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Cancer mortality does not differ by antiarrhythmic drug use: A population-based cohort of Finnish men.

ABSTRACT: In-vitro studies have suggested that the antiarrhythmic drug digoxin might restrain the growth of cancer cells by inhibiting Na+/K+-ATPase. We evaluated the association between cancer mortality and digoxin, sotalol and general antiarrhythmic drug use in a retrospective cohort study. The study population consists of 78,615 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer. Information on antiarrhythmic drug purchases was collected from the national prescription database. We used the Cox regression method to analyze separately overall cancer mortality and mortality from the most common types of cancer. During the median follow-up of 17.0 years after the baseline 28,936 (36.8%) men died, of these 8,889 due to cancer. 9,023 men (11.5%) had used antiarrhythmic drugs. Overall cancer mortality was elevated among antiarrhythmic drug users compared to non-users (HR 1.43, 95% CI 1.34-1.53). Similar results were observed separately for digoxin and for sotalol. However, the risk associations disappeared in long-term use and were modified by background co-morbidities. All in all, cancer mortality was elevated among antiarrhythmic drug users. This association is probably non-causal as it was related to short-term use and disappeared in long-term use. Our results do not support the anticancer effects of digoxin or any other antiarrhythmic drug.

SUBMITTER: Kaapu KJ

PROVIDER: S-EPMC6037774 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Cancer mortality does not differ by antiarrhythmic drug use: A population-based cohort of Finnish men.

Kaapu Kalle J KJ Rantaniemi Lauri L Talala Kirsi K Taari Kimmo K Tammela Teuvo L J TLJ Auvinen Anssi A Murtola Teemu J TJ

Scientific reports 20180709 1

In-vitro studies have suggested that the antiarrhythmic drug digoxin might restrain the growth of cancer cells by inhibiting Na+/K+-ATPase. We evaluated the association between cancer mortality and digoxin, sotalol and general antiarrhythmic drug use in a retrospective cohort study. The study population consists of 78,615 men originally identified for the Finnish Randomized Study of Screening for Prostate Cancer. Information on antiarrhythmic drug purchases was collected from the national prescr ...[more]

PMID: 29985440

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Project description:BackgroundMany antipsychotics elevate prolactin, a hormone implicated in breast cancer aetiology however no studies have investigated antipsychotic use in patients with breast cancer. This study investigated if antipsychotic use is associated with an increased risk of cancer-specific mortality among breast cancer patients.MethodsA cohort of 23,695 women newly diagnosed with a primary breast cancer between 1st January 1998 and 31st December 2012 was identified from the UK Clinical Practice Research Datalink linked to English cancer-registries and followed for until 30th September 2015. Time-dependent Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific mortality comparing use of antipsychotics with non-use, overall, and by prolactin elevating activitiy. Analyses were repeated restricting to patients with a history of severe mental illness to control for potential confounding by indication.ResultsIn total 848 patients were prescribed an antipsychotic and of which 162 died due to their breast cancer. Compared with non-use, antipsychotic use was associated with an increased risk of breast-cancer specific mortality (HR 2.25, 95%CI 1.90-2.67), but this did not follow a dose response relation. Restricting the cohort to patients with severe mental illness attenuated the association between antipsychotic use and breast cancer-specific mortality (HR 1.11, 95%CI 0.58-2.14).ConclusionsIn this population-based cohort of breast cancer patients, while the use of antipsychotics was associated with increased breast cancer-specific mortality, there was a lack of a dose response, and importantly null associations were observed in patients with severe mental illness, suggesting the observed association is likely a result of confounding by indication. This study provides an exemplar of confounding by indication, highlighting the importance of consideration of this important bias in studies of drug effects in cancer patients.

Project description:ObjectiveTo evaluate maternal medical and perinatal outcomes associated with antipsychotic drug use in pregnancy.DesignHigh dimensional propensity score (HDPS) matched cohort study.SettingMultiple linked population health administrative databases in the entire province of Ontario, Canada.ParticipantsAmong women who delivered a singleton infant between 2003 and 2012, and who were eligible for provincially funded drug coverage, those with ≥ 2 consecutive prescriptions for an antipsychotic medication during pregnancy, at least one of which was filled in the first or second trimester, were selected. Of these antipsychotic drug users, 1021 were matched 1:1 with 1021 non-users by means of a HDPS algorithm.Main outcome measuresThe main maternal medical outcomes were gestational diabetes, hypertensive disorders of pregnancy, and venous thromboembolism. The main perinatal outcomes were preterm birth (<37 weeks), and a birth weight <3rd or >97th centile. Conditional Poisson regression analysis was used to generate rate ratios and 95% confidence intervals, adjusting for additionally prescribed non-antipsychotic psychotropic medications.ResultsCompared with non-users, women prescribed an antipsychotic medication in pregnancy did not seem to be at higher risk of gestational diabetes (rate ratio 1.10 (95% CI 0.77 to 1.57)), hypertensive disorders of pregnancy (1.12 (0.70 to 1.78)), or venous thromboembolism (0.95 (0.40 to 2.27)). The preterm birth rate, though high among antipsychotic users (14.5%) and matched non-users (14.3%), was not relatively different (rate ratio 0.99 (0.78 to 1.26)). Neither birth weight <3rd centile or >97th centile was associated with antipsychotic drug use in pregnancy (rate ratios 1.21 (0.81 to 1.82) and 1.26 (0.69 to 2.29) respectively).ConclusionsAntipsychotic drug use in pregnancy had minimal evident impact on important maternal medical and short term perinatal outcomes. However, the rate of adverse outcomes is high enough to warrant careful assessment of maternal and fetal wellbeing among women prescribed an antipsychotic drug in pregnancy.

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Cancer mortality does not differ by antiarrhythmic drug use: A population-based cohort of Finnish men.

Publications

Cancer mortality does not differ by antiarrhythmic drug use: A population-based cohort of Finnish men.

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