients with STEMI. In a complex study including a stratified randomisation based on the intent to use unfractionated heparin, fondaparinux was associated with an overall 14% relative risk reduction or 1.5% absolute risk reduction (11.6% versus 9.7%, p<0.008) in death or non-fatal MI at 30 days.12 A significant early 0.9% absolute mortality benefit was also observed with this benefit persisting throughout the six-month follow-up. While bleeding rates were lower in the fondaparinux group, this benefit did not reach statistical significance, in contrast to the OASIS-5 study in patients with non-ST elevation MI.13 Furthermore, significant heterogeneity was seen in the results depending on the form of reperfusion therapy undertaken. Among patients receiving no reperfusion and those receiving fibrinolysis, fondaparinux was associated with significant and comparable benefit with hazard ratios for death or MI of 0.8 (95% CI 0.65-0.98, p=0.003) and 0.759 (95% CI 0.68-0.92, p=0.003), respectively. However, among those undergoing primary PCI, a non-significant excess risk was observed (4.9% unfractionated heparin versus 6% fondaparinux; HR 1.24, 95% CI 0.95-1.63, p=0.12; p for heterogeneity = 0.04). The mechanism of this difference is unclear, but may be related to the lower risk of this subpopulation and an increased risk of catheter thrombosis. Hence, while the data for this agent among patients undergoing pharmacologic reperfusion is strong, there appears to be little role for fondaparinux in catheter-based reperfusion.

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