IMPORTANCE: Non–vitamin K oral anticoagulants (NOACs) are increasingly prescribed for patients to treat or prevent arterial or venous thromboembolism. The following 4 NOAC agents are approved by the ...US Food and Drug Administration for clinical use: dabigatran etexilate, apixaban, edoxaban tosylate, and rivaroxaban. A good understanding of these agents’ pharmacologic properties is important for surgeons given their marked differences compared with warfarin sodium. This review highlights key practical issues surrounding the use of NOACs in the perioperative setting. OBSERVATIONS: The PubMed and Cochrane Library databases were searched for English-language studies from May 1, 2009, until May 1, 2017, for randomized clinical trials, meta-analyses, systematic reviews, observational studies, and clinical guidelines. From a systematic review of the published literature that included 70 articles and 166 404 patients, this study identified 5 key practical issues surrounding the use of NOACs in the perioperative setting. These include patient populations for which NOAC use is indicated and contraindicated, the timing of NOAC treatment cessation before invasive interventions, management of NOAC-treated patients requiring urgent interventions, the need for “bridging,” and the timing of NOAC treatment’s reinitiation after invasive interventions. Important findings are as follows: NOAC agents are not recommended for patients with mechanical heart valves or advanced kidney disease (creatinine clearance, <15 mL/min); minimal to no anticoagulant effect remains when therapy with a NOAC is withheld for 48 to 72 hours before surgery in the context of normal kidney function; a reversal agent is clinically available for dabigatran, while reversal agents for apixaban, edoxaban, and rivaroxaban are under regulatory review; and laboratory testing of the anticoagulant effects of NOACs are not routinely available. There is a paucity of high-quality data on the optimal timing of NOAC cessation and resumption in the perioperative period, particularly for patients who undergo procedures with high bleeding risk. CONCLUSIONS AND RELEVANCE: The anticoagulant effect of NOAC agents is predictable but not readily measurable in routine clinical practice. A number of uncertainties remain surrounding the use of these agents in the perioperative setting. Ongoing prospective studies and randomized clinical trials will provide greater clarity on these management issues in the near future.
Among atrial fibrillation (AF) patients, it is unclear whether the efficacy and safety of direct oral anticoagulants (DOAC) relative to warfarin is consistent across various levels of international ...normalized ratio (INR) control. To determine the efficacy and safety of DOAC agents compared with warfarin for patients with various levels of anticoagulation control as reflected by their time in therapeutic range (TTR), we conducted a systematic review and meta-analysis of published randomized controlled trials of DOAC versus (vs) warfarin which reported outcomes stratified by TTR. Based on reported center-based TTR (cTTR) ranges, degrees of INR control were categorized into 3 cTTR strata: low (<60%), intermediate (60% to 66%), and high (>66%). Pooled hazard ratios (HR) and 95% confidence intervals (CI) were determined for stroke or systemic embolism (SSE), major bleeding, and intracranial hemorrhage (ICH). Across all cTTR strata, DOAC-treated patients had lower risk of SSE versus warfarin, with a HR of 0.73 (95% CI 0.61 to 0.88) for the low, 0.76 (95% CI 0.59 to 0.98) intermediate; and 0.78 (95% CI 0.63 to 0.96) high cTTR subgroups. Compared with warfarin, DOAC-treated patients had lower risk of major bleeding in the low and intermediate cTTR strata, and similar risk in the highest cTTR stratum (HR 1.00, 95% CI 0.80 to 1.26). Patients treated with DOAC had lower risk of ICH compared with warfarin (HR 0.55, 95% CI; 0.40 to 0.74) which was observed across all cTTR strata. In conclusion, regardless of the degree of INR control, DOAC agents are preferable over warfarin as stroke prevention therapy for patients with AF.
Empagliflozin (EMPA) reduces heart failure hospitalization and mortality. The benefit in terms of ventricular arrhythmia and contractility has not been explored.
To determine the direct effects of ...EMPA on ventricular arrhythmia and cardiac contractility in an ex-vivo model of global ischemia-reperfusion (I/R).
Langendorff-perfused rabbit hearts were subjected to 30 min of complete perfusion arrest and reperfusion. Either EMPA (1 μM) or normal saline (controls) was then infused into the perfusate in a randomized fashion. Ten minutes following drug infusion, calcium imaging was performed. At the end of each experiment, the heart was electrically stimulated 5 times to assess the inducibility of ventricular fibrillation (VF). In a separate series of experiments, left ventricular (LV) pressure and epicardial NADH fluorescence were simultaneously recorded. LV specimens were then collected for western blotting.
