Steven V Manoukian

Hospital Corporation of America, Nashville, Tennessee, United States

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Publications (55)513.19 Total impact

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    ABSTRACT: The accuracy of the 12-lead electrocardiogram in detecting coronary artery occlusion is limited. We sought to determine the incidence, distribution, and outcomes of patients who have total occlusion of the culprit artery but present with non-ST-segment elevation myocardial infarction (NSTEMI). The randomized Acute Catheterization and Urgent Intervention Triage Strategy trial enrolled 13,819 patients presenting with non-ST-segment elevation acute coronary syndromes who underwent an early invasive strategy. The present study includes 1,319 patients with baseline biomarker elevation (NSTEMI) and no history of coronary artery bypass graft who underwent percutaneous coronary intervention of a single culprit vessel. We compared the baseline characteristics and outcomes according to whether the culprit vessel was occluded (baseline Thrombolysis In Myocardial Infarction [TIMI] 0 to 1) or patent (TIMI 2 to 3 flow) by angiographic core laboratory assessment. TIMI 0 to 1 flow in the culprit artery was present in 262 of 1,319 (19.9%) patients. The incidence of coronary occlusion was 28.4%, 19.3%, and 12.6% in patients with NSTEMI because of right coronary, left circumflex, and left anterior descending artery disease, respectively. Patients with an occluded culprit artery were more commonly men and had ST-segment deviation ≥1 mm. One-year outcomes, including death (3.5% vs 3.0%, p = 0.68) and myocardial infarction (8.4% vs 9.6%, p = 0.47), did not differ significantly between patients with versus without occluded culprit arteries, respectively. In conclusion, the present study demonstrates that the culprit artery is totally occluded in approximately 1 in 5 patients presenting with NSTEMI and single-vessel disease; however, the presence of total occlusion in NSTEMI was not associated with an incremental hazard of death or reinfarction at 1 year. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 11/2014; 115(4). DOI:10.1016/j.amjcard.2014.11.023 · 3.43 Impact Factor
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    ABSTRACT: There are limited data on the impact of anemia on clinical outcomes in unstable angina and non-ST-segment elevation myocardial infarction treated with an early invasive strategy. We sought to determine the short- and long-term clinical events among patients with and without anemia enrolled in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. Anemia was defined as baseline hemoglobin of <13 g/dl for men and <12 g/dl for women. The primary end points were composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) and major bleeding assessed in-hospital, at 1 month, and at 1 year. Among the 13,819 patients in the ACUITY trial, information regarding anemia was available in 13,032 (94.3%), 2,199 of whom (16.9%) had anemia. Patients with anemia compared with those without anemia had significantly increased adverse event rates in-hospital (composite ischemia 6.6% vs 4.8%, p = 0.0004; major bleeding 7.3% vs 3.3%, p <0.0001), at 1 month (composite ischemia 10% vs 7.2%, p <0.0001, major bleeding 8.8% vs 3.9%, p <0.0001), and 1 year (composite ischemia 21.7% vs 15.3%, p <0.0001). Anemia was an independent predictor of death at 1 year (hazard ratio 1.77, 95% confidence interval [CI] 1.29 to 2.44, p = 0.0005). Composite ischemia was significantly more common among patients who developed in-hospital non-coronary artery bypass surgery major bleeding compared with those who did not (anemic patients 1-year relative risk 2.19, 95% CI 1.67 to 2.88, p <0.0001; nonanemic patients relative risk 2.16, 95% CI 1.76 to 2.65, p <0.0001). In conclusion, in the ACUITY trial, baseline anemia was strongly associated with adverse early and late clinical events, especially in those who developed major bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 09/2014; 114(12):1823-1829. DOI:10.1016/j.amjcard.2014.09.023 · 3.43 Impact Factor
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    ABSTRACT: ST-segment elevation myocardial infarction (STEMI) is a major cause of morbidity and mortality in the United States. Emergency medical services (EMS) agencies play a critical role in its initial identification and treatment. We conducted this study to assess EMS management of STEMI care in the United States.
