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Coronary Artery Disease: HELP
Articles by Neil S. Kleiman
Based on 36 articles published since 2008

Between 2008 and 2019, Neal Kleiman wrote the following 36 articles about Coronary Artery Disease.
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Stenting: the Latest Frontier in Percutaneous Intervention. 2018

Kleiman, Neal. · ·Methodist Debakey Cardiovasc J · Pubmed #29623166.

ABSTRACT: -- No abstract --

2 Editorial Bringing it all together: integration of physiology with anatomy during cardiac catheterization. 2011

Kleiman, Neal S. · ·J Am Coll Cardiol · Pubmed #21903053.

ABSTRACT: -- No abstract --

3 Editorial Searching for the ceiling: new reflections on the disposition and metabolism of clopidogrel. 2008

Kleiman, Neal S. · ·JACC Cardiovasc Interv · Pubmed #19463376.

ABSTRACT: -- No abstract --

4 Review Long-Term Outcomes of Drug-Eluting Stents Versus Bare-Metal Stents in End-Stage Renal Disease Patients on Dialysis: A Systematic Review and Meta-Analysis. 2018

Khera, Sahil / Villablanca, Pedro A / Kolte, Dhaval / Gupta, Tanush / Hasan Khan, Mohammed / Velagapudi, Poonam / Kalra, Ankur / Kleiman, Neal / Aronow, Herbert D / Abbott, J Dawn / Rosenfield, Kenneth / Drachman, Douglas E / Bangalore, Sripal / Bhatt, Deepak L / Naidu, Srihari S. ·From the Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. · Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. · Division of Cardiology, Warren Alpert Medical School, Brown University, Providence, RI. · Division of Cardiology, New York Medical College and Westchester Medical Center, Valhalla, NY. · Harrington Heart & Vascular Institute at University Hospitals Cleveland Medical Center, Cleveland, OH. · Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX. · Division of Cardiology, New York University Medical Center, New York, NY. · Division of Cardiology, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, MA. ·Cardiol Rev · Pubmed #30157064.

ABSTRACT: There are no dedicated data to guide drug-eluting stent (DES) versus bare-metal stent (BMS) selection in patients with end-stage renal disease undergoing dialysis (ESRD-D). It is unclear whether long-term benefits of a specific stent type outweigh risks in this population at high risk for both bleeding and ischemic events. We performed a meta-analysis of nonrandomized studies extracted from PubMed, Scopus, and EMBASE, assessing the safety and effectiveness of DES versus BMS in ESRD-D patients. Odds ratios (OR) and 95% confidence intervals (CI) were computed with the Mantel-Haenszel method. Random-effects model was used for all analyses. A total of 17 nonrandomized studies (N = 63,157; 41,621 DES and 21,536 BMS) met the inclusion criteria and were included for the final quantitative analysis: median follow-up of 1 year (range: 9 months to 6 years). The use of DES in ESRD-D patients was associated with lower all-cause mortality (OR 0.75, 95% CI 0.64-0.89, P < 0.001) compared with BMS. The use of DES was also associated with lower rates of cardiovascular mortality (OR 0.75, 95% CI 0.60-0.99, P = 0.047) and target lesion/vessel revascularization (OR 0.78, 95% CI 0.64-0.94, P = 0.01). However, there were no differences in noncardiovascular mortality, myocardial infarction, stent thrombosis, stroke, or major bleeding in DES versus BMS. In this largest meta-analysis of long-term outcomes after percutaneous coronary intervention in ESRD-D patients, DES was associated with lower rates of all-cause mortality, target lesion/vessel revascularization, and cardiovascular death.

5 Review Reticulated Platelets: Changing Focus from Basics to Outcomes. 2018

Hannawi, Bashar / Hannawi, Yousef / Kleiman, Neal S. ·Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas, United States. · Division of the Cerebrovascular Diseases and Neurocritical Care, Department of Neurology, The Ohio State University, Columbus, Ohio, United States. ·Thromb Haemost · Pubmed #30103247.

ABSTRACT: Platelets play an essential role in the pathophysiology of atherothrombosis. Reticulated platelets (RPs) are the youngest platelet population in the circulation; their presence is an indicator of platelet turnover. Circulating levels of RPs are increased in patients with coronary artery disease and stroke. Preliminary indications are that the proportion of circulating RP is associated with the likelihood of ischaemic events such as acute coronary syndrome and stroke. Plausible mechanisms include: (1) increased participation of these platelets in thrombosis due to messenger ribonucleic acid that may be translated to active proteins, (2) lack of exposure to anti-platelet drugs since they are newly released from the bone marrow or (3) their presence is a non-specific marker of inflammation. In this state-of-the-art review, we discuss the implication of RP in coronary artery disease and in hypo-responsiveness to the most commonly used anti-platelet drugs.

6 Review Mechanical Circulatory Support in High-Risk Percutaneous Coronary Intervention. 2018

Aggarwal, Bhuvnesh / Aman, Wahaj / Jeroudi, Omar / Kleiman, Neal S. ·HOUSTON METHODIST DEBAKEY HEART & VASCULAR CENTER, HOUSTON METHODIST HOSPITAL, HOUSTON, TEXAS. ·Methodist Debakey Cardiovasc J · Pubmed #29623169.

