Management of Anticoagulation in Patients with Atrial Fibrillation Undergoing PCI: Double or Triple Therapy?

Purpose of Review

This review aims to discuss the use of antithrombotic therapy in patients with atrial fibrillation who undergo coronary stenting with emphasis on the use of double vs triple therapy.

Recent Findings

When combined with systemic anticoagulation, dual antiplatelet therapy results in an unacceptable increase in bleeding without any improvement in prevention of thrombotic events. Direct oral anticoagulants combined with single antiplatelet therapy have reduced bleeding compared with warfarin plus dual antiplatelet therapy. Triple anticoagulation therapy with warfarin or direct oral anticoagulants leads to an excess of bleeding and is not superior in preventing thrombotic events.

Summary

Recent randomized, controlled trials have shown a significant reduction in major bleeding events in patients treated with dual antithrombotic therapy compared with triple therapy without any difference in efficacy. These findings call into question whether triple therapy should remain a part of standard practice.

     

What Do Patients Want?

PURPOSE: Clinicians often make decisions for their patients, despite evidence that suggests that correspondence between patient and clinician decision making is poor. The management of colorectal cancer presents difficult decisions because the impact of treatment on quality of life might overshadow its survival efficacy. This study investigated whether patients are able to trade survival for quality of life as a means to express their preference for treatment options and to compare their preferences with those expressed by clinicians. METHODS: Patients undergoing curative surgery for colorectal cancer were interviewed postoperatively to elicit their preferences in four hypothetical treatment scenarios. A questionnaire was mailed to all Australian colorectal surgeons and medical oncologists that asked them to respond as if they themselves were patients. RESULTS: One hundred patients (91 percent), 43 colorectal surgeons (77 percent), and 103 medical oncologists (50 percent) participated. In all four scenarios, patients were able to trade survival for quality of life. Patients' responses varied between scenarios, both in willingness to trade and the average amount traded. There were significant differences between patients and clinicians. Clinicians were more willing than patients to trade survival to avoid a permanent colostomy in favor of chemoradiotherapy. Patients' strongest preference was to avoid chemotherapy, more than to avoid a permanent colostomy. CONCLUSIONS: Patients are able to trade survival as a measure of preference for quality of life and can do so differentially between treatment scenarios. Patients' preferences do not always accord with those of clinicians. Unless patients' preferences are explicitly sought and incorporated into clinical decision making, patients may not receive the treatment that is best for them.     

Do the Left Atrial Substrate Properties Correlate with the Left Atrial Mechanical Function? A Novel Insight from the Electromechanical Study in Patients with Atrial Fibrillation

Background: The atrial substrate is the determinant of occurrence and maintenance of atrial fibrillation (AF), which can induce remodeling of atrial function and structure. This study investigated the relationship between the left atrial (LA) substrate properties and LA mechanical function.
Methods: Forty-four consecutive patients (50.3 ± 10.7 years old, 33 men) who presented with sinus rhythm during echocardiographic study before receiving catheter ablation for AF were enrolled. The LA diameter, LA volume, ratio of early and late transmitral filling flow velocities (E/A), LA appendage flow velocity, and transmitral velocity-time integral (VTI) were measured by the echocardiography. The LA empty fraction (LAEF), which was obtained via dividing the difference between maximal and minimal LA volume by maximal LA volume, was calculated as a parameter of the global LA contractile function. The LA global contact voltage mapping (NavX system) was performed before pulmonary vein isolation.
Results: Mean LA voltage and LA low voltage zone index (LVZ index, area with voltage < 0.5 mV, divided by total LA surface area) showed significant correlation with LA diameter and volume, but only the LA LVZ index showed significant correlation with A-wave velocity, transmitral A-wave VTI, and LAEF (r =–0.340, –0.411, –0.426; P = 0.024, 0.006, 0.005, respectively). We divided the LA LVZ index into three groups (< 10%, 10–20%, > 20%). The LAEF got worse and the transmitral A-wave VTI percentage (divided by transmitral VTI) decreased as LA LVZ index increased.
Conclusions: The LA substrate properties showed close correlation with LA size, but only the LA LVZ index correlated with the LA mechanical function.     

Should We Test for CYP2C9 Before Initiating Anticoagulant Therapy in Patients with Atrial Fibrillation?