Post-ischemia, EMPA treatment was associated with reduction in the induction of VF >10s (rate of induction: 16.7 ± 3.3% vs. 60 ± 8.7% in control hearts, p = 0.003), improvement of LV developed pressure (LVDP; 68.10 ± 9.02% vs. 47.61 ± 5.15% in controls, p = 0.03) and reduction of NADH fluorescence (87.42 ± 2.79% vs. 112.88 ± 2.27% in control hearts, p = 0.04) along with an increase in NAD+/NADH ratio (2.75 ± 0.55 vs. 1.09 ± 0.32 in the control group, p = 0.04) A higher calcium amplitude alternans threshold was also observed with EMPA-treatment (5.42 ± 0.1 Hz vs. 4.75 ± 0.1 Hz in controls, p = 0.006). Sodium-glucose co-transporter-2 (SGLT2) expression was not detected in LV tissues.
EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.
In normoxic conditions, NADH is generated by the reduction of NAD+ in metabolic pathways by glucose oxidation and Krebs cycle. NADH is oxidized to NAD+ by ETC to produce ATP. ETC dysfunction during hypoxia (Red dotted arrow) is associated with the accumulation of NADH. Improvement of ETC function by EMPA (Blue solid arrow) leads to increase in NAD+/NADH ratio, improvement of contractile function, improvement of cytosolic calcium dynamics, and reduction of vulnerability to ventricular arrhythmias.
Glu: Glucose, Pyr: Pyruvate, TCA cycle: Tricarboxylic acid cycle (Krebs cycle), ETC: Electron transport chain, EMPA: Empagliflozin, I/R: Ischemia-reperfusion, SR: Sarcoplasmic reticulum. Display omitted
•Cardioprotective effects of Empagliflozin were evaluated in a model of global ischemia-reperfusion (I/R)•Empagliflozin increased contractility and decreased ventricular arrhythmia vulnerability•Improvements in mitochondrial redox state and cytosolic calcium dynamics were also noted with Empagliflozin treatment•In our Langendorff model, the cardioprotective effects of Empagliflozin were independent of SGLT2 inhibitory actions•These cardioprotective actions may explain the favorable effects of SGLT2i agents in heart failure which is independent of blood sugar control
It is assumed that electrical cardioversion (ECV) improves the quality of life (QoL) of patients with atrial fibrillation (AF) by restoring sinus rhythm (SR).
We examined the effect of ECV and rhythm ...status on QoL of patients with symptomatic persistent AF in a randomized controlled trial.
The elective cardioversion for prevention of symptomatic atrial fibrillation trial examined the efficacy of dronedarone around the time of ECV in maintaining SR. Quality of life was measured with the University of Toronto Atrial Fibrillation Severity Scale. The primary outcome was the change in AF symptom severity (∆AFSS) score over 6 months (0–35 points, with higher scores reflecting worse QoL and a minimal clinically important difference defined as ∆AFSS ≥3 points). Multivariable linear regression was performed to identify factors associated with changes in QoL.
We included 148 patients with complete AFSS scores at baseline and 6 months. Over 6 months, QoL improved irrespective of rhythm status (ΔAFSS scores for patients who (i) maintained SR; (ii) had AF relapse after successful ECV; and (iii) had unsuccessful ECV were −6.8 ± 6.4 points, −4.1 ± 6.2 points, and −4.0 ± 5.8 points respectively, P < .01 for all subgroups). After adjustment of baseline covariates, maintenance of SR was associated with QoL improvement (ΔAFSS: −3.8 points, 95% CI: −6.0 to −1.6 points, P < .01).
Maintenance of SR was associated with clinically relevant improvement in patients' QoL at 6 months. Patients with AF recurrence had a small but still relevant improvement in their QoL, potentially due to factors other than sinus rhythm.
The optimal long-term antithrombotic regimen for patients after successful catheter-based atrial fibrillation (AF) ablation is not well defined. Presently, practice variation exists, and the benefits ...of oral anticoagulation over antiplatelet therapy across the entire spectrum of stroke risk profile remain undefined in the postablation population. To date, there are no randomized trials to inform clinicians on this therapeutic question.
