hirudin and Gastrointestinal-Hemorrhage

We assessed the incidence, predictors, and outcomes of gastrointestinal bleeding (GIB) in patients with acute coronary syndromes (ACS).. GIB is a potential hemorrhagic complication in patients with ACS treated with antithrombotic and/or antiplatelet medications. The clinical outcomes associated with GIB in this setting have not been systematically studied.. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 13,819 patients with moderate- and high-risk ACS, enrolled at 450 centers in 17 countries between August 2003 and December 2005, were randomized to the open-label use of 1 of 3 antithrombin regimens (heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin monotherapy).. GIB within 30 days occurred in 178 patients (1.3%). Older age, baseline anemia, longer duration of study drug administration before angiogram, smoking, ST-segment deviation>or=1 mm, and diabetes were identified as independent predictors of GIB. On multivariable analysis, GIB was strongly associated with 30-day all-cause mortality (hazard ratio [HR]: 4.87 [interquartile range (IQR) 2.61 to 9.08], p<0.0001), cardiac mortality (HR: 5.35 [IQR 2.71 to 10.59], p<0.0001), and composite ischemia (HR: 1.94 [IQR 1.14 to 3.30], p=0.014), as well as with 1-year all-cause mortality (HR: 3.97 [IQR 2.64 to 5.99], p<0.0001), cardiac mortality (HR: 3.77 [IQR 2.14 to 6.63], p<0.0001), myocardial infarction (HR: 1.74 [IQR 1.01 to 3.02], p=0.047), and composite ischemia (HR: 1.90 [IQR 1.37 to 2.64], p=0.0001). Patients who experienced GIB had significantly higher rates of stent thrombosis compared with patients without GIB (5.8% vs. 2.4%, p=0.009).. GIB is a serious condition in the scenario of ACS and is independently associated with mortality and ischemic complications.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Coronary Artery Bypass; Female; Gastrointestinal Hemorrhage; Heparin; Hirudins; Humans; Incidence; Ischemia; Length of Stay; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Risk Assessment; Sex Factors; Stents; Thrombosis; Ticlopidine

Hirudin is a selective thrombin inhibitor with strong anticoagulant properties which could elicit gastro-intestinal bleeding. A double-blind cross-over study of the effects of hirudin on gastro-intestinal bleeding was therefore conducted on 12 healthy, consenting males. After labelling erythrocytes with 51Cr and returning them intravenously, stools were collected for 2 days to measure radioactivity and hence baseline faecal blood loss. After injection of hirudin or placebo stools were collected for 3 days. Partial thromboplastin time was measured sequentially after medication with hirudin or placebo. This procedure was repeated after injection of the alternate medication 1 week later. Hirudin was tolerated well. Mean faecal blood loss associated with hirudin was slightly higher than with placebo (1.63 ml vs 1.15 ml over 3 days; 95% confidence interval for the difference between hirudin and placebo was -0.68 to 1.63) but these differences are clinically irrelevant. After hirudin injection PTT was elevated to about twice the baseline values but returned to baseline within 12 h after the last hirudin injection.

Topics: Adolescent; Adult; Double-Blind Method; Gastrointestinal Hemorrhage; Hirudins; Humans; Male; Occult Blood; Partial Thromboplastin Time; Thrombin

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

Although bivalirudin use in percutaneous coronary intervention (PCI) results in less bleeding compared to unfractionated heparin (UFH) use, its safety in patients undergoing rotational atherectomy (RA) is unknown.. A cohort of 503 patients who underwent PCI with RA from 2000 to 2009 was studied. Patients receiving bivalirudin (n = 322) were compared to those (n = 181) treated with UFH +/- glycoprotein IIb/IIIa inhibitor (GPI) as PCI anticoagulation. Safety was assessed by the frequency of major bleeding (hematocrit drop > or =15%, intracerebral or gastro-intestinal bleeding) and need for transfusion. Efficacy was assessed by a composite end-point of in-hospital death, Q wave myocardial infarction (MI) or urgent coronary artery bypass graft (CABG).. Those in the bivalirudin group were older, more hypertensive, and had greater body mass index. The UFH group was more likely to have prior MI, prior CABG, and an acute coronary syndrome at baseline. GPI was used in 93 patients (52%) of the UFH group. No difference was found between groups for the composite of death/Q wave MI/urgent CABG (1.9% vs. 1.7%, respectively, in bivalirudin vs. UFH group; P = 0.2). The frequency of major bleeding (2.2% vs. 1.7%; P = 0.8) or transfusion (5.6% vs. 8.7%; P = 0.9) was also similar between groups. After adjustment, bivalirudin use was not associated with a reduction in death/Q wave MI/urgent CABG, major bleeding, or transfusion compared to UFH.. Bivalirudin use seems to be as safe and effective as UFH in patients undergoing RA.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Atherectomy, Coronary; Body Mass Index; Cohort Studies; Confidence Intervals; Coronary Artery Disease; District of Columbia; Female; Gastrointestinal Hemorrhage; Hematocrit; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Male; Multivariate Analysis; Odds Ratio; Peptide Fragments; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Propensity Score; Recombinant Proteins; Registries; Retrospective Studies; Risk Factors; Stents

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Atherectomy, Coronary; Coronary Artery Disease; District of Columbia; Gastrointestinal Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Treatment Outcome

Gastrointestinal bleeding (GIB) complicating percutaneous coronary intervention (PCI) results in high mortality, but clinical factors associated with and long-term outcomes of GIB are poorly understood. We sought to examine clinical and procedural factors associated with GIB complicating PCI. We also examined the impact of GIB on 30-day mortality and 1-year major adverse cardiac events (MACEs). Patients undergoing PCI from January 2000 to January 2010 were retrospectively analyzed for the occurrence of in-hospital GIB. Multivariable logistic regression and Cox proportional hazards regression were used to identify predictors of in-hospital GIB and 30-day mortality. Landmark analysis of patients surviving to hospital discharge was performed to assess the impact of GIB on 1-year MACEs. Of 20,621 patients who underwent PCI, 147 (0.72%) who developed in-hospital GIB were identified. Variables associated with increased risk of GIB included older age, shock, acute myocardial infarction, chronic renal insufficiency, lower baseline hematocrit, and glycoprotein IIb/IIIa inhibitors; bivalirudin decreased the risk. Unadjusted 30-day mortality rate of patients with GIB was 20.5% compared to 2.4% of patients without GIB. After multivariable adjustment, GIB and shock (and an interaction between the 2) were the most important correlates of 30-day mortality. In the population surviving to discharge, however, GIB was not associated with adjusted mortality or MACEs. In conclusion, GIB complicating PCI has a dramatic impact on 30-day mortality, and bivalirudin was associated with lower rates of GIB.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Antithrombins; Blood Transfusion; Drug-Eluting Stents; Female; Follow-Up Studies; Gastrointestinal Hemorrhage; Hirudins; Humans; Incidence; Inpatients; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Postoperative Hemorrhage; Prognosis; Recombinant Proteins; Retrospective Studies; Risk Factors; Survival Rate; Time Factors; United States