ABSTRACT: Due to advancing age and increasing comorbidities, the current population has a higher incidence of complex coronary artery disease, often without surgical options for revascularization. In this setting, hemodynamic support devices are an important adjunct in the interventionist's toolbox as they allow for a safer, more effective procedure. The following paper reviews the indications of various available mechanical support devices, highlights their clinical data and technical parameters, and offers a practical approach towards appropriate patient and device selection.

7 Review Platelet pathophysiology, pharmacology, and function in coronary artery disease. 2017

Ibrahim, Homam / Kleiman, Neal S. ·aDepartment of Cardiology, New York Langone Medical Center, New York, New York bDepartment of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, Texas, USA. ·Coron Artery Dis · Pubmed #28644213.

ABSTRACT: Platelets play a key role in the pathophysiology of coronary artery disease and acute coronary syndromes. Our understanding of platelet function in thrombus formation has increased considerably, resulting in the development of clinically effective treatment strategies and identification of new targets. An underappreciated platelet function is their contribution toward acute and chronic inflammatory processes including atherogenesis. In this review, we discuss the role of platelets in atherosclerosis and thrombosis, platelet function testing, and the pharmacology of currently available antiplatelet drugs.

8 Review Bioresorbable Scaffold: The Emerging Reality and Future Directions. 2017

Sotomi, Yohei / Onuma, Yoshinobu / Collet, Carlos / Tenekecioglu, Erhan / Virmani, Renu / Kleiman, Neal S / Serruys, Patrick W. ·From the Department of Cardiology, Academic Medical Center, University of Amsterdam, the Netherlands (Y.S., C.C.) · ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands (Y.O., E.T.) · Cardialysis, Rotterdam, the Netherlands (Y.O.) · CVPath, Institute Inc, Gaithersburg, MD (R.V.) · Department of Cardiology (NSK), Houston Methodist DeBakey Heart and Vascular Center, Texas (N.S.K.) · and NHLI, Imperial College London, United Kingdom (P.W.S.). ·Circ Res · Pubmed #28408454.

ABSTRACT: In the era of drug-eluting stents, large-scale randomized trials and all-comer registries have shown excellent clinical results. However, even the latest-generation drug-eluting stent has not managed to address all the limitations of permanent metallic coronary stents, such as the risks of target lesion revascularization, neoatherosclerosis, preclusion of late lumen enlargement, and the lack of reactive vasomotion. Furthermore, the risk of very late stent, although substantially reduced with newer-generation drug-eluting stent, still remains. These problems were anticipated to be solved with the advent of fully biodegradable devices. Fully bioresorbable coronary scaffolds have been designed to function transiently to prevent acute recoil, but have retained the capability to inhibit neointimal proliferation by eluting immunosuppressive drugs. Nevertheless, long-term follow-up data of the leading bioresorbable scaffold (Absorb) are becoming available and have raised a concern about the relatively higher incidence of scaffold thrombosis. To reduce the rate of clinical events, improvements in the device, as well as implantation procedure, are being evaluated. This review will focus on the current CE-mark approved bioresorbable scaffolds, their basic characteristics, and clinical results. In addition, we summarize the current limitations of bioresorbable scaffold and their possible solutions.

9 Review New-Generation Coronary Stents: Current Data and Future Directions. 2017

Kalra, Ankur / Rehman, Hasan / Khera, Sahil / Thyagarajan, Braghadheeswar / Bhatt, Deepak L / Kleiman, Neal S / Yeh, Robert W. ·Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX, USA. · Weill Cornell Medical College, New York, NY, USA. · Safety, Quality, Informatics and Leadership Program, 2016-17, Harvard Medical School, Boston, MA, USA. · New York Medical College, White Plains, NY, USA. · Department of Internal Medicine, Monmouth Medical Center, Long Branch, NJ, USA. · Brigham and Women's Heart and Vascular Center, Harvard Medical School, Boston, MA, USA. · The Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. ryeh@bidmc.harvard.edu. ·Curr Atheroscler Rep · Pubmed #28220461.

ABSTRACT: PURPOSE OF REVIEW: Drug-eluting stents are the mainstay in the treatment of coronary artery disease using percutaneous coronary intervention. Innovations developed to overcome the limitations of prior generations of stents include biodegradable polymer stents, drug-eluting stents without a polymer, and bioabsorbable scaffolds. Our review briefly discusses the clinical profiles of first- and second-generation coronary stents, and provides an up-to-date overview of design, technology, and clinical safety and efficacy profiles of newer generation coronary stents discussing the relevant clinical trials in this rapidly evolving area of interventional cardiology. RECENT FINDINGS: Drug-eluting stents have previously been shown to be superior to bare metal stents. Second-generation everolimus-eluting stents have proven to have superior outcomes compared with first-generation paclitaxel- and sirolimus-eluting stents, and the second-generation zotarolimus-eluting stents appear to be similar to the everolimus-eluting stents, though with a lesser degree of evidence. Stents with biodegradable polymers have not been shown to be superior to everolimus-eluting stents. Bioabsorbable scaffolds have not demonstrated better outcomes than current standard treatment with second-generation drug-eluting stents but have showed a concerning signal of late and very late stent thrombosis. Everolimus-eluting stents have the most favorable outcomes in terms of safety as well as efficacy in patients undergoing percutaneous coronary intervention. Newer innovations such as biodegradable polymers and bioabsorbable scaffolds lack clinical data to replace second-generation drug-eluting stents as standard of care.

