Lower Rates Of Major Bleeding Research Articles

The Potential Role of Edoxaban in Stroke Prevention Guidelines

With the emergence of edoxaban, the oral factor Xa inhibitors now appear consolidated as the dominant class of novel oral anticoagulants (NOACs) for stroke prevention in non-valvular atrial fibrillation (AF). The oral factor Xa inhibitors do not require an adequate time in therapeutic range to be effective, presenting a potential advantage over the vitamin K antagonists (VKAs). Guidelines are changing to reflect the increased choice of anticoagulants and as clinicians move away from the VKAs towards the relative safety and efficacy of NOACs, they must consider which one offers the best therapy for their patient. The ENGAGE-AF study was the latest phase III trial to report on the safety and efficacy of a new factor Xa inhibitor relative to warfarin. Both edoxaban 60mg once daily, and edoxaban 30mg once daily were found to be non-inferior compared to warfarin for the prevention of ischaemic stroke and systemic embolism, being associated with significantly lower rates of major bleeding, intracranial haemorrhage and cardiovascular death. A two-tiered dosing option may present clinicians with a further element of choice for the individual patient.

Antithrombotic Strategy in Non–ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention: Insights From the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry

The aim of this study was to examine the use of and outcomes associated with antithrombotic strategies in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI). A variety of antithrombotic strategies have been tested in clinical trials for NSTEMI patients treated with PCI. Antithrombotic strategies for NSTEMI patients undergoing PCI at 217 ACTION (Acute Coronary Treatment and Intervention Outcomes Network) hospitals from January 1, 2007, to December 31, 2007, (n = 11,085) were classified into commonly observed antithrombotic groups: heparin alone (Hep alone; low-molecular-weight heparin or unfractionated heparin), bivalirudin alone (Bival alone), heparin with glycoprotein IIb/IIIa inhibitors (Hep/GPI), and bivalirudin with GPI (Bival/GPI). Baseline characteristics are shown across treatment groups. In addition, unadjusted and adjusted rates of in-hospital major bleeding and death are shown. The standard strategy used was Hep/GPI (64%), followed by Hep or Bival alone (28%), and Bival/GPI (8%). Patients who received Hep or Bival alone were older with more comorbidities, higher baseline bleeding and mortality risk, and lower peak troponin. Compared with patients who received Hep/GPI , those who received Hep alone and Bival alone had lower rates of major bleeding (adjusted odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.42 to 0.65; adjusted OR: 0.48; 95% CI: 0.39 to 0.60; respectively), yet only patients who received Bival alone had lower mortality (adjusted OR: 0.39; 95% CI: 0.21 to 0.71). NSTEMI patients undergoing PCI are more likely to receive Bival or Hep alone when at higher baseline bleeding risk than when at lower baseline bleeding risk. Despite higher baseline risk, those receiving Bival or Hep alone had less bleeding.

Abstract 4949: Bleeding and Ischemic Complications in Patients With Acute Coronary Syndromes and Chronic Kidney Disease in Relation to Different Glycoprotein IIb/IIIa Inhibitors: Analysis From the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) Trial

Objectives: We evaluated outcomes of moderate- to high-risk patients (pts) with acute coronary syndromes (ACS) and chronic kidney disease (CKD) receiving alternative antithrombotic therapy in the ACUITY trial. Background : Knowledge of safety and efficacy of different antithrombotic medications is important considering the choice of therapy in pts with ACS having CKD. Methods: In the ACUITY trial, 2468(19.1%) pts had CKD (baseline creatinine clearance <60 ml/min) and 10,472 (80.9%) pts had preserved renal function. Pts were randomized to receive 1 of 3 antithrombotic regimens including heparin + glycoprotein IIb/IIIa inhibitors (H + GPI), bivalirudin (Biv) plus a GPI, or Biv alone. Type of GPI (abciximab or a small-molecule GPI [eptifibatide and tirofiban]) was at operator’s discretion. Dosages were adjusted for renal function. Patients treated with Biv + a GPI were excluded from this analysis. Results : 30-day outcomes are presented in the table . Regardless of antithrombotic regimen, CKD was associated with remarkable increase in ischemic events, and more than 2-fold increase in rates of major bleeding. In pts with CKD, there were no significant differences in rates of major bleeding among those who received H +a small-molecule GPIs vs abciximab (p=0.7). In pts with CKD, Biv monotherapy compared to H +a small-molecule GPIs resulted in remarkably lower rates of major bleeding (p=0.003) without increase in rates of ischemic events. Bivalirudin monotherapy resulted in non significantly lower rates of bleeding than H+abciximab (p=0.3). Conclusions: CKD is associated with higher rates of 30-day ischemic events and major bleeding. Rates of major bleeding did not differ significantly between small-molecule GPIs and abciximab when used in conjunction with heparin in pts with ACS and baseline CKD. In pts with or without CKD, bivalirudin monotherapy resulted in the lowest rates of hemorrhagic events without increasing risk of ischemic complications.

Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial

In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up. Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0.75 mg/kg intravenous bolus followed by 1.75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200-250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal from the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966. 1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15.6%vs 18.3%, hazard ratio [HR] 0.83, 95% CI 0.71-0.97, p=0.022), as a result of a lower rate of major bleeding in the bivalirudin group (5.8%vs 9.2%, HR 0.61, 0.48-0.78, p<0.0001). The rate of MACE was similar between groups (11.9%vs 11.9%, HR 1.00, 0.82-1.21, p=0.98). The 1-year rates of cardiac mortality (2.1%vs 3.8%, HR 0.57, 0.38-0.84, p=0.005) and all-cause mortality (3.5%vs 4.8%, HR 0.71, 0.51-0.98, p=0.037) were lower in the bivalirudin group than in the control group. In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI. Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.

Efficacy and Safety Profile of Dabigatran Etexilate for the Prevention of Venous Thromboembolism in Moderately Renally Impaired Patients after Total Knee or Hip Replacement Surgery.

Dabigatran etexilate (Pradaxa®), an oral direct thrombin inhibitor, was recently approved in Europe for the prevention of venous thromboembolism (VTE) in patients undergoing elective total knee replacement or total hip replacement surgery. In phase III clinical trials two doses were studied: 220 mg once daily and 150 mg once daily. A post hoc pooled analysis was performed in patients with moderate renal impairment (GFR ≥30 and < 50 mL/min). The efficacy and safety of 220 mg and 150 mg dabigatran etexilate were compared with 40 mg subcutaneous enoxaparin. The analysis included data from the RE-MODEL (Eriksson BI et al. J Thromb Haemost 2007; 5: 2178–2185) and the RE-NOVATE (Eriksson BI et al. Lancet 2007; 370: 949–956) pivotal trials. The primary efficacy endpoint in both studies and this analysis was total VTE and all cause mortality, similarly, the key pre-specified secondary efficacy endpoint was major VTE and VTE-related mortality. Bleeding events (primary safety endpoint) were blindly adjudicated and categorized as major bleeding events (MBE) including surgical site bleeds. Of the patients treated with 220 mg dabigatran etexilate (1825), 150 mg dabigatran etexilate (1866) and 40 mg enoxaparin (1848), 337 patients had moderate renal impairment. 68% of these patients were evaluable for the primary efficacy endpoint, 242 were evaluable for the secondary efficacy endpoint, and all patients were available for safety and bleeding. The incidence of total VTE and all cause mortality was 17.7%, 23.5% and 27.8% in the 220 mg, 150 mg dabigatran etexilate and enoxaparin groups respectively. When the secondary endpoint was analyzed a similar trend, with a descriptive statistical significance for a lower event rate in the 220 mg group, was seen (see table). MBEs occurred in 6 of 113 patients in the 220 mg dabigatran treated group (5.3%), in none of the patients in the 150 mg dabigatran etexilate treated group (0.0%), and in 6 of 128 patients receiving 40 mg enoxaparin (4.7%). Notably, 3 of the 6 major bleeding events in the 220mg group started before any oral dabigatran etexilate treatment. In conclusion, in patients with moderate renal impairment undergoing hip or knee replacement surgery, oral 150 mg dabigatran etexilate showed similar efficacy compared with subcutaneous 40 mg enoxaparin, with apparently lower rates of major bleeding. Because of the potential negative impact of major bleeding especially in this population the 150 mg once daily dabigatran etexilate dose is currently recommended for this group.Table 1: Efficacy and bleeding endpoints in patients with moderate renal impairment (p-value from Fisher's exact test compared to Enoxaparin)EventDabigatran etexilate 220 mg qdDabigatran etexilate 150 mg qdEnoxaparin 40 mg qdTotal VTE and all cause mortality17.7% (14/79) (CI 10.0%–27.9%) p=0.1423.5% (16/68) (CI 14.1%–35.4%) p=0.5927.8% (25/90) (CI 18.9%–38.2%)Major VTE and VTE related mortality1.2% (1/83) (CI 0.0%–6.5%) p=0.044.3% (3/70) (CI 0.9%–12.0%) p=0.359.0% (8/89) (CI 4.0%–16.9%)MBE5.3% (6/113) (CI 2.0%–11.2%) p=0.820.0% (0/96) (CI 0.0–3.8%) p=0.044.7% (6/128) (CI 1.7%–9.9%)

Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study

In the setting of percutaneous coronary intervention (PCI), due to a paucity of data, the optimal dose of aspirin is uncertain. We evaluated the safety of different doses of aspirin after PCI. In the PCI-CURE study, 2658 patients with acute coronary syndromes undergoing PCI were stratified into three aspirin dose groups >/=200 mg (high, n = 1064), 101-199 mg (moderate, n = 538), and </=100 mg (low, n = 1056). For efficacy, the moderate- (7.4%) and high-dose groups (8.6%) had similar rates of cardiovascular death, myocardial infarction, or stroke compared with the low-dose group (7.1%). For safety, major bleeding was increased with high-dose aspirin [3.9, 1.5, and 1.9% in the high-, moderate-, and low-dose groups; hazard ratio (HR) of high vs. low dose 2.05 (95% CI 1.20-3.50, P = 0.009]. The net adverse clinical events (death, MI, stroke, major bleeding) favoured low-over high-dose aspirin (8.4 vs. 11.0%, HR 1.31, 95% CI 1.00-1.73 P = 0.056). In this large observational analysis of patients undergoing PCI, low-dose aspirin appeared to be as effective as higher doses in preventing ischaemic events but was also associated with a lower rate of major bleeding and an improved net efficacy to safety balance.

Letter Regarding Article by Hylek et al, “Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation”

