6083Amiodarone in contemporary clinical practice: the rates of and reasons for permanent drug discontinuation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Mihajlovic ◽  
A Mihajlovic ◽  
M Marinkovic ◽  
V Kovacevic ◽  
L Vajagic ◽  
...  

Abstract Background and purpose Amiodarone is the most effective antiarrhythmic drug, but its long-term use is limited by organ toxicity. We studied the rates of and factors associated with permanent amiodarone discontinuation in clinical practice. Methods An ongoing prospective single-centre registry-based observational study included consecutive amiodarone-naïve patients treated for cardiac arrhythmias in a university hospital between January 2015 and December 2017. Amiodarone was administered in loading doses of 400–800 mg daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter. Results Of 1032 patients (mean age 61.5±11.4 years), 30.0% were females, and amiodarone was used for atrial fibrillation (AF, n=657, 63.7%), atrial flutter (n=187, 18.1%), other supraventricular arrhythmias (n=118, 11.4%), premature ventricular beats (n=239, 23.2%) or ventricular tachycardias (n=236, 22.9%). The most prevalent comorbidities were hypertension (n=761, 73.7%), coronary artery disease (n=283, 27.4%), heart failure (n=197, 19.2%), chronic kidney disease (n=266, 25.8%) and diabetes mellitus (n=196, 19.0%). Amiodarone was permanently discontinued due to its side effects in 103 patients (10.0%), physician's fear of complications in 73 (7.1%), patient preference in 4 (0.4%) or for miscellaneous reasons in 6 (0.6%). In another 161 patients (15.6%), the discontinuation was due to catheter ablation of index arrhythmia (n=90) or progression to permanent AF (n=71). On multivariable Cox-regression analysis, physician decision was significantly associated with amiodarone discontinuation (HR 4.2; 95% CI 3.3–5.5, p<0.001) along with the drug side effects (HR 3.0; 95% CI 2.4–3.8, p<0.001). Overall, amiodarone was permanently discontinued 347 patients (33.6%), after mean 21.4±25.2 months of treatment (median 13.0, IQR 203). The mean time to discontinuation was significantly shorter in patients with drug discontinued due to physician's decision (16.5±15.9 vs 22.7±26.9, p=0.013) and slightly longer in those with amiodarone side effects (24.9±25.8 vs 19.9±24.8 months, p=0.093) than in others. Side effects resulting in permanent amiodarone discontinuation were: hyperthyreosis (66, 6.4%), hypothyreosis (19, 1.8%), liver injury (5, 0.5%), bradycardia/AV block (9, 0.9%), QT prolongation (2, 0.2%) and corneal deposits (4, 0.4%). Pulmonary toxicity was not observed among study patients. Conclusion Our study showed that permanent amiodarone discontinuation in contemporary practice was due to its side effects in 10% of amiodarone-treated patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whilst the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in daily practice.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Mihajlovic ◽  
A Mihajlovic ◽  
M Marinkovic ◽  
V Kovacevic ◽  
L Vajagic ◽  
...  