10 Review Stenting of a left main coronary artery compressed by a dilated main pulmonary artery. 2013

Chaikriangkrai, Kongkiat / Polsani, Venkateshwar / Wei, Liu / Kleiman, Neal / Chang, Su Min. ·Department of Medicine, the Methodist Hospital, Houston, Texas. ·Catheter Cardiovasc Interv · Pubmed #23804497.

ABSTRACT: Left main coronary artery (LMCA) disease caused by external compression by a dilated main pulmonary artery (MPA) is an uncommon clinical entity but is one of the reversible causes of chest pain in patients with pulmonary hypertension. Traditionally, treatment of LMCA disease involves coronary artery bypass graft surgery. However, for LMCA compression by a dilated MPA, coronary angioplasty with stenting has recently been reported to have good outcomes and might be more suitable in some patients with high risk associated with surgery. Herein, we describe a 54-year-old man with pulmonary arterial hypertension and external compression of the LMCA by the dilated main pulmonary artery that was treated with angiographic and intravascular ultrasound-guided coronary angioplasty and stenting. Also we briefly review current literatures about LMCA compression by a dilated MPA.

11 Review Percutaneous coronary intervention vs. coronary artery bypass graft surgery for unprotected left main coronary artery disease in the drug-eluting stents era--an aggregate data meta-analysis of 11,148 patients. 2013

Alam, Mahboob / Huang, Henry D / Shahzad, Saima A / Kar, Biswajit / Virani, Salim S / Rogers, Paul A / Paniagua, David / Bozkurt, Biykem / Palacios, Igor / Kleiman, Neal S / Jneid, Hani. ·Baylor College of Medicine, Houston, TX 77030, USA. ·Circ J · Pubmed #23123552.

ABSTRACT: BACKGROUND: Patients with unprotected left main coronary artery (LMCA) disease are increasingly treated with percutaneous coronary intervention (PCI) using drug-eluting stents (DES), but its benefits compared with coronary artery bypass grafting (CABG) remain controversial. We hypothesized that PCI with DES for unprotected LMCA disease is safe and effective compared with CABG. METHODS AND RESULTS: We performed aggregate data meta-analyses of clinical outcomes [death; non-fatal myocardial infarction (MI); stroke; repeat revascularization; and major adverse cardiac and cerebrovascular events (MACCE)] in studies comparing PCI with DES vs. CABG in patients with LMCA disease. A comprehensive literature search (01/01/2003 to 12/01/2011) identified 27 studies comparing PCI and CABG (11,148 patients). Summary odds ratios (OR) were calculated using a random-effects model. At 30 days, PCI for unprotected LMCA disease was associated with lower MACCE [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.36-0.89) and stroke rates (OR 0.22, 95% CI 0.11-0.44) compared with CABG. At 12 months, the PCI group experienced higher rates of repeat revascularization (OR 3.72, 95% CI 2.75-5.03), but lower rates of stroke (OR 0.25, 95% CI 0.14-0.44) and all-cause death (OR 0.69, 95% CI 0.49-0.97). At the longest follow-up of 60 months, PCI was associated with equivalent mortality, lower rates of stroke (OR 0.42, 95% CI 0.28-0.62) and higher rates of MACCE (OR 1.30, 95% CI 1.10-1.55) and repeat revascularization (OR 3.54, 95% CI 2.75-4.54). CONCLUSIONS: In the DES era, PCI for unprotected LMCA disease is associated with equivalent mortality and MI, lower stroke rates and higher rates of repeat revascularization compared with CABG.

12 Review Assessment, mechanisms, and clinical implication of variability in platelet response to aspirin and clopidogrel therapy. 2009

Ben-Dor, Itsik / Kleiman, Neal S / Lev, Eli. ·Department of Cardiology, Rabin Medical Center and Tel Aviv University, Tel Aviv, Israel. ·Am J Cardiol · Pubmed #19576352.

ABSTRACT: Antiplatelet therapy is the mainstay of treatment for patients with cardiovascular disease. However, some patients experience adverse cardiac events despite treatment with single- or dual-antiplatelet (aspirin and clopidogrel) therapy. Some of those events could be caused by low responsiveness to aspirin or clopidogrel. The frequency of this phenomenon has been reported to range from 1% to 45% for the 2 drugs. This wide range arises from the lack of a "gold-standard" definition to assess antiplatelet drug response and differences in assays, agonist concentrations, and cut-off points. Regardless of the variability in the incidence of aspirin or clopidogrel low responsiveness, several studies have indicated a clear relation between clopidogrel or aspirin low responsiveness and cardiovascular events. The evidence for an association between adverse clinical events and the results of ex vivo platelet function tests is stronger for clopidogrel than for aspirin. Currently, there is no established therapeutic approach for managing low response to aspirin or clopidogrel that has been shown in large trials to have clinical benefit. This review focuses on laboratory testing of antiplatelet response to aspirin and clopidogrel, the prevalence of low response, potential mechanisms, clinical significance, and prognostic value of this phenomenon and alternative approaches to optimize treatment in patients with low response to the drugs.

13 Review Combining antiplatelet and anticoagulant therapies. 2009

Holmes, David R / Kereiakes, Dean J / Kleiman, Neal S / Moliterno, David J / Patti, Giuseppe / Grines, Cindy L. ·Mayo Clinic Department of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. holmes.david@mayo.edu ·J Am Coll Cardiol · Pubmed #19573725.

