Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).

Abstract

BACKGROUND:

Low-molecular-weight heparin (LMWH) has a more predictable anticoagulant effect than unfractionated heparin (UFH), is easier to administer, and does not require monitoring. Minimal data are available on LMWH combined with platelet glycoprotein (GP) IIb/IIIa inhibitors.

METHODS:

In the Platelet IIb/IIIa Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network B (PARAGON B) trial, patients with an acute coronary syndrome were randomized to receive the IIb/IIIa inhibitor lamifiban or a placebo. To rigorously explore the potential benefits of LWMH and GP IIb/IIIa inhibition, we analyzed the rates of ischemic complications and safety outcomes in PARAGON B.

RESULTS:

Approximately one fifth of the patients received LMWH (805 vs 4395 UFH). For the overall cohort, the incidence of death/myocardial infarction (MI)/severe recurrent ischemia (SRI) was 12.2%, and this composite end point was numerically lowest in the lamifiban with LMWH group (10.2%). Similarly, the incidence of death/MI was 11.0% for the entire cohort and lowest in the lamifiban and LMWH group (9.0%). The lower event rate for patients taking LMWH in the lamifiban group was sustained at 6 months, with a lower revascularization rate (51.5% vs 42.8%) and a lower composite of death/MI (13.8% vs 11.9%). Bleeding was comparable in the 2 heparin groups (1.4% with UFH vs 0.9% with LMWH). The propensity adjusted odds ratio for 30-day revascularization was significantly lower with LMWH (odds ratio 0.67, 95% CI 0.57-0.79, P <.001). There were no significant differences in death/MI/SRI at 30 days (P =.465), death/MI at 30 days (P =.264), and stroke at 30 days with the type of heparin use (P =.201) after propensity risk adjustment.

CONCLUSIONS:

In the PARAGON B trial, use of LMWH in conjunction with a GP IIb/IIIa inhibitor was safe and associated with a lower revascularization rate. These findings support the rationale and promise for combining GP IIb/IIIa blockers and LMWH for future management of acute coronary syndrome.

• Authors: Debabrata Mukherjee, Kenneth W Mahaffey, David J Moliterno, Robert A Harrington, Jay S Yadav, Karen S Pieper, Dianne Gallup, Christopher Dyke, Matthew T Roe, Lisa Berdan, Michael S Lauer, Matti Mänttäri, Harvey D White, Robert M Califf, Eric J Topol
• Journal: American heart journal (Am Heart J) Vol. 144 Issue 6 Pg. 995-1002 (Dec 2002) ISSN: 1097-6744 [Electronic] United States
• PMID: 12486423 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Anticoagulants
• Heparin, Low-Molecular-Weight
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Tyrosine
• Heparin
• lamifiban

Topics

• Acetates (therapeutic use)
• Acute Disease
• Aged
• Anticoagulants (therapeutic use)
• Coronary Disease (drug therapy, physiopathology, therapy)
• Data Interpretation, Statistical
• Drug Therapy, Combination
• Female
• Heparin (therapeutic use)
• Heparin, Low-Molecular-Weight (therapeutic use)
• Humans
• Male
• Middle Aged
• Myocardial Revascularization
• Platelet Aggregation Inhibitors (therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Randomized Controlled Trials as Topic
• Survival Analysis
• Tyrosine (analogs & derivatives, therapeutic use)