Evaluation of the risk of cardiovascular events with clarithromycin using both propensity score and self‐controlled study designs

Abstract Aim Some previous studies suggest a long term association between clarithromycin use and cardiovascular events. This study investigates this association for clarithromycin given as part of Helicobacter pylori treatment (HPT). Methods Our source population was the Clinical Practice Research Datalink (CPRD), a UK primary care database. We conducted a self‐controlled case series (SCCS), a case–time–control study (CTC) and a propensity score adjusted cohort study comparing the rate of cardiovascular events in the 3 years after exposure to HPT containing clarithromycin with exposure to clarithromycin free HPT. Outcomes were first incident diagnosis of myocardial infarction (MI), arrhythmia and stroke. For the cohort analysis we included secondary outcomes all cause and cardiovascular mortality. Results Twenty‐eight thousand five hundred and fifty‐two patients were included in the cohort. The incidence rate ratio of first MI within 1 year of exposure to HPT containing clarithromycin was 1.07 (95% CI 0.85, 1.34, P = 0.58) and within 90 days was 1.43 (95% CI 0.99, 2.09 P = 0.057) in the SCCS analysis. CTC and cohort results were consistent with these findings. Conclusions There was some evidence for a short term association for first MI but none for a long term association for any outcome.

[1]  Yonas Ghebremichael-Weldeselassie,et al.  Spline‐based self‐controlled case series method , 2017, Statistics in medicine.

[2]  L. Smeeth,et al.  Cardiovascular outcomes associated with use of clarithromycin : population based study Journal Item , 2018 .

[3]  H. Svanström,et al.  Use of clarithromycin and roxithromycin and risk of cardiac death: cohort study , 2014, BMJ : British Medical Journal.

[4]  C. Paddy Farrington,et al.  Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study , 2014, European heart journal.

[5]  Spiros C. Denaxas,et al.  Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study , 2013, BMJ.

[6]  A. Akram,et al.  Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies , 2013, BMJ.

[7]  J. Avorn,et al.  Treatment effects in the presence of unmeasured confounding: dealing with observations in the tails of the propensity score distribution--a simulation study. , 2010, American journal of epidemiology.

[8]  L. Smeeth,et al.  Validation and validity of diagnoses in the General Practice Research Database: a systematic review , 2010, British journal of clinical pharmacology.

[9]  Heather J Whitaker,et al.  The methodology of self-controlled case series studies , 2009, Statistical methods in medical research.

[10]  Heather J. Whitaker,et al.  Semiparametric analysis of case series data , 2006 .

[11]  Patrick Musonda,et al.  Tutorial in biostatistics: the self‐controlled case series method , 2006, Statistics in medicine.

[12]  Christian Gluud,et al.  Randomised placebo controlled multicentre trial to assess short term clarithromycin for patients with stable coronary heart disease: CLARICOR trial , 2005, BMJ : British Medical Journal.

[13]  S Suissa,et al.  THE CASE‐TIME-CONTROL DESIGN , 1995, Epidemiology.