Abstract Background and purpose Amiodarone is commonly use in patients with atrial fibrillation (AF), but the organ toxicity side effects limit its long-term use. We investigated the rates of and reasons for permanent amiodarone discontinuation among patients with AF in contemporary clinical practice. Methods A single-centre, ongoing, registry-based observational longitudinal study included consecutive AF patients prescribed with amiodarone in our hospital from January 2015 to December 2017. All patients underwent a loading protocol of 400–600 mg of amiodarone daily for 1–2 weeks, followed by 200–400mg daily for 4–8 weeks and 200mg daily or 1000mg weekly thereafter. Results Of 657 AF patients taking amiodarone (Mean age 62.2±11.0, female n=215 (32.6%), hypertension n=504 (76.7%), diabetes mellitus n=107 (16.3%), coronary arterial disease n=139 (19.8%), History of Myocardial infarction 86 (13.1%), Stroke/TIA 60 (9.1%), chronic kidney disease 157 (23.9%)), the drug was permanently discontinued in total of 248 patients (37.7%). The reasons for amiodarone discontinuation are shown in Figure. On multivariable Cox-regression analysis, physician's decision (HR 5.6; 95% CI 3.9–7.9, p<0.001) and amiodarone side effects (HR 3.9; 95% CI 2.9–5.1, p<0.001) were significantly associated with permanent amiodarone discontinuation. The overall time to discontinuation was 23.2±24.1 months. Compared with others, time to discontinuation was shorter in patients post AF ablation (17.3±21.3 vs 24.5±24.5, p=0.05), longer in those with AF progression (29.2±31.0 vs 20.9±20.3, p=0.014) and similar in patients with amiodarone side effects (23.7±17.7 vs 23.0±26.8, p=0.813). Pulmonary toxicity and proarrhythmia were not observed among study patients (Figure). Chart 1 Conclusion Our study showed that permanent discontinuation of amiodarone in contemporary clinical practice was due to the drug side effects in 12% of amiodarone-treated AF patients, occurring after a mean 2-year treatment course. The most prevalent side effect was thyroid dysfunction, whereas the prevalence of proarrhythmic effect was low. Notably, physician's fear of complications (which may not always be justified), also was an independent driver of permanent amiodarone discontinuation. More data are needed to inform optimal amiodarone use in AF patients in daily practice.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
M Mihajlovic ◽  
A Mihajlovic ◽  
M Marinkovic ◽  
V Kovacevic ◽  
J Simic ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background Amiodarone is the most prescribed antiarrhythmic drug, but drug-related side effects sometimes result in drug discontinuation. Not infrequently, physicians discontinue amiodarone without a medical reason. We explored the determinants of such permanent drug discontinuation.  Methods  A single-centre, longitudinal study included consecutive patients newly prescribed or already taking amiodarone when first seen in our health centre from January 2013 to December 2017. Baseline data were retrieved from the hospital electronic database and patients were scheduled for a follow-up visit in January to March 2019.  Results  Of 1212 patients taking amiodarone (mean age 64.2 ±11.2 yrs; female n= 358, 29.5%; median follow-up 22.5 months), the drug was permanently discontinued in 489 (40.3 %), see Figure. On univariate Cox regression analysis, female sex (HR 1.55; 95%CI 1.0-2.3; p = 0.032), non-multimorbidity (2.9; 2.0-4.3; p &lt; 0.001), LV EF (1.0; 1.0-1.1; p &lt; 0.001), NOAC therapy (1.9; 1.2-3.0; p = 0.003) and AF ablation (2.7; 1.5-4.6; P &lt; 0.001) were associated with amiodarone discontinuation. Age (0.9; 0.9-0.9; p &lt; 0.001), CAD (0.3; 0.2-0.5; p &lt; 0.001), HF (0.5; 0.3-0.9; p = 0.020), ventricular arrhythmias (0.1; 0.0-0.3; p &lt; 0.001), stroke (0.2; 0.1-0.9; p = 0.045), CKD (0.5; 0.3-0.9; p = 0.011), ICD (0.1; 0.0-0.6; P = 0.014), LV diastolic (0.9; 0.9-0.9; p = 0.001) and systolic diameter (0.9; 0.9-0.9; p &lt; 0.001), polypharmacy (0.5; 0.3-0.7; P &lt; 0.001), VKA therapy (0.6; 0.4-0.9; p = 0.027), aspirin (0.57; 0.4-0.9; p = 0.011), loop diuretic (0.5; 0.3-0.7; p &lt; 0.001), spironolactone (0.4; 0.2-0.7; p &lt; 0.001) and statin (0.6; 0.4-0.9; p = 0.009) therapy were associated with drug continuation. Multivariable risk factors for amiodarone discontinuation are showed in Table.  Conclusion Study showed that within the first two years of treatment, despite persistent indication, amiodarone was discontinued in 1 out of 10 patients in the absence of side effects, mostly in younger patients with less comorbidities, which may not always be justified. There is a need for qualitative research to elucidate the reasons for such physicians’ decisions. Table.Multivariable Cox Proportional HAZARD Regression analysis of permanent Amiodarone discontinuation due to physician decisionVariableHR95% CIP valueAge0.9700.95-0.990.003VT/VF/electrical storm0.1390.04-0.450.001VKA therapy0.5980.38-0.940.026Ablation of AF2.5391.38-4.690.003Number of comorbidities ≤32.0241.26-3.270.004VT ventricular tachycardia; VF: ventricular fibrillation.Abstract Figure.


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110065
Author(s):  
Hao Ren ◽  
Jie Liu ◽  
Jiwei Zhang ◽  
Baixi Zhuang ◽  
Weiguo Fu ◽  
...  

Objective To assess the association between post-balloon angioplasty dissection and the mid-term results of the AcoArt I trial evaluating complex femoropopliteal artery disease. Methods The outcome data for 144 patients from the AcoArt 1 trial were reanalysed. These patients were randomly divided into percutaneous transluminal angioplasty (PTA) and drug-coated balloons (DCB) groups. The primary endpoint was the primary patency (PP) rate and clinically-driven target lesion revascularisation at 24 months. Results After 24 months of follow-up, the PP rate of dissection cases in the PTA group was lower vs non-dissection cases. In patients receiving a bailout stent for dissection, the PP rate in the PTA group was lower vs the DCB group. Cox regression analysis showed that dissection decreased the PP rate; mild dissection reduced the PP rate as follows: 52%, PTA group and 19%, DCB group. With severe dissection, the PP rate reduction was as follows: 75%, PTA group and 73%, DCB group. Conclusions The mid-term follow-up showed that post-balloon angioplasty dissection reduced the PP rate in the PTA group but not in the DCB group. Additionally, in patients receiving a bailout stent for dissection, the DCB group had a better PP rate than the PTA group.


Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 798
Author(s):  
Ignacio Martin-Loeches ◽  
Adrian Ceccato ◽  
Marco Carbonara ◽  
Gianluigi li Bassi ◽  
Pierluigi di Natale ◽  
...  

Background: Cardiovascular failure (CVF) may complicate intensive care unit-acquired pneumonia (ICUAP) and radically alters the empirical treatment of this condition. The aim of this study was to determine the impact of CVF on outcome in patients with ICUAP. Methods: A prospective, single-center, observational study was conducted in six medical and surgical ICUs at a University Hospital. CVS was defined as a score of 3 or more on the cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score. At the onset of ICUAP, CVF was reported as absent, transient (if lasting ≤ 3 days) or persistent (>3 days). The primary outcome was 90-day mortality modelled through a Cox regression analysis. Secondary outcomes were 28-day mortality, hospital mortality, ICU length of stay (LOS) and hospital LOS. Results: 358 patients were enrolled: 203 (57%) without CVF, 82 (23%) with transient CVF, and 73 (20%) with persistent CVF. Patients with transient and persistent CVF were more severely ill and presented higher inflammatory response than those without CVF. Despite having similar severity and aetiology, the persistent CVF group more frequently received inadequate initial antibiotic treatment and presented more treatment failures than the transient CVF group. In the persistent CVF group, at day 3, a bacterial superinfection was more frequently detected. The 90-day mortality was significantly higher in the persistent CVF group (62%). The 28-day mortality rates for patients without CVF, with transient and with persistent CVF were 19, 35 and 41% respectively and ICU mortality was 60, 38 and 19% respectively. In the multivariate analysis chronic pulmonary conditions, lack of Pa02/FiO2 improvement at day 3, pulmonary superinfection at day 3 and persistent CVF were independently associated with 90-day mortality in ICUAP patients. Conclusions: Persistent CVF has a significant impact on the outcome of patients with ICUAP. Patients at risk from persistent CVF should be promptly recognized to optimize treatment and outcomes.


2021 ◽  
Author(s):  
Keunyoung Kim ◽  
In-Ju Kim ◽  
Kyoungjune Pak ◽  
Taewoo Kang ◽  
Young Mi Seol ◽  
...  

Abstract Background: This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer.Methods: The medical records of 288 patients who had undergone surgical resection for stages I–III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the averaged bilateral psoas muscle to the mean SUV of the liver.Results: Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for progression-free survival (PFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter PFS.Conclusions: A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.


2018 ◽  
Vol 35 (7) ◽  
pp. 700-707 ◽  
Author(s):  
Eleni Papakrivou ◽  
Demosthenes Makris ◽  
Efstratios Manoulakas ◽  
Marios Karvouniaris ◽  
Epaminondas Zakynthinos

Background: Ventilator-associated pneumonia (VAP) might be increased in cases with intra-abdominal hypertension (IAH). However, despite animal experimentation and physiological studies on humans in favor of this hypothesis, there is no definitive clinical data that IAH is associated with VAP. We therefore aimed to study whether IAH is a risk factor for increased incidence of VAP in critical care patients. This 1-center prospective observational cohort study was conducted in the intensive care unit of the University Hospital of Larissa, Greece, during 2013 to 2015. Consecutive patients were recruited if they presented risk factors for IAH at admission and were evaluated systematically for IAH and VAP for a 28-day period. Results: Forty-five (36.6%) of 123 patients presented IAH and 45 (36.6%) presented VAP; 24 patients presented VAP following IAH. Cox regression analysis showed that VAP was independently associated with IAH (1.06 [1.01-1.11]; P = .053), while there was an indication for an independent association between VAP and abdominal surgery (1.62 [0.87-3.03]; P = .11] and chronic obstructive pulmonary disease (1.79 [0.96-3.37]; P = .06). Conclusions: Intra-abdominal hypertension is an independent risk factor for increased VAP incidence in critically ill patients who present risk factors for IAH at admission to the ICU.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Prabhjot Grewal ◽  
Jeanwoo Yoo ◽  
Aikaterini Papamanoli ◽  
Azad Mojahedi ◽  
Simrat Dhaliwal ◽  
...  

Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.


Author(s):  
Mehmet Ali Erkurt ◽  
Fehmi Hindilerden ◽  
Omer Ekinci ◽  
Jale Yildiz ◽  
Mehmet Sinan Dal ◽  
...  

Objective: Pomalidomide is a new generation thalidomide analogue. Effectiveness as a single agent or combination with low dose dexamethasone has been in the treatment of relapse/refractory Multiple Myeloma (MM). The aim of the present study was to share the experience of different oncology centres with pomalidomide treatment in patients with relapsed/refractory MM. Materials and Methods: Seventy-three patients from 16 centres were enrolled into the study. The patients were followed for a median of 6 months. Relapsed/refractory MM patients who received at least one line of treatment before pomalidomide were included into the study.  ISS, R-ISS and Eastern Cooperative Oncology Group (ECOG) scores of the patients and treatment-related side effects were evaluated. Results: As a result of the median follow-up for 6 months, 36% (26/72) of the patients presented progression. The estimated median PFS was found 29 months. The Cox regression analysis revealed that ECOG affected PFS only, myeloma subtype; ISS and R-ISS scores did not affect PFS. The most common side effects with pomalidomide treatment in our population include neutropenia, infections, anaemia and thrombocytopenia. Conclusion: In our study, it was statistically shown that the ECOG score was effective in survival in relapsed / refractory MM patients treated by pomalidomide. Therefore, we recommend evaluation of the ECOG score for each patient before treatment in eligible cases.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Ahmadvazir ◽  
J Pradhan ◽  
R S Khattar ◽  
R Senior

Abstract Background The long-term clinical impact of carotid plaque burden (CPB) in patients with new onset suspected stable angina beyond stress echocardiography (SE) with no history of coronary artery disease (CAD) is not known. Methods Consecutive patients referred for SE, underwent simultaneous carotid ultrasonography to assess CPB. Patients were prospectively followed up for major adverse events (MAE). Results Of the 592 patients, 573 (age 59±11, 45% male) had follow-up data. During a mean of 7±1.2 years, 85 patients had first MAE (all-cause mortality and acute myocardial infarction: 67 (hard events) and 18 unplanned revascularisation). On multivariate Cox regression analysis, pre-test probability of CAD, peak wall thickness scoring index and CPB predicted MAE (p<0.0001 for all); however, only CPB retained significance for both hard events and hard cardiac events (p=0.008 and 0.001, respectively). MAE and hard events were least in patients with normal SE and absent carotid plaque (annualised event rate: 1.1% and 1.01%respectively) with significant increase in normal SE with plaque disease (2.4% and 2.05%, p=0.004 and 0.01 respectively). Presence of plaque did not impact on these outcomes in abnormal SE. Conclusions In patients with suspected stable angina, carotid atherosclerosis and myocardial ischemia in combination provided synergistic MAE information long term but atherosclerosis predicted hard events particularly in patients with normal SE but not in ischemic patients. This implies routine use of simultaneous carotid ultrasound following a normal SE for optimum prognostication


2020 ◽  
Vol 6 (1) ◽  
pp. e000758
Author(s):  
Johan Lahti ◽  
Jurdan Mendiguchia ◽  
Juha Ahtiainen ◽  
Luis Anula ◽  
Tuomas Kononen ◽  
...  

IntroductionHamstring muscle injuries (HMI) continue to plague professional football. Several scientific publications have encouraged a multifactorial approach; however, no multifactorial HMI risk reduction studies have been conducted in professional football. Furthermore, individualisation of HMI management programmes has only been researched in a rehabilitation setting. Therefore, this study aims to determine if a specific multifactorial and individualised programme can reduce HMI occurrence in professional football.Methods and analysisWe conducted a prospective cohort study over two seasons within the Finnish Premier League and compare the amount of HMI sustained during a control season to an intervention season. Injury data and sport exposure were collected during the two seasons (2019–2020), and a multifactorial and individualised HMI risk reduction programme will be implemented during intervention season (2020). After a hamstring screening protocol is completed, individual training will be defined for each player within several categories: lumbo-pelvic control, range of motion, posterior chain strength, sprint mechanical output and an additional non-individualised ‘training for all players’ category. Screening and respective updates to training programmes were conducted three times during the season. The outcome will be to compare if there is a significant effect of the intervention on the HMI occurrence using Cox regression analysis.Ethics and disseminationApproval for the injury and sport exposure data collection was obtained by the Saint-Etienne University Hospital Ethics Committee (request number: IORG0007394; record number IRBN322016/CHUSTE). Approval for the intervention season was obtained from the Central Finland healthcare District (request and record number: U6/2019).


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