Karen P Alexander

University of Texas Southwestern Medical Center, Dallas, Texas, United States

Are you Karen P Alexander?

Claim your profile

Publications (168)1194.66 Total impact

  • E Magnus Ohman, Karen P Alexander
    [Show abstract] [Hide abstract]
    ABSTRACT: Should therapies to treat chronic stable angina reduce the risk of major cardiovascular events such as death and myocardial infarction? Although this may be a laudable target, the majority of treatments that are currently in use, such as nitrates, calcium-channel blockers, and beta-blockers, have not been proved to achieve this goal. Still, these agents have been recommended as first-line therapy for angina(1) because of their presumptive safety in this context and their ability to lower blood pressure, reduce symptoms, and improve quality of life. The occurrence of angina is associated with reduced quality of life and increased resource use.(2) Angina, . . .
    New England Journal of Medicine 08/2014; · 54.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Blood transfusion is controversial for anemic patients with acute myocardial infarction (AMI), with some previous studies reporting increased risk of transfusion-associated mortality.
    Journal of the American College of Cardiology 08/2014; 64(8):811-9. · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Accumulated data suggest that low-dose aspirin after myocardial infarction (MI) may offer similar efficacy to higher dose aspirin with reduced risk of bleeding. Few data are available on contemporary aspirin dosing patterns after MI in the United States METHODS AND RESULTS: Aspirin dosing from 221 199 patients with MI (40.2% ST-segment-elevation MI) from 525 US hospitals enrolled in the National Cardiovascular Data Registry's (NCDR's) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines were described, overall and in clinically relevant subgroups. High-dose aspirin was defined as 325 mg and low dose as 81 mg. Between January 2007 and March 2011, 60.9% of patients with acute MI were discharged on high-dose aspirin, 35.6% on low-dose aspirin, and 3.5% on other doses. High-dose aspirin was prescribed at discharge to 73.0% of patients treated with percutaneous coronary intervention and 44.6% of patients managed medically. Among 9075 patients discharged on aspirin, thienopyridine, and warfarin, 44.0% were prescribed high-dose aspirin. Patients with an in-hospital major bleeding event were also frequently discharged on high-dose aspirin (56.7%). A 25-fold variation in the proportion prescribed high-dose aspirin at discharge was observed across participating centers.
    Circulation Cardiovascular Quality and Outcomes 08/2014; · 5.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although randomized clinical trials have compared clopidogrel with higher potency ADP receptor inhibitors (ADPris) among patients with myocardial infarction, little is known about the frequency and factors associated with switching between ADPris in clinical practice.
    Circulation Cardiovascular Interventions 08/2014; · 6.54 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transcatheter aortic valve replacement (TAVR) is a transformative innovation that provides treatment for high or prohibitive surgical risk patients with symptomatic severe aortic stenosis who either were previously not referred for or were denied operative intervention. Trials have demonstrated improvements in survival and symptoms after TAVR versus medical therapy; however, there remains a sizable group of patients who die or lack improvement in quality of life soon after TAVR. This raises important questions about the need to identify and acknowledge the possibility of futility in some patients considered for TAVR. In this very elderly population, a number of factors in addition to traditional risk stratification need to be considered including multimorbidity, disability, frailty, and cognition in order to assess the anticipated benefit of TAVR. Consideration by a multidisciplinary heart valve team with broad areas of expertise is critical for assessing likely benefit from TAVR. Moreover, these complicated decisions should take place with clear communication around desired health outcomes on behalf of the patient and provider. The decision that treatment with TAVR is futile should include alternative plans to optimize the patient's health state or, in some cases, discussions related to end-of-life care. We review issues to be considered when making and communicating these difficult decisions.
    JACC Cardiovascular Interventions 06/2014; · 7.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Debate exists regarding the efficacy of â-blockers in myocardial infarction and their required duration of usage in contemporary practice.