HomeCirculationVol. 116, No. 20Letter Regarding Article by Hylek et al, “Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter Regarding Article by Hylek et al, “Major Hemorrhage and Tolerability of Warfarin in the First Year of Therapy Among Elderly Patients With Atrial Fibrillation” Ayumu Ono and Ichiko Kawamura Toshiro Fujita Ayumu OnoAyumu Ono Otsuki Hospital, Kochi, Japan Search for more papers by this author and Ichiko KawamuraIchiko Kawamura Otsuki Hospital, Kochi, Japan Search for more papers by this author Toshiro FujitaToshiro Fujita Department of Internal Medicine, University of Tokyo, Tokyo, Japan Search for more papers by this author Originally published13 Nov 2007https://doi.org/10.1161/CIRCULATIONAHA.107.727255Circulation. 2007;116:e538To the Editor:We read with great interest the recent publication by Hylek et al1 in which they concluded that the rate of bleeding complications during warfarin therapy was substantially higher than previously reported in elderly patients with atrial fibrillation. They emphasize that published rates of major hemorrhage derived from younger noninception cohorts underestimate the bleeding that occurs in clinical practice, and the higher rate of bleeding in their study is attributable to the higher risk of bleeding in the early phase of warfarin therapy and the advanced age of their study subjects. However, the results are not necessarily generalizable to other clinical settings, because the patients enrolled in this cohort have more risk factors for bleeding than representative patients receiving warfarin in clinical practice.First, the patients received aspirin combined with warfarin at a remarkably higher rate (40%) than reported previously.2 The frequent use of aspirin may contribute to the higher rate of bleeding in patients receiving warfarin, because previous studies have demonstrated that combined anticoagulant-antiplatelet use increases bleeding risk without additive prevention of thromboembolic events. In recent trials comparing ximelagatron and warfarin, the combination therapy of aspirin with either ximelagatron or warfarin did not reduce the risk of stroke, systemic embolism, or myocardial infarction, but the addition of aspirin to warfarin or ximelagatron was associated with increased risk of bleeding, which was especially obvious when aspirin and warfarin were combined.3Second, the study included patients receiving warfarin in spite of their potential contraindications for anticoagulation, such as active malignancy, prior bleeding, and dementia. In general, patients with risk factors for bleeding should be considered as ineligible for anticoagulation.When physicians use warfarin in eligible patients at high risk but without contraindications, thromboembolism-associated atrial fibrillation can be adequately and safely prevented even in elderly patients. In fact, recent inception cohorts in which warfarin was newly started in elderly patients without contraindications or concomitant use of antiplatelets reported lower rates of major bleeding (<3% per 100 person-years)4,5 than the study by Hylek et al (7.2% per 100 person-years).1DisclosuresNone. References 1 Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation. 2007; 115: 2689–2696.LinkGoogle Scholar2 Fang MC, Stafford RS, Ruskin JN, Singer DE. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med. 2004; 164: 55–60.CrossrefMedlineGoogle Scholar3 Gorelick PB. Combining aspirin with oral anticoagulant therapy: is this a safe and effective practice in patients with atrial fibrillation? Stroke. 2007; 38: 1652–1654.LinkGoogle Scholar4 Kalra L, Yu G, Perez I, Lakhani A, Donaldson N. Prospective cohort study to determine if trial efficacy of anticoagulation for stroke prevention in atrial fibrillation translates into clinical effectiveness. BMJ. 2000: 320; 1236–1239.CrossrefMedlineGoogle Scholar5 Ruiz Ortiz M, Romo Penas E, Franco Zapata MF, Mesa Rubio D, Anguita Sanchez M, Lopez Granados A, Arizon del Prado JM, Valles Belsue F. Oral anticoagulation in patients aged 75 years or older with chronic non-valvar atrial fibrillation: effectiveness and safety in daily clinical practice. Heart. 2005; 91: 1225–1226.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Pani A, Pastori D, Senatore M, Romandini A, Colombo G, Agnelli F, Scaglione F and Colombo F (2020) Clinical and pharmacological characteristics of elderly patients admitted for bleeding: impact on in-hospital mortality, Annals of Medicine, 10.1080/07853890.2020.1808238, 52:7, (413-422), Online publication date: 2-Oct-2020. Bonnet-Zamponi D, Aumont M, Comets E, Bruhat C, Chauveheid M, Duval X, Huisse M, Diquet B, Berrut G, Mentre F, Delpierre S and Legrain S (2011) Heparin Bridging Therapy and Bleeding Events in Octogenarian Inpatients with Atrial Fibrillation Starting Anticoagulation: Results of an Ancillary Study, Journal of the American Geriatrics Society, 10.1111/j.1532-5415.2011.03649.x, 59:11, (2174-2178), Online publication date: 1-Nov-2011. November 13, 2007Vol 116, Issue 20 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.107.727255PMID: 17998467 Originally publishedNovember 13, 2007 PDF download Advertisement SubjectsAnticoagulantsArrhythmiasCerebrovascular Disease/Stroke

Influence of Renal Function on the Efficacy and Safety of Fondaparinux Relative to Enoxaparin in Non–ST-Segment Elevation Acute Coronary Syndromes

A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. Subgroup analysis of a randomized, controlled trial. Patients presenting to the hospital with non-ST-segment elevation ACS. 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.

Low-molecular-weight heparin, bemiparin, in the outpatient treatment and secondary prophylaxis of venous thromboembolism in standard clinical practice: the ESFERA Study

The objective of this study is to assess the clinical and economic outcomes associated with outpatient treatment and secondary prophylaxis of acute venous thromboembolism (VTE) with a low-molecular-weight heparin, bemiparin. This study was designed as an open-label, multicentre, prospective, cohort study in standard clinical practice. Sixty-three investigators from 54 Spanish centres participated in the study. Five hundred eighty-three patients (434 outpatients and 149 inpatients) with acute VTE were followed up for 98 days (median). Outcome measures were costs and adverse events during initial VTE treatment with bemiparin (outpatient vs. inpatient cohorts) and long-term treatment [bemiparin (BEM) vs. vitamin K antagonists (VKA) cohorts]. Mean total costs per patient were lower in the outpatient cohort as compared with those in the inpatient cohort (1206 vs. 5191 euros; difference = -3985 euros; p < 0.001), with similar rates of adverse events (5.1 outpatient vs. 7.4% inpatient; p = 0.196) over 98 days. Mean total costs per patient were similar in the BEM/BEM and BEM/VKA cohorts (3616 vs. 3831 euros; difference = -215 euros; p = 0.412), but patients on long-term bemiparin treatment had lower rates of major bleeding (0.4 vs. 1.7%; p = 0.047), minor bleeding (1.8 vs. 6%; p = 0.032) and total adverse events (2.9 vs. 9.5%; p = 0.007) than patients in the BEM/VKA cohort. Outpatient management of VTE with bemiparin in selected patients resulted in significant cost-savings compared to inpatient treatment, while maintaining effectiveness and safety. Bemiparin may be a safer and cost-neutral alternative to VKA for long-term treatment of VTE.

