Browsing by Subject "Platelet Aggregation Inhibitors"

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    ItemOpen Access
    A clinician's guide to the ABCs of cardiovascular disease prevention: the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and American College of Cardiology Cardiosource Approach to the Million Hearts Initiative.
    (Clinical cardiology, 2013-07) Hsu, Steven; Ton, Van-Khue; Dominique Ashen, M; Martin, Seth S; Gluckman, Ty J; Kohli, Payal; Sisson, Stephen D; Blumenthal, Roger S; Blaha, Michael J
    Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. Fortunately, it is often preventable with early adoption of lifestyle modification, prevention of risk factor onset, and aggressive treatment of existing risk factors. The Million Hearts Initiative is an effort by the Centers for Disease Control that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years. As part of this initiative, we present a simply organized "ABCDE" approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. ABCDE stands for assessment of risk, antiplatelet therapy, blood pressure management, cholesterol management, cigarette/tobacco cessation, diet and weight management, diabetes prevention and treatment, and exercise, interventions regularly used to reduce cardiovascular (CV) risk. Throughout this article we summarize recommendations related to each topic and reference landmark trials and data that support our approach. We believe that the ABCDE approach will be the core framework for addressing CV risk in our effort to prevent CVD.
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    Antiplatelet Therapy in Staphylococcus aureus Bacteremia: No Time Like the Past?
    (Antimicrobial agents and chemotherapy, 2022-06) Mourad, Ahmad; Holland, Thomas L; Turner, Nicholas A
    In this invited commentary, we reflect on the accompanying study by A. R. Caffrey, H. J. Appaneal, K. L. LaPlante, V. V. Lopes, et al. (Antimicrob Agents Chemother 66:e02117-21, 2022, https://doi.org/10.1128/aac.02117-21), which analyzed the impact of clopidogrel use on clinical outcomes in Staphylococcus aureus bacteremia.
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    Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality.
    (JAMA, 2018-02) Inohara, Taku; Xian, Ying; Liang, Li; Matsouaka, Roland A; Saver, Jeffrey L; Smith, Eric E; Schwamm, Lee H; Reeves, Mathew J; Hernandez, Adrian F; Bhatt, Deepak L; Peterson, Eric D; Fonarow, Gregg C
    Although non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH).To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulants [OACs]) and in-hospital mortality among patients with ICH.Retrospective cohort study of 141 311 patients with ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines-Stroke hospitals.Anticoagulation therapy before ICH, defined as any use of OACs within 7 days prior to hospital arrival.In-hospital mortality.Among 141 311 patients with ICH (mean [SD] age, 68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918 (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were taking concomitant single and dual antiplatelet agents, respectively. Patients with prior use of warfarin or NOACs were older and had higher prevalence of atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the National Institutes of Health Stroke Scale) was not significantly different across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20] for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with patients without prior use of OACs, the risk of in-hospital mortality was higher among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0% [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to 1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI, 1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with prior use of warfarin, patients with prior use of NOACs had a lower risk of in-hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI, 0.69 to 0.81]). The difference in mortality between NOAC-treated patients and warfarin-treated patients was numerically greater among patients with prior use of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to -3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8% to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value (.07) was not statistically significant.Among patients with ICH, prior use of NOACs or warfarin was associated with higher in-hospital mortality compared with no OACs. Prior use of NOACs, compared with prior use of warfarin, was associated with lower risk of in-hospital mortality.
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    Association of Preceding Antithrombotic Treatment With Acute Ischemic Stroke Severity and In-Hospital Outcomes Among Patients With Atrial Fibrillation.
