When cardiovascular medicines should be discontinued.

An integral component of the practice of medicine is focused on the initiation of medications, based on clinical practice guidelines and underlying trial evidence, which usually test the addition of novel medications intended for life-long use in short-term clinical trials. Much less attention is given to the question of medication discontinuation, especially after a lengthy period of treatment, during which patients age gets older and diseases may either progress or new diseases may emerge. Given the paucity of data, clinical practice guidelines offer little to no guidance on when and how to deprescribe cardiovascular medications. Such decisions are often left to the discretion of clinicians, who, together with their patients, express concern of potential adverse effects of medication discontinuation. Even in the absence of adverse effects, the continuation of medications without any proven effect may cause harm due to drug-drug interactions, the emergence of polypharmacy, and additional preventable spending to already strained health systems. Herein, several cardiovascular medications or medication classes are discussed that in the opinion of this author group should generally be discontinued, either for the prevention of potential harm, for a lack of benefit, or for the availability of better alternatives.

Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial.

BACKGROUND: There are no randomized data evaluating the safety or efficacy of apixaban for stroke prevention in patients with end-stage kidney disease on hemodialysis and with atrial fibrillation (AF). METHODS: The RENAL-AF trial (Renal Hemodialysis Patients Allocated Apixaban Versus Warfarin in Atrial Fibrillation) was a prospective, randomized, open-label, blinded-outcome evaluation (PROBE) of apixaban versus warfarin in patients receiving hemodialysis with AF and a CHA2DS2-VASc score ≥2. Patients were randomly assigned 1:1 to 5 mg of apixaban twice daily (2.5 mg twice daily for patients ≥80 years of age, weight ≤60 kg, or both) or dose-adjusted warfarin. The primary outcome was time to major or clinically relevant nonmajor bleeding. Secondary outcomes included stroke, mortality, and apixaban pharmacokinetics. Pharmacokinetic sampling was day 1, day 3, and month 1. RESULTS: From January 2017 through January 2019, 154 patients were randomly assigned to apixaban (n=82) or warfarin (n=72). The trial stopped prematurely because of enrollment challenges. Time in therapeutic range (international normalized ratio, 2.0-3.0) for warfarin-treated patients was 44% (interquartile range, 23%-59%). The 1-year rates for major or clinically relevant nonmajor bleeding were 32% and 26% in apixaban and warfarin groups, respectively (hazard ratio, 1.20 [95% CI, 0.63-2.30]), whereas 1-year rates for stroke or systemic embolism were 3.0% and 3.3% in apixaban and warfarin groups, respectively. Death was the most common major event in the apixaban (21 patients [26%]) and warfarin (13 patients [18%]) arms. The pharmacokinetic substudy enrolled the target 50 patients. Median steady-state 12-hour area under the curve was 2475 ng/mL×h (10th to 90th percentiles, 1342-3285) for 5 mg of apixaban twice daily and 1269 ng/mL×h (10th to 90th percentiles, 615-1946) for 2.5 mg of apixaban twice daily. There was substantial overlap between minimum apixaban blood concentration, 12-hour area under the curve, and maximum apixaban blood concentration for patients with and without a major or clinically relevant nonmajor bleeding event. CONCLUSIONS: There was inadequate power to draw any conclusion regarding rates of major or clinically relevant nonmajor bleeding comparing apixaban and warfarin in patients with AF and end-stage kidney disease on hemodialysis. Clinically relevant bleeding events were ≈10-fold more frequent than stroke or systemic embolism among this population on anticoagulation, highlighting the need for future randomized studies evaluating the risks versus benefits of anticoagulation among patients with AF and end-stage kidney disease on hemodialysis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02942407.

Prevention of Complications in the Cardiac Intensive Care Unit: A Scientific Statement From the American Heart Association.

Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non-CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk.

Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial.

BACKGROUND: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin. METHODS: The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models. RESULTS: Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome. CONCLUSIONS: A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Patterns of amiodarone use and outcomes in clinical practice for atrial fibrillation.