    The American journal of medicine. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prior studies have found that academic hospitals provide more consistent use of guideline-recommended therapies in patients with non-ST-segment myocardial infarction (NSTEMI) compared with nonacademic centers, yet it is unclear whether these care differences translate into longer-term outcome differences. Using data from the CRUSADE Registry linked to Center for Medicare & Medicaid Services claims, we compared 30-day and 1-year all-cause mortality among 12,194 older patients with NSTEMI (age ≥65 years) treated at 103 academic centers and 28,335 patients treated at 302 nonacademic centers from February 2003 to December 2006. Outcomes were first adjusted for clinical characteristics, followed by adjustment for hospital performance, on 13 acute and discharge guideline-recommended therapies using a shared frailty model (an extension of the Cox proportional hazard model). Compared with older patients with NSTEMI treated at nonacademic hospitals, those treated at academic hospitals had greater and more consistent use of evidence-based acute and discharge therapies, were more likely to receive in-hospital revascularization (61.1% vs 54.2%; P < .0001), and had modestly lower risk-adjusted 30-day mortality after adjustment for patient-level clinical characteristics (8.9% vs 10.2%, adjusted hazard ratio [HR] 0.89, 95% CI 0.80-0.99). These differences were attenuated (HR 0.94, 95% CI 0.83-1.02) after further adjustment for hospital delivery of evidence-based treatments, yet did not persist out to 1 year (unadjusted HR 0.92, 95% CI 0.84-1.01, P = .089). Patients with NSTEMI treated at academic centers are more likely to receive guideline-recommended therapies and had modestly better 30-day outcomes. Nevertheless, these differences do not persist out to 1 year.
    American heart journal 05/2014; 167(5):762-9. · 4.65 Impact Factor
  • Journal of the American College of Cardiology 04/2014; · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background-Major bleeding has received increasing attention as a target for quality improvement in care of patients with acute myocardial infarction. However, little is known about variation in bleeding across hospitals and whether variation is attributable to quality of hospital care, treatments, or case mix.Methods and Results-We characterized hospital variation in major bleeding events (an absolute hemoglobin drop ≥4 g/dL, intracranial hemorrhage, retroperitoneal bleed, or transfusion) among 99 200 patients with non-ST-segment elevation myocardial infarction in the National Cardiovascular Data Registry (NCDR) Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines (ACTIOM Registry-GWTG) between January 2007 and June 2010. A total of 9566 (9.6%) patients experienced a major bleeding event during hospitalization. The median of the estimated distribution of major bleeding rates across hospitals was 9.4% (interquartile range, 7.5%-11.7%), with some hospitals having bleeding rates >2.3 times higher than others (10th-90th percentile, 6.1%-14.2%). Multivariable hierarchical models revealed that differences in case mix explained 19.2% of the hospital variation in bleeding complications, where anticoagulation and antiplatelet strategies explained an incremental 9.9% and 6.8%, respectively. Together, 32.3% of hospital variation in major bleeding rates was attributable to differences in patient case mix and identifiable differences in treatment strategies in patients with non-ST-segment elevation myocardial infarction.Conclusions-In-hospital major bleeding rates varied widely across hospitals. Although patient factors and treatments explained less than one third of hospital-level variation, ≈70% of bleeding variation remains after adjustment. A better understanding of causes for substantial hospital-level bleeding variations is needed to help target high-risk patients or practices and to optimize care.
