Platelets function assessment in patients qualified for cardiac surgery - clinical problems and a newer diagnostic possibilities.

BACKGROUND: As the incidence of cardiovascular diseases increases, the use of antiplatelet therapy is widely recognized. This presents clinicians with the challenge of balancing the risk of thrombotic and bleeding complications. Platelet dysfunction is one of the causes of postoperative bleedings and their etiology is not fully understood. Platelets receptors point-of-care investigation is of a remarkable value in assessing patients risk of bleeding. Reliable assessment of platelet function can improve treatment. The aim of this study was to evaluate the activity of platelet receptors in patients qualified for cardiac surgery, taking into account organ dysfunctions and pharmacological therapy applied in these patients. METHODS: Seventy-one cardiac surgical patients were analyzed before surgery using multiple electrode aggregometry with the use of the ADP test and ASPI test. The cut-off values were determined based on the manufacturer's recommendations. Patients were divided into four groups: Group I (33/71 patients, without platelet dysfunctions), Group II (6/71 patients, ADP < 710 AU x min), Group III (13/71 patients, ASPI < 570 AU x min) and Group IV (19 / 71 patients, ADP < 710 AU x min and ASPI < 570 AU x min). Biochemical data defining the efficiency of the liver and kidneys, the list of preoperative drugs used and the requirement for transfusion throughout the study group were collected. RESULTS: The study group included 41 males (57.7%) and 30 females (42.3%), mean age 66 years. The majority of patients (94.4%) had platelet counts within the normal range, but platelet function was impaired in more than half of the studied patients (53.5%). No relationship was found between the biochemical markers of the kidneys and liver and the function of the ADP and ASPI receptors, while receptors activities were related (rs = 0.72, p < 0.001), and both associated with platelet count (rs = 0.55, p < 0.001 and rs = 0.42, p < 0.001, respectively). Platelet receptors activity was not related to the postoperative need for any type of transfusion as well as the applied preoperative pharmacological therapy. CONCLUSIONS: Early identification of patients at high risk of bleeding, using point-of-care platelet function assessment tests, enables a targeted therapeutic pathway. Due to the variety of factors affecting the activity of platelets, finding a specific cause of this pathology is extremely difficult. According to our study, the correlation between platelet receptor disorders and mild to moderate liver and kidney injury has not been demonstrated. However, platelet receptors dysfunction has been shown to be associated with a decreased number of platelets.

The comparative safety of abciximab versus eptifibatide in patients on dialysis undergoing percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).

OBJECTIVES: We sought to evaluate the patterns of use and outcomes associated with eptifibatide and abciximab administration among dialysis patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Contraindicated medications are frequently administered to dialysis patients undergoing PCI often resulting in adverse outcomes. Eptifibatide is a glycoprotein IIb/IIIa inhibitor that is often used during PCI and is contraindicated in dialysis. METHODS: We included dialysis patients who underwent PCI from January 2010 to September 2015 at 47 hospitals in Michigan. We compared outcomes between patients who received eptifibatide compared with abciximab. Both groups required concurrent treatment with unfractionated heparin only. In-hospital outcomes included repeat PCI, bleeding, major bleeding, need for transfusion, and death. Optimal full matching was used to adjust for non-random drug administration. RESULTS: Of 177 963 patients who underwent PCI, 4303 (2.4%) were on dialysis. Among those, 384 (8.9%) received eptifibatide and 100 (2.3%) received abciximab. Prior to matching, patients who received eptifibatide had higher pre-procedural hemoglobin levels (11.3 g/dL vs. 10.7 g/dL; P < 0.001) and less frequently had a history of myocardial infarction (36.5% vs. 52.0%; P = 0.005). After matching, there were no significant differences in in-hospital outcomes between eptifibatide and abciximab including transfusion (aOR: 1.15; 95%CI: 0.55-2.40; P = 0.70), bleeding (1.47; 0.64-3.40; P = 0.36), major bleeding (4.68; 0.42-52.3; P = 0.21), repeat PCI (0.38; 0.03-4.23; P = 0.43), and death (1.53; 0.2-9.05; P = 0.64). CONCLUSIONS: Despite being contraindicated in dialysis, eptifibatide was used approximately 3.5 times more frequently than abciximab among dialysis patients undergoing PCI but was associated with similar in-hospital outcomes.