ABSTRACT: Antiplatelet therapy is the cornerstone for both primary and secondary prevention therapies for ischemic events resulting from coronary atherosclerotic disease. Dual antiplatelet therapy (aspirin plus a thienopyridine, usually clopidogrel) has assumed a central role in the treatment of acute coronary syndromes and after coronary stent deployment. In addition to antiplatelet therapy, anticoagulant therapy might be indicated for stroke prevention in a variety of conditions that include atrial fibrillation, profound left ventricular dysfunction, and after mechanical prosthetic heart valve replacement. For this reason, the use of triple antithrombotic therapy (a dual antiplatelet regimen plus warfarin) is expected to become more prominent, given an aging patient population. But although triple therapy can prevent both thromboembolism and stent thrombosis, it is also associated with significant bleeding hazards. Furthermore, when bleeding events do occur, the challenge of balancing the risk of stent thrombosis or stroke and the need for hemostasis requires considerable expertise. It is both prudent and timely to review treatment strategies that employ combinations of antiplatelet and anticoagulant therapies as well as strategies aimed at reducing bleeding risk in patients treated with these therapies.

14 Clinical Trial Prognostic implications of creatine kinase-MB elevation after percutaneous coronary intervention: results from the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry. 2011

Lindsey, Jason B / Kennedy, Kevin F / Stolker, Joshua M / Gilchrist, Ian C / Mukherjee, Debabrata / Marso, Steven P / Pencina, Michael J / Kleiman, Neal S / Cohen, David J. ·Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO 64111, USA. ·Circ Cardiovasc Interv · Pubmed #21972402.

ABSTRACT: BACKGROUND: Creatine kinase-MB (CK-MB) elevation after percutaneous coronary intervention (PCI) has been associated with increased risk for mortality. Although most studies have defined periprocedural myocardial infarction (pMI) as an elevation in CK-MB >3× upper limit of normal (ULN), use of different CK-MB assays and variation in site-specific definitions of the ULN may limit the value of such relative thresholds. METHODS AND RESULTS: We used data from the multicenter Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry to examine the impact of variations in site-specific thresholds for CK-MB elevation on the incidence of pMI as well as the relationship between absolute peak levels of CK-MB after PCI and 1-year mortality. The study cohort consisted of 6347 patients who underwent nonemergent PCI and had normal CK-MB at baseline. Across the 59 study centers, the ULN for CK-MB ranged from 2.6 to 10.4 ng/mL (median, 5.0 ng/mL), and there was an inverse relationship between the site-specific ULN and the incidence of pMI (defined as CK-MB elevation >3× ULN). Although any postprocedure elevation of CK-MB was associated with an adverse prognosis, in categorical analyses, only CK-MB ≥50 ng/mL was independently associated with increased 1-year mortality (hazard ratio, 4.71; 95% confidence interval, 2.42 to 9.13; P<0.001). Spline analysis using peak CK-MB as a continuous variable suggested a graded, nonlinear relationship with 1-year mortality, with an inflection point at ≈30 ng/mL. CONCLUSIONS: Among unselected patients undergoing PCI, there is a graded relationship between CK-MB elevation after PCI and 1-year mortality that is particularly strong for large CK-MB elevations (>30 to 50 ng/mL). Future studies that include pMI as a clinical end point should consider using a core laboratory to assess CK-MB (to ensure consistency) and raising the threshold for defining pMI above current levels (to enhance clinical relevance).

15 Clinical Trial Evaluation of a new heparin agent in percutaneous coronary intervention: results of the phase 2 evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) Trial. 2010

Rao, Sunil V / Melloni, Chiara / Myles-Dimauro, Shelley / Broderick, Samuel / Kosinski, Andrzej S / Kleiman, Neal S / Dzavík, Vladimír / Tanguay, Jean Francois / Chandna, Harish / Gammon, Roger / Rivera, Ernesto / Alexander, John H / Fier, Ian / Roach, James / Becker, Richard C / Anonymous3890657. ·Duke Clinical Research Institute, Durham, NC, USA. sunil.rao@duke.edu ·Circulation · Pubmed #20368520.

ABSTRACT: BACKGROUND: Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low-molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low-molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention. METHODS AND RESULTS: Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention-related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable. CONCLUSIONS: This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400.

16 Clinical Trial Phase 1b randomized study of antidote-controlled modulation of factor IXa activity in patients with stable coronary artery disease. 2008

Chan, Mark Y / Cohen, Mauricio G / Dyke, Christopher K / Myles, Shelley K / Aberle, Laura G / Lin, Min / Walder, James / Steinhubl, Steven R / Gilchrist, Ian C / Kleiman, Neal S / Vorchheimer, David A / Chronos, Nicholas / Melloni, Chiara / Alexander, John H / Harrington, Robert A / Tonkens, Ross M / Becker, Richard C / Rusconi, Christopher P. ·Duke Clinical Research Institute, 2400 Pratt St, Terrace Level Room 0311, Durham, NC 27705, USA. ·Circulation · Pubmed #18506005.