Background

Genetic variants of the warfarin sensitivity gene CYP2C9 have been associated with increased bleeding risk during warfarin initiation. Studies also suggest that such patients remain at risk throughout treatment.

Objective

Would testing patients with non-valvular atrial fibrillation (AF) for CYP2C9 before initiating warfarin improve outcomes?

Design

Markov state transition decision model.

Setting

Ambulatory or inpatient settings necessitating new initiation of anticoagulation.

Patients

The base case was a 69-year-old man with newly diagnosed non-valvular AF. Interventions included: (1) warfarin, (2) aspirin, or (3) no antithrombotic therapy without genetic testing; and genetic testing followed by (4) aspirin or (5) no antithrombotic therapy in those with culprit CYP2C9 alleles.

Measures

Quality-adjusted life years (QALYs).

Results

In the base case, testing and treating patients with CYP2C9*2 and/or CYP2C9*3 with aspirin rather than warfarin was best (8.97 QALYs). However, warfarin without genetic testing was a close second (8.96 QALYs), a difference of roughly 5 days. Sensitivity analyses demonstrated that genetic testing followed by aspirin was best for patients at lower risk of embolic events. Warfarin without testing was preferred if the rate of embolic events was greater than 5% per year, or the risk of major bleeding while receiving warfarin was lower.

Conclusion

For patients at average risk for ischemic stroke due to AF and at average risk for major hemorrhage, treatment based on genetic testing offers no benefit compared to warfarin initiation without testing. The gain from testing may be larger in patients at lower risk of embolic events or at greater risk of bleeding.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-009-0927-7) contains supplementary material, which is available to authorized users.Key words: anticoagulant therapy, warfarin, genetic testing, pharmacogenetics, decision analysis, atrial fibrillation, stroke     

Is Cardiac Resynchronization Therapy an Antiarrhythmic Therapy for Atrial Fibrillation? A Systematic Review and Meta-Analysis

The impact of cardiac resynchronization therapy (CRT) on atrial fibrillation (AF) burden is poorly characterized. To assess the influence of CRT on AF, we performed a systematic literature search in MEDLINE using the MeSH headings “cardiac resynchronization therapy” or “cardiac pacing, artificial” and “atrial fibrillation.” Selected studies were peer-reviewed and written in English. Most studies enrolled patients meeting traditional CRT criteria. Ten observational studies and two secondary analyses of clinical trials were identified. Although ten studies suggest that CRT favorably impacts AF, one secondary analysis of a clinical trial showed no effect of CRT on new-onset AF. In a meta-analysis of three studies examining the effect of CRT on persistent or permanent AF, the combined rate of conversion from persistent or permanent AF to sinus rhythm was 0.107 (95 % confidence interval 0.069-0.163). Prospective studies, particularly among patients not meeting traditional CRT criteria, are needed.     

Electrical Storm in Patients with Implantable Cardioverter-Defibrillators: Can It Be Forecast?