Xanthohumol from hop cones (Humulus lupulus L.) prevents ADP-induced platelet reactivity.

Hop cones (Humulus lupulus L.), very rich source of phenolic compounds, possessing anticancer, antioxidant and anti-inflammatory activities, are considered as beneficial diet ingredients improving human health. In this study, the antiplatelet action of xanthohumol (XN), the principal flavonoid in hop cones, was investigated. XN significantly attenuated ADP-induced blood platelet aggregation (97.2 ± 35.7 AU for 6 µg/ml of XN vs. 120.4 ± 30.1 AU for 0.17% dimethyl sulfoxide (DMSO), p < 0.001) and significantly reduced the expression of fibrinogen receptor (activated form of GPIIbIIIa) on platelets' surface (47.6 ± 15.8 for 1.5 µg/ml XN, 44.6 ± 17.3% for 3 µg/ml XN vs. 54.5 ± 19.2% for control or 43.3 ± 18.4% for 6 µg/ml XN vs. 49.7 ± 19.4% for 0.17% DMSO, p < 0.05 or less). These findings suggest that the phenolic compounds originating from hops (XN) have a novel role as antiplatelet agents and can likely be used as dietary supplements in prophylactic approaches.

Assessment of Ticagrelor Versus Clopidogrel Treatment in Patients With ST-elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

AIMS: Ticagrelor improves the clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). However, few studies have directly compared the efficacy and safety of ticagrelor against clopidogrel, an oral, thienopyridine-class antiplatelet drug. This study compared the efficacy and safety of ticagrelor and clopidogrel in patients with STEMI undergoing PPCI. METHODS: We enrolled 400 patients with STEMI undergoing PPCI at the Zhujiang Hospital of Southern Medical University and the First Hospital of Qinhuangdao, China, between January 01, 2013 and April 30, 2015. All patients received 300 mg of aspirin and were randomized to receive one of the following treatments: (1) a loading dose of clopidogrel (600 mg) before PPCI followed by clopidogrel (75 mg once daily for 1 year) post PPCI or (2) a loading dose of ticagrelor (180 mg) before PPCI followed by ticagrelor (90 mg twice daily for 1 year) post PPCI. Some patients were treated by intracoronary bolus of a glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor [tirofiban (10 µg/kg) plus maintenance infusion (0.15 µg·kg·min) for 24-36 hours] in accordance with specified guidelines. The primary end points evaluated were major adverse cardiovascular and cerebrovascular event (MACCE) [defined as a composite of overall death, myocardial infarction (MI), unplanned revascularization, or stroke], stent thrombosis, and the composite end point of CV death, nonfatal MI, and stroke. The supplemental use of GPIIb/IIIa inhibitors in the clopidogrel and ticagrelor groups was monitored as another study end point, although the secondary safety end point evaluated was the incidence of bleeding events. RESULTS: Compared with the clopidogrel-treated group, ticagrelor treatment significantly reduced the incidence of MACCE [5 vs. 14; odds ratio (OR), 0.341; 95% confidence interval (CI), 0.120-0.964; P = 0.034] and the composite end points of cardiovascular death, nonfatal MI, and stroke (4 vs. 13; OR, 0.294; 95% CI, 0.094-0.916; P = 0.026). Fewer patients in the ticagrelor group received GPIIb/IIIa inhibitors after PPCI compared with those in the clopidogrel group (10 vs. 21; OR, 0.449; 95% CI, 0.206-0.979; P = 0.040). However, there were no significant differences between the groups in the incidences of all-cause mortality, nonfatal MI, unplanned revascularization, stroke, stent thrombosis (P = 0.522, P = 0.246, P = 0.246, P = 0.217, P = 0.246, respectively), or bleeding events (10 vs. 7; OR, 1.451; 95% CI, 0.541-3.891; P = 0.457). CONCLUSIONS: Among patients with STEMI undergoing PPCI, ticagrelor reduces the incidence of MACCE and the composite end point of cardiovascular death, nonfatal MI, and stroke compared with clopidogrel. Ticagrelor also reduces the need for GPIIb/IIIa inhibitors. However, no significant difference was observed in the risk of bleeding between the 2 groups.