ABSTRACT: BACKGROUND: Whether selective factor IXa inhibition produces an appropriate anticoagulant effect when combined with platelet-directed therapy in patients with stable coronary artery disease is unknown. REG1 consists of RB006 (drug), an injectable RNA aptamer that specifically binds and inhibits factor IXa, and RB007 (antidote), the complementary oligonucleotide that neutralizes its anti-IXa activity. METHODS AND RESULTS: We evaluated the safety, tolerability, and pharmacodynamic profile of REG1 in a randomized, double-blind, placebo-controlled study, assigning 50 subjects with coronary artery disease taking aspirin and/or clopidogrel to 4 dose levels of RB006 (15, 30, 50, and 75 mg) and RB007 (30, 60, 100, and 150 mg). The median age was 61 years (25th and 75th percentiles, 56 and 68 years), and 80% of patients were male. RB006 increased the activated partial thromboplastin time dose dependently; the median activated partial thromboplastin time at 10 minutes after a single intravenous bolus of 15, 30, 50, and 75 mg RB006 was 29.2 seconds (25th and 75th percentiles, 28.1 and 29.8 seconds), 34.6 seconds (25th and 75th percentiles, 30.9 and 40.0 seconds), 46.9 seconds (25th and 75th percentiles, 40.3 and 51.1 seconds), and 52.2 seconds (25th and 75th percentiles, 46.3 and 58.6) (P<0.0001; normal 25th and 75th percentiles, 27 and 40 seconds). RB007 reversed the activated partial thromboplastin time to baseline levels within a median of 1 minute (25th and 75th percentiles, 1 and 2 minutes) with no rebound increase through 7 days. No major bleeding or other serious adverse events occurred. CONCLUSIONS: This is the first experience of an RNA aptamer drug-antidote pair achieving inhibition and active restoration of factor IXa activity in combination with platelet-directed therapy in stable coronary artery disease. The preliminary clinical safety and predictable pharmacodynamic effects form the basis for ongoing studies in patients undergoing elective revascularization procedures.

17 Article Comparison of the use of hemodynamic support in patients ≥80 years versus patients <80 years during high-risk percutaneous coronary interventions (from the Multicenter PROTECT II Randomized Study). 2014

Pershad, Ashish / Fraij, Ghassan / Massaro, Joseph M / David, Shukri W / Kleiman, Neal S / Denktas, Ali E / Wilson, B Hadley / Dixon, Simon R / Ohman, E Magnus / Douglas, Pamela S / Moses, Jeffrey W / O'Neill, William W. ·Cavanagh Heart Center, Banner Good Samaritan Medical Center, Phoenix, Arizona. Electronic address: ashish.pershad@bannerhealth.com. · Cavanagh Heart Center, Banner Good Samaritan Medical Center, Phoenix, Arizona. · Harvard Clinical Research Institute, Boston, Massachusetts. · Providence Hospital and Medical Center, Southfield, Michigan. · Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. · University of Texas Memorial Hermann Health Science Center, Houston, Texas. · Carolina Medical Center, Charlotte, North Carolina. · Beaumont Hospital, Royal Oak, Michigan. · Duke University Medical Center, Durham, North Carolina. · Duke Clinical Research Institute, Durham, North Carolina. · Columbia University Medical Center New York Presbyterian Hospital, New York, New York. · Henry Ford Medical Center, Detroit, Michigan. ·Am J Cardiol · Pubmed #25037676.

ABSTRACT: The outcomes of hemodynamic support during high-risk percutaneous coronary intervention in the very elderly are unknown. We sought to compare outcomes between the patients ≥80 years versus patients <80 years enrolled in the PROTECT II (Prospective Randomized Clinical Trial of Hemodynamic Support with the Impella 2.5 versus Intra-Aortic Balloon Pump in Patients undergoing High Risk Percutaneous Coronary Intervention) randomized trial. Patients who underwent high-risk percutaneous coronary intervention with an unprotected left main or last patent conduit and a left ventricular ejection fraction ≤35% or with 3-vessel disease and a left ventricular ejection fraction ≤30% were randomized to receive an intra-aortic balloon pump or the Impella 2.5; 90-day (or the longest follow-up) outcomes were compared between patients ≥80 years (n = 59) and patients <80 years (n = 368). At 90 days, the composite end point of major adverse events and major adverse cerebral and cardiac events were similar between patients ≥80 and <80 years (45.6% vs 44.1%, p = 0.823, and 23.7% vs 26.8%, p = 0.622, respectively). There were no differences in death, stroke, or myocardial infarction rates between the 2 groups, but fewer repeat revascularization procedures were required in patients ≥80 years (1.7% vs 10.4%, p = 0.032). Bleeding and vascular complication rates were low and comparable between the 2 age groups (3.4% vs 2.4%, p = 0.671, and 6.8% vs 5.4%, p = 0.677, respectively). Multivariate analysis confirmed that age was not an independent predictor of major adverse events (odds ratio = 1.031, 95% confidence interval 0.459-2.315, p = 0.941), whereas Impella 2.5 was an independent predictor for improved outcomes irrespective of age (odds ratio = 0.601, 95% confidence interval 0.391-0.923, p = 0.020). In conclusion, the use of percutaneous circulatory support is reasonable and feasible in a selected octogenarian population with similar outcomes as those of younger selected patients. Irrespective of age, the use of Impella 2.5 was an independent predictor of favorable outcomes.

