sirolimus and bivalirudin

The randomized, LEADERS FREE trial showed superior safety and efficacy of a polymer-free DCS vs. a bare metal stent in high-bleeding risk patients with only one month dual antiplatelet treatment. We report characteristics and outcomes of the pre-specified group of elderly patients (aged ≥75).. Age >75 was one of the trial's inclusion criteria. The main additional criteria were: need for oral anticoagulants, recent bleeding, anemia, chronic renal failure and cancer. All patients received 1month DAPT only. Both primary endpoints (efficacy: clinically driven TLR and safety: composite of cardiac death, MI and stent thrombosis) as well as bleeding were recorded up to 390days.. 1564 elderly patients (63.4% of the population) were enrolled with a mean of 2 inclusion criteria/patient. The primary safety endpoint was reached less frequently in DCS than BMS patients (10.7 vs. 14.3%, p=0.03), as was the primary efficacy endpoint (5.8 vs. 10.8% p=0.0003). Major bleeding rates were high and similar in both groups (7.3 vs. 8.2%, p=0.55). For the 562 (23.4%) patients with age as sole entry criterion, trends were similar for DCS and BMS patients respectively: safety endpoint (7.3%vs.11.4% p=0.10) and Cd TLR (4.7 vs. 13.2% p=0.0003), but for both groups, major bleeding occurred less frequently than for elderly patients with more comorbid conditions (3.6%vs. 2.8%).. Compared to a BMS, use of a DCS together with a short one-month DAPT course was associated with significant safety and efficacy benefits for the elderly patients enrolled in LEADERS FREE.

Topics: Age Factors; Aged; Aged, 80 and over; Antithrombins; Double-Blind Method; Drug-Eluting Stents; Female; Hemorrhage; Hirudins; Humans; Male; Metals; Middle Aged; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Sirolimus; Stents; Treatment Outcome

The aim was to compare 2-year outcomes with the routine use of drug-eluting stents (DES) (>75% "off-label") with a comparable group treated with bare-metal stents (BMS).. Safety concerns >1 year from implantation have been raised about DES used "off-label." There are limited data comparing DES and BMS in "off-label" patients.. Clinical outcomes (nonfatal myocardial infarction [MI], all-cause mortality) were assessed in 1,164 consecutive patients who received BMS in the year before introduction of DES at Wake Forest University Baptist Medical Center and 1,285 consecutive patients who received DES after it became our routine choice. "On-label" stent use was defined as treatment for a single de novo lesion <30 mm, without recent MI or other major illnesses.. At 2 years, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.77 (95% confidence interval [CI] 0.62 to 0.95), for all-cause mortality 0.71 (0.54 to 0.92), and stent thrombosis (ST) 0.97 (0.49 to 1.91). "On-label" stent procedures were associated with lower risk of MI, death, and ST than "off-label" stent procedures. For "off-label" stent procedures, the hazard ratio for DES compared with BMS for nonfatal MI or death was 0.78 (95% CI 0.62 to 0.98), all-cause mortality 0.72 (0.54 to 0.94), and ST 0.91 (0.46 to 1.80). The hazard of nonfatal MI or death was similar or lower for DES than BMS in high-risk subgroups, including renal failure and recent MI.. The routine clinical use of drug-eluting stents for "off-label" indications was associated with lower nonfatal MI and death at 2 years than in a comparable group of patients treated with BMS.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Blood Vessel Prosthesis Implantation; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Heparin; Hirudins; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Proportional Hazards Models; Recombinant Proteins; Risk Factors; Secondary Prevention; Sirolimus; Treatment Outcome

Localized drug delivery with sustained elution characteristics from nanocarrier coated stents represents a viable therapeutic approach to circumvent concerns related to coronary stent therapy. We fabricated a Sirolimus (SRL) and Bivalirudin (BIV) releasing nanoparticles (NPs) coated stent for concurrent mitigation of vascular restenosis and acute stent thrombosis. SRL NPs were prepared by nanoprecipitation method whereas the BIV vesicles were generated using hydrophobic ion pair approach followed by micellization phenomenon. MTT assay and confocal microscopic analysis indicated superior anti-proliferative activity and higher cellular uptake of SRL NPs into human coronary artery smooth muscle cells, respectively. DSC and ATR-FTIR techniques confirmed the formation of complex between BIV and phosphatidylglycerol via some weak physical interactions. More than 2 fold rise in log P value was obtained for DSPG-BIV at 3:1 M ratio compared with native BIV solution. The SAXS analysis indicated formation of oligolamellar vesicles of DSPG-BIV complex which was preferentially entrapped into lipophilic lamellae of vesicles. APTT, PT, and TT tests revealed that the BIV vesicles caused significant prolongation of clotting time compared to native BIV solution. The SEM analysis showed uniform and defect free stent coating. In vitro release study demonstrated that SRL and BIV were eluted in a sustained manner from coated stents.

