A Pilot Study of Prasugrel Followed by Post‐Procedural Maintenance with Clopidogrel in Patients Receiving Percutaneous Coronary Intervention

Background

Dual anti‐platelet therapy including clopidogrel or prasugrel is standard of care for patients receiving stents. Prasugrel has quicker onset so it can be loaded later than clopidogrel with greater efficacy. However, prasugrel is much more expensive than clopidogrel.

Objectives

To describe the incidence of 30‐day death from cardiovascular causes, myocardial infarction, unstable angina requiring intervention, and minor and major bleeding in patients loaded with 60 mg of prasugrel prior to percutaneous coronary intervention (PCI) and then continued on 75 mg of clopidogrel daily after the procedure.

Methods

We reviewed sequential medical records of 102 patients (Mean age: 67.8, male 68.6%, smokers: 22.6%, BMI: 29.5%, hypertension: 90.2%, DM: 33.3%, average ejection fraction: 49.7%) who underwent PCI (3.9% STEMI, 12.7% NSTEMI, 35.3% unstable angina and 48.1% electively) at Baylor University Medical Center between October 2009 and December 2011 who were loaded with prasugrel 60 mg prior to procedure, and then continued on 75 mg clopidogrel daily.

Results

None of the patients died or experienced a myocardial infarction (MI) within 30 days of the procedure. Three patients experienced unstable angina requiring intervention but none had in‐stent thrombosis or restenosis on repeat angiography. None of the patients experienced a major bleeding event. One patient developed a gastrointestinal bleed which did not require blood transfusion and the bleeding it resolved on discontinuation of the clopidogrel.

Conclusion

In this retrospective pilot study, a strategy of loading patients needing PCI with prasugrel 60 mg immediately prior to coronary intervention, then continuation of anti‐platelet therapy with 75 mg clopidogrel daily was safe and effective. (J Interven Cardiol 2013;26:38–42)

     

国产注射用比伐卢定和肝素在冠状动脉介入治疗术中对血小板功能的影响

目的:探讨国产注射用比伐卢定和肝素在经皮冠状动脉介入治疗(PCI)术中对血小板功能的影响. 方法:选择36例择期行PCI的患者,术中用肝素(肝索组,n=18)或国产注射用比伐卢定(比伐卢定组,n=18)抗凝.分别在用药前、用药后10 min、用药结束、用药结束后30 min、用药结束后2 h静脉采血,检测二磷酸腺苷诱导的血小板最大聚集率和血浆P选择素水平. 结果:肝素组患者用药后血小板最大聚集率及血浆P选择索水平升高,用药后10 min与用药前比较,差异均有统计学意义(P均<0.05),其余各时间点与用药前比较,差异均无统计学意义(P均>0.05).比伐卢定组患者血小板最大聚集率及血浆P选择素水平,用药后10 min及用药结束与用药前比较均降低(P均<0.05),差异均有统计学意义;用药结束后30 min与用药前比较,差异无统计学意义(P>0.05). 结论:与常规肝素抗凝相比,国产注射用比伐卢定作为抗凝剂应用于PCI术中可以短时间内降低血小板活性、抑制血小板聚集,具有暂时性抗血小板的功能.     

Prognosis of Percutaneous Coronary Intervention and Coronary Artery Bypass Grafts for Ostial Right Coronary Lesions in Propensity‐Matched Individuals

Objective: Our aim was to evaluate the relative safety and efficacy of percutaneous coronary intervention (PCI) with drug‐eluting stents (DES) versus coronary artery bypass grafts (CABG) for the treatment of ostial right coronary stenosis (ORCS) lesions. Methods: Three hundred fifty‐nine cases of ORCS lesion were treated via CABG (n = 232) or PCI (n = 127) procedures. Propensity scores for undergoing the CABG procedure were estimated and used to match 105 pairs of patients between the two groups. Kaplan–Meier major adverse cardiac and cerebrovascular events (MACCE)‐free curves were constructed to compare long‐term MACCE‐free survival between the two groups. Results: For the 105 propensity‐matched pairs, patients were more likely to undergo repeat revascularization with CABG in the PCI group than in the CABG group during the first 30 days (4 cases vs. 0 case, P= 0.043, χ²= 4.08) and the 1‐year follow‐up (5 cases vs. 0 case, P= 0.02, χ²= 5.17). With a mean follow‐up of 12.04 ± 6.47 months and a total of 210.67 patient–years, the freedom from MACCE in the CABG group was significantly higher than that in the PCI group (Log rank test, χ²= 4.48, P= 0.03). There were no significant differences in the rates of death, myocardial infarction, nonfatal stroke, death/myocardium infarction/stroke, or repeated PCI between the two groups during the first 30 days and during the 1‐year follow‐up period. Conclusion: For OCRS lesions, CABG provided greater protection than PCI procedure in terms of freedom from MACCE, mainly due to the reduced number of repeated revascularization procedures. CABG should be considered as first‐choice revascularization strategy for ORCS lesions.     

