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Biomedical subjects

John A Bittl

Publications and source records attributed to John A Bittl.

At least 19 recordsLinked to original sources
PubMed2006

Provisional glycoprotein IIb/IIIa blockade in a randomized investigation of bivalirudin versus heparin plus planned glycoprotein IIb/IIIa inhibition during percutaneous coronary intervention: predictors and outcome in the Randomized Evaluation in Percutaneous coronary intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

BACKGROUND: The REPLACE-2 trial demonstrated the noninferiority of bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) blockade as compared with heparin plus planned GPIIb/IIIa blockade among patients undergoing percutaneous coronary revascularization. Provisional drug was used in 374 (6%) of the 6010 patients. We sought to analyze the predictors for provisional drug use and to assess the outcomes in this cohort. METHODS: Outcome among the 5.2% of patients in the heparin plus GPIIb/IIIa blockade group and the 7.2% of patients in the bivalirudin group who received provisional placebo or GPIIb/IIIa inhibitor, respectively, was compared against patients without provisional drug use and between randomized arms. Multivariate models identified predictors of provisional drug use and outcome at 30 days, 6 months, and 1 year. RESULTS: Myocardial infarction, repeat revascularization, and bleeding events occurred more frequently among patients who required provisional drug than those who did not, but there were no differences in 1-year mortality. Ischemic and hemorrhagic end points occurred at similar rates among patients receiving provisional drug in either the heparin plus GPIIb/IIIa group compared with the bivalirudin group. Independent predictors of provisional drug use were randomization to bivalirudin, recent infarction, multilesion intervention, impaired pretreatment coronary flow, and lesion complexity. Provisional drug use, but not randomization to bivalirudin, independently predicted 30-day and 6-month ischemic events. CONCLUSIONS: Provisional administration of a GPIIb/IIIa inhibitor is associated with more frequent ischemic and bleeding events, reflecting the procedural complications that led to the use of provisional drug. The proportion of bivalirudin-treated patients who will require provisional GPIIb/IIIa blockade, however, is not large enough to have a significant deleterious impact on the overall incidence of ischemic end points or to invalidate the strategy of bivalirudin plus provisional GPIIb/IIIa blockade.

Aged↗
PubMed2006

Outcomes of patients with acute coronary syndromes who are treated with bivalirudin during percutaneous coronary intervention: an analysis from the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial.

BACKGROUND: The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GPIIb/IIIa) inhibition is not inferior to heparin plus GPIIb/IIIa inhibition in patients undergoing percutaneous coronary intervention. The extent to which this applies to patients with acute coronary syndromes (ACS) is unclear. Therefore, we sought to determine if bivalirudin has similar efficacy in ACS patients as compared with "stable" patients in the REPLACE-2 trial. METHODS: We analyzed the outcomes of ACS patients compared with stable patients and the outcomes of ACS patients according to whether or not they had received bivalirudin, including the economic costs. The trial enrolled 1351 ACS patients (myocardial infarction within 7 days or unstable angina within 48 hours, but not on ongoing GPIIb/IIIa or heparin therapy) and 4554 stable patients. RESULTS: Patients with ACS had a similar rate of death or myocardial infarction at 30 days compared to stable patients (7.2% vs 6.7%, P = .51) and death at 1 year (1.6% vs 2.2%, P = .169), but a higher rate of urgent coronary artery bypass graft at 30 days (1.0% vs 0.3%, P = .002). Patients with ACS treated with bivalirudin had a similar rate of 30-day death, myocardial infarction, or urgent revascularization compared with ACS patients treated with heparin and GPIIb/IIIa inhibitors (8.7% vs 8.0%, P = .616) and death at 1 year (1.5% vs 1.8%, P = .701), but a higher rate of revascularization at 6 months (12% vs 8.4%, P = .04). Patients with ACS treated with bivalirudin had less major bleeding than ACS patients treated with heparin and GPIIb/IIIa inhibitors, although this was not statistically significant (2.7% vs 4.5%, P = .07). Mean 30-day costs for patients with ACS were dollar 12415 for those treated with bivalirudin and dollar 12806 for those treated with heparin plus GPIIb/IIIa inhibitors (P = .022). CONCLUSION: Bivalirudin with provisional GPIIb/IIIa inhibitor use in low-risk ACS patients (not receiving preprocedural GPIIb/IIIa blockade) appears to provide similar protection against death and myocardial infarction as the combination of heparin and GPIIb/IIIa inhibitors, although we observed a higher rate of revascularization at 6 months.