18 Article Statin therapy in patients with chronic kidney disease undergoing percutaneous coronary intervention (from the Evaluation of Drug Eluting Stents and Ischemic Events Registry). 2014

Dasari, Tarun W / Cohen, David J / Kleiman, Neal S / Keyes, Michelle J / Yen, Chen-Hsing / Hanna, Elias B / Saucedo, Jorge F. ·Department of Internal Medicine, Cardiology Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Electronic address: dasaritarun@gmail.com. · Department of Internal Medicine, Cardiology Section, St Luke's Mid America Heart Institute, Kansas City, Kansas. · Department of Internal Medicine, Cardiology Section, Methodist DeBakey Heart & Vascular Center, Houston, Texas. · Harvard Clinical Research Institute, Boston, Massachusetts. · Department of Internal Medicine, Cardiology Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. · NorthShore University Health System, Evanston, Illinois. ·Am J Cardiol · Pubmed #24342762.

ABSTRACT: Secondary prevention trials have demonstrated the efficacy of statins in reducing cardiovascular morbidity and mortality in patients with coronary artery disease and events after percutaneous coronary intervention (PCI). However, there are few data describing the clinical value of statins in patients with coronary artery disease and chronic kidney disease (CKD) undergoing PCI. Of 10,148 patients who entered into Evaluation of Drug Eluting Stents and Ischemic Events, a multicenter registry of unselected patients undergoing PCI from July 2004 to December 2007, we studied 2,306 patients with CKD (estimated glomerular filtration rate ≤60 ml/min based on the Modified Diet in Renal Disease calculation). Patients were stratified into those receiving statins at discharge (n = 1,833, 79%) or not (n = 473, 21%). Patients in the statin group had a greater prevalence of hypertension, recent myocardial infarction (MI), and use of β blockers and angiotensin-converting enzyme inhibitors. Outcomes were assessed from discharge through 1-year follow-up. One-year all-cause mortality was 5.7% in statin group versus 8.7% in the no statin group (adjusted hazard ratio 0.55, 95% confidence interval 0.34 to 0.88). The composite of death, MI, and repeat revascularization was lower in statin group (adjusted hazard ratio 0.71, 95% confidence interval 0.51 to 0.99). In conclusion, among patients with CKD undergoing PCI, the prescription of statins at hospital discharge was associated with a significant improvement in subsequent outcomes including mortality and composite end point of death, MI, and repeat revascularization.

19 Article Optimizing rotational atherectomy in high-risk percutaneous coronary interventions: insights from the PROTECT ΙΙ study. 2014

Cohen, Mauricio G / Ghatak, Abhijit / Kleiman, Neal S / Naidu, Srihari S / Massaro, Joseph M / Kirtane, Ajay J / Moses, Jeffrey / Magnus Ohman, E / Džavík, Vladimír / Palacios, Igor F / Heldman, Alan W / Popma, Jeffrey J / O'Neill, William W. ·University of Miami Miller School of Medicine, Miami, Florida. ·Catheter Cardiovasc Interv · Pubmed #24174321.

ABSTRACT: OBJECTIVE: To study rotational atherectomy (RA) outcomes in patients undergoing high-risk PCI randomized to receive hemodynamic support using either IABP or Impella 2.5 in the PROTECT II trial. BACKGROUND: RA of heavily calcified lesions is often necessary for complex PCI but can be associated with slow-flow, hypotension, and higher risk of periprocedural MI. METHODS: We compared baseline, angiographic, procedural characteristics, and outcomes of patients treated with and without RA. We examined also RA technique and outcomes. RESULTS: RA was used in 52 of 448 patients (32 with Impella vs 20 with IABP, P = 0.08). RA patients were older (72 vs. 67 yo, P = 0.0009), more likely to have prior CABG (48 vs. 32%, P = 0.017), higher STS (8.1 vs. 5.7, P = 0.012) and higher SYNTAX scores (37 vs. 29, P < 0.0001). At 90 days, RA use was associated with higher incidence of MI but no mortality difference. RA was used more aggressively with Impella resulting in higher rate of periprocedural MI (P < 0.01), with no difference in mortality between groups (P = 0.78). Repeat revascularization occurred less frequently with Impella (P < 0.001). There were no differences in 90-day major adverse events between IABP and Impella in patients undergoing RA (P = 0.29). In patients not treated with RA, fewer MAEs were observed with Impella compared with IABP (P = 0.03). CONCLUSIONS: Patients who were treated with RA had more comorbidities, and more complex and extensive coronary artery disease. In patients with Impella, more aggressive RA use resulted in fewer revascularization events but higher incidence of periprocedural MI.

20 Article Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways. 2013

Braun, Oscar Ö / Angiolillo, Dominick J / Ferreiro, Jose L / Jakubowski, Joseph A / Winters, Kenneth J / Effron, Mark B / Duvvuru, Suman / Costigan, Timothy M / Sundseth, Scott / Walker, Joseph R / Saucedo, Jorge F / Kleiman, Neal S / Varenhorst, Christoph. ·Oscar Ö Braun, MD PhD, Department of Cardiology, Skåne University Hospital, SE-221 85 Lund, Sweden, Tel: +46 707552356, Fax: +46 46157857, E-mail: oscar.braun@med.lu.se. ·Thromb Haemost · Pubmed #24009042.