The objective was to assess whether rivaroxaban is superior to acetylsalicylic acid (ASA) in reducing the risk of clinically overt stroke, systemic embolism, or covert stroke among patients without apparent recurrent atrial arrhythmias for at least 1 year after their most recent AF ablation procedure.
A prospective, multicenter, open-label, randomized trial with blinded assessment of outcomes is under way (NCT02168829). Atrial fibrillation patients with at least 1 stroke risk factor (as defined by the CHA2DS2-VASc score) and without known atrial arrhythmia recurrences for at least 12 months after ablation are randomized to rivaroxaban 15 mg or ASA 75-160 mg daily. The primary outcome is a composite of clinically overt stroke, systemic embolism, and covert stroke based on brain magnetic resonance imaging. Key secondary outcomes include major bleeding outcomes, intracranial hemorrhage, transient ischemic attack, neuropsychological testing, quality of life, and an economic analysis. Subjects will be followed for 3 years. The estimated overall sample size is 1,572 subjects (786 per arm).
The OCEAN trial is a multicenter randomized controlled trial evaluating 2 antithrombotic treatment strategies for patients with risk factors for stroke after apparently successful AF ablation. We hypothesize that rivaroxaban will reduce the occurrence of clinically overt stroke, systemic embolism, and covert stroke when compared with ASA alone.
Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and a P2Y
inhibitor is an established therapy for a broad spectrum of patients with cardiovascular disease. The ischemic benefit of DAPT is ...partially offset by its increased bleeding risk, with intracranial hemorrhage (ICH) being the most serious complication. Although uncommon (0.2%-0.3% annually), its cumulative burden can be substantial given the number of patients afflicted by cardiovascular disease worldwide. Patients with a history of stroke or transient ischemic attack harbor a particularly high risk for ICH when treated with DAPT. Prediction rules may assist clinicians when weighing the risk/benefit ratio of prescribing DAPT for patients with stroke/transient ischemic attack in the nonacute, ambulatory setting. Currently, there are no reversal agents that can rapidly and effectively reverse the effect of P2Y
inhibitors in routine practice, although a reversal agent for ticagrelor is under clinical investigation.
Although echocardiography is widely used to measure left ventricular ejection fraction (LVEF), its prognostic value has not been demonstrated in a broad range of patients including those acutely ...hospitalized for cardiac or noncardiac causes. We determined whether greater degrees of left ventricular systolic dysfunction were associated with progressively increasing risks of death or cardiovascular hospitalizations among patients in hospital or outpatient settings.
A total of 27,323 patients with LVEF measured and 19,445 matched controls were followed for 223,034 person-years. Outcomes of total mortality, cardiovascular death, cardiovascular hospitalizations, and heart failure hospitalizations were examined using cause-specific hazard competing-risks analysis.
In the study cohort (median age, 68 interquartile range, 58-77, 14,828 women 31.7%), the hazard ratios (95% CI) for all-cause death were 1.67 (1.57-1.77), 1.30 (1.24-1.36), and 1.17 (1.11-1.23) when LVEF was <25%, 25%-35%, or 36%-45% compared with LVEF 46%-55% (all P < .001). Rates of cardiovascular death were similarly higher with lower LVEF. The hazard ratios for cardiovascular hospitalization were 1.35 (1.27-1.42), 1.21 (1.16-1.27), and 1.13 (1.07-1.18) for LVEFs <25%, 25%-35%, and 36%-45%, respectively (all P < .001). The rate of heart failure hospitalizations was amplified, with hazard ratios of 1.71 (1.59-1.85), 1.39 (1.31-1.48), and 1.21 (1.13-1.29) for LVEFs <25%, 25%-35%, or 36%-45% (all P < .001). The rate of mortality and hospitalizations increased comparably with greater reductions in LVEF during both inpatient cardiac or noncardiac admissions (P < .001).
Quantitative echocardiographic LVEF stratified the risk of death and hospitalization in a wide range of clinical settings, including during noncardiac admissions.
•Greater degrees of reduced LVEF are related to progressively higher risks.•Lower LVEF causes a higher risk of events even for noncardiac hospital admission.•Vigilance is required for quality treatment of reduced LVEF in any clinical setting.
OCEAN trial update Verma, Atul; Wells, George; Ha, Andrew C.T. ...
The American heart journal,
June 2022, 2022-Jun, 2022-06-00, 20220601, Volume:
248
Journal Article
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