Anti-Xa Activity Relates to Survival and Efficacy in Unselected Acute Coronary Syndrome Patients Treated With Enoxaparin

Abstract

Background-Low-molecular-weight heparin (LMWH) is recommended in the treatment of unstable angina (UA)/non-ST-segment-elevation myocardial infarction (NSTEMI), but no relationship has ever been shown between anticoagulation levels obtained with LMWH treatment and clinical outcomes. Methods and Results-In all, 803 consecutive patients with UA/NSTEMI were treated with subcutaneous enoxaparin and were followed up for 30 days. The recommended dose of enoxaparin of 1 mg/kg BID was used throughout the population except when physicians decided on dose reduction because of a history of a recent bleeding event or because of a high bleeding risk. Anti-factor Xa activity was Ͼ0.5 IU/mL in 93% of patients; subtherapeutic anti-Xa levels (Ͻ0.5 IU/mL) were associated with lower doses of enoxaparin. The 30-day mortality rate was significantly associated with low anti-Xa levels (Ͻ0.5 IU/mL), with a Ͼ3-fold increase in mortality compared with the patients with anti-Xa levels in the target range of 0.5 to 1.2 IU/mL (Pϭ0.004). Multivariate analysis revealed low anti-Xa activity as an independent predictor of 30-day mortality at least as strong as age, left ventricular function, and renal function. In contrast, anti-Xa activity did not predict major bleeding complications within the range of anti-Xa levels observed in this study. Conclusions-In this large unselected cohort of patients with UA/NSTEMI patients, low anti-Xa activity on enoxaparin treatment is independently associated with 30-day mortality, which highlights the need for achieving at least the minimum prescribed anti-Xa level of 0.5 IU/mL with enoxaparin whenever possible.

Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis

“…The 24 studies [2-6, 10-11, 14-17, 18-21, 23-25, 27, 29, 31-33] were analyzed word by word. Three studies contained results that were related to the same study population [4,18,27]. The Collet et al study contained several LMWH preparations with 80% of individuals given enoxaparin, but no data could be distinguished for individual preparations or for enoxaparin dosing [10].…”

Enoxaparin dosing in the elderly using adjusted body weight

“…Among our Phase 1 cohort of 36 elderly subjects, we noted that standard enoxaparin dosing resulted in supra-therapeutic antiXa activity levels ([1.5 IU/ml) in 28% of instances. Peak Anti-Xa levels above the upper limit of the recommended therapeutic range (1.0-1.2 IU/ml) may be associated with an increased risk of bleeding [4][5][6]. Our findings showed significantly lower mean (but therapeutic) anti-Xa activity and the absence of highest-risk, supratherapeutic levels ([1.5 IU/ml) which could translate into lower hemorrhagic risk while maintaining clinical efficacy in patients using ABW enoxaparin dosing strategy.…”

“…Serum anti-Xa levels can be used to monitor hemorrhagic risk from enoxaparin, but testing is presently limited to select patient groups such as those with obesity or renal failure [4]. Therapeutic anti-Xa activity is generally defined as 0.5-1.0 IU/ml (with an upper range of 1.2 IU/ml in some studies) [5], with increased hemorrhagic risk reported at concentrations [1.5 IU/ml [6,7].…”

The appropriateness of enoxaparin use in Lebanese hospitals: a quality evaluation study

“…Similarly, Montalescot et al [18] observed that a dose reduction increases the risk of mortality and recurrent ischemic events.…”

“…A meta-analysis of 15 trials on enoxaparin use in this population was associated with two-to threefold increase in the risk of major bleeding [17]. Thus, the American College of Chest Physicians (ACCP) recommends that dosage adjustment be considered [10][11][12] (Table 1) to decrease the bleeding risk, but such reduction may be associated with loss of therapeutic efficacy [18,19].…”