BACKGROUND: Amiodarone is the most effective antiarrhythmic drug (AAD) for atrial fibrillation (AF), but it has a high incidence of adverse effects. METHODS: Using the ORBIT AF registry, patients with AF on amiodarone at enrollment, prescribed amiodarone during follow-up, or never on amiodarone were analyzed for the proportion treated with a guideline-based indication for amiodarone, the variability in amiodarone use across sites, and the outcomes (mortality, hospitalization, and stroke) among patients treated with amiodarone. Hierarchical logistic regression modeling with site-specific random intercepts compared rates of amiodarone use across 170 sites. A logistic regression model for propensity to receive amiodarone created a propensity-matched cohort. Cox proportional hazards modeling, stratified by matched pairs evaluated the association between amiodarone and outcomes. RESULTS: Among 6,987 AF patients, 867 (12%) were on amiodarone at baseline and 451 (6%) started on incident amiodarone during the 3-year follow-up. Use of amiodarone varied among sites from 3% in the lowest tertile to 21% in the highest (p<0.0001). Among those treated, 32% had documented contraindications to other AADs or had failed another AAD in the past. Mortality, cardiovascular hospitalization, and stroke were similar among matched patients on and not on amiodarone at baseline, while incident amiodarone use in matched patients was associated with higher all-cause mortality (adjusted HR 2.06, 95% CI 1.35-3.16). CONCLUSIONS: Use of amiodarone among AF patients in community practice is highly variable. More than 2 out of 3 patients treated with amiodarone appeared to be eligible for a different AAD.

Interacting medication use and the treatment effects of apixaban versus warfarin: results from the ARISTOTLE Trial.

Warfarin is dependent on multiple hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 metabolism. The aim of this analysis was to assess the impact of interacting medication use on the treatment effects of apixaban versus warfarin. Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications at randomization in ARISTOTLE (n = 18,201). Interacting medications for apixaban were identified as combined P-gp and 3A4 inhibitors or inducers while interacting medications for warfarin were defined as those highly probable for warfarin potentiation or inhibition. At randomization, 5547 (30.5%) patients were on an interacting medication, including 2722 on apixaban and 2825 on warfarin. Patients using an interacting medication were more likely to be female, taking aspirin, and have a history of prior bleeding and were less likely to have a prior stroke or transient ischemic attack. No significant differences were observed on the treatment effect of apixaban compared with warfarin in patients on and off interacting medications for outcomes including the primary efficacy outcome of stroke or systemic embolism (P for interaction = 0.79) or the primary safety outcome of major bleeding (P for interaction = 0.75). Use of interacting medications with anticoagulants occurs often in patients with atrial fibrillation. Despite the potential for altered exposure, interacting medication use was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in the ARISTOTLE trial.Trial registration ClinicalTrials.gov, NCT00412984.

Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association.

Cardiogenic shock is a high-acuity, potentially complex, and hemodynamically diverse state of end-organ hypoperfusion that is frequently associated with multisystem organ failure. Despite improving survival in recent years, patient morbidity and mortality remain high, and there are few evidence-based therapeutic interventions known to clearly improve patient outcomes. This scientific statement on cardiogenic shock summarizes the epidemiology, pathophysiology, causes, and outcomes of cardiogenic shock; reviews contemporary best medical, surgical, mechanical circulatory support, and palliative care practices; advocates for the development of regionalized systems of care; and outlines future research priorities.

Management of Patients on Non-Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association.

Non-vitamin K oral anticoagulants (NOACs) are now widely used as alternatives to warfarin for stroke prevention in atrial fibrillation and management of venous thromboembolism. In clinical practice, there is still widespread uncertainty on how to manage patients on NOACs who bleed or who are at risk for bleeding. Clinical trial data related to NOAC reversal for bleeding and perioperative management are sparse, and recommendations are largely derived from expert opinion. Knowledge of time of last ingestion of the NOAC and renal function is critical to managing these patients given that laboratory measurement is challenging because of the lack of commercially available assays in the United States. Idarucizumab is available as an antidote to rapidly reverse the effects of dabigatran. At present, there is no specific antidote available in the United States for the oral factor Xa inhibitors. Prothrombin concentrate may be considered in life-threatening bleeding. Healthcare institutions should adopt a NOAC reversal and perioperative management protocol developed with multidisciplinary input.

Cangrelor use prior to left ventricular assist device surgery: a case series.