    Circulation Cardiovascular Quality and Outcomes 03/2014; · 5.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A posterior myocardial infarction (PMI) is associated with significant morbidity and delays in recognition may prevent the timely revascularization of these patients. The present study sought to evaluate the reperfusion times and in-hospital outcomes among patients with an isolated PMI. Clinical characteristics and reperfusion times were compared between those with an isolated PMI and those with all other ST-elevation myocardial infarctions (STEMI) in the NCDR ACTION-GWTG Registry from 2007 to 2012. Logistic generalized estimating equations were used to examine risk-adjusted mortality. Among 117,739 subjects with a STEMI, 824 (0.7%) had evidence of an isolated PMI. The median time between patient arrival and initial electrocardiogram was similar between those with an isolated PMI and those with a non-PMI STEMI (6 vs. 6 minutes, P = .48). However, the median time from initial electrocardiogram to percutaneous coronary intervention was significantly longer among subjects with a PMI (69 vs 61 minutes, P < .01) and fewer patients achieved a door-to-balloon time less than 90 minutes (83% vs 89%, P < .01). After multivariable adjustment, in-hospital mortality was similar for PMI patients compared to those with a non-PMI STEMI (AOR: 1.11, 95% CI: 0.83-1.50). The door-to-balloon times are significantly longer for those with an isolated PMI resulting in fewer patients receiving reperfusion within the guideline recommended time period. Ongoing educational initiatives to increase recognition of a PMI are needed to improve the reperfusion times and outcomes associated with this condition.
    American heart journal 03/2014; 167(3):350-4. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Symptomatic heart failure (HF) and reduced ejection fraction (REF) are both associated with mortality, but the long-term outcomes associated with the development of HF in older non-ST-segment elevation myocardial infarction (NSTEMI) patients with preserved systolic function and REF are uncertain. We analyzed a total of 26,291 NSTEMI patients ≥65 years discharged alive in the CRUSADE Registry who had linked Medicare data. We evaluated 30-day and 1-year risks of mortality and HF readmission in 4 cohorts of patients stratified by symptomatic HF and ejection fraction: (1) no HF-PEF, (2) no HF-REF, (3) HF-PEF, and (4) HF-REF. A total of 14,280 NSTEMI patients (54.3%) had no HF-PEF, 3,345 (12.7%) had no HF-REF, 4,913 (18.7%) had HF-PEF, and 3,753 (14.3%) had HF-REF. Compared with no HF-PEF patients, the 30-day mortality risk was higher among patients with no HF-REF (4.9% vs 1.7%, adjusted hazard ratio 2.11, 95% CI 1.69-2.63), HF-PEF (5.9% vs 1.7%, adjusted hazard ratio 1.99, 95% CI 1.64-2.41), and highest among those with HF-REF (9.3% vs 1.7%, adjusted hazard ratio 2.70, 95% CI 2.23-3.26). Similar relationships were noted in the adjusted 1-year mortality and the risks of 30-day and 1-year HF readmission. Symptomatic HF and REF during the index NSTEMI hospitalization are both associated with an increased risk of short- and long-term mortality as well as HF readmission with an apparent additive prognostic impact of both factors.
    American heart journal 02/2014; 167(2):267-273.e1. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study is to assess trends in evidence-based therapy use and short- and long-term mortality over time among older patients with non-ST-segment elevation myocardial infarction (NSTEMI). With the prevalence of national quality improvement efforts, the use of evidence-based therapies has improved over time among patients with NSTEMI, yet it is unclear whether these improvements have been associated with significant change in short- and long-term mortality for older patients. We linked detailed clinical data for 28,603 NSTEMI patients aged ≥65 years at 171 hospitals in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry with longitudinal Centers for Medicare & Medicaid claims data and compared trends in annual unadjusted and risk-adjusted inhospital and long-term mortality from 2003 to 2006. The median age of our NSTEMI study population was 77 years, 48% were female, and 87% were white. Overall, inhospital and 1-year mortality rates were 6.0% and 24.5%, respectively. When compared with patients treated in 2003, NSTEMI patients treated in 2006 were more likely to receive guideline-recommended inhospital medications and early invasive treatment. Inhospital mortality decreased significantly over the study period (5.5% vs 7.2% [adjusted odds ratio 0.82, 95% CI 0.67-1.00, P = .045] for 2006 vs 2003), but there was no significant change in 1-year mortality from the index admission (24.0% vs 26.0% [adjusted hazard ratio 0.99, 95% CI 0.90-1.08] for 2006 vs 2003). Between 2003 and 2006, there was a significant reduction in inhospital mortality that corresponded to an increase in the use of evidence-based NSTEMI care. Nevertheless, long-term outcomes have not changed over time, suggesting a need for improved care transition and longitudinal secondary prevention.
