Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events

Collet, Jean‐Philippe; Montalescot, Gilles; Agnelli, Giancarlo; Werf, Frans Van de; Gurfinkel, Enrique P.; López‐Sendón, José; Laufenberg, Christopher V.; Klutman, Martin; Gowda, Neelam; Gulba, Dietrich C.

doi:10.1093/eurheartj/ehi337

Cited by 66 publications

(47 citation statements)

References 26 publications

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“…Excessive doses of drugs, especially in elderly patients or those suffering from renal failure, may also lead to an increased risk of bleeding (38) . These risk factors have been confi rmed in other reports, (39) . It is remarkable that a steep increase in bleeding risk is observed for moderate to mild levels of renal dysfunction.…”

Section: Bleeding In Acute Coronary Syndromesupporting

confidence: 76%

Anti-thrombotic therapy in non-ST elevation acute coronary syndrome KAA Fox

Fox

2017

SAHJ

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Platelet activation and thrombin generation are implicated in the pathogenesis of acute coronary syndrome, in the development of major thrombotic complications of the condition, and in the interventional treatments to treat obstructive coronary lesions (principally, percutaneous coronary intervention). Despite treatment with aspirin and heparin there remained a clinically important risk of thrombotic complications both in hospital and following discharge. Newer anti-platelet therapies (thienopyridines and glycoprotein IIb/IIIa inhibitors) reduced platelet mediated complications, but with an increase in bleeding risk. Similarly, low molecular weight heparins reduced thrombotic complcations but with a modest increase in bleeding. Newer anti-thrombins (anti Xa inhibitors and direct thrombin inhibitors) demonstrate similar or improved effi cacy, but with reduced bleeding. Insuffi cient attention has been paid to reducing bleeding complications and recent evidence suggests that major bleeding conveys a signifi cant increase in the risk of death. In addition, clearance of antithrombotic agents by the kidney is impaired in those with renal dysfunction, including in the elderly, and this may contribute to the risks of bleeding. In unselected populations with non-ST elevation ACS more than half the population have a creatinine clearance below 60 ml/min. Reducing the doses of anti-thrombins in patients with renal dysfunction may reduce bleeding complications. The optimal anti-thrombotic strategy in patients with non-ST elevation ACS requires the clinician to consider not only the risk of the patient for thrombotic complcations, but also the hazards of bleeding. Newer anti-thrombotic agents, for the fi rst time, offer potential benefi ts in bleeding risk with similar or improved effi cacy. ABSTRACT4 ARTICLE 1 5 the irreversible nature of the ADP antagonism, current guidelines suggest that clopidogrel should be withheld for 5 days prior to CABG surgery (7) .In candidates for very urgent CABG a small molecule glycoprotein IIb/IIIa inhibitor (eptifi batide or tirofi ban) can be used prior to surgery (8) .In non-ST segment elevation ACS, the ESC and AHA/ACC guidelines recommend at least 9 and up to12 months' treatment with clopidogrel (8) .Longer term treatment in patients with a spectrum of vascular risk was examined in the large scale CHARISMA trial (9) . Overall, the results do not support long-term therapy with clopidogrel in addition to aspirin. Those with ischaemic events (MI, stroke or peripheral vascular events) appear to benefi t more than patients simply at high vascular risk (9) . Glycoprotein IIb/IIIa receptor antagonistsThe glycoprotein IIb/IIIa receptor plays a key role in platelet aggregation through linkages involving fi brinogen or von Willebrand Factor. Intravenous glycoprotein IIb/IIIa receptor antagonists have been extensively tested in patients with acute coronary syndromes and in a meta-analysis of all the major randomised trials the absolute risk reduction for death or myocardial infarction at 30 d...

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Section: Bleeding In Acute Coronary Syndromesupporting

confidence: 76%

Anti-thrombotic therapy in non-ST elevation acute coronary syndrome KAA Fox

Fox

2017

SAHJ

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“…An analysis of GRACE evaluated the association of CKD with outcomes among patients with non-ST-segment-elevation ACS treated with either LMWH or UFH. 66 Based on CrCl <30 mL/min (43 patients received UFH and 37 received LMWH), 30 to 59 mL/min (70 patients received UFH and 49 received LMWH), and >60 mL/min (50 patients received UFH and 45 received LMWH), results of this analysis showed that LMWH was associated with lower 30-day mortality (4.2% versus 6.2%; P<0.0001) and a lower rate of in-hospital major bleeds (2.1% versus 3.3%; P=0.0006), but the mortality and in-hospital major bleeding benefit was not statistically significant in the group with CrCl <30 mL/min.…”

Section: Enoxaparinmentioning

confidence: 99%

Pharmacotherapy in Chronic Kidney Disease Patients Presenting With Acute Coronary Syndrome

Washam¹,

Herzog²,

Beitelshees³

et al. 2015

Circulation

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“…Bleeding rates were significantly lower with low-molecularweight heparin plus GPIIb/IIIa inhibitors than with unfractionated heparin plus GPIIb/IIIa inhibitors. 108 Bivalirudin provides comparable suppression of ischemic events with a decrease in bleeding events compared with heparin and GPIIb/IIIa inhibition. 109 -111 Among 5710 patients referred to PCI from the Second Randomized Evaluation in PCI Linking Bivalirudin to Reduced Clinical Events (REPLACE-2) study, stage 3 to 4 CKD was associated with increased ischemic events, bleeding complications, and 1-year mortality.…”

Section: Anticoagulant Therapymentioning

confidence: 99%