    American Journal of Emergency Medicine 04/2014; 32(8). DOI:10.1016/j.ajem.2014.04.029 · 1.15 Impact Factor
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    ABSTRACT: Objective ST-segment elevation myocardial infarction (STEMI) is a major cause of morbidity and mortality in the United States. Emergency Medical Services (EMS) agencies play a critical role in its initial identification and treatment. We conducted this study to assess EMS management of STEMI care in the U.S. Methods A structured questionnaire was administered to leaders of EMS agencies to define the elements of STEMI care related to four core measures: 1) ECG capability at the scene, 2) destination protocols, 3) catheterization laboratory activation before hospital arrival, and 4) 12-lead ECG quality review. Geographic areas were grouped into large metropolitan, small metropolitan, micropolitan and noncore (or rural) by using Urban Influence Codes, with a stratified analysis. Results Data were included based on responses from 5,296 EMS agencies (36% of those in the U.S.) serving 91% of the U.S. population, with at least one valid response from each of the 50 states and the District of Columbia. Approximately 63% of agencies obtained ECGs at the scene using providers trained in ECG acquisition and interpretation. A total of 46% of EMS systems used protocols to determine hospital destination, cardiac catheterization laboratory activation, and communications with the receiving hospital. Over 75% of EMS systems used their own agency funds to purchase equipment, train personnel and provide administrative oversight. A total of 49% of agencies have quality review programs in place. In general, EMS systems covering higher population densities had easier access to resources needed to maintain STEMI systems of care. EMS systems that have adopted all four core elements cover 14% of the U.S. population. Conclusions There are large differences in EMS systems of STEMI care in the United States. The majority of EMS agencies have implemented at least one of the four core elements of STEMI care with many having implemented multiple elements.
  • Michele D Voeltz, Steven V Manoukian
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    ABSTRACT: The benefit of long-term dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes, drug-eluting stents and those at high risk for thromboembolic events has been well established in a number of well-designed randomized controlled studies. Current research in this area has focused on the development of novel antiplatelet agents for clinical use. The BRIDGE trial evaluated the use of cangrelor as a bridge to coronary artery bypass graft surgery in patients receiving extended DAPT. The BRIDGE trial results confirm the efficacy and safety of cangrelor in this population. This study is novel as it attempts to address the lapse in thienopyridine therapy required for many surgical and invasive procedures. The future of antiplatelet agents, particularly cangrelor, must also focus on bridging for high-risk patients undergoing noncoronary artery bypass graft surgical procedures. Overall, the BRIDGE trial represents a significant advance for patients appropriate for long-term DAPT.
    Expert Review of Cardiovascular Therapy 07/2013; 11(7):811-6. DOI:10.1586/14779072.2013.811972
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    ABSTRACT: Objective: Oral P2Y12 platelet receptor inhibitors are a cornerstone of reducing complications in patients with acute coronary syndromes or coronary stents. Guidelines advocate discontinuing treatment with P2Y12 platelet receptor inhibitors before surgery. Cangrelor, a short-acting, reversible, intravenously administered P2Y12 platelet inhibitor is effective in achieving appropriate platelet inhibition in patients who are awaiting coronary artery bypass grafting (CABG) and require P2Y12 inhibition. The objective of this study was to assess the effects of preoperative cangrelor on the incidence of perioperative complications, which are currently unknown.Methods: Patients (n = 210) requiring preoperative clinical administration of thienopyridine therapy were randomized in a multicenter, double-blinded study to receive cangrelor or placebo while awaiting CABG after discontinuation of the thienopyridine. Optimal platelet reactivity, which was defined as <240 P2Y12 platelet reaction units, was measured with serial point-of-care testing (VerifyNow). Pre- and postoperative outcomes, bleeding values, and transfusion rates were compared. To quantify potential risk factors for bleeding, we developed a multivariate logistic model.Results: The differences between the groups in bleeding and perioperative transfusion rates were not significantly different. The rate of CABG-related bleeding was 11.8% (12/102) in cangrelor-treated patients and 10.4% (10/96) in the placebo group (P = .763). Transfusion rates for the groups were similar. Serious postoperative adverse events for the cangrelor and placebo groups were 7.8% (8/102) and 5.2% (5/96), respectively (P = .454).Conclusions: Compared with placebo, bridging patients with cangrelor prior to CABG effectively maintains platelet inhibition without increasing post-CABG complications, including bleeding and the need for transfusions. These data suggest cangrelor treatment is a potential strategy for bridging patients requiring P2Y12 receptor inhibition while they await surgery.