    American heart journal 01/2014; 167(1):36-42.e1. · 4.65 Impact Factor
  • Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Timely and appropriate use of antiplatelet and anticoagulant therapies has been shown to improve outcomes among ST-segment elevation myocardial infarction (STEMI) patients, but have not been well described in patients transferred for primary percutaneous coronary intervention (PCI). Methods We examined 16,801 (26%) transfer and 47,329 direct-arrival STEMI patients treated with primary PCI at 441 Acute Coronary Treatment and Intervention Outcomes Network Registry®-Get With The Guidelines™ hospitals. Medication use was compared between transfer and direct-arrival patients to determine if these therapies were delayed or dosed in excess. Results Although transfer patients were more likely to receive antiplatelet and anticoagulant therapies prior to catheterization, they had longer delays to initiation of heparin (35 vs. 25 minutes), clopidogrel (119 vs. 84 minutes) and glycoprotein IIb/IIIa inhibitor (GPI; 107 vs. 60 minutes, p<0.0001 for both). Administration of low molecular weight heparin (LMWH) and GPI at the STEMI-referring hospital was associated with longer delays to reperfusion compared with deferred administration at the STEMI-receiving hospital, while early use of unfractionated heparin was not. Among treated patients, those transferred were more likely to receive excess heparin dosing (unfractionated heparin: adjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.04–1.58, LMWH: OR 1.54, 95% CI 1.09–2.18) and are associated with higher risks of major bleeding complications (adjusted OR 1.10, 95% CI 1.03–1.17). Conclusions STEMI patients transferred for primary PCI in community practice are at risk for delayed and excessively dosed antithrombotic therapy, highlighting the need for continued quality improvement to maximize the appropriate use of these important adjunctive therapies.
    American Heart Journal. 01/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Prior MI is a known risk factor for long-term mortality among acute MI patients, but its prevalence and implications for the short-term outcomes of patients with a new, acute MI remains uncertain. Methods We studied a total of 319,152 consecutively enrolled STEMI and NSTEMI patients in the NCDR® ACTION Registry®-GWTG™ (01/2007–03/2012). Baseline characteristics, home and in-hospital treatments, mortality rates, and major bleeding were compared separately for STEMI and NSTEMI by prior MI status, with adjustment for mortality and major bleeding. Results Prior MI was documented in 19% of STEMI (n = 124,535) and 29% of NSTEMI (n = 194,617) patients, who were older, more likely to have comorbidities, prior revascularization, and were more commonly taking secondary prevention medications at home. Guideline-recommended treatments in-hospital and at discharge did not differ in prior MI STEMI patients, but invasive management was lower for prior MI NSTEMI patients. The frequency of in-hospital mortality was higher for prior MI STEMI (5.9% vs. 5.2%) and NSTEMI patients (4.3% vs. 3.4%). After adjustment, the excess mortality risk associated with prior MI was no longer present for STEMI (OR = 1.06, 95% CI: 0.97–1.15), with only modest excess risk for NSTEMI (OR = 1.10, 95% CI: 1.04–1.15). The risk of in-hospital major bleeding was marginally lower for prior MI NSTEMI. Conclusion More than 20% of patients with acute MI treated in contemporary practice have a history of a prior MI; despite differences in the baseline risk profile, there was little difference in the adjusted risk of in-hospital mortality by prior MI status.