Impact of Glycoprotein IIb/IIIa Inhibitors Use on Outcomes After Lower Extremity Endovascular Interventions From Nationwide Inpatient Sample (2006-2011).

OBJECTIVE: The aim of our study was to study the impact of glycoprotein IIb/IIIa inhibitors (GPI) on in-hospital outcomes. BACKGROUND: There is paucity of data regarding the impact of GPI on the outcomes following peripheral endovascular interventions. METHODS: The study cohort was derived from Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) database between the years 2006 and 2011. Peripheral endovascular interventions and GPI utilization were identified using appropriate ICD-9 Diagnostic and procedural codes. Two-level hierarchical multivariate mixed models were created. The study outcomes were: primary (in-hospital mortality and amputation studied separately) and secondary (composite of in-hospital mortality and postprocedural complications). Hospitalization costs were also assessed. RESULTS: GPI utilization (OR, 95% CI, P-value) was independently predictive of lower amputation rates (0.36, 0.27-0.49, <0.001). There was no significant difference in terms of in-hospital mortality (0.59, 0.31-1.14, P 0.117), although GPI use predicted worse secondary outcomes (1.23, 1.03-1.47, 0.023). Following propensity matching, the amputation rate was lower (3.2% vs. 8%, P < 0.001), while hospitalization costs were higher in the cohort that received GPI ($21,091 ± 404 vs. 19,407 ± 133, P < 0.001). CONCLUSIONS: Multivariate analysis revealed GPI use in peripheral endovascular interventions to be suggestive of an increase in composite end-point of in-hospital mortality and postprocedural complications, no impact on in-hospital mortality alone, significantly lower rate of amputation, and increase in hospitalization costs. © 2016 Wiley Periodicals, Inc.

Cost Effectiveness of Antiplatelet and Antithrombotic Therapy in the Setting of Acute Coronary Syndrome: Current Perspective and Literature Review.

Acute coronary syndromes (ACS) are associated with high rates of morbidity and mortality. The advances of antiplatelet and anticoagulation therapy over several years time have resulted in improved in cardiac outcomes, but with increased health care costs. Multiple cost-effectiveness studies have been performed to evaluate the use of available antiplatelet agents and anticoagulation in the setting of both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Early on, the use of glycoprotein IIb/IIIa receptor inhibitors (GPIs) proved to be economically attractive in the management of ACS; however, the introduction of P2Y12 receptor antagonists limited their use to a bail out agents in complex interventions. Generic clopidogrel is probably still an economically attractive P2Y12 receptor antagonist choice, especially in low-risk ACS, while both ticagrelor and prasugrel present an economically attractive alternative option, especially in high-risk ACS and patients at risk for stent thrombosis. While enoxaparin presents an economically dominant alternative to heparin in NSTE-ACS, its role in STEMI in the contemporary era is unclear. During percutaneous coronary intervention (PCI), bivalirudin monotherapy was shown to be an economically dominant alternative to the combination of heparin and GPI in ACS. However, new studies may suggest that using heparin monotherapy may offer an attractive alternative. The comparative and cost effectiveness of different combinations of antiplatelet and antithrombotic therapy will be the focus of future expected clinical and economic assessments.

Practice patterns and clinical outcomes among non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients presenting to primary and tertiary hospitals: insights from the EARLY glycoprotein IIb/IIIa inhibition in NSTE-ACS (EARLY-ACS) trial.