Glycoprotein IIb-IIIa receptor inhibition with eptifibatide in percutaneous intervention for symptomatic peripheral vascular disease: The circulate pilot trial

The benefits of glycoprotein (GP) IIb-IIIa inhibitors in percutaneous coronary intervention are well established, but the experience with these agents in the setting of peripheral interventions is limited. In this single-center pilot trial, the safety and feasibility of adjunctive treatment with the GP IIb-IIIa inhibitor eptifibatide (INTEGRILIN, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, and Schering-Plough Corporation, Kenilworth, New Jersey) was evaluated in 85 patients undergoing percutaneous transluminal angioplasty or stenting for severe claudication or critical limb ischemia. Eptifibatide treatment was safe, with low rates of major bleeding (3.5%) and thrombocytopenia (1.2%); one patient developed a post-procedure compartment syndrome requiring fasciotomy. The procedure was technically successful (defined as <30% residual stenosis or >50% increase in vessel diameter) in 84 of 85 (98.8%) patients. None of the patients required target vessel revascularization (TVR) during hospitalization, and only 1 patient (1.2%) required TVR within 30 days. These results demonstrate that adjunctive use of eptifibatide during percutaneous peripheral intervention is safe and supports further studies to establish the potential efficacy of GP IIb-IIIa inhibitors in this setting.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary interventionResults from the REPLACE-2 trial

The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p &lt; 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p &lt; 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: Results from the REPLACE-2 trial

The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Guidelines for Stroke Prevention in Patients with Atrial Fibrillation

Atrial fibrillation (AF) is a major independent risk factor for stroke. AF is most commonly associated with nonvalvular cardiovascular disease and is especially frequent among the elderly. The annual risk for stroke in patients with AF is approximately 5% with a wide range depending on the presence of additional risk factors. For patients who cannot successfully be converted and maintained in normal sinus rhythm (NSR), antithrombotic therapy is an effective method for preventing stroke. The 2 drugs which are indicated for stroke prophylaxis in patients with AF are warfarin and aspirin. For primary prevention, warfarin reduces the risk of stroke approximately 68%. Aspirin therapy is less effective, resulting in a 20 to 30% risk reduction. Combination therapy with aspirin and low intensity warfarin adjusted to an International Normalised Ratio (INR) of 1.2 to 1.5 has not been shown to be superior to standard intensity warfarin with a target INR of 2.0 to 3.0. In patients with AF and a prior history of stroke or transient ischaemic attack (TIA), the absolute risk reduction with warfarin is even greater because of the high risk of stroke in this population. In contrast, aspirin has not been shown to significantly reduce the risk of stroke in patients with AF when used for secondary prevention. When appropriately managed, warfarin is associated with a low risk of major bleeding. In controlled trials of highly selected patients, the annual rate of intracranial haemorrhage (ICH) with warfarin was approximately 0.3%. Studies have shown that specialty anticoagulation clinics can achieve similar low rates of major bleeding. However, these results cannot be extrapolated to the general population. Factors which have been identified as predictors of bleeding include advanced age, number of medications and most importantly, the intensity of anticoagulation. INR values above 4.0 have been associated with an increased risk of major bleeding while values below 2.0 have been associated with thrombosis. Slow careful dosage titration, regular laboratory monitoring and patient education can substantially reduce the risk of complications. In patients with AF, antithrombotic therapy has been shown to be cost effective. For high risk patients, warfarin is the most cost-effective therapy, provided the risks for bleeding are minimised. In contrast, aspirin is the most cost-effective agent for low risk patients. Current practice guidelines for stroke prophylaxis recommend warfarin (target INR 2.5: range 2.0 to 3.0) for AF patients at high risk for stroke including those over 75 years of age or younger patients with additional risk factors. Aspirin should be reserved for low risk patients or those unable to take warfarin. Although these recommendations are strongly supported by the clinical trial evidence, studies show that many patients are not receiving appropriate antithrombotic therapy. In particular, warfarin is underutilised in high risk elderly patients. Additional studies are needed to identify barriers that prevent implementation of the clinical trial findings into clinical practice.