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Heart & Lung : the Journal of Critical... 2023Guideline recommendations regarding the preferred preventive measures for postoperative atrial fibrillation (POAF) are unclear, nor have we found any review articles... (Review)
Review
BACKGROUND
Guideline recommendations regarding the preferred preventive measures for postoperative atrial fibrillation (POAF) are unclear, nor have we found any review articles addressing the combination of amiodarone and beta-blockers for the prevention of POAF.
OBJECTIVES
To investigate the efficacy and safety of combination beta-blockers and amiodarone in the prevention of POAF while also comparing the use of amiodarone and beta-blockers individually.
METHODS
We used Pubmed as the primary resource. POAF incidence was the primary outcome of this study. The secondary outcomes were hospital length of stay (LOS), ICU LOS, treatment-related drug discontinuation (TRDD), and mortality. The random-effects model assessed all pooled outcomes with 95% confidence intervals. Statistical significance was set at p≤0.05.
RESULTS
The amiodarone subgroup of POAF incidence saw a Risk Ratio (RR) of 0.81 [0.63, 1.06], p=0.12, while the combination subgroup resulted in a RR of 0.63 [0.49, 0.80], p <0.001. TRDD for the amiodarone subgroup resulted in a RR of 0.68 [0.25, 1.82], p=0.44, while the combination subgroup saw a RR of 0.84 [0.57, 1.23], p=0.36. For mortality, the amiodarone subgroup resulted in a RR of 0.97 [0.48, 1.98], p=0.93, while the combination subgroup resulted in a RR of 1.04 [0.27, 4.05], p=0.96. Both hospital and ICU LOS saw no significant difference between treatment arms for both the combination subgroup and amiodarone alone. Except for the incidence of postoperative atrial fibrillation (POAF) in the combination prophylaxis group, most of the measured outcomes did not meet the optimized information size (OIS) that was estimated.
CONCLUSION
Combination prophylaxis with amiodarone and beta-blockers significantly lowered risks of POAF incidence in comparison to beta-blockers alone while also having comparative mortality and TRDD outcomes.
PubMed: 37619317
DOI: 10.1016/j.hrtlng.2023.08.006 -
Journal of Clinical Pharmacology Dec 2023Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen... (Review)
Review
Amiodarone is an antiarrhythmic drug with a significant adverse effect profile, including neurotoxicity. While ataxia, neuropathy, and tremors are more commonly seen forms of amiodarone neurotoxicity, very few cases of nystagmus are reported. We report the case of an 86-year-old man who presented with abrupt-onset ataxia, dizziness, and inability to ambulate, 10 days after initiating amiodarone for atrial fibrillation. His examination revealed gaze-evoked nystagmus along with features of cerebellar dysfunction. After excluding other etiologies, amiodarone was stopped. His nystagmus resolved, and his ataxia improved within 48 h of stopping amiodarone. Due to the rarity of this drug-induced adverse effect, we performed a systematic review of available case reports in the literature (PubMed and Scopus) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and presented our findings. Nystagmus is a rarely reported adverse effect of amiodarone, which can occur within days to months of starting the medication. Treatment includes stopping the drug and monitoring for resolution of nystagmus.
Topics: Aged, 80 and over; Humans; Male; Amiodarone; Anti-Arrhythmia Agents; Ataxia; Atrial Fibrillation; Dizziness; Drug-Related Side Effects and Adverse Reactions; Tremor; Case Reports as Topic
PubMed: 37571970
DOI: 10.1002/jcph.2330 -
Journal of Clinical Medicine Jul 2023Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review... (Review)
Review
BACKGROUND
Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery; it is associated with morbidity and mortality. We undertook this review to compare the effects of rhythm vs. rate control in this population.
METHODS
We searched MEDLINE, Embase and CENTRAL to March 2023. We included randomized trials and observational studies comparing rhythm to rate control in cardiac surgery patients with POAF. We used a random-effects model to meta-analyze data and rated the quality of evidence using GRADE.
