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Use of Pregabalin and Worsening Heart Failure: A Nationwide Cohort Study

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Abstract

Introduction

Concerns regarding the increased risk of worsening heart failure with pregabalin have been raised. We assessed the association between use of pregabalin and risk of worsening heart failure in routine clinical practice.

Methods

We conducted a population-based cohort study in Denmark using data from nationwide registers, from 1 January 2008 to 31 December 2017. The study population consisted of patients 50 years of age or older with a diagnosis of heart failure who were new users of pregabalin or gabapentin (active comparator). We matched a total of 1395 new users of pregabalin to 1395 new users of gabapentin on a propensity score based on 55 covariates. Using proportional hazards regression, we estimated hazard ratios (HRs) for worsening heart failure (hospitalization with, or death from, heart failure) within 90 days of the start of treatment.

Results

We observed 33 patients with worsening heart failure among users of pregabalin [incidence rate (IR) 105.7 per 1000 person-years] versus 43 patients among users of gabapentin (IR 133.8 per 1000 person-years), corresponding to an HR of 0.79 [95% confidence interval (CI) 0.50–1.23]. The corresponding absolute risk difference was − 28.6 (95% CI − 66.8 to 31.3) per 1000 person-years. In sensitivity analysis using duloxetine as an alternative active comparator, including 847 new users of pregabalin and 847 new users of duloxetine, the results were similar (HR 1.08, 95% CI 0.60–1.94).

Conclusions

The present study found no evidence to support an association between the use of pregabalin and increased risk of worsening heart failure, compared with gabapentin and duloxetine.

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References

  1. European Medicines Agency. Summary of Product Characteristics: Lyrica (version last updated 7/12/2018).

  2. Montastruc F, Loo SY, Renoux C. Trends in first gabapentin and pregabalin prescriptions in primary care in the United Kingdom, 1993–2017. JAMA. 2018;320:2149–51.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Johansen ME. Gabapentinoid use in the United States 2002 through 2015. JAMA Intern Med. 2018;178:292–4.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Larsen HL. Misbrug af gabapentin og pregabalin—forsigtighed ved behandling af personer med opioidmisbrug. Rationel Farmakoterapi. 2018;7:3­–4.

    Google Scholar 

  5. Zaccara G, Perucca P, Gangemi PF. The adverse event profile of pregabalin across different disorders: a meta-analysis. Eur J Clin Pharmacol. 2012;68:903–12.

    Article  CAS  PubMed  Google Scholar 

  6. Onakpoya IJ, Thomas ET, Lee JJ, Goldacre B, Heneghan CJ. Benefits and harms of pregabalin in the management of neuropathic pain: a rapid review and meta-analysis of randomised clinical trials. BMJ Open. 2019;9:e023600.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sayer G, Bhat G. The renin–angiotensin–aldosterone system and heart failure. Cardiol Clin. 2014;32:21–32.

    Article  PubMed  Google Scholar 

  8. Murphy N, Mockler M, Ryder M, Ledwidge M, McDonald K. Decompensation of chronic heart failure associated with pregabalin in patients with neuropathic pain. J Card Fail. 2007;13:227–9.

    Article  PubMed  Google Scholar 

  9. Page RL, Cantu M, Lindenfeld J, Hergott LJ, Lowes BD. Possible heart failure exacerbation associated with pregabalin: case discussion and literature review. J Cardiovasc Med (Hagerstown). 2008;9:922–5.

    Article  Google Scholar 

  10. De Smedt RHE, Jaarsma T, van den Broek SAJ, Haaijer-Ruskamp FM. Decompensation of chronic heart failure associated with pregabalin in a 73-year-old patient with postherpetic neuralgia: a case report. Br J Clin Pharmacol. 2008;66:327–8.

    Article  PubMed  PubMed Central  Google Scholar 

  11. US FDA. Lyrica: full prescribing information, NDA 021446 (version updated 23 Mar 2019).

  12. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure. J Am Coll Cardiol. 2013;62:e147–239.

    Article  PubMed  Google Scholar 

  13. Ho JM-W, McDonald EM, Luo J, Gomes T, Antoniou T, Mamdani MM, et al. Pregabalin and heart failure: a population-based study. Pharmacoepidemiol Drug Saf. 2017;26:1087–92.

    Article  CAS  PubMed  Google Scholar 

  14. Wettermark B, Brandt L, Kieler H, Bodén R. Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment. Int J Clin Pract. 2014;68:104–10.

    Article  CAS  PubMed  Google Scholar 

  15. Danish Medicines Agency (Lægemiddelstyrelsen). Summary of Product Characteristics: Gabapentin “AbZ”, hard capsules (version last updated 29 Jun 2018).