    (JAMA, 2017-03) Xian, Ying; O'Brien, Emily C; Liang, Li; Xu, Haolin; Schwamm, Lee H; Fonarow, Gregg C; Bhatt, Deepak L; Smith, Eric E; Olson, DaiWai M; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Lytle, Barbara L; Pencina, Michael J; Hernandez, Adrian F; Peterson, Eric D
    Importance:Antithrombotic therapies are known to prevent stroke for patients with atrial fibrillation (AF) but are often underused in community practice. Objectives:To examine the prevalence of patients with acute ischemic stroke with known history of AF who were not receiving guideline-recommended antithrombotic treatment before stroke and to determine the association of preceding antithrombotic therapy with stroke severity and in-hospital outcomes. Design, Setting, and Participants:Retrospective observational study of 94 474 patients with acute ischemic stroke and known history of AF admitted from October 2012 through March 2015 to 1622 hospitals participating in the Get With the Guidelines-Stroke program. Exposures:Antithrombotic therapy before stroke. Main Outcomes and Measures:Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS; range of 0-42, with a higher score indicating greater stroke severity and a score ≥16 indicating moderate or severe stroke), and in-hospital mortality. Results:Of 94 474 patients (mean [SD] age, 79.9 [11.0] years; 57.0% women), 7176 (7.6%) were receiving therapeutic warfarin (international normalized ratio [INR] ≥2) and 8290 (8.8%) were receiving non-vitamin K antagonist oral anticoagulants (NOACs) preceding the stroke. A total of 79 008 patients (83.6%) were not receiving therapeutic anticoagulation; 12 751 (13.5%) had subtherapeutic warfarin anticoagulation (INR <2) at the time of stroke, 37 674 (39.9%) were receiving antiplatelet therapy only, and 28 583 (30.3%) were not receiving any antithrombotic treatment. Among 91 155 high-risk patients (prestroke CHA2DS2-VASc score ≥2), 76 071 (83.5%) were not receiving therapeutic warfarin or NOACs before stroke. The unadjusted rates of moderate or severe stroke were lower among patients receiving therapeutic warfarin (15.8% [95% CI, 14.8%-16.7%]) and NOACs (17.5% [95% CI, 16.6%-18.4%]) than among those receiving no antithrombotic therapy (27.1% [95% CI, 26.6%-27.7%]), antiplatelet therapy only (24.8% [95% CI, 24.3%-25.3%]), or subtherapeutic warfarin (25.8% [95% CI, 25.0%-26.6%]); unadjusted rates of in-hospital mortality also were lower for those receiving therapeutic warfarin (6.4% [95% CI, 5.8%-7.0%]) and NOACs (6.3% [95% CI, 5.7%-6.8%]) compared with those receiving no antithrombotic therapy (9.3% [95% CI, 8.9%-9.6%]), antiplatelet therapy only (8.1% [95% CI, 7.8%-8.3%]), or subtherapeutic warfarin (8.8% [95% CI, 8.3%-9.3%]). After adjusting for potential confounders, compared with no antithrombotic treatment, preceding use of therapeutic warfarin, NOACs, or antiplatelet therapy was associated with lower odds of moderate or severe stroke (adjusted odds ratio [95% CI], 0.56 [0.51-0.60], 0.65 [0.61-0.71], and 0.88 [0.84-0.92], respectively) and in-hospital mortality (adjusted odds ratio [95% CI], 0.75 [0.67-0.85], 0.79 [0.72-0.88], and 0.83 [0.78-0.88], respectively). Conclusions and Relevance:Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.
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    Cardiovascular and Limb Outcomes in Patients With Diabetes and Peripheral Artery Disease: The EUCLID Trial.
    (Journal of the American College of Cardiology, 2018-12) Low Wang, Cecilia C; Blomster, Juuso I; Heizer, Gretchen; Berger, Jeffrey S; Baumgartner, Iris; Fowkes, F Gerry R; Held, Peter; Katona, Brian G; Norgren, Lars; Jones, W Schuyler; Lopes, Renato D; Olin, Jeffrey W; Rockhold, Frank W; Mahaffey, Kenneth W; Patel, Manesh R; Hiatt, William R; EUCLID Trial Executive Committee and Investigators
    BACKGROUND:Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management. OBJECTIVES:The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone. METHODS:In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA1c) that might affect risk for major cardiovascular and limb outcomes. RESULTS:A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). CONCLUSIONS:Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).
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    Comparing Inverse Probability of Treatment Weighting and Instrumental Variable Methods for the Evaluation of Adenosine Diphosphate Receptor Inhibitors After Percutaneous Coronary Intervention.
