Are activated clotting times helpful in the management of anticoagulation with subcutaneous low-molecular-weight heparin?

BACKGROUND: Enoxaparin has recently been shown to be superior to unfractionated heparin in patients with unstable angina/non-ST-elevation myocardial infarction. Theoretical advantages of low-molecular-weight heparin versus unfractionated heparin include a higher ratio of anti-Xa to anti-IIa activity (3:1 for enoxaparin), a more predictable dose response that precludes the need for frequent monitoring, and the convenience of subcutaneous administration. Both activated partial thromboplastin time and activated clotting time (ACT) are used to monitor anticoagulation with heparin, and ACTs are now standard during percutaneous coronary intervention (PCI) with heparin. At doses of up to 90 mg, subcutaneous enoxaparin leads to a modest dose-related increase in activated partial thromboplastin time, but the effect on ACT is unknown. METHODS: Thrombolysis In Myocardial Infarction (TIMI) 11A was a multicenter, dose-ranging trial to evaluate the safety and tolerability of subcutaneous enoxaparin in patients with unstable angina/non-ST-elevation myocardial infarction. We obtained peak (mean 4.3 hours after enoxaparin) and trough (mean 11.5 hours after enoxaparin) anti-Xa levels and ACTs for 26 patients in the TIMI 11A trial. RESULTS: Despite doses of enoxaparin in the range of 89 +/- 19 mg every 12 hours and significant increases in anti-Xa levels even at trough, there was no change in the ACT measured by HemoTec and only a small increase with Hemachron. The correlation of peak Hemachron ACT with peak anti-Xa levels was poor (R = 0.5, P =.08). CONCLUSIONS: In contrast to heparin, ACTs are not useful for assessment of anticoagulation with subcutaneous enoxaparin and should not be relied on in patients receiving enoxaparin who require acute PCI. Studies to determine the optimal dose, safety, and efficacy of enoxaparin in patients undergoing PCI are underway.

Coronary angioplasty in heart transplant recipients: a quantitative angiographic long-term follow-up study.

Late morbidity and death as a result of transplant-related coronary vascular disease is a major unresolved problem for heart transplant recipients. Treatment of discrete coronary lesions in transplanted coronary arteries with angioplasty may be beneficial, but the long-term outcome and factors affecting restenosis are not known. To determine the effects of angioplasty on coronary caliber and the correlates of late restenosis, we studied the results of 25 balloon angioplasty procedures for physiologically significant coronary artery stenosis (> 15 mm Hg translesional pressure gradient) in nine heart transplant recipients. All patients underwent repeat coronary angiography within 6 months of angioplasty. Angiograms were analyzed by the Reiber-CAAS method of quantitative angiography. Procedural success rate was 100%, and there were no major complications. The minimum cross-sectional area of the lesion increased from 0.8 +/- 0.5 mm2 to 3.1 +/- 1.7 mm2 immediately after dilation. Percent area stenosis decreased from 89% +/- 7% to 62% +/- 13%. Six (24%) of 25 lesions developed late physiologically significant restenosis, defined as greater than 15 mm Hg translesional pressure gradient, and 10 of 25 had angiographic restenosis, defined as 50% area stenosis by quantitative angiography. The loss in minimum cross-sectional area of the lesion at late follow-up was related significantly to the minimum cross-sectional area (r = 0.67; p < 0.001) and percent area stenosis (r = 0.62; p < 0.01) immediately after angioplasty and the gain in minimum area (r = 0.62; p < 0.01) or loss in percent area stenosis (0.51%; p = 0.02) during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)