Bleeding frequently occurs in patients undergoing placement of a left ventricular assist device (LVAD). Clinical factors that have been identified as contributing to peri-procedural bleeding include LVAD implantation after an acute myocardial infarction and preoperative use of antiplatelet agents. In this report, we describe the use of cangrelor for preoperative antiplatelet bridging to LVAD in five post myocardial infarction patients with cardiogenic shock that had recently undergone percutaneous coronary intervention. During the cangrelor bridging period, no cases of thrombotic or major bleeding events occurred. During the first week following LVAD implantation, two patients experienced a major bleeding (each case required chest exploration for suspected hemorrhage). To our knowledge, this is the first series describing cangrelor use for antiplatelet bridging in patients undergoing LVAD implantation. While this series suggest cangrelor could possibly be a safe and effective antiplatelet bridging strategy, further research is needed to identify the optimal antithrombotic strategy in cardiogenic shock patients undergoing LVAD implantation who have recently undergoing percutaneous coronary intervention.

Diagnostic Accuracy of Screening Tests and Treatment for Post-Acute Coronary Syndrome Depression: A Systematic Review.

BACKGROUND: Patients who have had an acute coronary syndrome (ACS) event have an increased risk for depression. PURPOSE: To evaluate the diagnostic accuracy of depression screening instruments and to compare safety and effectiveness of depression treatments in adults within 3 months of an ACS event. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL, and Cochrane Database of Systematic Reviews from January 2003 to August 2017, and a manual search of citations from key primary and review articles. STUDY SELECTION: English-language studies of post-ACS patients that evaluated the diagnostic accuracy of depression screening tools or compared the safety and effectiveness of a broad range of pharmacologic and nonpharmacologic depression treatments. DATA EXTRACTION: 2 investigators independently screened each article for inclusion; abstracted the data; and rated the quality, applicability, and strength of evidence. DATA SYNTHESIS: Evidence from 6 of the 10 included studies showed that a range of depression screening instruments produces acceptable levels of diagnostic sensitivity, specificity, and negative predictive values (70% to 100%) but low positive predictive values (below 50%). The Beck Depression Inventory-II was the most studied tool. A large study found that a combination of cognitive behavioral therapy (CBT) and antidepressant medication improved depression symptoms, mental health-related function, and overall life satisfaction more than usual care. LIMITATION: Few studies, no evaluation of the influence of screening on clinical outcomes, and no studies addressing several clinical interventions of interest. CONCLUSION: Depression screening instruments produce diagnostic accuracy metrics that are similar in post-ACS patients and other clinical populations. Depression interventions have an uncertain effect on cardiovascular outcomes, but CBT combined with antidepressant medication produces modest improvement in psychosocial outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).

Is There Still a Role for Digoxin in the Management of Atrial Fibrillation?

PURPOSE OF REVIEW: A number of recent observational analyses have assessed clinical outcomes associated with digoxin use in patients with atrial fibrillation. In this review, we review these data and provide suggestions on the contemporary use of digoxin in patients with atrial fibrillation as supported by the recent evidence. RECENT FINDINGS: Observational data from clinical trials and registries have provided variable results on the safety and efficacy of chronic digoxin use in patients with atrial fibrillation. In general, results have been consistent with an associated increase in adverse clinical outcomes with digoxin use in atrial fibrillation patients without heart failure. In atrial fibrillation patients with heart failure, while the weight of evidence suggested an associated risk with digoxin therapy, the results are inconsistent. In patients with atrial fibrillation without heart failure, digoxin should generally be avoided. In atrial fibrillation patients with heart failure, digoxin should generally be reserved for patients that do not achieve adequate rate control or are not tolerant of other rate control therapies.

Polypharmacy and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Patients with atrial fibrillation (AF) often take multiple medications. METHODS AND RESULTS: We examined characteristics and compared adjusted outcomes between rivaroxaban and warfarin according to number of concomitant baseline medications and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study. At baseline, 5101 patients (36%) were on 0 to 4 medications, 7298 (51%) were on 5 to 9, and 1865 (13%) were on ≥ 10. Although polypharmacy was not associated with higher risk of stroke or non-central nervous system embolism (adjusted hazard ratio, 1.02 for ≥ 10 versus 0-4 medications; 95% confidence interval, 0.76-1.38), it was associated with higher risks of the combined end point of stroke, non-central nervous system embolism, vascular death, or myocardial infarction (adjusted hazard ratio, 1.41 for ≥ 10 versus 0-4 medications; 95% confidence interval, 1.18-1.68) and nonmajor clinically relevant or major bleeding (adjusted hazard ratio, 1.47 for ≥ 10 versus 0-4 medications; 95% confidence interval, 1.31-1.65). There was no significant difference in primary efficacy (adjusted interaction P=0.99) or safety outcomes (adjusted interaction P=0.87) between treatment groups by number of medications. Patients treated with 0 to 4 medications had lower rates of major bleeding with rivaroxaban (adjusted hazard ratio, 0.71; 95% confidence interval, 0.52-0.95; interaction P=0.0074). There was no evidence of differential outcomes in those treated with ≥ 1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors. CONCLUSIONS: In a population of patients with atrial fibrillation, two thirds were on ≥ 5 medications. Increasing medication use was associated with higher risk of bleeding but not stroke. Rivaroxaban was tolerated across complex patients on multiple medications. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767.