RESULTS
From 8,110 citations, we identified 8 randomized trials (990 patients). Drug regimens used for rhythm control included amiodarone in four trials, other class III anti-arrhythmics in one trial, class I anti-arrhythmics in four trials and either a class I or III anti-arrhythmic in one trial. Rhythm control compared to rate control did not result in a significant difference in length of stay (mean difference -0.8 days; 95% CI -3.0 to +1.4, I = 97%), AF recurrence within 1 week (130 events; risk ratio [RR] 1.1; 95%CI 0.6-1.9, I = 54%), AF recurrence up to 1 month (37 events; RR 0.9; 95%CI 0.5-1.8, I = 0%), AF recurrence up to 3 months (10 events; RR 1.0; 95%CI 0.3-3.4, I = 0%) or mortality (25 events; RR 1.6; 95%CI 0.7-3.5, I = 0%). Effect measures from seven observational studies (1428 patients) did not differ appreciably from those in randomized trials.
CONCLUSIONS
Although atrial fibrillation is common after cardiac surgery, limited low-quality data guide its management. Limited available evidence suggests no clear advantage to either rhythm or rate control. A large-scale randomized trial is needed to inform this important clinical question.
PubMed: 37445569
DOI: 10.3390/jcm12134534 -
Therapeutic Drug Monitoring Aug 2023Amiodarone is a class III antiarrhythmic drug used to prevent supraventricular and ventricular tachyarrhythmias. It has substantial toxicity; however, the use of...
BACKGROUND
Amiodarone is a class III antiarrhythmic drug used to prevent supraventricular and ventricular tachyarrhythmias. It has substantial toxicity; however, the use of therapeutic drug monitoring (TDM) seems unclear in the absence of a therapeutic range or an association between amiodarone blood concentration and effect. In this review, the authors examined the reported amiodarone blood concentration measurements in the last 10 years and subsequently noted the frequency by which TDM was used to optimize therapy.
METHODS
In March 2022, the Embase and MEDLINE databases were searched for articles published in English in the previous 10 years using the keywords "amiodarone," "therapeutic drug monitoring," or "serum/plasma/blood".
RESULTS
This study included 19 of the 478 articles identified. TDM has not been studied in conjunction with regular amiodarone maintenance therapy. One study used TDM during the initial treatment phase but the amiodarone dose was not changed. In 3 other case reports, TDM was used to guide amiodarone treatment through drug-drug interactions, and plasma levels of the active metabolite mono-N-desethyl-amiodarone (MDEA) verified 2 amiodarone toxicities.
CONCLUSIONS
Because the antiarrhythmic effect of amiodarone is not correlated with blood concentrations and is easily detectable by electrocardiogram, the routine use of TDM in maintenance therapy is controversial, as evidenced by a scarcity of published literature in the recent decade. Furthermore, amiodarone toxicity is evident with normal/low amiodarone or MDEA levels; hence, TDM of amiodarone provides no therapeutic benefit to patients.
Topics: Humans; Amiodarone; Drug Monitoring; Anti-Arrhythmia Agents
PubMed: 36631415
DOI: 10.1097/FTD.0000000000001079 -
Minerva Cardiology and Angiology Dec 2023To evaluate the clinical outcomes of oral mexiletine (oMXT) to treat ventricular tachyarrhythmias (VTAs) in the era of implantable cardioverter-defibrillator (ICD)...
INTRODUCTION
To evaluate the clinical outcomes of oral mexiletine (oMXT) to treat ventricular tachyarrhythmias (VTAs) in the era of implantable cardioverter-defibrillator (ICD) technology.
EVIDENCE ACQUISITION
A systematic search was conducted using PubMed, Embase and Cochrane databases following the PRISMA guidelines to collect literature data reporting oMXT efficacy and safety outcomes in treating VTAs in ICD recipients.