Aged↗
PubMed2006

Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial.

BACKGROUND: Platelet-initiated acute thrombosis and coronary embolization are fundamental in the pathophysiology of complications during percutaneous coronary intervention (PCI). Cangrelor (formerly AR-C69931MX) is a novel, rapidly acting, intravenous, specific antagonist of platelet aggregation via binding to the adenosine diphosphate (ADP) P2Y12 receptor subtype. The primary aims of this study were to assess the initial safety and pharmacodynamics of cangrelor in patients undergoing PCI. METHODS: In part 1, patients undergoing PCI were randomized to an 18- to 24-hour of either placebo, 1-, 2-, or 4-microg/kg per minute cangrelor in addition to aspirin and heparin beginning before PCI. In part 2, patients were randomized to receive either cangrelor (4 microg/kg per minute) or abciximab before PCI. The primary end point was the composite incidence of major and minor bleeding through 7 days. Secondary end points included the occurrence of major adverse coronary events (death, MI, and unplanned repeat coronary intervention) through 30 days plus ex vivo platelet aggregation and bleeding times. RESULTS: Two hundred patients (3 dosage groups and placebo) were studied in part 1, and 199 additional patients were then randomized in the second part, comparing 1 dose of cangrelor and abciximab. Combined major and minor bleeding occurred in 13% of those receiving cangrelor and in 8% in those randomized to placebo (P = non significant [NS]) during part 1 and in 7% receiving cangrelor compared with 10% randomized to abciximab (P = NS), during part 2. The 30-day composite incidence of adverse cardiac events was similar between those receiving cangrelor and those receiving abciximab during part 2 (7.6% vs 5.3%, respectively, P = NS). Mean inhibition of ex vivo platelet aggregation in response to 3 micromol/L ADP at steady state was 100% for both cangrelor 4 microg/kg per minute and abciximab groups in part 2. After termination of infusion, platelet aggregation returned to baseline response more rapidly with cangrelor compared with abciximab. There was a trend toward longer bleeding time prolongation and lower platelet count with abciximab compared with cangrelor. CONCLUSIONS: This initial experience with intravenous cangrelor during PCI suggests an acceptable risk of bleeding and adverse cardiac events while achieving rapid, reversible inhibition of platelet aggregation via competitive binding to the ADP P2Y12 platelet receptor with less prolongation of bleeding time then the glycoprotein IIb/IIIa receptor antagonist abciximab.

Abciximab↗
PubMed2006

Ischemic and bleeding outcomes in women treated with bivalirudin during percutaneous coronary intervention: a subgroup analysis of the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial.

BACKGROUND: Outcomes in women undergoing percutaneous coronary intervention (PCI) in the contemporary era are poorly defined. The REPLACE-2 trial demonstrated that bivalirudin with provisional glycoprotein IIb/IIIa (GpIIb-IIIa) blockade is noninferior to heparin with planned GpIIb-IIIa blockade during PCI, with regard to ischemic and bleeding end points. OBJECTIVES: The aim of this study was to define sex-based clinical ischemic and bleeding outcomes from the REPLACE-2 trial. METHODS: A retrospective sex-based subgroup analysis of the REPLACE-2 trial comparing clinical ischemic and inhospital bleeding end points was conducted. RESULTS: Compared with men in REPLACE-2, women were older, had more diabetes, congestive heart failure and hypertension, and less prior revascularization and myocardial infarction. Female sex was a univariate predictor of death and bleeding complications. Among women treated with either bivalirudin or heparin, there was no significant difference in the individual or composite ischemic end points of death, myocardial infarction, or urgent revascularization at 30 days or 6 months. Protocol-defined major bleeding, minor bleeding, and access site bleeding were less frequent with bivalirudin compared with heparin. Multivariable modeling found no significant interactions between sexes, with the composite ischemic end point, major bleeding, or 1-year mortality. CONCLUSIONS: Women remain at higher risk for poorer outcomes with contemporary PCI, likely because of comorbidities. Bivalirudin with provisional GpIIb-IIIa confers similar protection against ischemic end points compared with heparin and planned GpIIb-IIIa blockade and significantly reduces the inherent bleeding risk of women undergoing contemporary PCI.

