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.

     

Variability in Non–Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction: The Influence of Renal Function Estimation Formulae

Background

Non–vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from estimated glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease.

Aspirin—Anticoagulant Combination in Patients with Non Valvular Atrial Fibrillation Commentary on the FFAACS Study Results

The prevention of the thromboembolic complications of chronic atrial fibrillation remains a therapeutic challenge because they cannot be completely suppressed by vitamin K antagonists with a target international normalized ratio between 2 and 3. Evaluation of the combination at that international normalized ratio level with antiplatelet therapy was the aim of the placebo-controlled double-blind Fluindione Fibrillation Auriculaire, Aspirine et Contraste Spontané (FFAACS) study with fluindione (as anticoagulant) and aspirin (100 mg) in patients with chronic atrial fibrillation at high risk of thromboembolic complications. The study was prematurely stopped because of insufficient recruitment rate resulting in very low power. An increase of minor bleeding complications was observed in the combination arm. Given these preliminary results, this combination cannot be recommended in such patients. The question remains with respect to antithrombotic therapy in patients with atrial fibrillation if the risk of severe bleeding complications outweighs the benefit of avoiding ischemic stroke.     

Thyroid Hormone Replacement Therapy Attenuates Atrial Remodeling and Reduces Atrial Fibrillation Inducibility in a Rat Myocardial Infarction–Heart Failure Model

BackgroundHeart failure (HF) is associated with increased atrial fibrillation (AF) risk. Accumulating evidence suggests the presence of myocardial tissue hypothyroidism in HF, which may contribute to HF development. In a recent report we demonstrated that hypothyroidism, like hyperthyroidism, leads to increased AF inducibility. The present study was designed to investigate the effect of thyroid hormone (TH) replacement therapy on AF arrhythmogenesis in HF.Methods and ResultsMyocardial infarction (MI) was produced in rats by means of coronary artery ligation. Rats with large MIs (>40%) were randomized into L-thyroxine (T₄; n = 14) and placebo (n = 15) groups 2 weeks after MI. Rats received 3.3 mg T₄ (in 60-day release form) or placebo pellets for 2 months. Compared with the placebo, T₄ treatment improved cardiac function and decreased left ventricular internal diameters as well as left atrial diameter. T₄ treatment attenuated atrial effective refractory period prolongation (45 ± 1.5 ms in placebo group vs 37 ± 1.6 ms in T₄ group; P < .01) and reduced AF inducibility (AF/atrial flutter/tachycardia were inducible in 11/15 rats [73%] in the placebo- vs 4/14 rats [29%] in the T₄-treated group; P < .05). Arrhythmia reduction was associated with decreased atrial fibrosis but was not associated with connexin 43 changes.ConclusionsTo our knowledge this is the first study demonstrating that TH replacement therapy in HF attenuates atrial remodeling and reduces AF inducibility after MI-HF. Clinical studies are needed to confirm such benefits in human patients.     

Cost–Effectiveness of Different Strategies for Stroke Prevention in Patients with Atrial Fibrillation in a Health Resource-Limited Setting

Purpose

To compare the lifetime cost and effectiveness of five alternative chronic atrial fibrillation (AF) management strategies: rivaroxaban, warfarin, aspirin plus clopidogrel, aspirin and no prevention.

Methods

An individual-level state-transition model was developed to track the lifetime disease course associated with AF. The clinical and utility data were derived from published studies. The cost data were estimated based on local charges and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty on the results.

Results

For base-case patients with a CHADS₂ score of 3, the cost per additional quality-adjusted life-years (QALYs) gained for rivaroxaban compared with no prevention, aspirin, aspirin plus clopidogrel and warfarin was $116,884, $153,944, $155,979 and $216,273, respectively. CHADS₂ score had a substantial impact on the model outcomes for different prevention strategies. The time distribution of warfarin international normalised ratio (INR), stroke and intracranial haemorrhage (ICH) risks, cost of rivaroxaban and utility of warfarin therapy had substantial impacts on the results. Based on a willingness-to-pay threshold of $16,350/QALY, no prevention strategy was the preferred therapy for a patient with a low risk for stroke and a high risk for ICH; aspirin was preferred for patients with a moderate risk for stroke and ICH; and warfarin was preferred for patients with a high risk for stroke and a low risk of ICH.

Conclusion

In the context of limited health resources, rivaroxaban is unlikely to be cost-effective, although it provided more health benefits comparing with other strategies. Additionally, warfarin with good INR control might be more suitable for AF patients in developing regions.     

Does Preoperative Atrial Fibrillation Portend a Poorer Prognosis in Patients Undergoing Isolated Aortic Valve Replacement? A Multicentre Australian Study

Background

Preoperative atrial fibrillation (preop-AF) has been associated with poorer early and late outcomes after cardiac surgery. Few studies, however, have evaluated the impact of preop-AF on early and late outcomes after isolated aortic valve replacement (AVR).