The aim of this retrospective study was to determine the prevalence and predictors of electrical storm in 227 patients who had received implantable cardioverter-defibrillators (ICDs) and had been monitored for 31.7 ± 15.6 months. Of these, 174 (77%) were men. The mean age was 55.8 ± 15.5 years (range, 20–85 yr), and the mean left ventricular ejection fraction (LVEF) was 0.30 ± 0.14. One hundred forty-six of the patients (64%) had underlying coronary artery disease. Cardioverter-defibrillators were implanted for secondary (80%) and primary (20%) prevention.Of the 227 patients, 117 (52%) experienced events that required ICD therapy. Thirty patients (mean age, 57.26 ± 14.3 yr) had ≥3 episodes requiring ICD therapy in a 24-hour period and were considered to have electrical storm. The mean number of events was 12.75 ± 15 per patient. Arrhythmia-clustering occurred an average of 6.1 ± 6.7 months after ICD implantation. Clinical variables with the most significant association with electrical storm were low LVEF (P = 0.04; hazard ratio of 0.261, and 95% confidence interval of 0.08–0.86) and higher use of class IA antiarrhythmic drugs (P = 0.018, hazard ratio of 3.84, and 95% confidence interval of 1.47–10.05). Amiodarone treatment and use of β-blockers were not significant predictors when subjected to multivariate analysis.We conclude that electrical storm is most likely to occur in patients with lower LVEF and that the use of Class IA antiarrhythmic drugs is a risk factor.Key words: Antiarrhythmia agents, arrhythmias, cardiac/prevention & control, cardiac pacing, artificial, defibrillators, implantable, electric countershock, electrical storm, heart failure, tachycardia, ventricular/therapy, ventricular dysfunction, leftImplantable cardioverter-defibrillators (ICDs) have become the main therapeutic tool for use in patients with life-threatening ventricular arrhythmias.^1–3 Studies have shown that 50% to 70% of ICD patients receive appropriate device therapy within 2 years of implantation.^4,5 In most patients, the total number of delivered discharges remains low. However, some patients receive multiple appropriate shocks during a short period of time consequent to recurrent or incessant ventricular tachycardia (VT) or ventricular fibrillation (VF); either of these conditions is termed an arrhythmic or electrical storm. The delivery of multiple appropriate ICD discharges for termination of recurrent ventricular tachyarrhythmias has been reported to occur in 10% to 20% of patients, depending on the duration of the observational study period.^5–7 The prognostic implication of electrical storm is unclear: some early studies did not show increased mortality rates, but more recent trials have shown a highly significant association between electrical storm and subsequent fatal events.^6,8There are few data concerning electrical storm in ICD patients. Only a few studies have reported the incidence and clinical characteristics of electrical storm in these patients.^5–7,9,10 Consequently, the impact of antiarrhythmic therapy on subsequent events (including electrical storm) is not well understood. The aim of this study was to determine the prevalence and predictors of electrical storm in ICD patients.     

Expanding the Benefits of Implantable Cardioverter-Defibrillator Therapy: “Is Less More”?

Implantable cardioverter-defibrillator (ICD) therapy improves survival in patients with significant left ventricular systolic dysfunction. Although this lifesaving therapy has many benefits, inappropriate ICD shocks may increase morbidity and mortality. With rates of inappropriate therapy quoted as high as 35% at 3 years after device implantation, numerous strategies have been evaluated to decrease the overall incidence of inappropriate therapy. Changes in programming algorithms, which allow for longer detection windows for rhythm analysis, extended the use of antitachycardia pacing, and improved supraventricular tachycardia discriminators, hold promise for decreasing inappropriate ICD therapy. In this review, we discuss the data summarizing the adverse effects of ICD shocks on outcomes, clinical trial-based programming algorithms to decrease inappropriate shocks, and the expanded role of antitachycardia pacing in ventricular arrhythmia management.     

Are Routine Arrhythmia Inductions Necessary in Patients with Pectoral Implantable Cardioverter Defibrillators?

INTRODUCTION: The value of ventricular arrhythmia inductions as part of routine implantable cardioverter defibrillator (ICD) follow-up in new-generation pectoral ICDs is unknown. METHODS AND RESULTS: We performed a retrospective analysis of a prospectively collected database analyzing data from 153 patients with pectoral ICDs who had routine arrhythmia inductions at predismissal, and 3 months and 1 year after implantation. Routine predismissal ventricular fibrillation (VF) induction yielded important findings in 8.8% of patients, all in patients with implantation defibrillation threshold (DFT) > or = 15 J or with concomitant pacemaker systems. At 3 months and 1 year, routine VF induction yielded important findings in 5.9% and 3.8% of tested patients, respectively, all in patients who had high DFT on prior testing. Ventricular tachycardia (VT) induction at predismissal, and 3 months and 1 year after implantation resulted in programming change in 37.4%, 28.1%, and 13.8% of tested patients, almost all in patients with inducible VT on baseline electrophysiologic study and clinical episodes since implantation. CONCLUSION: Although helpful in identifying potentially important ICD malfunctions, routine arrhythmia inductions during the first year after ICD implantation may not be necessary in all cases. VF inductions have a low yield in patients with previously low DFTs who lack concomitant pacemakers. VT inductions have a low yield in patients without baseline inducible VT and in the absence of clinical events. Definite recommendations regarding patient selection must await larger prospective studies as well as consensus in the medical community about what comprises an acceptable risk justifying avoidance of the costs and inconveniences of routine arrhythmia inductions.