ABSTRACT: Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

21 Article Red cell distribution width as a bleeding predictor after percutaneous coronary intervention. 2013

Fatemi, Omid / Torguson, Rebecca / Chen, Fang / Ahmad, Soha / Badr, Salem / Satler, Lowell F / Pichard, Augusto D / Kleiman, Neal S / Waksman, Ron. ·MedStar Washington Hospital Center, Washington, DC 20010, USA. ·Am Heart J · Pubmed #23816028.

ABSTRACT: BACKGROUND: Red cell distribution width (RDW), a measure of variability in the size of circulating erythrocytes, is an independent predictor of mortality in cardiovascular disease and in patients undergoing percutaneous coronary intervention (PCI). We set out to determine if RDW is a prognostic marker of major bleeding post-PCI. METHODS: The study population included 6,689 patients who were subjected to PCI. The RDW was derived from a complete blood count drawn before PCI. Major inhospital bleeding was defined as a hematocrit decrease ≥12%, hemoglobin drop of ≥4, transfusion of ≥2 units of packed red blood cells, retroperitoneal, or gastrointestinal or intracranial bleeding. Multivariable logistic analysis of major inhospital bleeding was performed using a logistic regression model that comprised the National Cardiovascular Data Registry (NCDR) risk score model as a single variable. RESULTS: Major bleeding (P < .001), vascular complications (P = .005), and transfusions (P < .001) were significantly higher in patients with higher baseline RDW values. After adjustment for known bleeding correlates, RDW was a significant predictor for major bleeding (odds ratio 1.12, 95% CI 1.06-1.19, P < .001). Although the c statistic of the NCDR risk prediction model changed from 0.730 to 0.737 (P = .032), the net reclassification improvement increased significantly after the addition of RDW as a continuous variable (17.3% CI 6.7%-28%, P = .002). CONCLUSIONS: Red cell distribution width, an easily obtainable marker, has an independent, linear relationship with major bleeding post-PCI and incrementally improves the well-validated NCDR risk prediction model. These data suggest that further investigation is necessary to determine the relationship of RDW and post-PCI bleeding.

22 Article Comparison by meta-analysis of percutaneous coronary intervention versus coronary artery bypass grafting in patients with a mean age of ≥70 years. 2013

Alam, Mahboob / Virani, Salim S / Shahzad, Saima A / Siddiqui, Sahar / Siddiqui, Khaleeq H / Mumtaz, Shahzad A / Kleiman, Neal S / Coselli, Joseph S / Lakkis, Nasser M / Jneid, Hani. ·Baylor College of Medicine, Houston, TX, USA. malam@bcm.tmc.edu ·Am J Cardiol · Pubmed #23726179.

ABSTRACT: A paucity of published data evaluating the outcomes of older patients (age ≥70 years) undergoing revascularization for unprotected left main coronary artery disease is available. We performed aggregate data meta-analyses of the clinical outcomes (all-cause mortality, nonfatal myocardial infarction, stroke, repeat revascularization, and major adverse cardiac and cerebrovascular events at 30 days and 12 and 22 months) in studies comparing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with a mean age of ≥70 years and unprotected left main coronary artery disease. A comprehensive, time-unlimited literature search to January 31, 2013 identified 10 studies with a total of 2,386 patients (PCI, n = 909; CABG, n = 1,477). Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using the random-effects model. The patients in the PCI group were more likely than those in the CABG group to present with acute coronary syndrome (59.6% vs 44.8%, p <0.001). PCI was associated with a shorter hospital stay (4.2 ± 0.8 vs 8.3 ± 0.01 days, p <0.001). No significant differences were found between PCI and CABG for all cause-mortality, nonfatal myocardial infarction, and major adverse cardiac and cerebrovascular events at 30 days and 12 and 22 months. However, PCI was associated with lower rates of stroke at 30 days (OR 0.14, 95% CI 0.02 to 0.76) and 12 months (OR 0.14, 95% CI 0.03 to 0.60) and higher rates of repeat revascularization at 22 months (OR 4.34, 95% CI 2.69 to 7.01). These findings were consistent with the findings from a subgroup analysis of patients aged ≥75 years. In conclusion, older patients (age ≥70 years) with unprotected left main coronary artery disease had comparable rates of all-cause mortality, nonfatal myocardial infarction, and major adverse cardiac and cerebrovascular events after PCI or CABG. The patients undergoing PCI had a shorter hospital stay and lower rates of early stroke; however, they experienced higher repeat revascularization rates at longer term follow-up.

23 Article In-hospital and one year outcomes with drug-eluting versus bare metal stents in large native coronary arteries: a report from the Evaluation of Drug-Eluting Stents and Ischemic Events registry. 2013

Gordon, Paul C / Cohen, David J / Kleiman, Neal S / Montgomery, Jay A / Semder, Christopher A / Kennedy, Kevin F / Keyes, Michelle J / Piana, Robert N / Anonymous4470723. ·Division of Cardiology, The Miriam Hospital, Providence, Rhode Island. ·Catheter Cardiovasc Interv · Pubmed #22511502.