EVIDENCE SYNTHESIS
Final analysis included four studies accounting for a total of 91 patients with recurrent VTAs treated with oMXT. Amiodarone therapy was initially attempted in most patients (91.2%), while catheter ablation was performed in one-third of patients. VTA recurrences were observed in 55/91 patients (60.4%) during oMXT treatment compared to 91/91 (100%) before treatment (P<0.001). Appropriate therapies occurred in 55/88 ICD patients (62.5%) during oMXT treatment compared to 80/88 (90.9%) before treatment (P<0.001). After oMXT introduction, there was a significant reduction of the individual burden of VTA episodes and appropriate ICD therapies per patient, showing Hedges'g values of -1.103 (P=0.002) and -1.474 (P=0.008), respectively. Safety analysis showed a sample-weighted overall side-effect rate of 30%, while 21% of patients required drug reduction or discontinuation. Aggregated meta-regression analysis of the included studies and remote literature revealed a linear correlation between oMXT dosage and the overall side effects rate (r = 0.48; P=0.014).
CONCLUSIONS
Oral mexiletine provides an adjunctive treatment to manage VTAs and reduces appropriate therapies in ICD patients with moderate efficacy and acceptable safety profiles. These observations await confirmation through randomised clinical trials.
Topics: Humans; Mexiletine; Defibrillators, Implantable; Anti-Arrhythmia Agents; Treatment Outcome; Tachycardia, Ventricular
PubMed: 36305779
DOI: 10.23736/S2724-5683.22.06176-2 -
Cardiovascular Drugs and Therapy Aug 2023Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug... (Meta-Analysis)
Meta-Analysis Review
Non-vitamin K Antagonist Oral Anticoagulants (NOACs) Versus Warfarin in Patients with Atrial Fibrillation Using P-gp and/or CYP450-Interacting Drugs: a Systematic Review and Meta-analysis.
PURPOSE
Non-vitamin K antagonist oral anticoagulants (NOACs) are excreted by P-glycoprotein (P-gp) and some are metabolized by CYP450 enzymes such as CYP3A4. Although fewer drug interactions are present with NOACs, it is unclear whether NOACs should also be preferred over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) using pharmacokinetically interacting drugs. Therefore, the benefit-risk profile of NOACs versus VKAs was investigated in AF patients treated with P-gp and/or CYP450-interacting drugs.
METHODS
Using PubMed and Embase, randomized controlled trials and observational studies on the effectiveness and safety of NOACs versus VKAs in AF patients using P-gp and/or CYP450-interacting drugs were included. A meta-analysis was performed, calculating relative risks (RR) and 95% confidence intervals (CI) with the Mantel-Haenszel method.
RESULTS
Twelve studies were included, investigating 10,793 NOAC and 10,096 VKA users treated with P-gp/CYP3A4 inhibitors, whereas no studies on P-gp and/or CYP450-inducing drugs were identified. Compared to VKAs, NOACs were associated with a borderline non-significantly lower stroke or systemic embolism (stroke/SE) risk (RR 0.85, 95%CI (0.72-1.01)), significantly lower intracranial bleeding (RR 0.47, 95%CI (0.34-0.65)) and all-cause mortality risks (RR 0.87, 95%CI (0.79-0.95), but significantly higher gastrointestinal bleeding risk (RR 1.74, 95%CI (1.06-2.86)). Among AF patients using amiodarone, NOACs were associated with significantly lower stroke/SE (RR 0.71, 95%CI (0.54-0.93)) and intracranial bleeding risks (RR 0.51, 95%CI (0.29-0.88)), but significantly higher gastrointestinal bleeding risk (RR 2.15, 95%CI (1.24-3.72)) than VKAs.
CONCLUSION
The benefit-risk profile of NOACs compared to VKAs was preserved in AF patients using P-gp/CYP3A4 inhibitors, including amiodarone.
Topics: Humans; Warfarin; Anticoagulants; Atrial Fibrillation; ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Cytochrome P-450 CYP3A Inhibitors; Stroke; Intracranial Hemorrhages; Gastrointestinal Hemorrhage; Embolism; Amiodarone
PubMed: 34637052
DOI: 10.1007/s10557-021-07279-8