Altered Maturation Status and Possible Immune Exhaustion of CD8 T Lymphocytes in the Peripheral Blood of Patients Presenting With Acute Coronary Syndromes.

OBJECTIVE: Inflammation in response to oxidized lipoproteins is thought to play a key role in acute coronary syndromes (ACS), but the pattern of immune activation has not been fully characterized. We sought to perform detailed phenotypic and functional analysis of CD8 T lymphocytes from patients presenting with ACS to determine activation patterns and potential immunologic correlates of ACS. APPROACH AND RESULTS: We used polychromatic flow cytometry to analyze the cytokine production profiles of naïve, effector, and memory CD8 T cells in patients with ACS compared with control subjects with stable coronary artery disease. ACS was associated with an altered distribution of circulating CD8(+) T-cell maturation subsets with reduced proportions of naïve cells and expansion of effector memory cells. ACS was also accompanied by impaired interleukin-2 production by phenotypically naïve CD8 T cells. These results were validated in a second replication cohort. Naïve CD8 cells from patients with ACS also had increased expression of programmed cell death-1, which correlated with interleukin-2 hypoproduction. In vitro, stimulation of CD8 T cells with oxidized low-density lipoprotein was sufficient to cause programmed cell death-1 upregulation and diminished interleukin-2 production by naïve CD8 T cells. CONCLUSIONS: In this exploratory analysis, naïve CD8(+) T cells from patients with ACS show phenotypic and functional characteristics of immune exhaustion: impaired interleukin-2 production and programmed cell death-1 upregulation. Exposure to oxidized low-density lipoprotein recapitulates these features in vitro. These data provide evidence that oxidized low-density lipoprotein could play a role in immune exhaustion, and this immunophenotype may be a biomarker for ACS.

Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).

BACKGROUND: Digoxin is a widely used drug for ventricular rate control in patients with atrial fibrillation (AF), despite a scarcity of randomised trial data. We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). METHODS: For this retrospective analysis, we included and classified patients from ROCKET AF on the basis of digoxin use at baseline and during the study. Patients in ROCKET AF were recruited from 45 countries and had AF and risk factors putting them at moderate-to-high risk of stroke, with or without heart failure. We used Cox proportional hazards regression models adjusted for baseline characteristics and drugs to investigate the association of digoxin with all-cause mortality, vascular death, and sudden death. ROCKET AF was registered with ClinicalTrials.gov, number NCT00403767. FINDINGS: In 14,171 randomly assigned patients, digoxin was used at baseline in 5239 (37%). Patients given digoxin were more likely to be female (42% vs 38%) and have a history of heart failure (73% vs 56%), diabetes (43% vs 38%), and persistent AF (88% vs 77%; p<0·0001 for each comparison). After adjustment, digoxin was associated with increased all-cause mortality (5·41 vs 4·30 events per 100 patients-years; hazard ratio 1·17; 95% CI 1·04-1·32; p=0·0093), vascular death (3·55 vs 2·69 per 100 patient-years; 1·19; 1·03-1·39, p=0·0201), and sudden death (1·68 vs 1·12 events per 100 patient-years; 1·36; 1·08-1·70, p=0·0076). INTERPRETATION: Digoxin treatment was associated with a significant increase in all-cause mortality, vascular death, and sudden death in patients with AF. This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects. A randomised trial of digoxin in treatment of AF patients with and without heart failure is needed. FUNDING: Janssen Research & Development and Bayer HealthCare AG.

Why develop antidotes and reversal agents for non-vitamin K oral anticoagulants?

