An Automated Strategy for Bedside aPTT Determination and Unfractionated Heparin Infusion Adjustment in Acute Coronary Syndromes: Insights from PARAGON A

Abstract

Background: Intravenous unfractionated heparin remains a cornerstone of anticoagulation therapy for patients with acute coronary syndromes, but regulation to a target aPTT is challenging. We assessed unfractionated heparin infusion regulation by bedside, whole-blood aPTT testing and computerized, algorithmic infusion adjustment, and further evaluated the relationship of achieving the target aPTT with clinical outcomes.

Methods and Results: We studied 1,275 patients randomized to unfractionated heparin in PARAGON-A, which tested lamifiban with or without unfractionated heparin versus unfractionated heparin. All patients had baseline and 6-hour blinded, bedside aPTTs, then aPTTs per algorithm. A central computer translated encrypted values to algorithmic dose-adjustment commands. We assessed the ability to achieve and maintain aPTTs of 50–70 seconds and associations of 6- and 12-hour aPTTs and time-to-target with 30-day outcomes.

Overall, the median 6-hour aPTT was 50–70 seconds and remained so throughout infusion. Individually, only 33.6% of patients achieved 6-hour target-range aPTTs, and only 40% of all aPTTs were in-range. After achieving target, only 42% of subsequent measures were in-range. Thirty-day death or myocardial infarction (death/MI) increased non-significantly as time-to-target increased (p = 0.08). Thirty-day mortality was similar if target aPTT was reached, regardless of timing. Death/MI trended lower if target aPTT was reached by 8 hours (p = 0.10). The best clinical outcomes were associated with in-range aPTTs.

Conclusions: This study represents the most systematic monitoring and regulation of unfractionated heparin anticoagulation to date. Although average anticoagulation achieved target range, wide inter- and intra-patient variability may have important implications for clinical outcomes.

Abbreviated abstract: Using systematic aPTT testing and computer-directed, algorithmic unfractionated heparin infusion adjustment in 1,275 acute coronary syndrome patients, the overall median aPTT was 50–70 seconds. However, only 33.6% of patients achieved this target 6-hour aPTT range. Only 40% of all aPTTs, and after achieving target, only 42% of subsequent measures, were in this range. Thirty-day death or myocardial infarction increased with increasing time to target aPTT (for trend, p = 0.08). The best outcomes were associated with 6- and 12-hour aPTTs in the target range. Wide inter- and intra-patient variability despite highly systematic, controlled unfractionated heparin infusion regulation has important implications for unfractionated heparin use.