    American Heart Journal. 01/2014;
  • Journal of the American College of Cardiology 01/2014; · 14.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background-Prior studies have found that obese patients have paradoxically lower in-hospital mortality after non-ST-segment-elevation myocardial infarction than their normal-weight counterparts, yet whether these associations persist long term is unknown.Methods and Results-We linked detailed clinical data for patients with non-ST-segment-elevation myocardial infarction aged ≥65 years in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Registry to Medicare claims data to obtain longitudinal outcomes. Using height and weight measured on admission, patients were categorized into 6 body mass index (BMI [kilograms per meter squared]) groups. Multivariable Cox proportional hazards models were used to estimate the association between BMI and (1) all-cause mortality, (2) all-cause readmission, (3) cardiovascular readmission, and (4) noncardiovascular readmission for 3 years after hospital discharge. Among older patients with non-ST-segment-elevation myocardial infarction (n=34 465), 36.3% were overweight and 27.7% were obese. Obese patients were younger and more likely to have hypertension, diabetes mellitus, and dyslipidemia than normal or underweight patients. Relative to normal-weight patients, long-term mortality was lower for patients classified as overweight (BMI, 25.0-29.9), obese class I (BMI, 30.0-34.9), and obese class II (BMI, 35.0-39.9), but not obese class III (BMI ≥40.0). In contrast, 3-year all-cause and cardiovascular readmission were similar across BMI categories. Relative to normal-weight patients, noncardiovascular readmissions were similar for obese class I but higher for obese class II and obese class III.Conclusions-All-cause long-term mortality was generally lower for overweight and obese older patients after non-ST-segment-elevation myocardial infarction relative to those with normal weight. Longitudinal readmissions were similar or higher with increasing BMI.
    Circulation Cardiovascular Quality and Outcomes 12/2013; · 5.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prior studies have observed that smokers have paradoxically favorable 1-year mortality rates after acute coronary syndromes, but it is unknown whether this association extends to long-term outcomes and to older patients. We identified 38,628 patients aged ≥65 years participating in the CRUSADE Registry between February 2003 and December 2006 with non-ST-segment elevation myocardial infarction and linked these patients to Medicare claims data to assess longitudinal outcomes. Cox proportional hazard models were used to examine the association between smoking, 30-day, and long-term outcomes. Overall, 4,876 (13%) were current/recent smokers and 33,752 (87%) were nonsmokers. Compared with nonsmokers, smokers were younger and more likely to be male and to receive in-hospital revascularization (all P < .001) but less likely to have hypertension, diabetes mellitus, and renal insufficiency. Compared with nonsmokers, the unadjusted 30-day mortality was lower (8.7% vs 10.3%, P = .0004), but the adjusted 30-day mortality was similar (adjusted hazard ratio [HR] 1.08, 95% CI 0.97-1.20). Over a median of 3.6 years of follow-up, smokers had lower crude long-term mortality rates (53% vs 55% at 6 years, P = .001) but significantly higher long-term mortality rates after adjustment (adjusted HR 1.28, 95% CI 1.21-1.34). Smokers also had higher risks of all-cause readmission (HR 1.13, 95% CI 1.09-1.17) and recurrent myocardial infarction (HR 1.23, 95% CI 1.13-1.34). Among older non-ST-segment elevation myocardial infarction patients, we found that smokers had significantly higher long-term risks for both mortality and recurrent myocardial infarction. These results support ongoing efforts to promote smoking cessation, even among older patients.
    American heart journal 12/2013; 166(6):1056-1062. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We sought to describe real-world patterns of care in NSTEMI patients across different risk profiles for bleeding and mortality. The NCDR ACTION Registry-GWTG in-hospital mortality and major bleeding risk scores were developed to assess patient risk and optimize treatment decisions. However, little is known about the alignment of contemporary clinical management patterns with these risk estimates. We studied 61,366 NSTEMI patients in the NCDR ACTION-Registry-GWTG from January 2007 to March 2009, stratifying them into four groups based on estimated risk of mortality and major bleeding. There were 24,709 (40.3%) patients in each of the concordant risk groups (low:low; high:high) and 5974 (9.7%) in each of the discordant risk groups (low:high; high:low). Subjects at high estimated risk for both mortality and major bleeding were least likely to receive guideline-based adjunctive pharmacotherapy or to undergo angiography within 48 hours but most likely to receive an excess dose of an antithrombotic agent. Patients at low estimated risk for mortality and bleeding received the most intensive adjunctive therapy and were most likely to undergo invasive angiography. There are significant differences in contemporary patterns of care across varying risk profiles of mortality and major bleeding. Despite practice patterns which seem to emphasize avoiding harm with reduced use of antithrombotic therapy, patients at high risk for major bleeding continue to receive excess doses of antithrombotic therapy. Additional performance improvement efforts are needed to optimize outcomes in NSTEMI patients with high risk for both bleeding and mortality.