OBJECTIVES: We evaluated patients at tertiary [both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) capable] and primary hospitals in the EARLY-ACS trial. BACKGROUND: Early invasive management is recommended for high-risk non-ST-segment elevation acute coronary syndromes. METHODS: We evaluated outcomes in 9,204 patients presenting to: tertiary sites, primary sites with transfer to tertiary sites ("transferred") and those who remained at primary sites ("non-transfer"). RESULTS: There were 348 tertiary (n = 7,455 patients) and 89 primary hospitals [n = 1,749 patients (729 transferred; 1,020 non-transfer)]. Significant delays occurred in time from symptom onset to angiography (49 hr), PCI (53h), and CABG (178 hr) for transferred patients (P < 0.001). Non-transfer patients had less 30-day death/myocardial infarction [9.4% vs. 11.7% (tertiary); adjusted odds ratio (OR): 0.78 (0.62-0.97), P = 0.026]; transferred (14.0%) and tertiary patients were similar [adjusted OR: 1.23 (0.98-1.53), P = 0.074]. Non-transfer patients had lower 1-year mortality [4.3% vs. 6.3% (tertiary); adjusted hazard ratio (HR): 0.64 (0.47-0.87), P = 0.005]: there was no difference between transferred and tertiary patients [5.2% vs. 6.3%; adjusted HR: 0.80 (0.58-1.12), P = 0.202]. Despite similar rates of catheterization, GUSTO severe/moderate bleeding within 120 hr was less in non-transfer [3.1% vs. 6.7% (tertiary); adjusted OR: 0.47 (0.32-0.68), P < 0.001], whereas transferred (6.1%) and tertiary patients were similar [adjusted OR: 0.94 (0.68-1.30), P = 0.693]. There was no difference in non-CABG bleeding. CONCLUSIONS: Timely angiography and revascularization were often not achieved in transferred patients. Non-transferred patients presenting to primary sites had the lowest event rates and the best long-term survival.

Impact of worsening renal dysfunction on the comparative efficacy of bivalirudin and platelet glycoprotein IIb/IIIa inhibitors: insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

BACKGROUND: Use of bivalirudin has been associated with a reduction in the incidence of bleeding in patients undergoing percutaneous coronary intervention. Patients with chronic kidney disease, a known predictor of post-percutaneous coronary intervention bleeding, are under-represented in clinical trials. METHODS AND RESULTS: We evaluated the outcome of 64,052 patients who underwent percutaneous coronary intervention from 2007 to 2009 at 33 hospitals in Michigan and were treated with bivalirudin (28,378) or with heparin and glycoprotein IIb/IIIa inhibitors (35,674). Propensity-matched analysis was adjusted for the nonrandomized use of the 2 strategies. Patients treated with bivalirudin were older, had a lower glomerular filtration rate, and had more comorbidities. Use of bivalirudin was associated with fewer transfusions (2.8% versus 4.2%; P<0.0001), gastrointestinal bleeds (0.5% versus 1.3%; P<0.0001), and vascular complications (1.0% versus 2.5%; P<0.0001), with no difference in survival. Bleeding complications were more common with worsening renal function, but use of bivalirudin was associated with less bleeding across the continuum of renal dysfunction. CONCLUSIONS: The risk of bleeding after percutaneous coronary intervention increases with worsening chronic kidney disease. Bivalirudin was associated with a dramatically reduced risk of bleeding across all categories of renal dysfunction. Our study findings suggest that bivalirudin monotherapy is an acceptable, if not the more appropriate alternative, to heparin and glycoprotein IIb/IIIa inhibitors in patients with chronic kidney disease.

Antiplatelet therapy in patients undergoing percutaneous coronary intervention: economic considerations.

Percutaneous coronary intervention (PCI) is one of the most common medical procedures performed for treatment of coronary artery disease. Antiplatelet medications as adjunctive therapy for PCI are used routinely, with indications for specific agents or their combinations varying depending on the clinical scenario. While the cost-effectiveness of well-established agents has been extensively studied, newer drugs have not been evaluated as thoroughly. In addition, the clinical application of some antiplatelet drugs has recently changed, thus making older studies of cost effectiveness less applicable to the current landscape of clinical practice. This article reviews cost-effectiveness considerations of antiplatelet therapies in the treatment of coronary artery disease in patients undergoing PCI. Aspirin, P2Y12 inhibitors including clopidogrel and the newer agents prasugrel and ticagrelor, as well as glycoprotein (GP) IIb/IIIa inhibitors, are discussed. Overall, the use of dual antiplatelet therapy with aspirin and a P2Y12 inhibitor in patients undergoing PCI improves ischaemic outcomes and appears to be cost effective. The few available studies suggest that the recently approved medications prasugrel and ticagrelor are cost-effective alternatives to clopidogrel. However, no direct comparison between these two newer agents is available. The indications for GP IIb/IIIa inhibitors have changed in the current PCI era, and there is a paucity of cost-effectiveness data for their use in contemporary care.

In stent restenosis and thrombosis assessment after EP224283 injection in a rat model.

