1196 Correspondence / American Journal of Emergency Medicine 35 (2017) 1190-1206

Digoxin use in atrial fibrillation

We read with great interest the article by Shuang Wu and colleagues in the American Journal of Emergency Medicine [1]. In this elegant study the authors assessed the predictors of digoxin use and its relationto mortality in ED patients. This study revealed that younger age, lower body mass index values, and existence of permanent atrial fibrillation, heart failure, chronic obstructive pulmonary disease, and valvular heart disease were pre- dictors of digoxin treatment. The study also showed that digoxin therapy was not related to significantly increased risk of all-cause mortality, cardiovascu- lar death, and sudden cardiac death after adjustment for known risk factors. Digoxin has been used for more than 100 years for treatment of heart failure and for Rate control in atrial fibrillation [2]. Although the use of digoxin has declined with the introduction of more evidence- based and effective medications as well as interventional procedures for atrial fibrillation and heart failure management, it is still either overused or used inappropriately in patients with atrial fibrillation. Di- goxin should not be used to treat patients with preserved left ventricle ejection fraction or if they had no atrial fibrillation and evidence is emerging that digoxin use in patients with atrial fibrillation (without heart failure) may be associated with harm [3]. In the American College of Cardiology/the American Heart Association/the Heart Rhythm Socie-

http://dx.doi.org/10.1016/j.ajem.2017.05.040

References

1. Wu Shuang, Yang Yan-min, Zhu Jun, Ren Jia-meng, Wang Juan, Zhang Han, et al. Predic- tors of digoxin use and risk of mortality in ED patients with atrial fibrillation: results from the Chinese AF registry. Yajem 2017. http://dx.doi.org/10.1016/j.ajem.2017.04.070.
2. Ehle M, Patel C, Giugliano RP. Digoxin: clinical highlights: a review of digoxin and its use in contemporary medicine. Crit Pathw Cardiol 2011 Jun;10(2):93-8.
3. Biteker M, Duman D, Dayan A, Can MM, Tekkesin AI. inappropriate use of digoxin in elderly patients presenting to an outpatient cardiology clinic of a tertiary hospital in Turkey. Turk Kardiyol Dern Ars 2011 Jul;39(5):365-70.
4. January CT, Wann LS, Alpert JS, et al. AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/Amer- ican Heart Association Task Force on Practice Guidelines and the Heart Rhythm Soci- ety. Circulation 2014;130(23):e272-4 (2014).
5. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. ESC Commit- tee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the man- agement of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012 Nov;33(21):2719-47. http://dx.doi.org/ 10.1093/eurheartj/ehs253.
6. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Car- diology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2012;14(8):803-69.
7. Biteker M, Basaran O, Dogan V, Beton O, Tekinalp M, Cagri Aykan A, et al. Real-life use

   of digoxin in patients with non-valvular atrial fibrillation: data from the RAMSES study. J Clin Pharm Ther 2016 Dec;41(6):711-7.

   The authors respond

   

   ty (ACC/AHA/HRS) guidelines for rate control in atrial fibrillation, digox-

   in is recommended to control resting heart rate in patients with HF having reduced ejection fraction [4]. The European Society of Cardiology (ESC) atrial fibrillation guidelines recommend digoxin as third choice after beta-blockers and calcium antagonists for rate control in patients with atrial fibrillation either alone or in combination [5].

   In HF, the ESC guidelines recommend digoxin in patients with HF, who are unable to tolerate a beta-blocker or who had persisting symp- toms despite treatment with a beta-blockers [6].

   In a recent study we investigated the prevalence, indications and ap- propriateness of digoxin prescription in a large, real-world population of non-valvular atrial fibrillation patients [7]. Our study showed that in a real-world cohort of non-valvular atrial fibrillation, nearly one- fifth of the patients were receiving digoxin. Compared to the non-digox- in group, patients of the digoxin group were older with a higher risk for stroke, had a greater prevalence rate of comorbidities and a higher rate of receiving thromboProphylactic treatment. As many as 60% of digoxin users had inappropriate indications. Therefore, we think that appropri- ateness of digoxin use in ED patients should have been evaluated by Shuang Wu and colleagues.