  16. Kildemoes HW, Sorensen HT, Hallas J. The Danish National Prescription Registry. Scand J Public Health. 2011;39:38–41.

    Article  PubMed  Google Scholar 

  17. Lynge E, Sandegaard JL, Rebolj M. The Danish National Patient Register. Scand J Public Health. 2011;39:30–3.

    Article  PubMed  Google Scholar 

  18. Freynhagen R, Serpell M, Emir B, Whalen E, Parsons B, Clair A, et al. A comprehensive drug safety evaluation of pregabalin in peripheral neuropathic pain. Pain Pract. 2015;15:47–57.

    Article  PubMed  Google Scholar 

  19. Sundbøll J, Adelborg K, Munch T, Frøslev T, Sørensen HT, Bøtker HE, et al. Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study. BMJ Open. 2016;6:e012832.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nielsen S, Nielsen FE. Positive predictive value and impact of misdiagnosis of a heart failure diagnosis in administrative registers among patients admitted to a University Hospital cardiac care unit. Clin Epidemiol. 2010;2:235.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Brookhart MA, Schneeweiss S, Rothman KJ, Glynn RJ, Avorn J, Stürmer T. Variable selection for propensity score models. Am J Epidemiol. 2006;163:1149–56.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33:1242–58.

    Article  PubMed  Google Scholar 

  23. European Medicines Agency. EPAR—procedural steps taken and scientific information after the authorisation Lyrica (version updated 7/12/2018).

  24. Danish Medicines Agency (Lægemiddelstyrelsen). Summary of Product Characteristics: Duloxetin “2care4” (version last updated 2 Dec 2019).

  25. Park K, Kim S, Ko Y-J, Park B-J. Duloxetine and cardiovascular adverse events: a systematic review and meta-analysis. J Psychiatr Res. 2020;124:109–14.

    Article  PubMed  Google Scholar 

  26. de Landaluce LO, Carbonell P, Asensio C, Escoda N, López P, Laporte JR. Gabapentin and pregabalin and risk of atrial fibrillation in the elderly: a population-based cohort study in an electronic prescription database. Drug Saf. 2018;41:1325–31.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark

    Marie Lund, Gry Poulsen, Björn Pasternak, Niklas Worm Andersson, Mads Melbye & Henrik Svanström

  2. Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospitals, Copenhagen NV, Denmark

    Marie Lund & Niklas Worm Andersson

  3. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Björn Pasternak & Henrik Svanström

  4. Department of Clinical Medicine, University of Copenhagen, Copenhagen N, Denmark

    Mads Melbye

  5. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Mads Melbye

Authors
  1. Marie Lund
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  2. Gry Poulsen
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  3. Björn Pasternak
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  4. Niklas Worm Andersson
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  6. Henrik Svanström
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Contributions

Conception and design: ML, GP, BP, NWA, MM, and HS. Acquisition, analysis, or interpretation of data: ML, GP, BP, NWA, MM, and HS. Drafting of the manuscript: ML and GP. Critical revision of the manuscript for important intellectual content: BP, NWA, MM, and HS. Statistical analysis: GP. Obtaining funding: HS. Supervision: MM, BP, and HS

Corresponding author

Correspondence to Marie Lund.

Ethics declarations

Funding

This study was funded by Lundbeck Foundation (R219-2016-270). Dr Pasternak was supported by an investigator grant from the Strategic Research Area Epidemiology program at Karolinska Institutet.

Conflict of interest

Marie Lund reports personal fees from Dansk Lægemiddel Information A/S, outside the submitted work. Henrik Svanström is an employee of IQVIA and has received consulting fees from Celgene, outside the submitted work. Gry Poulsen, Björn Pasternak, Niklas Worm Andersson and Mads Melbye declare they have no conflicts of interest.

Ethics Approval

This study was approved by the Danish Data Protection Agency. Approval by an Ethics Committee is not needed for register-based research in Denmark.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Availability of Data and Material

The data underlying the presented results in this paper can be shared by sending a request via the regular mechanism for obtaining access to data from the Danish National Registers (https://sundhedsdatastyrelsen.dk/da/forskerservice).

Code Availability

Computer codes for the statistical analyses are available on request.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 828 kb)

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Lund, M., Poulsen, G., Pasternak, B. et al. Use of Pregabalin and Worsening Heart Failure: A Nationwide Cohort Study. Drug Saf 43, 1035–1044 (2020). https://doi.org/10.1007/s40264-020-00969-6

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  • DOI: https://doi.org/10.1007/s40264-020-00969-6

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