Aged↗
PubMed2005

Direct thrombin inhibitors in acute coronary syndromes: effect in patients undergoing early percutaneous coronary intervention.

AIMS: We evaluated the effect of direct thrombin inhibitors (DTIs) in patients undergoing early percutaneous coronary intervention (PCI), using the DTI Trialists' Collaboration database of 35,970 patients from 11 randomized trials of DTIs vs. heparin. METHODS AND RESULTS: We performed a Cox proportional hazards regression analysis with PCI as a time-dependent covariate to assess the independent impact of DTIs according to the performance of early PCI. PCI was performed in 7049 patients in the first 72 h after randomization. In trials in which PCI was not planned, DTIs were associated with a 10% relative risk reduction in death or myocardial infarction at 30 days (HR=0.90, 95% CI: 0.84-0.97). This benefit was found to be greater in patients undergoing early PCI (HR=0.66, 95% CI: 0.48-0.91) than those undergoing non-early PCI (HR=0.94, 95% CI: 0.86-1.03). After adjustment for baseline characteristics and propensity to undergo PCI, the risk of death or myocardial infarction remained lower with DTI (HR=0.62, 95% CI: 0.44-0.89). CONCLUSION: After adjustment for baseline differences and propensity to undergo early PCI, DTIs appeared to be more effective than heparin in reducing death or re-infarction among patients undergoing early PCI.

Acute Disease↗
PubMed2005

Use of bivalirudin during percutaneous coronary intervention in patients with diabetes mellitus: an analysis from the randomized evaluation in percutaneous coronary intervention linking angiomax to reduced clinical events (REPLACE)-2 trial.

OBJECTIVES: The objective of this study was to confirm that the efficacy and safety of percutaneous coronary intervention (PCI) in diabetic patients are not compromised by a bivalirudin-based antithrombotic strategy. BACKGROUND: Previous studies have shown a survival benefit with use of platelet glycoprotein (GP) IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP IIb/IIIa inhibition. The relative efficacy of these two strategies in diabetic patients has not been studied. METHODS: We evaluated the diabetic patients enrolled in the REPLACE-2 trial to assess the impact of these antithrombotic strategies on the short- and long-term outcome after PCI. RESULTS: The REPLACE-2 trial enrolled 1,624 diabetic patients and 4,368 non-diabetic patients. Compared with non-diabetic patients, diabetic patients had similar short-term outcome but higher mortality at 1 year (3.06% vs. 1.85%, p = 0.004). There was no difference in short-term or long-term ischemic events among the diabetic patients randomized to the two arms. Specifically, the 1-year mortality rate was non-significantly lower in the bivalirudin arm, suggesting no differential survival impact of the two strategies (2.3% vs. 3.9%). There was less minor bleeding in the bivalirudin arm in diabetic patients (12.6% vs. 24.4%, p < 0.001), whereas no difference was seen in the incidence of major bleeding (3.0% vs. 3.3%, p = 0.69). CONCLUSIONS: Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with provisional GP IIb/IIIa inhibitors in diabetic patients is associated with no differences in clinical outcomes at 30 days, a trend toward lesser mortality at 1 year, and a reduction in minor bleeding.

Aged↗
PubMed2005

Prospective assessment of hemodialysis access patency after percutaneous intervention: Cox proportional hazards analysis.