    (JAMA cardiology, 2016-09) Federspiel, Jerome J; Anstrom, Kevin J; Xian, Ying; McCoy, Lisa A; Effron, Mark B; Faries, Douglas E; Zettler, Marjorie; Mauri, Laura; Yeh, Robert W; Peterson, Eric D; Wang, Tracy Y; Treatment With Adenosine Diphosphate Receptor Inhibitors–Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) Investigators
    IMPORTANCE:There is increasing interest in performing comparative effectiveness analyses in large observational databases, yet these analyses must adjust for treatment selection issues. OBJECTIVES:To conduct comparative safety and efficacy analyses of prasugrel vs clopidogrel bisulfate after percutaneous coronary intervention and to evaluate inverse probability of treatment weighting (a propensity score method) and instrumental variable methods. DESIGN, SETTING, AND PARTICIPANTS:This study used data from the Treatment With Adenosine Diphosphate Receptor Inhibitors-Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study. Included in the study were patients undergoing percutaneous coronary intervention for myocardial infarction, 26.0% of whom received prasugrel. The study dates were April 4, 2010, to October 31, 2012. EXPOSURES:Choice of initial antiplatelet agent (prasugrel or clopidogrel). MAIN OUTCOMES AND MEASURES:Safety and efficacy outcomes included 1-year composite major adverse cardiovascular events, moderate to severe bleeding, and stent thrombosis. Hospitalizations for pneumonia, bone fractures, and planned percutaneous coronary intervention were used as the falsification end points. RESULTS:The study cohort comprised 11 784 participants (mean [SD] age, 60.0 [11.6] years, and 28.0% were female). Using inverse probability of treatment weighting adjustment, prasugrel and clopidogrel had similar major adverse cardiovascular events (hazard ratio [HR], 0.98; 95% CI, 0.83-1.16) and bleeding outcomes (1.18; 0.77-1.80), but prasugrel had a lower rate of stent thrombosis (0.51; 0.31-0.85). Using instrumental variable methods, prasugrel use was associated with a lower rate of the major adverse cardiovascular event end point (HR, 0.68; 95% CI, 0.47-1.00) but nonsignificant differences in the rates of bleeding (0.95; 0.41-2.08) and stent thrombosis (0.67; 0.16-2.00). There was no significant treatment difference noted in any of the falsification end-point rates when analyses were performed using inverse probability of treatment weighting, although the bone fracture end point approached statistical significance. Nevertheless, a lower rate of pneumonia-related hospitalizations was noted in the prasugrel-treated patients when analyses were performed using instrumental variable methods. CONCLUSIONS AND RELEVANCE:Conclusions regarding the safety and efficacy of antiplatelet therapy varied depending on analytic technique, and none were concordant with the results from randomized trials. In addition, both statistical strategies demonstrated concerning associations when tested in the falsification analyses. A high level of scrutiny and careful attention to assumptions and validity are required when interpreting complex analyses of observational data.
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    Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry.
    (J Am Heart Assoc, 2014-04-14) Sherwood, Matthew W; Wiviott, Stephen D; Peng, S Andrew; Roe, Matthew T; Delemos, James; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: P2Y12 antagonist therapy improves outcomes in acute myocardial infarction (MI) patients. Novel agents in this class are now available in the US. We studied the introduction of prasugrel into contemporary MI practice to understand the appropriateness of its use and assess for changes in antiplatelet management practices. METHODS AND RESULTS: Using ACTION Registry-GWTG (Get-with-the-Guidelines), we evaluated patterns of P2Y12 antagonist use within 24 hours of admission in 100 228 ST elevation myocardial infarction (STEMI) and 158 492 Non-ST elevation myocardial infarction (NSTEMI) patients at 548 hospitals between October 2009 and September 2012. Rates of early P2Y12 antagonist use were approximately 90% among STEMI and 57% among NSTEMI patients. From 2009 to 2012, prasugrel use increased significantly from 3% to 18% (5% to 30% in STEMI; 2% to 10% in NSTEMI; P for trend <0.001 for all). During the same period, we observed a decrease in use of early but not discharge P2Y12 antagonist among NSTEMI patients. Although contraindicated, 3.0% of patients with prior stroke received prasugrel. Prasugrel was used in 1.9% of patients ≥75 years and 4.5% of patients with weight <60 kg. In both STEMI and NSTEMI, prasugrel was most frequently used in patients at the lowest predicted risk for bleeding and mortality. Despite lack of supporting evidence, prasugrel was initiated before cardiac catheterization in 18% of NSTEMI patients. CONCLUSIONS: With prasugrel as an antiplatelet treatment option, contemporary practice shows low uptake of prasugrel and delays in P2Y12 antagonist initiation among NSTEMI patients. We also note concerning evidence of inappropriate use of prasugrel, and inadequate targeting of this more potent therapy to maximize the benefit/risk ratio.
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    Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of-Hospital Bleeding after Percutaneous Coronary Interventions.
