Anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction: a meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors

Abstract

Objectives To investigate the relative benefits of unfractionated heparin, low molecular weight heparin(LMWH), fondaparinux, and bivalirudin as treatment options for patients with ST segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI).Design Mixed treatment comparison and direct comparison meta-analysis of randomized trials in the era of stents and P2Y12 inhibitors.Data sources and study selection A search of Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) for randomized trials comparing unfractionated heparin plus glycoprotein IIb/IIIa inhibitor(GpIIb/IIIa inhibitor), unfractionated heparin, bivalirudin, fondaparinux, or LMWH plus GpIIb/IIIa inhibitor for patients undergoing primary PCI.Outcomes The primary efficacy outcome was short term (in hospital or within 30 days) major adverse cardiovascular event; the primary safety outcome was short term major bleeding.Results We identified 22 randomized trials that enrolled 22 434 patients. In the mixed treatment comparison models, when compared with unfractionated heparin plus GpIIb/IIIa inhibitor, unfractionated heparin was associated with a higher risk of major adverse cardiovascular events (relative risk 1.49 (95% confidence interval 1.21 to 1.84), as were bivalirudin (relative risk 1.34 (1.01 to 1.78)) and fondaparinux (1.78 (1.01 to 3.14)). LMWH plus GpIIb/IIIa inhibitor showed highest treatment efficacy, followed (in order) by unfractionated heparin plus GpIIb/IIIa inhibitor, bivalirudin, unfractionated heparin, and fondaparinux. Bivalirudin was associated with lower major bleeding risk compared with unfractionated heparin plus GpIIb/IIIa inhibitor (relative risk 0.47 (0.30 to 0.74)) or unfractionated heparin (0.58 (0.37 to 0.90)). Bivalirudin, followed by unfractionated heparin, LMWH plus GpIIb/IIIa inhibitor, unfractionated heparin plus GpIIb/IIIa inhibitor, and fondaparinux were the hierarchy for treatment safety. Results were similar in direct comparison meta-analyses: bivalirudin was associated with a 39%, 44%, and 65% higher risk of myocardial infarction, urgent revascularization, and stent thrombosis respectively when compared with unfractionated heparin with or without GpIIb/IIIa inhibitor. However, bivalirudin was associated with a 48% lower risk of major bleeding compared with unfractionated heparin plus GpIIb/IIIa inhibitor and 32% lower compared with unfractionated heparin alone.Conclusions In patients undergoing primary PCI, unfractionated heparin plus GpIIb/IIIa inhibitor and LMWH plus GpIIb/IIIa inhibitor were most efficacious, with the lowest rate of major adverse cardiovascular events, whereas bivalirudin was safest, with the lowest bleeding. These relationships should be considered in selecting anticoagulant therapies in patients undergoing primary PCI.

Efficacy and safety of different regimens for primary open‐angle glaucoma or ocular hypertension: a systematic review and network meta‐analysis

“…2011; Bangalore et al. 2014). Larger SUCRA values indicate higher rank of the treatment (Salanti et al.…”

“…2011; Bangalore et al. 2014). In addition, a clustered ranking plot was constructed using SUCRA values for efficacy (ΔIOP) and safety (hyperaemia) outcomes to obtain information on meaningful groups of treatments that maximize benefits for efficacy and safety outcomes.…”

Part 5: Acute Coronary Syndromes

“…62 Such association is also consistently reported in other published in-hospital studies and meta-analyses of this agent in patients undergoing PCI. 66,67 While the benefit of bivalirudin over UFH alone in reducing bleeding complications has been shown, this benefit has been challenged by the additional consistent risk of stent thrombosis. This stent thrombosis risk was considered by the task force in making its treatment recommendations.…”

What is the best anticoagulant therapy during primary percutaneous coronary intervention for acute myocardial infarction?

“…28 In this meta-analysis, the risk of 30-day MACE was higher with UFH (RR = 1.49), bivalirudin (RR = 1.34), and fondaparinux (RR = 1.78) as compared with UFH + GPI. LMWH + GPI had the greatest treatment efficacy followed by UFH + P2Y 12 inhibitors (~87%), primarily radial access (~80%), and employing selective rather than uniform GPI, administration to similar extent in both arms (~13%).…”

“…Bivalirudin monotherapy was associated with a lower major bleeding risk compared with UFH + GPI (RR = 0.47) or UFH (RR = 0.58). 28 In another meta-analysis, the 5 randomized trials discussed above (HORIZONS-AMI, BRAVE-4, BRIGHT, HEAT PPCI, and EUROMAX) involving ~10000 patients with STEMI, bivalirudin therapy as compared with heparin therapy was associated with a significant reduction in protocol--defined major bleeding (odds ratio [OR] = 0.64; P <0.0001) or Thrombolysis in Myocardial Infarction major bleeding (OR = 0.62; P = 0.001), but no difference in overall all-cause mortality (OR = 0.88; P = 0.17), 30-day mortality (OR = 0.90; P = 0.40), or overall MI (OR = 0.86; P = 0.18). Bivalirudin was associated with similar overall definite/probable stent thrombosis (OR = 1.18; P = 0.22) but higher rates of 30-day MI (OR = 1.40; P = 0.04) and 30-day definite/probable stent thrombosis (that included acute stent thrombosis) (OR = 1.64; P = 0.004).…”