Outcomes of Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention Receiving an Oral Anticoagulant and Dual Antiplatelet Therapy: A Comparison of Clopidogrel Versus Prasugrel From the TRANSLATE-ACS Study

ObjectivesThe purpose of this study was to determine whether bleeding risk varies depending on which P2Y₁₂ receptor inhibitor agent is used.BackgroundPrior studies have shown significant bleeding risk among patients treated with triple therapy (i.e., oral anticoagulant, P2Y₁₂ receptor inhibitor, and aspirin).MethodsWe evaluated patients with acute myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) at 233 hospitals in the United States enrolled in the TRANSLATE-ACS (Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome) study (April 2010 to October 2012). Using inverse probability-weighted propensity modeling, we compared 6-month adjusted risks of Bleeding Academic Research Consortium (BARC) bleeding, stratifying by whether or not bleeding was associated with rehospitalization among patients discharged on aspirin + anticoagulant + clopidogrel (triple-C), aspirin + anticoagulant + prasugrel (triple-P), aspirin + clopidogrel (dual-C), or aspirin + prasugrel (dual-P).ResultsOf 11,756 MI patients, 526 (4.5%) were discharged on triple-C, 91 (0.8%) on triple-P, 7,715 (66%) on dual-C, and 3,424 (29%) on dual-P. Compared with dual-therapy patients, triple-therapy patients had significantly higher any BARC-defined bleeding. Triple-P was associated with a greater risk of any BARC-defined bleeding events compared with triple-C. This finding was driven mostly by an increased risk of bleeding events that were patient-reported only and did not require rehospitalization. There were no significant differences in bleeding requiring rehospitalization between the triple-P and -C groups.ConclusionsAmong MI patients, the addition of an oral anticoagulant was associated with a significantly greater risk of any BARC-defined bleeding relative to dual antiplatelet therapy, regardless of which P2Y₁₂ receptor inhibitor was selected. Among patients on triple therapy, prasugrel use was associated with higher patient-reported–only bleeding, but not bleeding requiring rehospitalization, than clopidogrel-treated patients.     

Bivalirudin versus Unfractionated Heparin during Percutaneous Coronary Intervention in Patients at High Risk for Bleeding

Low/medium-bleeding-risk populations undergoing percutaneous coronary intervention (PCI) show significantly less bleeding with bivalirudin (BIV) than with unfractionated heparin (UFH), but this has not been established for high-risk patients. We performed a randomized double-blind prospective trial comparing efficacy and safety of BIV versus UFH combined with dual antiplatelet therapy during PCI among 100 high-risk patients with non-ST elevation myocardial infarction (NSTEMI) or angina pectoris. The baseline characteristics were similar in both treatment arms. A radial approach was used in 84% of patients with a higher rate in the BIV group (90 vs. 78%, p < 0.05). Study end points were: major and minor bleeding, port-of-entry complications, major adverse cardiac events (MACE) in-hospital, and at long-term follow-up. There was one case of major gastrointestinal bleeding in the BIV group and 7% minor bleeding complications in both categories. Rate of periprocedural myocardial infarction (PPMI) in the BIV group was twice that in the UFH group (20 vs. 10%, p < 0.16). In-hospital MACE rate was higher in BIV patients as well (12 vs. 2%, p = 0.1). By univariate analysis, the femoral approach was the predictor of PPMI and in-hospital MACE. In a multivariate model, the independent predictor of PPMI was previous MI (odds ratio, 7.7; p < 0.0158). PPMI was 49.7 times more likely with the femoral approach plus BIV than the nonfemoral approach plus UFH (p < 0.0021). At 41.5 ± 14 months'' follow-up, end points did not significantly differ between the groups. In patients at high risk for bleeding undergoing PCI, BIV was not superior to UFH for bleeding complications, and early and late clinical outcomes.     

Bivalirudin in Percutaneous Coronary Interventions and Acute Coronary Syndromes: New Concepts, New Directions

Inhibition of thrombin and platelets during percutaneous coronary intervention (PCI), using a combination of unfractionated heparin and aspirin, is designed primarily to minimize the rare but devastating potential acute thrombotic complications of the procedure. Direct thrombin inhibitors, such as bivalirudin (formerly Hirulog, The Medicines Company, Cambridge, MA), offer specific theoretic advantages over unfractionated heparin as antithrombin therapy. This review focuses on the pharmacologic promise and the clinical performance of bivalirudin in PCI, and in the pharmacologic management of acute coronary syndromes. Clinical experience with bivalirudin in PCI preceded recent dramatic advances in mechanical interventional techniques and the emergence of novel potent platelet inhibitors. The role of bivalirudin and other direct thrombin inhibitors in the modern era of coronary intervention therefore requires further elucidation.     