    (Chinese medical journal, 2018-02) Zhao, Xue-Yan; Li, Jian-Xin; Tang, Xiao-Fang; Xian, Ying; Xu, Jing-Jing; Song, Ying; Jiang, Lin; Xu, Lian-Jun; Chen, Jue; Zhang, Yin; Song, Lei; Gao, Li-Jian; Gao, Zhan; Zhang, Jun; Wu, Yuan; Qiao, Shu-Bin; Yang, Yue-Jin; Gao, Run-Lin; Xu, Bo; Yuan, Jin-Qing
    BACKGROUND:There is scanty evidence concerning the ability of Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and Urgent Intervention Triage Strategy and Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS) scores to predict out-of-hospital bleeding risk after percutaneous coronary interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual antiplatelet therapy. We aimed to assess and compare the long-term prognostic value of these scores regarding out-of-hospital bleeding risk in such patients. METHODS:We performed a prospective observational study of 10,724 patients undergoing PCI between January and December 2013 in Fuwai Hospital, China. All patients were followed up for 2 years and evaluated through the Fuwai Hospital Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to Bleeding Academic Research Consortium Definition criteria. RESULTS:During a 2-year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both significantly higher in the MB than non-MB groups. Both scores showed a moderate predictive value for MB in the whole study cohort (area under the receiver-operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI], 0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001, respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579, 95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001, respectively). However, neither score was a significant predictor in the non-ACS subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup. CONCLUSIONS:CRUSADE and ACUITY-HORIZONS scores showed statistically significant but relatively limited long-term prognostic value for out-of-hospital MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS subgroup.
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    Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.
    (J Am Heart Assoc, 2015-10-29) Sherwood, Matthew W; Melloni, Chiara; Jones, W Schuyler; Washam, Jeffrey B; Hasselblad, Vic; Dolor, Rowena J
    BACKGROUND: Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel. METHODS AND RESULTS: Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs. CONCLUSIONS: Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.
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    Lifetime cost-effectiveness analysis of ticagrelor in patients with acute coronary syndromes based on the PLATO trial: a Singapore healthcare perspective.
    (Singapore medical journal, 2013-03) Chin, Chee Tang; Mellstrom, Carl; Chua, Terrance Siang Jin; Matchar, David Bruce

    Introduction

    Ticagrelor is a novel antiplatelet drug developed to reduce atherothrombosis. The PLATO trial compared ticagrelor and aspirin to clopidogrel and aspirin in patients with acute coronary syndromes (ACS). Ticagrelor was found to be superior in the primary composite endpoint of cardiovascular death, myocardial infarction or stroke, without increasing major bleeding events. The current study estimates the lifetime cost-effectiveness of ticagrelor relative to generic clopidogrel from a Singapore public healthcare perspective.

    Methods

    This study used a two-part cost-effectiveness model. The first part was a 12-month decision tree (using PLATO trial data) to estimate the rates of major cardiovascular events, healthcare costs and health-related quality of life. The second part was a Markov model estimating lifetime quality-adjusted survival and costs conditional on events during the initial 12 months. Daily drug costs applied were SGD 1.05 (generic clopidogrel) and SGD 6.00 (ticagrelor). Cost per quality-adjusted life years (QALY) was estimated from a Singapore public healthcare perspective using life tables and short-term costs from Singapore, and long-term costs from South Korea. Deterministic and probabilistic sensitivity analyses were performed.

    Results

    Ticagrelor was associated with a lifetime QALY gain of 0.13, primarily driven by lower mortality. The resulting incremental cost per QALY gained was SGD 10,136.00. Probabilistic sensitivity analysis indicated that ticagrelor had a > 99% probability of being cost-effective, given the lower recommended WHO willingness-to-pay threshold of one GDP/capita per QALY.

    Conclusion

    Based on PLATO trial data, one-year treatment with ticagrelor versus generic clopidogrel in patients with ACS, relative to WHO reference standards, is cost-effective from a Singapore public healthcare perspective.
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    Multifaceted Intervention to Improve P2Y12 Inhibitor Adherence After Percutaneous Coronary Intervention: A Stepped Wedge Trial.
