Use of azithromycin and risk of ventricular arrhythmia

Trifirò, Gianluca; Ridder, Maria de; Sultana, Janet; Oteri, Alessandro; Rijnbeek, Peter R.; Pecchioli, Serena; Mazzaglia, Giampiero; Bezemer, Irene D.; Garbe, Edeltraut; Schink, Tania; Poluzzi, Elisabetta; Frøslev, Trine; Molokhia, Mariam; Diemberger, Igor; Sturkenboom, Miriam

doi:10.1503/cmaj.160355

Cited by 44 publications

(49 citation statements)

References 31 publications

(39 reference statements)

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“…13 In contrast, Svanstrom et al demonstrated no increased risk of death from cardiovascular causes from azithromycin in a large population of middle-aged adults in Denmark, compared with penicillin V, 10 and Trifiro et al found no risk of ventricular arrhythmia (VA) from azithromycin when compared with amoxicillin. 15 The divergent findings noted in the previously described studies may be attributable to differences in study populations. The increased risk associated with azithromycin has been most prominent in studies that included high-risk patients (eg, patients already experiencing cardiovascular diseases).…”

mentioning

confidence: 79%

“…In another study, Chou et al found cardiac risk not only for macrolides, but also for fluoroquinolones, when compared with amoxicillin‐clavulanate use . In contrast, Svanstrom et al demonstrated no increased risk of death from cardiovascular causes from azithromycin in a large population of middle‐aged adults in Denmark, compared with penicillin V, and Trifiro et al found no risk of ventricular arrhythmia (VA) from azithromycin when compared with amoxicillin …”

Section: Introductionmentioning

confidence: 99%

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Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Polgreen

Riedle

Cavanaugh

et al. 2018

JAHA

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BackgroundSome studies have found that antimicrobials, especially macrolides, increase the risk of cardiovascular death. We investigated potential cardiac‐related events associated with antimicrobial use in a population of patients with acute myocardial infarction.Methods and ResultsFor 185 010 Medicare beneficiaries, we recorded prescriptions for azithromycin, clarithromycin, levofloxacin, moxifloxacin, doxycycline, and amoxicillin‐clavulanate. In the following week, we recorded death, acute myocardial infarction, atrial fibrillation or atrial flutter, a non–atrial fibrillation/atrial flutter arrhythmia, or ventricular arrhythmia. We fit unadjusted and adjusted logistic regression models using generalized estimating equations. Adjusted models included patients’ comorbidities, medications, procedures, demographics, insurance status, time since index acute myocardial infarction, number of visits, and the influenza rate. In unadjusted analyses, macrolides and fluoroquinolones were associated with a risk of cardiac events. However, the risk associated with macrolide use was substantially attenuated after adjustment for a wide range of variables, and the risk associated with fluoroquinolones was no longer statistically significant. For example, for azithromycin, the odds ratio for any cardiac event or death was 1.35 (95% confidence interval, 1.27–1.44; P<0.0001), but after controlling for a wide range of covariates, the odds ratio decreased to 1.01 (95% confidence interval, 0.95–1.08; P<0.6688).ConclusionsControlling for covariates explains much of the adverse cardiac risk associated with antimicrobial use found in other studies. Most antimicrobials are not associated with risk of cardiac events, and others, specifically azithromycin and clarithromycin, may pose a small risk of certain cardiac events. However, the modest potential risks attributable to these antimicrobials must be weighed against the drugs’ considerable and immediate benefits.

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confidence: 79%

Section: Introductionmentioning

confidence: 99%

Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Polgreen

Riedle

Cavanaugh

et al. 2018

JAHA

View full text Add to dashboard Cite

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“…Other groups have been investigating a variety of data mining methodologies to query health records for identification of ADRs based primarily on clinical features . One notable effort is the Sentinel Initiative funded by the United States Food and Drug Administration.…”

Section: Discussionmentioning

confidence: 99%

“…Other groups have been investigating a variety of data mining methodologies to query health records for identification of ADRs based primarily on clinical features. [11][12][13][14][15][16] One notable effort is the Sen- 11,20,21 Our dataset had limited structured diagnostic coding, which made it challenging for us to explore algorithms that rely on codes such as ICD-9.…”

Section: Negative Controlsmentioning

confidence: 99%

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries

Tham

Ang

et al. 2017

Pharmacoepidemiology and Drug

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Purpose: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system. Methods:We implemented the original CERT algorithm, comparing extreme laboratory results pre-and post-drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015.Results: The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug-laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug-induced hepatic and renal toxicities. Discussion:We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supple- reporting from its contributors, and susceptibility to under-reporting as well as over-reporting (eg, due to media interest), (2) incomplete or missing data, hindering causality assessment, and (3) difficulty in detecting duplicate reports. | Selection of drugs for evaluationAmong the 10 drugs analysed in the original CERT paper, one drug (ketorolac) was not used at NUH, while 3 oncologic drugs (etoposide, fluorouracil, and methotrexate) were incompletely captured because oncologic drugs are mainly ordered and recorded in another database.To have a direct head-to-head comparison of algorithm performance from the EMRs of two different health care institutions, we first analysed only 6 drugs described in the original CERT publication (round 1, Table 1).In round 2, we investigated an additional 47 drugs (Table 2).Factors considered in drug selection were drug usage volume and the likelihood of the drug being started during hospitalisation. Drugs with high usage were prioritised to provide sufficient number of cases for analysis. We also included negative controls (chlorpheniramine, metronidazole, and risedronic acid) with no ADRs detectable by abnormal laboratory test results in the reference standard. KEY POINTS• The Comparison on Extreme Laboratory Tests (CERT) algor...

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“…QTc altered after trimethroprim-sulfamethoxazole may be rare [53]. Two studies on non-septic patients [54,55] showed no difference in the incidence of arrhythmia between different groups of macrolides, indicating that illness severity is probably the most important factor. A recent meta-analysis found no significant potential for provoking arrhythmias in macrolides [56].…”

Section: Medicationmentioning

confidence: 99%

Management of arrhythmia in sepsis and septic shock

Borggrefe¹,

Matoušek²,

Malý³

et al. 2017

Anaesthesiol Intensive Ther

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The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of the sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when the sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents. Electric cardioversion is indicated in unstable patients with an absence of contraindications and is more feasible in combination with an antiarrhythmic agent. Besides amiodarone being preferred for its lower cardiodepressant side effect compared to other agents, drugs with a different degree of betablocking activity are very useful in supraventricular arrhythmias and septic shock, providing echocardiography is routinely used to support their indications within the current summary of product characteristics. A typical patient benefiting from propafenone is without significant structural heart disease, i.e. typically with normal to moderately reduced left ventricular systolic function. Future research should be channelled towards echocardiography-guided prospective controlled trials on antiarrhythmic therapy which may clarify the issue of rhythm versus rate control, the effects of various antiarrhythmic drugs, and a place for electric cardioversion in critically ill patients in septic shock.

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Use of azithromycin and risk of ventricular arrhythmia

Cited by 44 publications

References 31 publications

Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Estimated Cardiac Risk Associated With Macrolides and Fluoroquinolones Decreases Substantially When Adjusting for Patient Characteristics and Comorbidities

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries

Management of arrhythmia in sepsis and septic shock

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