    Heart Surgery Forum 04/2013; 16(2):E60-9. DOI:10.1532/HSF98.20121103
  • Peter B. Berger, Michael C. Janzen, Steven V. Manoukian
    JACC Cardiovascular Interventions 02/2013; 6(2):S11. DOI:10.1016/j.jcin.2012.12.036 · 7.44 Impact Factor
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    ABSTRACT: This study sought to assess the contemporary outcomes of patients with prior coronary artery bypass graft (CABG) who present with moderate and high-risk acute coronary syndromes (ACS) and are treated with an early invasive strategy and contemporary antithrombin regimens. The prognosis of patients with ACS and prior CABG in relation to triage strategy and contemporary antithrombotic regimens is unknown. In the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial, 2,475 of 13,764 patients (18.0%) with ACS managed with an early invasive strategy had previously undergone CABG. Their outcomes were examined according to treatment and randomized antithrombin regimen. Prior CABG was associated with older age, more frequent comorbidities, higher Thrombolysis In Myocardial Infarction risk score, and lower left ventricular ejection fraction. Patients with versus without prior CABG were less likely to undergo (repeat) CABG and were more likely to be managed medically. At 1 year, patients with versus without prior CABG had higher rates of major adverse cardiac events (MACE) (22.5% vs. 15.2%, p < 0.0001) due to greater mortality (5.4% vs. 3.9%, p < 0.0001), myocardial infarction (10.0% vs. 6.8%, p < 0.0001), and unplanned revascularization (13.1% vs. 8.2%, p < 0.0001). History of CABG was an independent predictor of MACE. The 1-year MACE rates were not significantly different after randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor (odds ratio: 1.24, 95% confidence interval: 0.90 to 1.70). Despite the progress in the treatment of coronary artery disease, patients with prior CABG and ACS have a poor prognosis, substantially worse than for those without prior CABG. Whereas bivalirudin monotherapy was an acceptable treatment for these patients, it did not improve their prognoses.
    JACC. Cardiovascular Interventions 09/2012; 5(9):919-26. DOI:10.1016/j.jcin.2012.06.009 · 7.44 Impact Factor
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    ABSTRACT: Thienopyridines are among the most widely prescribed medications, but their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 to 7 days prior to surgery to minimize bleeding. To evaluate the use of cangrelor, an intravenous, reversible P2Y(12) platelet inhibitor for bridging thienopyridine-treated patients to coronary artery bypass grafting (CABG) surgery. Prospective, randomized, double-blind, placebo-controlled, multicenter trial, involving 210 patients with an acute coronary syndrome (ACS) or treated with a coronary stent and receiving a thienopyridine awaiting CABG surgery to receive either cangrelor or placebo after an initial open-label, dose-finding phase (n = 11) conducted between January 2009 and April 2011. Interventions Thienopyridines were stopped and patients were administered cangrelor or placebo for at least 48 hours, which was discontinued 1 to 6 hours before CABG surgery. The primary efficacy end point was platelet reactivity (measured in P2Y(12) reaction units [PRUs]), assessed daily. The main safety end point was excessive CABG surgery-related bleeding. The dose of cangrelor determined in 10 patients in the open-label stage was 0.75 μg/kg per minute. In the randomized phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary end point, PRU <240; 98.8% (83 of 84) vs 19.0% (16 of 84); relative risk [RR], 5.2 [95% CI, 3.3-8.1] P < .001). Excessive CABG surgery-related bleeding occurred in 11.8% (12 of 102) vs 10.4% (10 of 96) in the cangrelor and placebo groups, respectively (RR, 1.1 [95% CI, 0.5-2.5] P = .763). There were no significant differences in major bleeding prior to CABG surgery, although minor bleeding episodes were numerically higher with cangrelor. Among patients who discontinue thienopyridine therapy prior to cardiac surgery, the use of cangrelor compared with placebo resulted in a higher rate of maintenance of platelet inhibition. Identifier: NCT00767507.