Vascular access failure is the greatest limitation of successful hemodialysis, but the factors associated with long-term patency have not been fully elucidated. Outcomes in a consecutive series of 294 thrombosed or failing accesses [128 fistulas (43.5%) and 166 grafts (56.5%) in 179 patients] were analyzed with life table and multivariable Cox proportional hazards analysis. Initial success was achieved in 275 of 294 accesses (95.6%). The median patency after intervention was 206 days (interquartile range, 79-457 days). Fistulas had longer median patency after intervention than grafts (286 vs. 170 days). Nonthrombosed accesses had longer median patency than thrombosed accesses (238 vs. 136 days), but thrombosed fistulas had similar median patency as thrombosed grafts (140 vs. 136 days). The selective use of stents as a bailout for failed balloon dilatation did not significantly reduce long-term patency (196 days for stented accesses vs. 210 days for unstented accesses). Long-term patency was inversely related to final access pressure, but access patency was not related to the presence of central venous occlusions, graft age, patient age, sex, or diabetes. Catheter-based intervention of thrombosed and failing dialysis accesses significantly prolongs patency and usefulness of dialysis accesses. The expanding use of fistulas, improved detection of early access failure, and selective use of bailout stents should enhance long-term access patency.

Arteriovenous Shunt, Surgical↗
PubMed2005

Bivalirudin vs heparin in percutaneous coronary intervention: a pooled analysis.

OBJECTIVE: This study evaluates outcomes with bivalirudin vs heparin in various patient subgroups and the overall population during percutaneous coronary interventions (PCI). BACKGROUND: Recent data suggest that bivalirudin, a reversible direct thrombin inhibitor, provides ischemic protection superior to heparin and comparable to heparin plus glycoprotein (GP) IIb/IIIa inhibitors but with significantly fewer bleeding complications. Whether this advantage persists in different subgroups has not been fully defined. To our knowledge, this is the largest pooled analysis of bivalirudin to date. METHODS: Four randomized controlled trials were identified that compared bivalirudin to heparin (with or without GP IIb/IIIa inhibitors) in PCI. The incidence of death, myocardial infarction (MI), revascularization, and major bleeding at 48 hours was compared between these two agents overall and in patients with and without diabetes mellitus, hypertension, renal insufficiency, and advanced age. RESULTS: The trials consisted of 11,638 patients (bivalirudin, 5,861; heparin, 5,777). There were no significant differences in patient characteristics between the two groups. At 48 hours, the incidence of death, MI, revascularization, and major bleeding was significantly reduced in the bivalirudin group (7.8% vs 1.08%, P < .001); individual ischemic end points were significantly reduced for death (0.01% vs 0.02%, P = .049) and revascularization (2.0% vs 2.7%, P = .02), with similar reductions for major bleeding (2.7% vs 5.8%, P < .001). Subgroup analysis was generally consistent with the overall findings. CONCLUSION: This analysis further supports the superiority of bivalirudin compared with heparin. Bivalirudin provides excellent ischemic protection with a significant reduction of bleeding complications, even in high-risk subgroups.

Angioplasty, Balloon, Coronary↗
PubMed2004

Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial.

CONTEXT: In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, bivalirudin with provisional glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibition was found to be noninferior to heparin plus planned Gp IIb/IIIa blockade in the prevention of acute ischemic end points and was associated with significantly less bleeding by 30 days after percutaneous coronary intervention (PCI). OBJECTIVE: To determine whether the efficacy of bivalirudin remains comparable with that of heparin plus Gp IIb/IIIa blockade over 6 months and 1 year. DESIGN, SETTING, AND PARTICIPANTS: Follow-up study to 1 year of a randomized, double-blind trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. INTERVENTIONS: Patients were randomly assigned to receive intravenously bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition, or to receive heparin (65 U/kg bolus), with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. MAIN OUTCOME MEASURES: Incidence of death, myocardial infarction, or repeat revascularization by 6 months and death by 12 months after enrollment. RESULTS: At 6 months, death occurred in 1.4% of patients in the heparin plus Gp IIb/IIIa group and in 1.0% of patients in the bivalirudin group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.43-1.14; P =.15). Myocardial infarction occurred in 7.4% and 8.2% of patients, respectively (HR, 1.12; 95% CI, 0.93-1.34; P =.24), and repeat revascularization was required in 11.4% and 12.1% of patients, respectively (HR, 1.06; 95% CI, 0.91-1.23; P =.45). By 1 year, death occurred in 2.46% of patients treated with heparin plus Gp IIb/IIIa blockade and in 1.89% of patients treated with bivalirudin (HR, 0.78; 95% CI, 0.55-1.11; P =.16). Nonsignificant trends toward lower 1-year mortality with bivalirudin were present in all patient subgroups analyzed and were of greatest magnitude among high-risk patients. CONCLUSION: Long-term clinical outcome with bivalirudin and provisional Gp IIb/IIIa blockade is comparable with that of heparin plus planned Gp IIb/IIIa inhibition during contemporary PCI.