    American heart journal 12/2013; 166(6):1043-1049.e1. · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Incomplete revascularization (ICR) after percutaneous coronary intervention (PCI) is common and is associated with increased rates of rehospitalization, revascularization, and mortality. Adjunctive pharmacotherapy with ranolazine, an inhibitor of the late sodium current with anti-ischemic properties, may be effective in reducing recurrent events after PCI in patients with ICR. RIVER-PCI is a phase 3, randomized, double-blind, placebo-controlled, international event-driven clinical trial evaluating the efficacy of ranolazine in patients with a history of chronic angina and ICR after PCI. Approximately 2,600 participants with ICR post-PCI will be randomized in a 1:1 ratio to ranolazine or matched placebo within 14 days of an index PCI. The primary end point of the trial is time to the first occurrence of ischemia-driven revascularization or ischemia-driven hospitalization without revascularization. Participants will be followed up for a minimum of 1 year and until at least 720 confirmed primary end point events have occurred. Secondary end points include sudden cardiac death, cardiovascular death, myocardial infarction, and measures of quality of life and cost-effectiveness. The evaluation of long-term safety will include all-cause mortality, stroke, transient ischemic attack, and hospitalization for heart failure. Enrollment commenced in November 2011 and was completed in summer 2013. RIVER-PCI is a novel, large-scale, international, randomized, double-blind, placebo-controlled clinical trial evaluating the role of ranolazine in the long-term medical management of patients with ICR post-PCI.
    American heart journal 12/2013; 166(6):953-959.e3. · 4.65 Impact Factor

Publication Stats

3k Citations
1,194.66 Total Impact Points


  • 2014
    • University of Texas Southwestern Medical Center
      Dallas, Texas, United States
  • 1998–2014
    • North Carolina Clinical Research
      Raleigh, North Carolina, United States
  • 1997–2014
    • Duke University Medical Center
      • • Duke Clinical Research Institute
      • • Department of Medicine
      Durham, North Carolina, United States
  • 2013
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
    • Columbia University
      New York City, New York, United States
    • Copenhagen University Hospital Gentofte
      Hellebæk, Capital Region, Denmark
    • Renji Hospital
      Shanghai, Shanghai Shi, China
  • 2010–2013
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
    • Saint Luke's Health System (KS, USA)
      Kansas City, Kansas, United States
    • Brigham and Women's Hospital
      • Center for Brain Mind Medicine
      Boston, MA, United States
  • 2012
    • University of Missouri - Kansas City
      • Saint Luke's Mid America Heart Institute
      Kansas City, MO, United States
    • Yale University
      • Department of Internal Medicine
      New Haven, CT, United States
  • 2009–2012
    • McGill University
      • Division of Cardiology
      Montréal, Quebec, Canada
    • University of the Sciences in Philadelphia
      • Department of Pharmacy Practice and Pharmacy Administration
      Philadelphia, PA, United States
    • Cardiovascular Research Foundation
      New York City, New York, United States
    • Washington University in St. Louis
      • Division of Cardiovascular Division
      Saint Louis, MO, United States
  • 2011
    • St. Luke's Hospital (MO, USA)
      Saint Louis, Michigan, United States
    • National Heart Centre Singapore
      Tumasik, Singapore