    JAMA The Journal of the American Medical Association 01/2012; 307(3):265-74. DOI:10.1001/jama.2011.2002 · 30.39 Impact Factor
  • 23rd Annual Transcatheter Cardiovascular Therapeutics (TCT), San Francisco, USA; 11/2011
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    ABSTRACT: In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not reduce cardiovascular events compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity (OTR) after percutaneous coronary intervention, defined as OTR ≥230 P2Y12 reaction units according to the VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine the relationship between outcomes and OTR over the course of the trial. OTR was measured at 12 to 24 hours and 30±7 days after percutaneous coronary intervention. Cox proportional hazards models with OTR as a time-varying covariate were used to determine the association between OTR and the primary end point of cardiovascular death, myocardial infarction, and stent thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet function data. OTR <208 P2Y12 reaction units was significantly associated with a lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95% confidence interval, 0.04 to 0.79; P=0.02) and at 6 months (hazard ratio, 0.43; 95% confidence interval, 0.23 to 0.82; P=0.01). After adjustment for other significant predictors of outcome, OTR <208 P2Y12 reaction units remained independently associated with the primary end point at 60 days (hazard ratio, 0.23; 95% confidence interval, 0.05 to 0.98; P=0.047) and tended to be associated at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04; P=0.065). In the GRAVITAS trial, achievement of on-clopidogrel reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous coronary intervention or during follow-up was associated with a lower risk for cardiovascular events. The efficacy of an individualized strategy to target a level of OTR below this threshold merits investigation. Clinical Trial Registration- Unique identifier: NCT00645918.
    Circulation 09/2011; 124(10):1132-7. DOI:10.1161/CIRCULATIONAHA.111.029165 · 14.95 Impact Factor
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    ABSTRACT: This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality. Bleeding complications after PCI have been independently associated with early and late mortality. This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)-related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality. A non-CABG-related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG-related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p < 0.001. Ranked in order of severity, TIMI major bleeding, blood transfusion without TIMI bleed, TIMI minor bleeding requiring blood transfusion, and TIMI minor bleeding not requiring blood transfusion were independent predictors of subsequent mortality with hazard ratios of 4.89, 2.91, 2.73, and 1.66, respectively. Isolated hematomas were not predictive of subsequent mortality. Non-CABG-related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.
    JACC. Cardiovascular Interventions 06/2011; 4(6):654-64. · 7.44 Impact Factor
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    JACC Cardiovascular Interventions 06/2011; 4(6):654-664. DOI:10.1016/j.jcin.2011.02.011 · 7.44 Impact Factor
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    ABSTRACT: High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention (PCI), but a treatment strategy for this issue is not well defined. To evaluate the effect of high-dose compared with standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. Randomized, double-blind, active-control trial (Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [GRAVITAS]) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. High-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. The primary end point was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) definition. A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days. At 6 months, the primary end point had occurred in 25 of 1109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1105 patients (2.3%) receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.76; P = .97). Severe or moderate bleeding was not increased with the high-dose regimen (15 [1.4%] vs 25 [2.3%], HR, 0.59; 95% CI, 0.31-1.11; P = .10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% (95% CI, 18%-26%) absolute reduction in the rate of high on-treatment reactivity at 30 days (62%; 95% CI, 59%-65% vs 40%; 95% CI, 37%-43%; P < .001). Among patients with high on-treatment reactivity after PCI with drug-eluting stents, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis. Identifier: NCT00645918.
