Relation of Digoxin Use in Atrial Fibrillation and the Risk of All-Cause Mortality in Patients ≥65 Years of Age With Versus Without Heart Failure

Shah, Mitesh; Tsadok, Meytal Avgil; Jackevicius, Cynthia A.; Essebag, Vidal; Behlouli, Hassan; Pilote, Louise

doi:10.1016/j.amjcard.2014.05.013

Cited by 60 publications

(47 citation statements)

References 20 publications

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“…Conflicting data exist regarding adverse outcomes that are associated with digoxin use in patients with AF 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16. While several retrospective studies and meta‐analyses have demonstrated an association between digoxin use and all‐cause mortality, cardiovascular death, and sudden cardiac death (SCD),6, 7, 8, 9, 10, 11, 12, 13 other studies have not found a compelling association 14, 15, 16.…”

Section: Introductionmentioning

confidence: 99%

“…While several retrospective studies and meta‐analyses have demonstrated an association between digoxin use and all‐cause mortality, cardiovascular death, and sudden cardiac death (SCD),6, 7, 8, 9, 10, 11, 12, 13 other studies have not found a compelling association 14, 15, 16. These contradictory results can be attributed to the nature of observational studies and to digoxin prescription biases.…”

Section: Introductionmentioning

confidence: 99%

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Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Eisen

Ruff

Braunwald

et al. 2017

JAHA

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BackgroundDigoxin is widely used in patients with atrial fibrillation despite the lack of randomized controlled trials. Observational studies report conflicting results regarding its association with mortality, perhaps because of residual confounding by the presence of heart failure (HF).Methods and ResultsIn the ENGAGE AF‐TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation‐Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow‐up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted hazard ratio, 1.51; 95% CI, 1.10–2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36–2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all‐cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic shock (P<0.01 for each), but not with noncardiovascular death, stroke/systemic embolism, or myocardial infarction.ConclusionsIn this observational analysis of patients with atrial fibrillation without investigator‐reported HF, digoxin use was significantly associated with sudden cardiac death. While residual confounding cannot be excluded, the association between digoxin use and worse clinical outcomes highlights the need to examine digoxin use, particularly when prescribed to control heart rate in patients with atrial fibrillation in a randomized trial.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00781391.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Eisen

Ruff

Braunwald

et al. 2017

JAHA

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“…Additionally, we were not able to assess the type of AF (e.g., paroxysmal, persistent, permanent) and the results may vary when accounting for this aspect of the arrhythmia. The exact doses of digoxin and other AF medications were unknown and possibly influenced the relationship between digoxin and the outcomes examined (e.g., drug--drug interactions) [27].…”

Section: Limitations Of the Studymentioning

confidence: 99%

Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation

et al. 2016

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Background: There is growing controversy regarding the association between digoxin and mortality in atrial fibrillation (AF). (pooled HR 1.47;) than AF patients with heart failure (pooled HR 1.21; interaction p = 0.06). Conclusions: Digoxin use in AF is associated with increased risk of all-cause and cardiovascular mortalities. The effect size was larger for AF patients without heart failure than AF patients with heart failure. The study suggests further directed analyses to study the effect that is suggested by this meta-analysis, especially in AF without heart failure. (Cardiol J 2016; 23, 3: 333-343)

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“…14) Digitalis has conventionally been used in heart failure patients because of its lack of a negative inotropic effect, although it takes several hours to attain sufficient action and some studies have warned that digitalis use was associated with elevated risk for all-cause mortality in patients with heart failure. 15) Amiodarone is available not only for rhythm control but also rate control, 16) whereas the half-life period is very long and it is difficult to adjust its dose within an appropriate range. Another intravenous β blocker, esmolol, also has high β1 selectivity and a short half-life period, 17,18) and its strong negative inotropic effect sometimes results in severe hypotension.…”

Section: Discussionmentioning

confidence: 99%

An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension

et al. 2015

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SummaryTachyarrhythmias such as atrial fibrillation (AF) or atrial flutter (AFL) sometimes invoke life-threatening collapse of hemodynamics in patients with severe heart failure. Recently, landiolol, an ultra-short acting β1-selective antagonist, has been reported to be safe and useful for the treatment of supraventricular tachyarrhythmias with reduced left ventricular function. Here we report a case of advanced heart failure with severe hypotension who was treated successfully by landiolol for rapid AF. The patient was a 20-year old male with dilated cardiomyopathy. He presented with low output syndrome in spite of optimal medical therapy and was referred to our department to consider ventricular assist device implantation and heart transplantation. Soon after admission, he developed rapid atrial fibrillation at 180 beats per minute (bpm) followed by severe hypotension and liver enzyme elevation. Low dose landiolol at 2 μg/kg/minute was started because digoxin was not effective. After landiolol administration, his heart rate decreased to 110 bpm, and finally returned to sinus rhythm without hemodynamic deterioration. Intra-aortic balloon pumping was inserted soon after sinus recovery and he was discharged successfully with an implantable left ventricular assist device. (Int Heart J 2015; 56: 564-567) Key words: Atrial fibrillation, Stage D heart failure, Negative chronotropic effect, Ventricular assist device I t is well known that β blocker treatment is crucial for the improvement of prognosis among patients with systolic heart failure. 1-3) However, the usage of β blockers during the acute phase of decompensated heart failure is still a matter of debate. Propranolol, a classic intravenous form of β blocker, has been used widely for perioperative arrhythmias. However, there are concerns about bronchospasm due to the non-selectivity of β adrenergic receptors. Their long half-life period may also result in the prolongation of adverse events if they occur.Landiolol was developed in Japan and introduced as an ultra-short acting intravenous β blocker. It has very high selectivity for β1 receptors and is rapidly degraded by carboxylesterase and cholinesterase in the liver and blood, respectively. Recently, many papers have reported on the benefits of landiolol for the control of perioperative tachyarrhythmias. 4) However, the indication of landiolol has been limited in patients with preserved ejection fraction, and only digoxin is indicated to control heart rate in patients with severe left ventricular (LV) dysfunction.The J-Land study (Japanese landiolol versus digoxin study) demonstrated that landiolol achieved faster control of heart rate among AF/AFL patients with LV dysfunction compared with digoxin. 5,6) The safety profiles were comparable between the two drugs. In the J-Land study, however, patients with severe LV dysfunction (ejection fraction: EF < 25%) or severe hypotension (systolic blood pressure < 90 mmHg) were excluded and there has been limited experience of landiolol among such patients. We here r...

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Relation of Digoxin Use in Atrial Fibrillation and the Risk of All-Cause Mortality in Patients ≥65 Years of Age With Versus Without Heart Failure

Cited by 60 publications

References 20 publications

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial

Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation

An Experience of Landiolol Use for an Advanced Heart Failure Patient With Severe Hypotension

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