    (Journal of the American Heart Association, 2022-07) Ho, P Michael; O'Donnell, Colin I; McCreight, Marina; Bavry, Anthony A; Bosworth, Hayden B; Girotra, Saket; Grossman, P Michael; Helfrich, Christian; Latif, Faisal; Lu, David; Matheny, Michael; Mavromatis, Kreton; Ortiz, Jose; Parashar, Amitabh; Ratliff, Devona M; Grunwald, Gary K; Gillette, Michael; Jneid, Hani
    Background P2Y12 inhibitor medications are critical following percutaneous coronary intervention (PCI); however, adherence remains suboptimal. Our objective was to assess the effectiveness of a multifaceted intervention to improve P2Y12 inhibitor adherence following PCI. Methods and Results This was a modified stepped wedge trial of 52 eligible hospitals, of which 15 were randomly selected and agreed to participate (29 hospitals declined, and 8 eligible hospitals were not contacted). At each intervention hospital, patient recruitment occurred for 6 months and enrolled patients were followed up for 1 year after PCI. Three control groups were used: patients at intervention hospitals undergoing PCI (1) before the intervention period (preintervention); (2) after the intervention period (postintervention); or (3) at the 8 hospitals not contacted (concurrent controls). The intervention consisted of 4 components: (1) P2Y12 inhibitor delivered to patients' bedside after PCI; (2) education on importance of P2Y12 inhibitors; (3) automated reminder telephone calls to refill medication; and (4) outreach to patients if they delayed refilling P2Y12 inhibitor. The primary outcomes were as follows: (1) proportion of patients with delays filling P2Y12 inhibitor at hospital discharge and (2) proportion of patients who were adherent in the year after PCI using pharmacy refill data. Primary analysis compared intervention with preintervention control patients. There were 1377 (intent-to-treat) potentially eligible patients, of whom 803 (per protocol) were approached at intervention sites versus 5910 preintervention, 2807 postintervention, and 4736 concurrent control patients. In the intent-to-treat analysis, intervention patients were less likely to delay filling P2Y12 at hospital discharge (-3.4%; 98.3% CI, -1.2% to -5.6%) and more likely to be adherent to P2Y12 (4.1%; 98.3% CI, 1.0%-7.1%) at 1 year, but had more clinical events (3.2%; 98.3% CI, 2.3%-4.1%) driven by repeated PCI compared with preintervention patients. In post hoc analysis looking at myocardial infarction, stroke, and death, intervention patients had lower event rates compared with preintervention patients (-1.7%; 98.3% CI, -2.3% to -1.1%). Conclusions A 4-component intervention targeting P2Y12 inhibitor adherence was difficult to implement. The intervention produced mixed results. It improved P2Y12 adherence, but there was also an increase in repeat PCI. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609842.
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    National Trends in Emergency Department Care Processes for Acute Myocardial Infarction in the United States, 2005 to 2015.
    (Journal of the American Heart Association, 2020-10) Pendyal, Akshay; Rothenberg, Craig; Scofi, Jean E; Krumholz, Harlan M; Safdar, Basmah; Dreyer, Rachel P; Venkatesh, Arjun K
    Background Despite investments to improve quality of emergency care for patients with acute myocardial infarction (AMI), few studies have described national, real-world trends in AMI care in the emergency department (ED). We aimed to describe trends in the epidemiology and quality of AMI care in US EDs over a recent 11-year period, from 2005 to 2015. Methods and Results We conducted an observational study of ED visits for AMI using the National Hospital Ambulatory Medical Care Survey, a nationally representative probability sample of US EDs. AMI visits were classified as ST-segment-elevation myocardial infarction (STEMI) and non-STEMI. Outcomes included annual incidence of AMI, median ED length of stay, ED disposition type, and ED administration of evidence-based medications. Annual ED visits for AMI decreased from 1 493 145 in 2005 to 581 924 in 2015. Estimated yearly incidence of ED visits for STEMI decreased from 1 402 768 to 315 813. The proportion of STEMI sent for immediate, same-hospital catheterization increased from 12% to 37%. Among patients with STEMI sent directly for catheterization, median ED length of stay decreased from 62 to 37 minutes. ED administration of antithrombotic and nonaspirin antiplatelet agents rose for STEMI (23%-31% and 10%-27%, respectively). Conclusions National, real-world trends in the epidemiology of AMI in the ED parallel those of clinical registries, with decreases in AMI incidence and STEMI proportion. ED care processes for STEMI mirror evolving guidelines that favor high-intensity antiplatelet therapy, early invasive strategies, and regionalization of care.
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    Outcomes According to Cardiac Catheterization Referral and Clopidogrel Use Among Medicare Patients With Non-ST-Segment Elevation Myocardial Infarction Discharged Without In-hospital Revascularization.