    JAMA The Journal of the American Medical Association 03/2011; 305(11):1097-105. DOI:10.1001/jama.2011.290 · 30.39 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the incidence and clinical consequences of acquired thrombocytopenia in patients with acute coronary syndromes (ACS) in the ACUITY trial. We examined 10,836 patients with ACS randomized to receive heparin plus glycoprotein (GP) IIb/IIIa inhibitor, bivalirudin plus GP IIb/IIIa inhibitor, or bivalirudin monotherapy. Acquired thrombocytopenia developed in 740 (6.8%) patients; mild (100,000-150,000 platelets/mm³), moderate (50,000-100,000 platelets/mm³), and severe (< 50,000 platelets/mm³) developed in 656 (6%), 51 (0.5%), and 33 (0.3%) patients, respectively. Patients with acquired thrombocytopenia, compared with those without, were more likely to develop major bleeding (14% vs 4.3%, P < .0001) at 30 days and had higher rates of mortality (6.5% vs 3.4%, P < .0001) at 1 year. By multivariate analysis, acquired thrombocytopenia was an independent predictor of major bleeding at 30 days (hazard ratio [HR] 1.68, 95% CI 1.04-2.72, P = .03). Moderate and severe acquired thrombocytopenia were predictors of mortality at 1 year (HR 2.89, 95% CI 0.92-9.06, P = .06, and HR 3.41, 95% CI 1.09-10.68, P = .03, respectively). Compared to heparin plus GP IIb/IIIa inhibitor, bivalirudin monotherapy was associated with less declines in platelet count by >25% (7.6% vs 5.6%, P = .0009) and >50% (1.4% vs 0.7%, P = .004) from baseline. Acquired thrombocytopenia occurs in approximately 1 in 14 patients with ACS treated with antithrombin and antiplatelet medications and is strongly associated with hemorrhagic and ischemic complications. Compared to an anticoagulant regimen including a GP IIb/IIIa inhibitor, administration of bivalirudin monotherapy appears to be associated with less frequent declines in platelet count.
    American heart journal 02/2011; 161(2):298-306.e1. DOI:10.1016/j.ahj.2010.10.035 · 4.56 Impact Factor
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    ABSTRACT: Thrombocytopenia (TP) is a common abnormality in patients presenting with acute coronary syndrome. Whether baseline TP has any influence on the outcome of patients treated with primary angioplasty for acute myocardial infarction is unknown. We sought to detect the impact of baseline TP on the early and late outcomes of patients with ST-elevation myocardial infarction in the HORIZONS-AMI trial that included a protocol of immediate angiography and primary percutaneous coronary intervention. Baseline TP was found in 4.2% of patients and was associated with a higher incidence of cardiovascular mortality, major bleeding, and major cardiovascular events at short- and long-term follow-up. The 30-day rates of death, major bleeding, major cardiac events, and major cardiac events plus major bleeding were 6.2%, 11.9%, 9.6%, and 18.5% in the TP group, respectively, compared with 2.1%, 7%, 5.2%, and 10.8% in those without TP (P < .05 for all). Similarly, event rates at 2 years were 11.3%, 12.7%, 24.7%, and 30.8% compared with 5.1%, 7.9%, 18.5%, and 23.3% (P < .05). By multivariate analysis, baseline TP was an independent predictor of 30-day net adverse clinical events but not of any 2-year events. We found that baseline TP in patients with ST-elevation myocardial infarction undergoing routine angiography and primary percutaneous coronary intervention is strongly associated with early adverse events and is a maker of late events, related to both ischemia and bleeding.
    American heart journal 02/2011; 161(2):391-6. DOI:10.1016/j.ahj.2010.11.001 · 4.56 Impact Factor
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    Elias B Hanna, Sunil V Rao, Steven V Manoukian, Jorge F Saucedo
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    ABSTRACT: The use of glycoprotein IIb/IIIa inhibitors (GPI) reduces ischemic events in patients undergoing percutaneous coronary intervention (PCI). However, the same properties that confer this benefit lead to an increased bleeding risk. Recent studies have shown a less robust net clinical benefit of GPI in the current era of routine thienopyridine and direct thrombin inhibitor use. To optimize the net clinical benefit of GPI, these agents need to be selectively used in patients most likely to benefit from their anti-ischemic effect, namely patients undergoing PCI for non-ST-segment elevation myocardial infarction, select patients undergoing primary PCI, and select patients undergoing PCI without appropriate pre-loading with a thienopyridine. Moreover, strategies to minimize bleeding should be applied in these patients and include shorter GPI infusions (in some patients), dose adjustments of heparin and GPI, careful access site management with more frequent use of the transradial approach, use of smaller sheaths, and identification of patients at high bleeding risk. This review provides an update of the current literature that supports these measures, an insight on the tailored use of GPI, and a potential direction for future research addressing combined antithrombotic therapies.