OBJECTIVE: After stent implantation, platelet aggregation and thrombus formation are thought to play a key role in the early phase of in-stent restenosis (ISR). Drug-eluting stents have reduced ISR, but are associated with healing-related issues or hypersensitivity reactions, leading to an increased risk of late acute stent thrombosis. EP224283 is a new dual-action antithrombotic molecule combining a GPIIbIIIa antagonist and a factor Xa inhibitor. We investigated its efficacy on restenosis in a rat model of ISR and on platelet adhesion. METHODS AND RESULTS: Rat aortas were stented and the animals received either EP224283 or vehicle subcutaneously every 48 h. At day 7 and day 28 after surgery, the stented aortas were removed and processed for morphometric analysis or protein analysis. At day 28, EP224283 significantly reduced neointima growth (in the range of 20%). Protein analysis revealed that EP224283 reduced cell proliferation pathways: ERK1/2 and Akt were down-regulated and p38 up-regulated. Expression of Ki67 was also reduced. In vitro assessment depicted a reduction of platelet activation and platelet adhesion among treated rats. CONCLUSION: These results show a beneficial effect of EP224283 on in-stent restenosis and on stent thrombogenicity that may improve results after stent implantation. Further investigations are required to assess the efficacy of a local delivery of EP224283 on both acute thrombosis and ISR.

Comparative assessment of platelet GpIIb/IIIa receptor occupancy ratio with Eptifibatide/Tirofiban in patients presenting with ACS and undergoing PCI.

BACKGROUND: The level of platelet inhibition by a Glycoprotein IIb/IIIa (GpIIb/IIIa) antagonist therapy necessary to minimize thrombotic complications in patients undergoing percutaneous coronary intervention (PCI) is a subject of debate. The degree of platelet inhibition obtained 10 min after start of GpIIb/IIIa antagonist therapy predicts adverse events after PCI. The aim of this study was to look at platelet inhibition and to compare platelet GpIIb/IIIa receptors occupancy ratio (GpRO) with Eptifibatide and Tirofiban using various dose regimens and correlate with 30-day clinical outcomes in patients presenting with high-risk acute coronary syndromes (ACS) and undergoing PCI. METHODS: The patients were divided into four sub groups: (1) Eptifibatide two intracoronary bolus (180 µg/kg) alone (E(B)); or (2) two intravenous bolus (180 µg/kg) followed by infusion at 2 µg/kg/min for 24 h (E(B + Inf)); and (3) Tirofiban standard bolus dose (0.4 µg/kg) over 30 min followed by infusion at 0.1 µg/kg/min (T(Std)); or (4) at ADVANCE dose bolus (25 µg/kg) over 3 min, followed by infusion at 0.1 µg/kg/min (T(Adv)). Number of GpIIb/IIIa receptors was assessed by flow cytometry at baseline and 10 min after the bolus and percentage of free receptors was determined to calculate the GpRO. Patients were followed for 30 days for any major adverse cardiac events (MACE). RESULTS: 200 consecutive patients (including 74% with ST-elevation ACS) were enrolled. GpRO in groups E(B) (n = 48) and E(B + Inf) (n = 44) were 62.7% ± 27.2% and 61.4% ± 6.1% respectively while in the groups T(Std) (n = 96) and T(Adv) (n = 12) groups were 35.1% ± 17.74% and 68.8% ± 27.3% respectively. The GpRO was similar in E(B), E(B + Inf) and T(Adv) groups and was significantly higher than T(Std) group (p < 0.0001). The 30-day MACE rates in E(B) (4.2%), E(B + Inf) (4.5%) and T(Adv) (4.2%) were significantly lower than T(Std) group (12.5%) (p < 0.01). CONCLUSIONS: Standard dose Tirofiban results in significantly lower rates of GpIIb/IIIa receptor occupancy ratio and this correlated with higher incidence of 30-day MACE in high-risk ACS patients undergoing PCI.

Applicability of the European Society of Cardiology guidelines on management of acute coronary syndromes to people with haemophilia - an assessment by the ADVANCE Working Group.