   Murat Biteker, MD, Associate Prof

   Bulent Ozlek, MD* Eda Ozlek, MD

   Mugla University, Faculty of Medicine, Department of Cardiology, Turkey

   *Corresponding author at: Mugla Sitki Kocman Universitesi Tip Fakultesi, Orhaniye Mah. Haluk Ozsoy Cad., 48000, Mugla, Turkey E-mail address: [email protected] (B. tOzlek)

   Funda Sungur Biteker, MD

   Yatagan State Hospital, Department of Infectious Diseases and Clinical

   Microbiology, Turkey

   Nesrin Basaran, Assistant Prof Edip Guvenc Cekic, Assistant Prof

   Mugla University, Faculty of Medicine, Department of Pharmacology

   Turkey

   12 May 2017

   Keywords:

   Methicillin-resistant Staphylococcus aureus

   Nosocomial pneumonia Linezolid

   Vancomycin

   Sequential organ failure assessment

   We thank the authors for their valuable comments on our article [1]. We compared the effects of linezolid (LZD) and vancomycin (VCM) in nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in the elderly.

   In our study, we adopted the inclusion criteria for the identification of MRSA isolated from cultures of the respiratory tract, sputum, and blood [2,3], but no cases of bacteremia with negative sputum culture were included in the study. Therefore, patients harboring MRSA septice- mia following lung injury were not included.

   VCM was not continuously administered, and the dosage was ad- justed according to therapeutic drug monitoring. For patients with cre- atinine clearance (CrCl) N 50 ml/min, VCM was administered at 15- 30 mg/kg every 12 h. For patients with CrCl of 10-50 ml/min, VCM was administered at 15 mg/kg every 24 h. There were no patients with CrCl b 10 ml/min. The average body weight and average age of our patients was 59.7 kg and 76.9 years, respectively, with expected de- creased renal reserve. Most of the physicians selected a dose of 15 mg/kg every 12 or 24 h (1-2 g/day), according to the patients’ renal function. The Minimal inhibitory concentrations of VCM are 0.5 or 1.0 ug/ml. We considered that these concentrations are sufficient to treat MRSA pneumonia.

   Our admission policy to the intensive care unit (ICU) is not clearly stated, and admission is decided by the attending physician. As we stat- ed in the Discussion section, patients treated with LZD had more oppor- tunity to receive ICU care than patients treated with vancomycin. Because this was a retrospective study with a small number of patients, this bias might have affected the primary outcome.

   As pointed out, there are some missing data for the Sequential Organ Failure Assessment Score. No statistically significant differences were observed due to the nature of the current study with several limitations.

   Correspondence / American Journal of Emergency Medicine 35 (2017) 1190-1206 1197

   Finally, regarding the interpretation of the results of two random- ized, controlled trials, in a recent trial that compared LZD with VCM for the treatment of nosocomial MRSA pneumonia, although 60-day mortality was similar for the two antibiotics, a subanalysis suggested that LZD produced clinically successful rates in patients aged 65 years or older [4].

   In our article, we stated the limitations of the current study. We made a weak conclusion that LZD may improve mortality in elderly pa- tients with nosocomial MRSA pneumonia, as demonstrated by reduced 30-day mortality and statistically significant reduction in SOFA scores. Further studies will be required to confirm the effectiveness of LZD for nosocomial MRSA pneumonia in elderly patients.

   Hiroaki Takada Division of Critical Care Medicine and Trauma, National Hospital Organization Disaster Medical Center, 3256 Midori, Tachikawa, Tokyo

   190-0014, Japan

   Toru Hifumi

   emergency medical center, Kagawa University Hospital, 1750-1 Ikenobe,

   Miki, Kita, Kagawa 761-0793, Japan E-mail address: [email protected]

   Naoki Nishimoto

   Clinical research support center, Kagawa University Hospital, 1750-1

   Ikenobe, Miki, Kita, Kagawa 761-0793, Japan

   24 May 2017

   http://dx.doi.org/10.1016/j.ajem.2017.05.041

   References

   Takada H, Hifumi T, Nishimoto N, et al. Linezolid versus vancomycin for nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus in the elderly: a retro- spective cohort analysis: effeciveness of linezolid in the elderly 2017;35:245-8.