Over the past several years, non-vitamin K oral anticoagulants (NOACs) have been introduced into clinical practice for the treatment of venous thromboembolism and prevention of stroke in patients with nonvalvular atrial fibrillation. Clinical trials have shown these agents to have similar or less risk of major bleeding as compared to warfarin therapy. Moreover, when patients do experience a major bleeding event administration of advanced factor products is rare, and post-bleed outcomes are similar in those receiving a NOAC compared to those receiving warfarin. However, there are situations where urgent reversal of NOAC anticoagulation would be desirable. The following review focuses on the outcomes and management strategies for patients experiencing a major bleed with warfarin or NOAC agents and describes the rationale for the development of therapies capable of targeted NOAC-reversal.

Perioperative beta blockade in noncardiac surgery: a systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.

OBJECTIVE: To review the literature systematically to determine whether initiation of beta blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality rates. METHODS: PubMed (up to April 2013), Embase (up to April 2013), Cochrane Central Register of Controlled Trials (up to March 2013), and conference abstracts (January 2011 to April 2013) were searched for randomized controlled trials (RCTs) and cohort studies comparing perioperative beta blockade with inactive control during noncardiac surgery. Pooled relative risks (RRs) were calculated under the random-effects model. We conducted subgroup analyses to assess how the DECREASE-I (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), DECREASE-IV, and POISE-1 (Perioperative Ischemic Evaluation) trials influenced our conclusions. RESULTS: We identified 17 studies, of which 16 were RCTs (12 043 participants) and 1 was a cohort study (348 participants). Aside from the DECREASE trials, all other RCTs initiated beta blockade within 1 day or less prior to surgery. Among RCTs, beta blockade decreased nonfatal myocardial infarction (MI) (RR: 0.69; 95% confidence interval [CI]: 0.58 to 0.82) but increased nonfatal stroke (RR: 1.76; 95% CI: 1.07 to 2.91), hypotension (RR: 1.47; 95% CI: 1.34 to 1.60), and bradycardia (RR: 2.61; 95% CI: 2.18 to 3.12). These findings were qualitatively unchanged after the DECREASE and POISE-1 trials were excluded. Effects on mortality rate differed significantly between the DECREASE trials and other trials. Beta blockers were associated with a trend toward reduced all-cause mortality rate in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22) but with increased all-cause mortality rate in other trials (RR: 1.30; 95% CI: 1.03 to 1.64). Beta blockers reduced cardiovascular mortality rate in the DECREASE trials (RR: 0.17; 95% CI: 0.05 to 0.64) but were associated with trends toward increased cardiovascular mortality rate in other trials (RR: 1.25; 95% CI: 0.92 to 1.71). These differences were qualitatively unchanged after the POISE-1 trial was excluded. CONCLUSIONS: Perioperative beta blockade started within 1 day or less before noncardiac surgery prevents nonfatal MI but increases risks of stroke, death, hypotension, and bradycardia. Without the controversial DECREASE studies, there are insufficient data on beta blockade started 2 or more days prior to surgery. Multicenter RCTs are needed to address this knowledge gap.

Dual antiplatelet therapy with or without oral anticoagulation in the postdischarge management of acute coronary syndrome patients with an indication for long term anticoagulation: a systematic review.

Currently, there is a lack of consensus among guidelines for the postdischarge treatment of patients presenting with acute coronary syndrome (ACS) who have a long-term indication for anticoagulation. We conducted a systematic review comparing the safety and effectiveness of dual antiplatelet therapy (DAPT) and triple therapy (TT; defined as DAPT plus an oral anticoagulant) in patients with ACS and a long-term indication for anticoagulation. We searched for clinical studies in MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews published between January 1995 and September 2013. Each investigator screened and abstracted data, assessed applicability and quality, and graded the strength of evidence. Meta-analysis of direct comparison was performed when outcomes and follow-up periods were comparable. Fourteen observational studies were identified that contained comparative effectiveness data on DAPT versus TT. No difference in the odds of mortality (OR 1.04, 95% CI 0.59-1.83) or stroke (OR 1.01, 95% CI 0.38-2.67) at 1-5 years was found between TT and DAPT. Major bleeding at 1-5 years (OR 1.46, 95% CI 1.07-2.00) and nonfatal MI at 1-5 years (OR 1.85, 95% CI 1.13-3.02) occurred more frequently in patients receiving TT. The results of this systematic review demonstrate that treatment with TT was associated with increased rates of nonfatal MI and major bleeding when compared with treatment with DAPT in the postdischarge management of ACS patients with an indication for oral anticoagulation. Until results of ongoing randomized trials assessing antithrombotic therapies define optimal management strategies, the current analysis suggests using caution when prescribing TT to these patients.