There are no evidence-based guidelines for antithrombotic management in people with haemophilia (PWH) presenting with acute coronary syndrome (ACS). The aim of the study was to review the current European Society of Cardiology guidelines, and to consider how best they should be adapted for PWH. Structured communication techniques based on a Delphi-like methodology were used to achieve expert consensus on key aspects of clinical management. The main final statements are as follows: (i) ACS and myocardial revascularization should be managed promptly by a multidisciplinary team that includes a haemophilia expert, (ii) each comprehensive care centre for adult PWH should have a formal clinical referral pathway with a cardiology centre with an emergency unit and 24 h availability of percutaneous coronary intervention (PCI), (iii) PCI should be performed as soon as possible under adequate clotting factor protection, (iv) bare metal stents are preferred to drug-eluting stents, (v) anticoagulants should only be used in PWH after replacement therapy, (vi) minimum trough levels should not fall below 5-15% in PWH on dual antiplatelet therapy, (vii) the duration of dual antiplatelet therapy after ACS and PCI should be limited to a minimum, (viii) the use of GPIIb-IIIa inhibitors is not recommended in PWH other than in exceptional circumstances, (ix) the use of fibrinolysis may be justified in PWH when primary PCI (within 90 min) is not available ideally under adequate clotting factor management. It is hoped that the results of this initiative will help to guide optimal management of ACS in PWH.

Cost analysis of bivalirudin versus reference anticoagulants without GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention for acute coronary syndrome in routine clinical practice. Pompidou registry.

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to other anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study analyzed the cost/efficacy profile of bivalirudin-based anticoagulation strategy versus non bivalirudin-based anticoagulant strategy without use of GP IIb/IIIa inhibitors in routine clinical practice. From January 2009 to December 2010, 216 patients who underwent PCI for ACS at hospital Georges-Pompidou without GP IIb/IIIa inhibitors were studied. Of these patients, 24 (11%) received bivalirudin and 192 (88%) received others anticoagulants (mainly unfractionated heparin or low molecular weight heparin). Ischemic events and bleeding or transfusion were slightly lower in bivalirudin group (0 vs. 4.2%, P=0.60 and 4.2 vs. 8.9%, P=0.70, respectively). In spite of a higher cost of the medication, the overall cost of the bivalirudin strategy was slightly lower (9167±3688 € vs. 14,016±14,749 €, P=0.23), in relation with a shorter average duration of the hospital stay. In conclusion, in this limited, single-center, population of patients with ACS, the clinical efficacy and safety of bivalirudin appeared at least as good as that of reference anticoagulants in real world clinical practice, with no increase in overall costs.

Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry.

BACKGROUND: Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy. METHODS AND RESULTS: From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment-elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60-2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%). CONCLUSIONS: Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.

Comparison of percutaneous coronary intervention safety before and during the establishment of a transradial program at a teaching hospital.

This study sought to examine the safety of percutaneous coronary intervention (PCI) before and during de novo establishment of a transradial (TR) program at a teaching hospital. TR access remains underused in the United States, where cardiology fellowship programs continue to produce cardiologists with little TR experience. Establishment of TR programs at teaching hospitals may affect PCI safety. Starting in July 2009 a TR program was established at a teaching hospital. PCI-related data for academic years 2008 to 2009 (Y1) and 2009 to 2010 (Y2) were prospectively collected and retrospectively analyzed. Of 1,366 PCIs performed over 2 years, 0.1% in Y1 and 28.7% in Y2 were performed by TR access. No major complications were identified in 194 consecutive patients undergoing TR PCI, and combined bleeding and vascular complication rates were lower in Y2 versus Y1 (0.7% vs 2.0%, p = 0.05). Patients treated in Y2 versus Y1 and by TR versus transfemoral approach required slightly more fluoroscopy but similar contrast volumes and had similar procedural durations, lengths of stay, and predischarge mortality rates. PCI success rates were 97% in Y1, 97% in Y2, and 98% in TR cases. TR PCIs were performed by 13 cardiology fellows and 9 attending physicians, none of whom routinely performed TR PCI previously. In conclusion, de novo establishment of a TR program improved PCI safety at a teaching hospital. TR programs are likely to improve PCI safety at other teaching hospitals and should be established in all cardiology fellowship training programs.

Bivalirudin therapy is associated with improved clinical and economic outcomes in ST-elevation myocardial infarction patients undergoing percutaneous coronary intervention: results from an observational database.