    (J Am Heart Assoc, 2016-03-14) Hess, Connie N; Hellkamp, Anne S; Roe, Matthew T; Thomas, Laine; Scirica, Benjamin M; Peng, S Andrew; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: While use of P2Y12 receptor inhibitor is recommended by guidelines, few studies have examined its effectiveness among older non-ST-segment elevation myocardial infarction patients who did not undergo coronary revascularization. METHODS AND RESULTS: We included unrevascularized non-ST-segment elevation myocardial infarction patients ≥65 years discharged home from 463 ACTION Registry-GWTG hospitals from 2007 to 2010. Rates of discharge clopidogrel use were described for patients with no angiography, angiography without obstructive coronary artery disease (CAD; ≥50% stenosis in ≥1 vessel), and angiography with obstructive CAD. Two-year outcomes were ascertained from linked Medicare data and included composite major adverse cardiac events (defined as all-cause death, myocardial infarction readmission, or revascularization), and individual components. Outcomes associated with clopidogrel use were adjusted using inverse probability-weighted propensity modeling. Of 14 154 unrevascularized patients, 54.7% (n=7745) did not undergo angiography, 10.6% (n=1494) had angiography without CAD, and 34.7% (n=4915) had angiography with CAD. Discharge clopidogrel was prescribed for 42.2% of all unrevascularized patients: 37.8% without angiography, 34.1% without obstructive CAD at angiography, and 51.6% with obstructive CAD at angiography. Discharge clopidogrel use was not associated with major adverse cardiac events in any group: without angiography (adjusted hazard ratio [95% CI]: 0.99 [0.93-1.06]), angiography without CAD (1.04 [0.74-1.47]), and angiography with CAD (1.12 [1.00-1.25], Pinteraction=0.20). CONCLUSIONS: We found no association between discharge clopidogrel use and long-term risk of major adverse cardiac events among older, unrevascularized non-ST-segment elevation myocardial infarction patients. Clopidogrel use in this population requires further prospective evaluation.
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    Perioperative Considerations in Management of the Severely Bleeding Coagulopathic Patient.
    (Anesthesiology, 2023-05) Erdoes, Gabor; Faraoni, David; Koster, Andreas; Steiner, Marie E; Ghadimi, Kamrouz; Levy, Jerrold H
    Inherited and acquired coagulopathy are frequently associated with major bleeding in severe trauma, cardiac surgery with cardiopulmonary bypass, and postpartum hemorrhage. Perioperative management is multifactorial and includes preoperative optimization and discontinuation of anticoagulants and antiplatelet therapy in elective procedures. Prophylactic or therapeutic use of antifibrinolytic agents is strongly recommended in guidelines and has been shown to reduce bleeding and need for allogeneic blood administration. In the context of bleeding induced by anticoagulants and/or antiplatelet therapy, reversal strategies should be considered when available. Targeted goal-directed therapy using viscoelastic point-of-care monitoring is increasingly used to guide the administration of coagulation factors and allogenic blood products. In addition, damage control surgery, which includes tamponade of large wound areas, leaving surgical fields open, and other temporary maneuvers, should be considered when bleeding is refractory to hemostatic measures.
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    Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy for Medically Managed Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.
    (Journal of the American Heart Association, 2016-11-04) Cornel, Jan H; Ohman, E Magnus; Neely, Benjamin; Jakubowski, Joseph A; Bhatt, Deepak L; White, Harvey D; Ardissino, Diego; Fox, Keith AA; Prabhakaran, Dorairaj; Armstrong, Paul W; Erlinge, David; Tantry, Udaya S; Gurbel, Paul A; Roe, Matthew T
    The relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention.We analyzed 2428 medically managed acute coronary syndromes patients from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding. Exploratory analyses used 3-level composites that incorporated mild and minimal GUSTO and TIMI events. Continuous measures of PRUs (per 10-unit decrease) were not independently associated with the 2-level GUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites. However, the PRU cut point of 75 differentiated bleeding risk with the 3-level composites of GUSTO (26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001).Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.
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    Risks and Benefits Associated With Prestroke Antiplatelet Therapy Among Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator.