Abciximab↗
PubMed2004

Comparison of bivalirudin versus heparin during percutaneous coronary intervention (the Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events [REPLACE]-1 trial).

To assess the efficacy of the direct thrombin inhibitor bivalirudin relative to heparin during contemporary coronary intervention, 1,056 patients who underwent elective or urgent revascularization were randomized in a large-scale pilot study to receive heparin (70 U/kg initial bolus) or bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/hour infusion during the procedure). All patients received aspirin; pretreatment with clopidogrel was encouraged, and glycoprotein (GP) IIb/IIIa blockade was at the physician's discretion. Stents were placed in 85% of patients; 72% received a GP IIb/IIIa inhibitor, and 56% were pretreated with clopidogrel. Activated clotting times were higher among patients randomized to bivalirudin than among those given heparin before device activation (median 359 vs 293 seconds, p <0.001). The composite efficacy end point of death, myocardial infarction, or repeat revascularization before hospital discharge or within 48 hours occurred in 5.6% and 6.9% of patients in the bivalirudin and heparin groups, respectively (p = 0.40). Major bleeding occurred in 2.1% versus 2.7% of patients randomized to bivalirudin or heparin, respectively (p = 0.52). This trial represents the largest prospective dataset of bivalirudin administered concomitantly with planned GP IIb/IIIa blockade and provides evidence of the safety and efficacy of this combined antithrombotic approach.

Aged↗
PubMed2004

Meta-analysis of randomized trials of percutaneous transluminal coronary angioplasty versus atherectomy, cutting balloon atherotomy, or laser angioplasty.

OBJECTIVES: We conducted a systematic overview (meta-analysis) of randomized trials of balloon angioplasty versus coronary atherectomy, laser angioplasty, or cutting balloon atherotomy to evaluate the effects of plaque modification during percutaneous coronary intervention. BACKGROUND: Several mechanical approaches have been developed that ablate or section atheromatous plaque during percutaneous coronary interventions to optimize acute results, minimize intimal injury, and reduce complications and restenosis. METHODS: Sixteen trials (9,222 patients) constitute the randomized controlled experience with atherectomy, laser, or atherotomy versus balloon angioplasty with or without coronary stenting. Each trial tested the hypothesis that ablative therapy would result in better clinical or angiographic results than balloon dilation alone. RESULTS: Short-term death rates (<31 days) were not improved by the use of ablative procedures (0.3% vs. 0.4%, odds ratio [OR] 0.94 [95% confidence interval 0.46 to 1.92]), but periprocedural myocardial infarctions (4.4% vs. 2.5%, OR 1.83 [95% CI 1.43 to 2.34]) and major adverse cardiac events (5.1% vs. 3.3%, OR 1.54 [95% CI 1.25 to 1.89]) were increased. Angiographic restenosis rates (6,958 patients) were not improved with the ablative devices (38.9% vs. 37.4%, OR 1.06 [95% CI 0.97 to 1.17]). No reduction in revascularization rates (25.2% vs. 24.5%, OR 1.04 [95% CI 0.94 to 1.14]) or cumulative adverse cardiac events rates up to one year after treatment were seen with ablative devices (27.8% vs. 26.1%, OR 1.09 [95% CI 0.99 to 1.20]). CONCLUSIONS: The combined experience from randomized trials suggests that ablative devices failed to achieve predefined clinical and angiographic outcomes. This meta-analysis does not support the hypothesis that routine ablation or sectioning of atheromatous tissue is beneficial during percutaneous coronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2003

Bivalirudin provides increasing benefit with decreasing renal function: a meta-analysis of randomized trials.

Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.

Adult↗