Longitudinal Geographic Miss (LGM) in Robotic Assisted Versus Manual Percutaneous Coronary Interventions

Objectives

To evaluate the impact of robotic‐assisted percutaneous coronary intervention (RA‐PCI) versus manual PCI (M‐PCI) on the incidence of Longitudinal Geographic Miss (LGM).

Background

The safety and feasibility of RA‐PCI has been established in preclinical animal trials and human clinical trials. Patients with LGM have been shown to have worse clinical outcomes including significantly increased incidences of MACE.

Methods

Patients with significant coronary artery disease underwent RA‐PCI in the PRECISE study (n=164) and standard M‐PCI in the STLLR trial (n = 1,509). Longitudinal geographic miss was defined as cases where the entire length of the injured or stenotic segment was not fully covered by the total length of the stent. The incidence of LGM was compared between RA‐PCI and M‐PCI cohorts.

Results

The RA‐PCI cohort had a significantly greater prevalence of previous MI, previous coronary revascularization, and unstable angina. The robotic cohort exhibited a lower incidence of LGM when compared to the M‐PCI patients, 12.2% to 43.1%, respectively (P < 0.0001). To account for the differences in baseline characteristics between the two studies, a propensity score analysis was conducted. The propensity modeling showed similar rates of LGM in both a larger group of patients that met key PRECISE study inclusion/exclusion criteria adjusted for propensity score (9.3% vs 55.0%; P < 0.0001) and in a smaller, matched on propensity score, subset of patients (10.3% vs 64.1%; P < 0.0001).

Conclusion

Robotic‐assisted PCI had significantly lower incidence of LGM compared to standard M‐PCI. Reducing LGM potentially improves long‐term clinical outcomes through reduction in MACE. (J Interven Cardiol 2015;28:449–455)

     

Collagen Plug Vascular Closure Devices and Reduced Risk of Bleeding with Bivalirudin Versus Heparin Plus Abciximab in Patients Undergoing Percutaneous Coronary Intervention for Non ST‐Segment Elevation Myocardial Infarction

Introduction

In ISAR‐REACT‐4 (abciximab and heparin vs. bivalirudin for non‐ST‐elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI.

Methods

Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end‐point of this analysis was the 30‐day incidence of ISAR‐REACT‐4 major bleeding.

Results

A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR‐ REACT‐4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end‐points or net clinical outcome (Pint > 0.56).

Conclusions

In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.

     

Prasugrel Versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Trials

Purpose

Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel is the mainstay of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to systematically perform a head-to-head comparison of ticagrelor vs prasugrel in terms of efficacy and safety.

Methods

We searched PubMed/Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomized controlled trials (RCTs). The primary outcome was adverse cardiovascular events and secondary outcome was bleeding events. A random-effects meta-analysis was used to obtain the pooled estimate of each outcome.

Results

Nine RCTs with a total number of 6990 patients (3550 treated with prasugrel and 3481 treated with ticagrelor) were included. No significant difference between prasugrel and ticagrelor was observed in terms of mortality (OR 0.86, 95% CI 0.66 to 1.13, P?=?0.28), major adverse cardiovascular events (MACEs) (OR 0.85, 95% CI 0.70 to 1.03, P?=?0.10), non-fatal myocardial infarction (OR 0.78, 95% CI 0.57 to 1.06, P?=?0.11), stroke (OR 1.02, 95% CI 0.60 to 1.72, P?=?0.95), stent thrombosis (OR 0.76, 95% CI 0.47 to 1.21, P?=?0.25), thrombolysis in myocardial infarction (TIMI) defined major (OR 0.94, 95% CI 0.19 to 4.67, P?=?0.94), minor (OR 0.35, 95% CI 0.08 to 1.62, P?=?0.18) and minimal (OR 0.48, 95% CI 0.19 to 1.18, P?=?0.11) bleeding and Bleeding Academic Research Consortium (BARC) defined bleeding (OR 1.06, 95% CI 0.82 to 1.36, P?=?0.68).

Conclusion

In patients with ACS undergoing PCI, both prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events.