    (JAMA neurology, 2016-01) Xian, Ying; Federspiel, Jerome J; Grau-Sepulveda, Maria; Hernandez, Adrian F; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Reeves, Mathew J; Thomas, Laine; Webb, Laura; Bettger, Janet Prvu; Laskowitz, Daniel T; Fonarow, Gregg C; Peterson, Eric D
    Intravenous tissue plasminogen activator (tPA) is known to improve outcomes in ischemic stroke; however, many patients may have been receiving antiplatelet therapy before acute ischemic stroke and could face an increased risk for bleeding when treated with tPA.To assess the risks and benefits associated with prestroke antiplatelet therapy among patients with ischemic stroke who receive intravenous tPA.This observational study used data from the American Heart Association and American Stroke Association Get With the Guidelines-Stroke registry, which included 85 072 adult patients with ischemic stroke who received intravenous tPA in 1545 registry hospitals from January 1, 2009, through March 31, 2015. Data were analyzed during the same period.Prestroke antiplatelet therapy before tPA administration for acute ischemic stroke.Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge ambulatory status, and modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]).Of the 85 072 registry patients, 38 844 (45.7%) were receiving antiplatelet therapy before admission; 46 228 patients (54.3%) were not. Patients receiving antiplatelet therapy were older (median [25th-75th percentile] age, 76 [65-84] vs 68 [56-80] years) and had a higher prevalence of cardiovascular risk factors. The unadjusted rate of sICH was higher in patients receiving antiplatelet therapy (5.0% vs 3.7%). After risk adjustment, prior use of antiplatelet agents remained associated with higher odds of sICH compared with no use (adjusted odds ratio [AOR], 1.18 [95% CI, 1.10-1.28]; absolute difference, +0.68% [95% CI, 0.36%-1.01%]; number needed to harm [NNH], 147). Among patients enrolled on October 1, 2012, or later, the highest odds (95% CIs) of sICH were found in 15 116 patients receiving aspirin alone (AOR, 1.19 [1.06- 1.34]; absolute difference [95% CI], +0.68% [0.21%-1.20%]; NNH, 147) and 2397 patients receiving dual antiplatelet treatment of aspirin and clopidogrel (AOR, 1.47 [1.16-1.86]; absolute difference, +1.67% [0.58%-3.00%]; NNH, 60). The risk for in-hospital mortality was similar between those who were and were not receiving antiplatelet therapy after adjustment (8.0% vs 6.6%; AOR, 1.00 [0.94-1.06]; nonsignificant absolute difference, -0.01% [-0.37% to 0.36%]). However, patients receiving antiplatelet therapy had a greater risk-adjusted likelihood of independent ambulation (42.1% vs 46.6%; AOR, 1.13 [1.08-1.17]; absolute difference, +2.23% [1.55%-2.92%]; number needed to treat, 43) and better functional outcomes (modified Rankin Scale score, 0-1) at discharge (24.1% vs 27.8%; AOR, 1.14; 1.07-1.22; absolute difference, +1.99% [0.78%-3.22%]; number needed to treat, 50).Among patients with an acute ischemic stroke treated with intravenous tPA, those receiving antiplatelet therapy before the stroke had a higher risk for sICH but better functional outcomes than those who were not receiving antiplatelet therapy.
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    Sex-based differences in outcomes after percutaneous coronary intervention for acute myocardial infarction: a report from TRANSLATE-ACS.
    (J Am Heart Assoc, 2014-02-07) Hess, Connie N; McCoy, Lisa A; Duggirala, Hesha J; Tavris, Dale R; O'Callaghan, Kathryn; Douglas, Pamela S; Peterson, Eric D; Wang, Tracy Y
    BACKGROUND: Data regarding sex-based outcomes after percutaneous coronary intervention (PCI) for myocardial infarction are mixed. We sought to examine whether sex differences in outcomes exist in contemporary practice. METHODS AND RESULTS: We examined acute myocardial infarction patients undergoing PCI between April 2010 and October 2012 at 210 US hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study. Outcomes included 1-year risk of major adverse cardiac events and bleeding according to Global Utilization of Strategies To Open Occluded Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definitions. Among 6218 patients, 27.5% (n=1712) were female. Compared with men, women were older, had more comorbidities, and had lower functional status. Use of multivessel PCI and drug-eluting stents was similar between sexes, while women received less prasugrel. Unadjusted cumulative incidence of 1-year major adverse cardiac events was higher for women than for men (15.7% versus 13.6%, P=0.02), but female sex was no longer associated with higher incidence of major adverse cardiac events after multivariable adjustment (hazard ratio 0.98, 95% CI 0.83 to 1.15). Female sex was associated with higher risks of post-PCI GUSTO bleeding (9.1% versus 5.7%, P<0.0001) and postdischarge BARC bleeding (39.6% versus 27.9%, P<0.0001). Differences persisted after adjustment (GUSTO: hazard ratio 1.32, 95% CI 1.06 to 1.64; BARC: incidence rate ratio 1.42, 95% CI 1.27 to 1.56). CONCLUSIONS: Female and male myocardial infarction patients undergoing PCI differ regarding demographic, clinical, and treatment profiles. These differences appear to explain the higher observed major adverse cardiac event rate but not higher adjusted bleeding risk for women versus men.
