Miney Paquette

Depression and risk of sudden cardiac death after acute myocardial infarction: testing for the confounding effects of fatigue.

OBJECTIVES This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death (SCD) risk, controlling for fatigue symptoms. METHODS Myocardial infarction (MI) patients (N = 671) participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial completed measures of depression, hostility, and social support. RESULTS After controlling for significant biological predictors, psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts (RR = 1.04; 95% CI = 1.01-1.06; p < .007), lower social participation (RR = 0.98; 95% CI = 0.96-1.00; p < .05), and, in placebo-treated patients, elevated depressive symptoms (RR = 2.45; 95% CI = 1.14-5.35; p < .02). Fatigue was associated with SCD (RR = 1.31; 95% CI = 1.11-1.53; p < .001), and, when included in the model, diminished the influence of depression (RR = 1.73; 95% CI = 0.75-3.98; p = .20). When the cognitive-affective depressive symptoms were examined separately from somatic symptoms, there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue (RR = 1.09; 95% CI = 0.99-1.19, p < .06). CONCLUSIONS Symptoms of depression and fatigue overlap in patients with MI. The trend for the cognitive-affective symptoms of depression to be associated with SCD risk, even after controlling for dyspnea/fatigue, suggests that the association between depression and mortality after AMI cannot be entirely explained as a confound of cardiac-related fatigue. The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI.

POOR ADHERENCE TO PLACEBO OR AMIODARONE THERAPY PREDICTS MORTALITY : RESULTS FROM THE CAMIAT STUDY

OBJECTIVE This study examined the relationship between adherence, mortality, and psychosocial factors. METHODS Subjects were 1141 patients participating in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial. Poor adherence to study medication (amiodarone or placebo), measured by pill count over 2 years, was defined as the lower 20th percentile of the pill count distribution. Predictors of adherence were also studied and included demographic and cardiac variables and, in a subset of participants (N = 671), measures of depression, distress, hostility, and social support. RESULTS In survival analysis controlling for cardiac and demographic variables, poor adherence in the placebo and amiodarone groups was associated with an increased risk of sudden cardiac death (relative risk (RR) = 2.11, 95% confidence interval (CI) = 1.03-4.56, p < .05; and RR = 3.15, 95% CI = 1.34-7.44, p < .01, respectively), total cardiac mortality (RR = 2.04, 95% CI = 1.12-3.72, p < .02; and RR = 2.49, 95% CI = 1.32-4.72, p < .01, respectively), and all-cause mortality (RR = 2.25, 95% CI = 1.27-3.97, p < .001; and RR = 2.34, 95% CI = 1.32-4.17, p < .004, respectively). Logistic regression analysis identified two predictors of poor adherence to placebo: age > 70 years (odds ratio = 2.18, 95% CI = 1.11-4.29, p < .03) and social activities in the month before the index heart attack (odds ratio = 1.02, 95% CI = 1.00-1.04, p < .05). CONCLUSIONS Poor adherence is associated with a greater risk of mortality. The relationship between adherence and social activities suggests a higher motivation to adhere to treatment in individuals more engaged in enjoyable activities.

Antithrombotic Treatment Patterns in Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIA-AF Registry, Phase II

BACKGROUND The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) was designed to provide prospectively collected information on patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke, with the aim of addressing treatment patterns and questions of effectiveness and safety. METHODS AND RESULTS In this predefined analysis from GLORIA-AF, the baseline characteristics and initial antithrombotic management of the first 10,000 patients in Phase II of this large Registry Program are presented. Overall, 32.3% of patients received vitamin K antagonists (VKAs) and 47.7% received non-VKA oral anticoagulants (NOACs), while 12.3% received antiplatelet treatment and 7.6% did not receive any antithrombotic treatment. Among patients with CHA2DS2-VASc score ≥2, 6.7% received no antithrombotic treatment and 10.0% received aspirin. In Europe, treatment with dabigatran was as common as treatment with VKAs (38.8% and 37.8%, respectively). More than half of the patients were treated with NOACs (52.4%), while antiplatelet treatment was given to 5.7%, and 4.1% did not receive any antithrombotic treatment. In North America, treatment with dabigatran (25.0%) was as common as with VKAs (26.1%), but overall NOAC use was more common (52.1%) than with VKAs (26.1%); however, 14.1% received antiplatelet treatment, while 7.6% received no antithrombotic treatment. In Asia, treatment with VKAs (31.9%) was more prevalent than NOACs (25.5%), but antiplatelet treatment was given to 25.8%, and 16.9% did not receive any antithrombotic treatment. In Asia, only 60.7% of patients with high stroke risk received oral anticoagulants (OACs). Paroxysmal atrial fibrillation and minimally symptomatic (or asymptomatic) patients were often undertreated with OACs. CONCLUSION In this analysis, OAC use was high in Europe and North America, with overall NOAC use higher than VKA use. A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated, while Asian patients had a high proportion of aspirin use and nontreatment.

Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry

Introduction  Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results  Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion  Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.

Left ventricular performance during acute rate control in atrial fibrillation: the importance of heart rate and agent used.

Background: The relation between heart rate and left ventricular function during rate control in atrial fibrillation is incompletely understood. Methods: Twenty-four patients (age 67 ± 11 years) with symptomatic recent onset rapid atrial fibrillation and rapid ventricular rate (> 110 bpm) were randomly assigned to receive either intravenous digoxin (13 mcg/kg) or intravenous diltiazem (0.25 mg/kg bolus plus a maintenance infusion). A portable radionuclide detector was used to collect validated measures of relative left ventricular volumes, along with heart rate data, every 15 seconds for 6 hours. Results: Heart rate decreased significantly at 15 minutes and 180 minutes in the diltiazem group (from 133 ± 18 bpm to 111 ± 26 bpm [P < .01] to 94 ± 24 bpm [P < .001]) but not in the digoxin group (from 129 ± 18 bpm to 126 ± 17 bpm [P = NS] to 118 ± 15 bpm [P = NS]). Left ventricular ejection fraction improved in both groups to a similar extent (from 39 ± 10% to 50 ± 8%, [P < .05] after diltiazem, and from 38 ± 8% to 52 ± 11% [P < .05] after digoxin at baseline vs 180 minutes, respectively). The ejection fraction vs heart rate slope was steeper in the digoxin group than in the diltiazem group (-0.34 ± 0.18 vs -0.16 ± 0.17, P = .048) indicating a more pronounced improvement in ejection fraction per unit decrease in heart rate. Conclusion: In patients with acute atrial fibrillation, digoxin led to similar improvements in ejection fraction compared to diltiazem despite a slower and less potent heart rate slowing.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.

PERSISTENCE WITH THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION: THE GLORIA-AF REGISTRY

Background: Current guidelines recommend long-term oral anticoagulation (OAC) for stroke prevention in patients with non-valvular atrial fibrillation (AF), at risk for stroke. Treatment discontinuation rates are high in patients treated with vitamin K antagonists (VKA), with only half remaining on

Clinical InvestigationsTwo-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: GLORIA-AF Registry☆

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: GLORIA-AF Registry

Background and purpose GLORIA‐AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA‐AF who are newly diagnosed with non‐valvular AF and at risk of stroke. Methods Consecutive enrollment into phase II of GLORIA‐AF was initiated following approval of dabigatran for stroke prevention in non‐valvular AF. Within this Phase II, 2937 dabigatran patients completed 2‐year follow‐up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n = 2932) were used to estimate incidence rates. Results Overall incidence rates per 100 person‐years of 0.63 (95% confidence interval [CI], 0.42‐0.92) for stroke, 1.12 (0.83‐1.49) for major bleeding, 0.47 (0.29‐0.72) for myocardial infarction, and 2.69 (2.22‐3.23) for all‐cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30‐0.94), 1.00 (0.64‐1.47), 0.48 (0.25‐0.83), and 2.07 (1.55‐2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33‐1.20), 1.16 (0.70‐1.80), 0.43 (0.17‐0.88), and 3.16 (2.36‐4.15). Conclusions These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow‐up, consistent with the results from clinical trials as well as contemporary real‐world studies. What is known • Non–vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. What is new • This study shows that in non‐valvular AF patient population, with up to 2 years of follow‐up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow‐up.