     

Novel Approaches for Preventing or Limiting Events (Naples) III Trial: Randomized Comparison of Bivalirudin Versus Unfractionated Heparin in Patients at Increased Risk of Bleeding Undergoing Transfemoral Elective Coronary Stenting

ObjectivesThis study sought to assess the safety and the efficacy of bivalirudin compared with unfractionated heparin (UFH) alone in the subset of patients at increased risk of bleeding undergoing transfemoral elective percutaneous coronary intervention (PCI).BackgroundBivalirudin, a synthetic direct thrombin inhibitor, determines a significant decrease of in-hospital bleeding following PCI.MethodsThis is a single-center, investigator-initiated, randomized, double-blind, controlled trial. Consecutive biomarker-negative patients at increased bleeding risk undergoing PCI through the femoral approach were randomized to UFH (UFH group; n = 419) or bivalirudin (bivalirudin group; n = 418). The primary endpoint was the rate of in-hospital major bleeding.ResultsThe primary endpoint occurred in 11 patients (2.6%) in the UFH group versus 14 patients (3.3%) in the bivalirudin group (odds ratio: 0.78; 95% confidence interval: 0.35 to 1.72; p = 0.54). Distribution of access-site and non–access-site bleeding was 18% and 82% in the UFH group versus 50% and 50% in the bivalirudin group (p = 0.10).ConclusionsThe results of this randomized study, carried out at a single institution, suggest that there is no difference in major bleeding rate between bivalirudin and UFH in increased-risk patients undergoing transfemoral PCI. (Novel Approaches in Preventing and Limiting Events III Trial: Bivalirudin in High-Risk Bleeding Patients [NAPLES III]; NCT01465503)     

Comparison of Prasugrel and Bivalirudin vs Clopidogrel and Heparin in Patients With ST‐Segment Elevation Myocardial Infarction: Design and Rationale of the Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 Trial

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST‐segment elevation myocardial infarction (STEMI). Effective and safe adjunct antithrombotic therapy is a major determinant for short‐ and long‐term outcomes after primary PCI. Two separate studies have shown significant benefits vs conventional therapy for 2 recently approved drugs. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS‐AMI) trial, bivalirudin after pretreatment with clopidogrel resulted in improved net clinical outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors. However, during the first 24 hours after PCI, there was an increase in stent thrombosis rates with bivalirudin. In the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel—Thrombolysis In Myocardial Infarction (TRITON‐TIMI) 38 trial, prasugrel was superior to clopidogrel in patients with acute coronary syndrome with and without ST‐segment elevation. The synergic actions of prasugrel and bivalirudin may maximize the benefit of antithrombotic therapy for STEMI patients undergoing primary PCI. However, no specifically designed studies have so far compared the combination of prasugrel plus bivalirudin with that of clopidogrel plus unfractionated heparin in these patients. The Bavarian Reperfusion Alternatives Evaluation (BRAVE) 4 study is a randomized, open‐label, multicenter trial aimed to test the hypothesis that a strategy based on prasugrel plus bivalirudin is superior to a strategy based on clopidogrel plus unfractionated heparin in terms of net clinical outcome in STEMI patients with planned primary PCI.     

Early Outcomes With Direct Flow Medical Versus First‐Generation Transcatheter Aortic Valve Devices: A Single‐Center Propensity‐Matched Analysis

Objectives

To compare early outcomes between Direct Flow Medical (DFM) and 1^st‐generation transcatheter aortic valve replacement (TAVR) devices.

Background

The effectiveness of new‐generation TAVR devices compared with earlier generations is unclear.

Methods and Results

Overall, 496 patients treated between November 2007 and March 2014 were included: 44 (8.7%) treated with DFM, 179 (36.9%) with Medtronic CoreValve (MCV) and 273 (54.4%) with Edwards Sapien / Sapien XT (SXT) valve. Because of differences in baseline characteristics, propensity‐score matching among patients treated in the same time span (March 2012–March 2014) was performed. The primary objective was the VARC‐2 device success composite endpoint. Propensity‐score matching identified 41 patients in each group. A higher device success composite endpoint was observed in DFM (DFM 97.6% vs. MCV 65.9% vs. SXT 92.7%; P < 0.001). This was attributed to a significantly lower incidence of moderate‐to‐severe post‐procedural aortic regurgitation (AR; 2.4% vs. 22% vs. 7.3%; P < 0.001), lower rate of valve embolization (0% vs. 7.3% vs. 0%; 0.041) and need for a 2nd valve implantation (0% vs. 7.3% vs. 0%; P = 0.041).

Conclusions

DFM was associated with higher rates of device success and a lower incidence of post‐procedural AR. New generation devices appear to address several of the limitations of earlier generation devices. (J Interven Cardiol 2015;28:583–593)