8. Hifumi T, Jinbo I, Okada I, et al. The impact of age on outcomes of elderly ED patients ventilated due to community acquired pneumonia. Am J Emerg Med 2015;33: 277-81.
9. Walkey AJ, O’Donnell MR, Wiener RS. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneu- monia: a meta-analysis of randomized controlled trials. Chest 2011;139:1148-55.
10. Wunderink RG, Niederman MS, Kollef MH, et al. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 2012;54:621-9.

    Linezolid versus vancomycin in Methicillin Resistant Staphylococcus aureus nosocomial pneumonia in the elderly

    

    administrations per day. This appears to be of paramount importance since the through level described in the article (i.e. 15-20 ug/ml) might not be sufficient to treat MRSA pneumonia in certain circumstances like shock, or bacterial strains harboring high minimal inhibitory concentra- tions. Furthermore, we would like to highlight that no details are provid- ed regarding the number of patients really achieving these through levels of antibiotics. Third, as already stated by the authors, no details are pro- vided concerning the intensive care unit admission policy in the in- vestigating centres. Authors described that a substantially, though not significant, higher number of patients treated with linezolid were admit- ted in ICU. As previously described in elderly population, admission policy in ICU can lead to non-admission decision influencing the outcome [2]. As authors describe a similar baseline severity in both subgroups of patients, this could explain the difference in ICU admission, and subsequently bias the analysis of outcome as well. Fourth, the analysis of SOFA scores evo- lution over time raises questions. Renal SOFA score ANOVA is different in the linezolid group of patients, with significant differences observed only at day 1 and 3. Nevertheless, on the dedicated figure, it appears that the renal SOFA score is much lower at day 7 and 14 in the linezolid group as compared to vancomycin subgroup of patients. This raises the question of the Power of the study. As a matter of fact, a very small num- ber of patients were included. Furthermore some missing data (whose number is not provided) were declared, and the multiple imputations method was used to address this issue. Therefore, the number of missing data, and the precise analysis of variables at each step of the analysis should be provided to get a complete picture of the whole analysis. For in- stance, regarding the mechanisms of vancomycin renal toxicity [3],a dif- ference at 7 and 14 days would have been more likely than at 1 and 3 days. Last, in much larger, well conducted studies comparing linezolid and vancomycin, no difference on mortality was observed [4,5]. In one of this study, the elderly population, as described by Takada et al. represents roughly half of the population [4]. It is therefore likely that such a low number of included patients could be underpowered to lead to a different conclusion.

    Altogether, such a high mortality in the vancomycin group, without

    fatality in the linezolid group, leading to a statistical difference, questions the power of the study. We consider it is mainly hypothesis generating, and think that further data are warranted before concluding on the precise indications of antibiotics for MRSA pneumonia in the elderly population.

    Conflict of interest

    None.

    Funding

    None.

    Dear Editor,

    We read with great interest the article by Takada et al. [1] regarding comparative effectiveness of linezolid versus vancomycin in the elderly patients. Nevertheless, some methodological concerns exist, somewhat limiting the conclusions.

    First, the microbiological confirmation of pneumonia is debatable. As a matter of fact, both respiratory samples, sputum cultures and blood samples could lead to the diagnosis of Methicillin Resistant Staphylococ- cus aureus (MRSA) pneumonia. Nevertheless, authors did not describe the microbiological results in their population. Therefore, one could imagine that some patients included harbored MRSA septicemia with secondary lung injury, without pneumonia, which could have blurred the analysis of outcome. Second, more details have to be provided re- garding vancomycin administration. From the paper, it is not known whether vancomycin is administered continuously, or in several

    Julie Dupont, MD Dominique Prat, MD

    Reanimation polyvalente et surveillance continue, Hopital Antoine beclere,

    Universite Paris Sud, F-92140 Clamart, France

    Benjamin Sztrymf, MD, PhD

    Reanimation polyvalente et surveillance continue, Hopital Antoine beclere,

    Universite Paris Sud, F-92140 Clamart, France Inserm U999, Centre hospitalier Marie Lannelongue, F-92060, La Plessis

    Robinson, France Corresponding author at: Reanimation polyvalente et surveillance continue, Hopital Antoine beclere, 157 rue de la porte de Trivaux, 92140

    Clamart, France.

    E-mail address: [email protected].

    20 March 2017

    http://dx.doi.org/10.1016/j.ajem.2017.05.043