Admission international normalized ratio levels, early treatment strategies, and major bleeding risk among non-ST-segment-elevation myocardial infarction patients on home warfarin therapy: insights from the National Cardiovascular Data Registry.

BACKGROUND: Non-ST-segment-elevation myocardial infarction patients on home warfarin pose treatment concerns because of their potential increased risk of bleeding. Expert opinion from the American College of Cardiology/American Heart Association guidelines suggest holding anticoagulants and initiating antiplatelet therapy among therapeutically anticoagulated non-ST-segment-elevation myocardial infarction patients. Yet, little is known about contemporary treatment patterns and bleeding risks in this population. METHODS AND RESULTS: We stratified 5787 non-ST-segment-elevation myocardial infarction patients on home warfarin therapy using data from the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines by admission international normalized ratio (INR) levels: subtherapeutic (INR <2), therapeutic (INR, 2-3), and supratherapeutic (INR >3). Multivariable logistic generalized estimating equations models were constructed to examine the associations between admission INR level, early antithrombotic treatment and invasive therapy, and risk of in-hospital major bleeding. Among these patients, 46%, 35%, and 19% had subtherapeutic, therapeutic, and supratherapeutic admission INR levels, respectively. Risk of major bleeding was higher among patients with therapeutic (15%; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.03-1.50) and supratherapeutic (22%; odds ratio, 1.60; 95% CI, 1.30-1.97) anticoagulation compared with the subtherapeutic group (12%). Among patients with admission INR ≥2, 45% were treated with early (within 24 hours) heparin, 35% with early clopidogrel, 14% with early glycoprotein IIb/IIIa inhibitor, and 36% with early invasive strategy. Early antithrombotic treatment was associated with increased bleeding risk (odds ratio, 1.40 [95% CI, 1.14-1.72] for heparin; 1.50 [95% CI, 1.22-1.84] for clopidogrel; and 1.82 [95% CI, 1.43-2.32] for glycoprotein IIb/IIIa inhibitor); however, an early invasive strategy was not (odds ratio, 1.09; 95% CI, 0.86-1.37). No significant interactions were observed between INR level and use of each early treatment in its association with bleeding. CONCLUSIONS: National patterns of early antithrombotic treatment for non-ST-segment-elevation myocardial infarction patients on home warfarin diverge from expert opinion provided by current practice guidelines. Early antithrombotic treatment was associated with increased bleeding risk regardless of admission INR level.

Evaluation of dose requirements for prolonged bivalirudin administration in patients with renal insufficiency and suspected heparin-induced thrombocytopenia.

Bivalirudin, a direct thrombin inhibitor, is indicated for patients with suspected heparin-induced thrombocytopenia (HIT) with anticipated percutaneous coronary intervention (PCI). Data is limited on dose selection among patients with renal insufficiency, particularly with prolonged infusion durations. The study cohort comprised 73 patients with renal dysfunction who received bivalirudin for suspected HIT with or without acute coronary syndrome. We reviewed individual pharmacy and medical records for laboratory and bivalirudin dosing information, medical comorbidities, and adverse clinical outcomes during administration. When estimated glomerular filtration rate (eGFR) was calculated by the Cockcroft-Gault (CG; ml/min) formula, the average bivalirudin dose (mg/kg/h) achieving a therapeutic activated partial thromboplastin time (aPTT) was 0.07 ± 0.04, 0.15 ± 0.08, and 0.16 ± 0.07 for patients with eGFR between 15-30, 31-60, and >60, respectively. When eGFR was calculated by the modification of diet in renal disease (MDRD; ml/min/1.73 m(2)) formula, the average bivalirudin dose achieving a therapeutic aPTT was 0.07 ± 0.04, 0.12 ± 0.07, and 0.20 ± 0.07 for patients with eGFR between 15-30, 31-60, >60, respectively. The difference between the dose achieving a therapeutic aPTT for patients with eGFR >60 when calculated by MDRD versus CG was completely abolished when obese patients were excluded from the CG cohort. The results of our series of patients with renal dysfunction receiving prolonged duration of bivalirudin in the setting of acute coronary syndrome (ACS) suggests that dose adjustment is safe and should be considered for patients with moderate to severe renal impairment (eGFR < 60 ml/min/1.73 m(2)).