    JACC. Cardiovascular Interventions 12/2010; 3(12):1209-19. DOI:10.1016/j.jcin.2010.09.015 · 7.44 Impact Factor
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    Michael A Gaglia, Steven V Manoukian, Ron Waksman
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    ABSTRACT: Antiplatelet therapy is a cornerstone of the management of patients with acute coronary syndromes or for those undergoing percutaneous coronary intervention. As the intricacies of platelet biology and mechanisms of thrombus formation are revealed, novel antiplatelet therapies have emerged. Bleeding risk, however, has grown in concert with more potent platelet inhibition. This article reviews platelet biology and receptors to provide a foundation for understanding of antiplatelelet therapy. It also highlights recent advances in antiplatelet therapy, with a focus on mechanisms of action, pharmacodynamic data, and the balance of thrombotic versus bleeding outcomes.
    American heart journal 10/2010; 160(4):595-604. DOI:10.1016/j.ahj.2010.06.007 · 4.56 Impact Factor
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    ABSTRACT: The aim of this study was to develop a practical risk score to predict the risk and implications of major bleeding in acute coronary syndromes (ACS). Hemorrhagic complications have been strongly linked with subsequent mortality in patients with ACS. A total of 17,421 patients with ACS (including non-ST-segment elevation myocardial infarction [MI], ST-segment elevation MI, and biomarker negative ACS) were studied in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) and the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trials. An integer risk score for major bleeding within 30 days was developed from a multivariable logistic regression model. Non-coronary artery bypass graft surgery (CABG)-related major bleeding within 30 days occurred in 744 patients (7.3%) and had 6 independent baseline predictors (female sex, advanced age, elevated serum creatinine and white blood cell count, anemia, non-ST-segment elevation MI, or ST-segment elevation MI) and 1 treatment-related variable (use of heparin + a glycoprotein IIb/IIIa inhibitor rather than bivalirudin alone) (model c-statistic = 0.74). The integer risk score differentiated patients with a 30-day rate of non-CABG-related major bleeding ranging from 1% to over 40%. In a time-updated covariate-adjusted Cox proportional hazards regression model, major bleeding was an independent predictor of a 3.2-fold increase in mortality. The link to mortality risk was strongest for non-CABG-related Thrombolysis In Myocardial Infarction (TIMI)-defined major bleeding followed by non-TIMI major bleeding with or without blood transfusions, whereas isolated large hematomas and CABG-related bleeding were not significantly associated with subsequent mortality. Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non-CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.
    Journal of the American College of Cardiology 06/2010; 55(23):2556-66. DOI:10.1016/j.jacc.2009.09.076 · 15.34 Impact Factor
  • Steven V Manoukian
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    ABSTRACT: Antithrombotic therapy, including antiplatelet and antithrombin agents, effectively reduces the risk of ischemic events in patients with acute coronary syndromes (ACS) and those undergoing percutaneous coronary intervention (PCI). Unfortunately, these agents intrinsically increase the risk of bleeding complications, which in turn are associated with adverse outcomes, particularly mortality. Accordingly, there is great value in improving the understanding of bleeding complications, including the definitions employed, severity and types of bleeding, as well as the patient characteristics, clinical presentations, and treatment variables that are associated with an increased risk of bleeding. The ultimate goal is to optimize patient outcomes by employing pharmacological and nonpharmacological strategies that minimize bleeding risk while maintaining efficacy. The objective of this article is to present the criteria by which bleeding is expressed and discuss the correlation between bleeding and adverse outcomes, as well as the relative impact of bleeding compared with ischemic events such as myocardial infarction on mortality. Furthermore, the relationship between bleeding and modifications of long-term treatment and methods to predict and prevent bleeding will be explored.
    The Journal of invasive cardiology 03/2010; 22(3):132-41. · 0.82 Impact Factor

Publication Stats

3k Citations
513.19 Total Impact Points


  • 2014
    • Hospital Corporation of America
      Nashville, Tennessee, United States
  • 2008–2014
    • Sarah Cannon Research Institute
      Nashville, Tennessee, United States
  • 2013
    • Henry Ford Hospital
      • Department of Internal Medicine
      Detroit, Michigan, United States
  • 2007–2011
    • Emory University
      Atlanta, Georgia, United States
    • New York University
      • Medicine
      New York City, NY, United States
  • 2010
    • Cardiovascular Research Foundation
      New York, New York, United States
  • 2009
    • Centre Hospitalier Universitaire de Caen
      Caen, Lower Normandy, France