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    Ticagrelor versus clopidogrel in patients with symptomatic peripheral artery disease and prior coronary artery disease: Insights from the EUCLID trial.
    (Vascular medicine (London, England), 2018-12) Berger, Jeffrey S; Abramson, Beth L; Lopes, Renato D; Heizer, Gretchen; Rockhold, Frank W; Baumgartner, Iris; Fowkes, F Gerry R; Held, Peter; Katona, Brian G; Norgren, Lars; Jones, W Schuyler; Millegård, Marcus; Blomster, Juuso; Reist, Craig; Hiatt, William R; Patel, Manesh R; Mahaffey, Kenneth W
    Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular morbidity and mortality. We sought to evaluate the risk of concomitant coronary artery disease (CAD) in patients with symptomatic PAD versus PAD without diagnosed CAD, and whether ticagrelor was superior to clopidogrel in reducing that risk. The EUCLID trial randomized 13,885 patients with PAD to antithrombotic monotherapy with ticagrelor or clopidogrel. CAD was defined as prior myocardial infarction (MI), percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery. Median follow-up was 30 months. Among 4032 (29%) patients with PAD and CAD, 63% had prior MI, 54% prior PCI, and 38% prior CABG. After adjustment for baseline characteristics, patients with PAD and CAD had significantly higher rates of the primary endpoint (cardiovascular death/MI/stroke, 15.3% vs 8.9%, hazard ratio (HR) 1.50, 95% CI: 1.13-1.99; p=0.005), but no statistically significant increase in acute limb ischemia (HR 1.28, 95% CI: 0.57-2.85; p=0.55) or major bleeding (HR 1.10, 95% CI: 0.49-2.48; p=0.81) versus PAD without CAD. Among patients with PAD and CAD, there was no differential treatment effect between ticagrelor versus clopidogrel for the primary efficacy endpoint (HR 1.02, 95% CI: 0.87-1.19; p=0.84), acute limb ischemia (HR 1.03, 95% CI: 0.63-1.69; p=0.89), or major bleeding (HR 1.06, 95% CI: 0.66-1.69; p=0.81). There was a statistically significant interaction between prior coronary stent placement and study treatment ( p=0.03) with a numerical reduction in the primary efficacy endpoint with ticagrelor versus clopidogrel (13.8% vs 16.8%, HR 0.82, 95% CI: 0.65-1.03; p=0.09). Patients with PAD and prior CAD had higher composite rates of cardiovascular death, MI, and ischemic stroke versus PAD without diagnosed CAD. There were no significant differences between ticagrelor and clopidogrel in cardiovascular events or major bleeding. ClinicalTrials.gov Identifier: NCT01732822.
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    Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or Transient Ischemic Attack.
    (Journal of the American Heart Association, 2016-03-21) Li, Zixiao; Wang, Yilong; Zhao, Xingquan; Liu, Liping; Wang, David; Wang, Chunxue; Meng, Xia; Li, Hao; Pan, Yuesong; Wang, Xianwei; Wang, Chunjuan; Yang, Xiaomeng; Zhang, Changqing; Jing, Jing; Xian, Ying; Johnston, S Claiborne; Wang, Yongjun; CHANCE Investigators
    BACKGROUND:The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours. METHODS AND RESULTS:This was a subanalysis of the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients randomized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90-day follow-up. Recurrent ischemic stroke and progressive ischemic stroke were analyzed. Multivariable Cox modeling showed that randomization within 12 hours was an independent predictor of ischemic stroke events (hazard ratio [95% CI] 1.25 [1.04-1.49], P=0.02). Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 158 (12.34%) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 (9.59%) of 1293 patients taking clopidogrel-aspirin (P=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% versus 8.91%, P=0.03) but not progressive ischemic stroke (3.02% versus 3.43%, P=0.28). There was no significant difference in hemorrhagic events (P=0.39). CONCLUSIONS:Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90-day follow-up and did not increase the hemorrhagic risk. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00979589.