ABSTRACT: OBJECTIVES: We sought to compare the clinical outcomes after percutaneous coronary revascularization of large coronary arteries using drug-eluting (DES) or bare-metal (BMS) stents. BACKGROUND: In de novo native coronary lesions with reference diameters of 2.5-3.5 mm, DES reduce target lesion revascularization (TLR) with no increase in death or myocardial infarction (MI). The relative efficacy of DES in larger coronary artery lesions is less certain. METHODS: From the prospective Evaluation of Drug-Eluting Stents and Ischemic Events registry, we identified patients undergoing stenting of de novo lesions in native coronary arteries 3.5-5.0 mm in diameter (n = 1,485). In-hospital and 1-year clinical outcomes were compared for BMS (n = 282) and DES (n = 1,203) patients, using propensity stratification to adjust for differences in potential confounding factors. RESULTS: Most patient characteristics were similar for the two groups, but BMS patients were more likely to have been treated in the setting of ST elevation MI, whereas DES patients had more bifurcation lesions, smaller vessels, and longer total stent lengths. In risk-adjusted analyses, the composite endpoint of 1-year death, MI or TLR was similar for BMS and DES (standardized rate: 11.9% vs. 8.5%, P = 0.10). DES was associated with a 62% reduction in the risk of TLR, although the absolute difference in event rates was small (standardized rates 4.6% vs. 1.8%, P = 0.016). CONCLUSIONS: Among relatively unselected patients undergoing PCI of large native coronary arteries, use of DES was associated with a modest reduction in rates of TLR, with a neutral effect on other ischemic endpoints.

24 Article Repeat revascularization after contemporary percutaneous coronary intervention: an evaluation of staged, target lesion, and other unplanned revascularization procedures during the first year. 2012

Stolker, Joshua M / Cohen, David J / Kennedy, Kevin F / Pencina, Michael J / Lindsey, Jason B / Mauri, Laura / Cutlip, Donald E / Kleiman, Neal S / Anonymous2770740. ·Division of Cardiology, Saint Louis University, MO 63110, USA. jstolker@yahoo.com ·Circ Cardiovasc Interv · Pubmed #23093553.

ABSTRACT: BACKGROUND: Although drug-eluting stents and intensive secondary prevention have contributed to improved outcomes after percutaneous coronary intervention (PCI), repeat revascularization remains relatively common in contemporary practice. We used data from the multicenter Evaluation of Drug-Eluting Stents and Ischemic Events registry to evaluate the relative frequency and timing of staged revascularization, target lesion revascularization (TLR), and other nontarget revascularization during the first year after contemporary PCI. METHODS AND RESULTS: Patients with staged revascularization, TLR, and other unplanned procedures (elsewhere in the target vessel or in other coronary arteries) were evaluated in time-dependent models using Kaplan-Meier life-table estimation. Predictors of TLR and unplanned revascularization at nontarget sites were identified using logistic regression. Between July 2004 to June 2007, 10 144 patients undergoing PCI were enrolled at 55 US hospitals, of whom 86% were treated with at least 1 drug-eluting stent. Twelve percent required repeat revascularization within the first year (3% staged; 9% unplanned). More than 75% of staged revascularizations were performed <30 days after index PCI, although there was significant variation in this practice across hospitals (range, 0%-54%). TLR occurred in 4.5% of patients, with higher hazard rates between 2 to 9 months after PCI, whereas the risk of unplanned non-TLR (4.4% cumulative incidence) was constant over time. CONCLUSIONS: Among unselected patients undergoing PCI in the drug-eluting stent era, the incidence of repeat revascularization at 1 year is ≈12%. Among unplanned procedures, only half are performed for TLR. To achieve further improvements in PCI outcomes, future efforts should concentrate as much on identifying ischemia-producing lesions and intensifying secondary prevention therapies as on the prevention of restenosis.

25 Article Impact of drug eluting stent length on outcomes of percutaneous coronary intervention (from the EVENT registry). 2012

Caputo, Ronald P / Goel, Ankush / Pencina, Michael / Cohen, David J / Kleiman, Neal S / Yen, Chen-Hsing / Waksman, Ron / Tolerico, Paul / Dhar, Gaurav / Gordon, Paul / Bach, Richard G / Lopez, John J. ·St. Joseph's Hospital, Syracuse, NY, USA. ·Am J Cardiol · Pubmed #22560770.

ABSTRACT: In randomized trials, longer drug-eluting stent (DES) length has been associated with adverse clinical events. We used data from the EVENT registry to examine the impact of DES length on outcomes in routine clinical practice. We identified 5,425 unselected consecutive patients from the EVENT registry who had a single vessel treated with DES for nonemergency indications from 2004 through 2007. The association between stented length and short- and long-term outcomes was analyzed in ordinal categories (<15, 15 to 19, 20 to 24, and >24 mm) and as a continuous variable. There were few differences in baseline characteristics across categories. At 1 year, there was a stepwise increase in major adverse cardiac events (composite of death, myocardial infarction [MI], and target lesion revascularization [TLR]) with increasing stent length (8.0%, 10.1%, 11.8%, and 14.8%, p <0.001) and a similar relation with TLR (3.0%, 3.1%, 3.3%, and 5.0%, p = 0.02). After adjusting for demographic, clinical, angiographic, and treatment characteristics, longer stent length remained associated with 1-year major adverse cardiac events (adjusted hazard ratio 1.17 per 10-mm increase stent length) and TLR (hazard ratio 1.20 per 10 mm), but not with stent thrombosis. In conclusion, longer DES length is associated with increased adverse events, predominantly periprocedural MI, but also an increased rate of TLR.