Topics: Coronary Restenosis; Drug-Eluting Stents; Hirudins; Humans; Peptide Fragments; Recombinant Proteins; Scattering, Small Angle; Sirolimus; Stents; Thrombosis; X-Ray Diffraction

We attempted to test the feasibility of application of the MADS classification system in the largest stent trial to date and evaluate the preliminary clinical implications of this approach.. In the randomized GLOBAL LEADERS trial, testing two different antiplatelet strategies in patients undergoing PCI with bivalirudin and biolimus-eluting stents, the e-CRF was dedicated to bifurcation treatment according to the MADS classification. Based on this e-CRF, the techniques used for bifurcations treatment in GLOBAL LEADERS were described and compared with two large, all-comer registries of bifurcations treatment (I-BIGIS and COBIS), used as historical controls.. Among 15,991 patients enrolled in the trial, 22,921 lesions treated at the index and staged procedure were available for analysis and 2,757 of these lesions were bifurcations and 7 were trifurcation lesions. The e-CRF-based MADS classification was achieved in 2,757 of these lesions (100%). 80.3% of bifurcations were treated using a single stent, 18.9% using 2 stents and 0.7% using 3 stents. Overall, the "main across side first" approach (A) was used in 77.4% with the "side branch first" approach (S) being the second most frequently used technique (10.2%). A single stent was used in the majority of the "A" approach (87.9%). A reduction in the use of 2-stent techniques (from 33.9 to 18.9%) was observed between GLOBAL LEADERS and I-BIGIS. The "A" approach was the most frequently used technique in GLOBAL LEADERS, while in COBIS the "S" strategy was most frequently employed.. Application of the MADS classification through an e-CRF was feasible in the largest stent trial today and provided useful information about the trends observed overtime in the treatment of bifurcation lesions.

Topics: Antithrombins; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Feasibility Studies; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Recombinant Proteins; Sirolimus; Terminology as Topic; Treatment Outcome

The use of bivalirudin in percutaneous coronary interventions has been shown to be clinically safe and effective, and may be associated with shorter hospital stays and lower costs than heparin + glycoprotein (GP) IIb/IIIa inhibition. This study compared the utilization, clinical outcomes and costs associated with the planned use of bivalirudin versus heparin + GP IIb/IIIa inhibition in drug-eluting stent (DES) patients without acute myocardial infarction (MI).. We retrospectively studied 1,842 patients who underwent DES placement between May 2003 and December 2004. Planned treatment with heparin + GP IIb/IIIa inhibition was administered to 1,305 and planned bivalirudin alone was administered to 537 patients. Clinical follow ups (mean = 782 +/- 204 days) were obtained via telephone or mailed surveys in 1,813 patients (98.4%). Propensity analysis was utilized to adjust for between-groups baseline differences.. The unadjusted data revealed similar in-hospital outcomes in both groups. After propensity adjustment, the rate of vascular complications was significantly lower in the bivalirudin-treated group (0.2% vs. 1.2%; p = 0.04). At 1 year, clinical outcomes were similar in both groups. The overall unadjusted and adjusted cost analysis revealed similar mean hospital costs (11,384 U.S. dollars vs. 11,018 U.S. dollars; p = ns) and length of stay (2.9 days vs. 2.8 days; p = ns) in both groups. The unadjusted and adjusted mean hospital costs were significantly lower in patients treated with bivalirudin versus patients who received heparin + abciximab.. These observations suggest that bivalirudin is a safe, cost-effective alternative to heparin + GP IIb/IIIa inhibition in patients undergoing DES in the absence of acute MI.

Topics: Abciximab; Aged; Antibodies, Monoclonal; Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Drug Therapy, Combination; Eptifibatide; Female; Heparin; Hirudins; Humans; Immunoglobulin Fab Fragments; Immunosuppressive Agents; Length of Stay; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Peptide Fragments; Peptides; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Retrospective Studies; Sirolimus; Stents; Tirofiban; Treatment Outcome; Tyrosine

Topics: Anticoagulants; Coronary Artery Disease; Costs and Cost Analysis; Drug Delivery Systems; Heparin; Hirudins; Humans; Immunosuppressive Agents; Length of Stay; Myocardial Infarction; Paclitaxel; Peptide Fragments; Platelet Glycoprotein GPIIb-IIIa Complex; Recombinant Proteins; Sirolimus; Stents

Sirolimus-eluting stents (SESs) reduce restenosis compared with bare metal stents. Safety issues with drug-eluting stents are particularly important given concerns of possible increased thrombogenicity. Compared with heparin plus glycoprotein IIb/IIIa inhibitors, the direct thrombin inhibitor bivalirudin has been shown to reduce the risk of hemorrhagic complications in patients receiving bare metal stents, with similar efficacy in preventing ischemic complications. The safety and efficacy of percutaneous coronary intervention (PCI) with SESs and bivalirudin anticoagulation have not been prospectively studied. This prospective study performed at 9 United States hospitals evaluated 1,182 patients referred for PCI with SESs in whom the procedural anticoagulant was bivalirudin. Clopidogrel was administered before PCI in 79% of patients, and only 5.3% received procedural glycoprotein IIb/IIIa inhibitors. At 30 days, major adverse cardiac events occurred in 7.1% of patients, including 0.3% mortality, 4.4% myocardial infarction (defined as creatine kinase-MB >3x normal), 1.7% target vessel revascularization, and 0.6% stent thrombosis. Major bleeding occurred in only 0.8% of patients. Thus, use of bivalirudin as the procedural anticoagulant to support SES implantation in a "real world" population of patients undergoing PCI results in low rates of major adverse cardiac events, stent thrombosis, and major bleeding.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Coated Materials, Biocompatible; Coronary Disease; Coronary Restenosis; Follow-Up Studies; Hirudins; Hospital Mortality; Humans; Immunosuppressive Agents; Middle Aged; Peptide Fragments; Prospective Studies; Recombinant Proteins; Risk Factors; Safety; Sirolimus; Stents; Treatment Outcome; United States

Bivalirudin (Angiomax) is increasingly used as a substitute for heparin in a variety of percutaneous coronary interventions. This retrospective, observational study aimed to evaluate the efficacy and safety of bivalirudin compared with heparin as an antithrombotic regimen in patients treated with sirolimus-eluting stents (Cypher) and found that bivalirudin is clinically safe and feasible, with fewer vascular and ischemic complications compared with heparin.

Topics: Anticoagulants; Drug Carriers; Female; Heparin; Hirudins; Humans; Male; Middle Aged; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Sirolimus; Stents; Thrombosis