BACKGROUND: Randomized trials show improved outcomes among acute coronary syndrome patients treated with bivalirudin. The objective of this analysis was to compare clinical and economic outcomes in ST-elevation myocardial infarction (STEMI) patients encountered in routine clinical practice undergoing primary percutaneous coronary intervention (PPCI), treated with bivalirudin or heparin+GP IIb/IIIa receptor inhibitor (heparin+GPI). METHODS AND RESULTS: STEMI admissions from January 1, 2004 through March 31, 2008 among patients receiving PPCI and bivalirudin or heparin+GPI in the Premier hospital database were identified. The probability of receiving bivalirudin was estimated using individual and hospital variables; using propensity scores, each bivalirudin patient was matched to 3 heparin+GPI treated patients. The primary outcome was in-hospital death. Rates of bleeding, transfusion, length of stay, and in-hospital cost were secondary outcomes. There were 59,917 STEMI PPCIs receiving bivalirudin (n=6735) or heparin+GPI (n=53,182). Seventy-nine percent of bivalirudin patients matched, resulting in 21,316 STEMI PPCIs for analysis. Compared with heparin+GPI patients, bivalirudin patients had fewer deaths (3.2% versus 4.0%; P=0.011) and less inpatient bleeding (clinically apparent bleeding [6.9% versus 10.5%, P<0.0001], clinically apparent bleeding with transfusion [1.6% versus 3.0%, P<0.0001], and transfusion [5.9% versus 7.6%, P<0.0001]). Patients receiving bivalirudin had shorter average length of stay (mean 4.3 versus 4.5 days; P<0.0001), with lower in-hospital cost (mean $18,640 versus $19,967 [median $14,462 versus $16,003], P<0.0001). CONCLUSIONS: This large "real-world" retrospective analysis demonstrates that bivalirudin therapy compared with heparin+GPI is associated with a lower rate of inpatient death, inpatient bleeding, and decreased overall in-hospital cost in STEMI patients undergoing PPCI.

[Assessment of dynamic coronary plaque changes and the clinical consequences in type-II diabetic patients: a serial intracoronary ultrasound study]. / Evaluación de los cambios dinámicos de las placas coronarias y sus consecuencias clínicas en pacientes con diabetes mellitus tipo 2: un estudio de ecografía intracoronaria seriada.

INTRODUCTION AND OBJECTIVES: One of the aims of secondary prevention is to achieve plaque stabilization. This study sought to investigate the clinical consequences and predictive factors of the change in the type of plaque (CTP) as assessed by serial intracoronary ultrasound in type II diabetic patients with known coronary artery disease. METHODS: 237 segments (45 patients) from the DIABETES I, II, and III trials were included. Intracoronary ultrasound from motorized pullbacks (0.5mm/s) after index procedure and at 9-month angiographic follow-up was performed in the same coronary segment. Nontreated mild lesions (angiographic stenosis <25%) with ≥0.5mm plaque thickening and ≥5mm of length assessed by intracoronary ultrasound were included. As different types of plaques may be encountered throughout a given coronary lesion, each study lesion was divided into 3 segments for serial quantitative and qualitative analyses. Statistical adjustment by multiple lesion segments per patient (generalized estimating equations method) was performed. A CTP was defined as any qualitative change in plaque type at follow-up. At 1-year follow-up, major adverse cardiac events - death, myocardial infarction and target vessel revascularization) - were recorded. RESULTS: A CTP was observed in 48 lesions (20.2%) and occurred more frequently (52.1%) in mixed plaques. Independent predictors of CTP were glycated hemoglobin levels (odds ratio [OR] 1.2; 95% confidence interval [CI] 1.01-1.5; P=.04); glycoprotein IIb-IIIa inhibitors (OR 0.3; 95% CI 0.1-0.7; P=.004) and statin administration (OR 0.3; 95% CI 0.1-0.8; P=.02). At 1-year follow-up CTP was associated with an increase in major adverse cardiac events rate (CTP 20.8% vs non-CTP 13.8%, P=.008; hazard ratio=1.9, 95% CI 1.3-1.9, P=.01). CONCLUSIONS: Qualitative changes in mild stenosis documented by intracoronary ultrasound in type II diabetics are associated with suboptimal secondary prevention and may have clinical consequences. Full English text available from: www.revespcardiol.org.

A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial.

BACKGROUND: In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. METHODS AND RESULTS: Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 µg/kg) plus 12-hr infusion (0.15 µg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. CONCLUSION: With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.