Methods

Data obtained prospectively between June 2001 and December 2009 by the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database Program was retrospectively analyzed. Patients who underwent concomitant atrial arrhythmia surgery/ablation were excluded. Demographic and operative data were compared between patients undergoing isolated AVR who presented with preop-AF and those in sinus rhythm. The independent effect of preop-AF on 12 short-term complications and long-term survival was determined using binary logistic and cox regression, respectively.

Results

Isolated AVR surgery was performed in 2789 patients; 380 (13.6%) presented with preop-AF. Preop-AF patients were generally older (mean age, 73 vs 68 years; P < 0.001) and presented more often with comorbidities including congestive heart failure, diabetes, and cerebrovascular disease (all P < 0.05). There was a trend toward increased 30-day mortality in patients with preop-AF on multivariate analysis (P = 0.051). The incidence of early complications was similar in both groups on multivariate analysis (P > 0.05). Preop-AF was independently associated with reduced long-term survival (hazard ratio, 1.36; 95% confidence interval, 1.01-1.83; P = 0.041).

Conclusions

Preop-AF is associated with an increased risk of late mortality after isolated AVR. As such, concomitant atrial ablation with AVR should be prospectively studied.     

TAVR in Patients with a Low STS Score: A Cohort Study with a Mean Follow Up of 2 Years

BackgroundPartner 2 and SURTAVI trials (mean STS score of 5.8 and 4.5) support extending TAVR into the intermediate risk group. We present our results of TAVR in a group with mean STS score of 2.9 and 2 year follow up.MethodsThis is a prospective cohort study of 46 consecutive patients undergoing TAVR between 2011 and 2016. All patients had severe symptomatic AS. Age, functional status, coronary disease, co-morbidity and imaging parameters were assessed. Patients were followed up for 12–60 months.Results46 patients with a mean age of 75 years were enrolled. Mean EF 56%, mean MG 52 mm Hg and mean PG 87 mm Hg. The mean STS score was 2.9. Forty-two underwent transfemoral and 4 transaortic TAVR. Forty-five of 46 valves were implanted successfully. One patient had moderate perivalvular regurgitation (PVR). Post-procedure mean MG was 11 mm Hg. There was one procedure related stroke and one intraprocedural death. Five patients (10.8%) required a permanent pacemaker. 30-day mortality was 2 of 46 (4.3%). Mean follow up was 28 months. Mean MG at 2 years was 12 mm Hg. Late cardiac mortality occurred in 1 patient.ConclusionTAVR in this group with a low STS score was successful with excellent valve performance. Although the STS score identifies intermediate and high risk patients, it does not account for the overall frailty and limited mobility of many elderly patients placing them at a higher surgical risk despite their low STS scores. A scoring system that captures all such factors is required. Finally, a large scale randomized trial with long term follow up determining the validity of TAVR in truly low risk individuals is necessary.     

Neuromuscular Electrical Stimulation Versus Traditional Therapy in Patients with Parkinson’s Disease and Oropharyngeal Dysphagia: Effects on Quality of Life

This study compares the effects of traditional logopedic dysphagia treatment with those of neuromuscular electrical stimulation (NMES) as adjunct to therapy on the quality of life in patients with Parkinson's disease and oropharyngeal dysphagia. Eighty-eight patients were randomized over three treatment groups. Traditional logopedic dysphagia treatment and traditional logopedic dysphagia treatment combined with NMES at sensor or motor level stimulation were compared. At three times (pretreatment, post-treatment, and 3?months following treatment), two quality-of-life questionnaires (SWAL-QOL and MD Anderson Dysphagia Inventory) and a single-item Dysphagia Severity Scale were scored. The Functional Oral Intake Scale was used to assess the dietary intake. After therapy, all groups showed significant improvement on the Dysphagia Severity Scale and restricted positive effects on quality of life. Minimal group differences were found. These effects remained unchanged 3?months following treatment. No significant correlations were found between dietary intake and quality of life. Logopedic dysphagia treatment results in a restricted increased quality of life in patients with Parkinson's disease. In this randomized controlled trial, all groups showed significant therapy effects on the Dysphagia Severity Scale and restricted improvements on the SWAL-QOL and the MDADI. However, only slight nonsignificant differences between groups were found.     

Rate of Progression of Aortic Stenosis and its Impact on Outcomes in Patients With Radiation-Associated Cardiac Disease: A Matched Cohort Study

Objectives

The aim of this study was to study differences in progression of aortic stenosis (AS) in patients with mediastinal radiotherapy (XRT)-associated moderate AS versus a matched cohort during the same time frame, and to ascertain need for aortic valve replacement (AVR) and longer-term survival.