Drug Safety

, Volume 41, Issue 6, pp 555–564 | Cite as

The Risk for Lung Cancer Incidence with Calcium Channel Blockers: A Systematic Review and Meta-Analysis of Observational Studies

  • Victoria Rotshild
  • Laurent Azoulay
  • Majd Zarifeh
  • Reem Masarwa
  • Bruria Hirsh-Raccah
  • Amichai Perlman
  • Mordechai Muszkat
  • Ilan MatokEmail author
Original Research Article



There are conflicting findings regarding the association between the use of calcium channel blockers (CCBs) and the risk of lung cancer. Considering the public health importance of lung cancer prevention, and emerging evidence of a significant biologic role of calcium channel regulation in the development of lung cancer, we conducted a meta-analysis to assess the risk of lung cancer in CCB users compared with non-CCB users.

Materials and Methods

We conducted a comprehensive systematic search of leading medical databases for observational studies published up to December 2017 that examined CCB use and the risk of lung cancer. We used random-effects models to pool results. The impact of duration of CCB use on the estimated effect size was explored using random effects meta-regression.


Ten studies (six cohort and four case–control studies) that evaluated the overall cancer risk among 38,758 CCB users were included in the analysis. Overall risk ratio (RR) for CCB use and lung cancer was 1.15 (95% confidence interval [CI] 1.01–1.32). Subgroup analysis by duration of CCB use suggested that the observed increase in lung cancer risk was driven by the results of five studies with prolonged (≥ 4 years) exposure (RR 1.18; 95% CI 1.08–1.30).


Our analysis suggests exposure to CCBs is associated with an increased risk of lung cancer. Considering their widespread use, and the paucity of data on the long-term effects of chronic exposure to CCBs, these results are reason for concern and warrant further investigation.

Systematic Review Registration

The protocol for this study was registered at the PROSPERO registry of systematic reviews (registry number: CRD42017056362).


Compliance with Ethical Standards

Conflicts of interest

Victoria Rotshild, Laurent Azoulay, Majd Zarifeh, Reem Masarwa, Bruria Hirsh- Raccah, Amichai Perlman, Mordechai Muszkat, and Ilan Matok have no conflicts of interest that are directly relevant to the content of this study.


The study was partially supported by the Israel Cancer Association and Esther Blinko Fund. The study funder has no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. All the researchers are independent of the founders.

Supplementary material

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Supplementary material 1 (PDF 426 kb)
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Supplementary material 2 (PDF 417 kb)
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Supplementary material 3 (PDF 566 kb)
40264_2018_644_MOESM4_ESM.pdf (543 kb)
Supplementary material 4 (PDF 542 kb)
40264_2018_644_MOESM5_ESM.pdf (410 kb)
Supplementary material 5 (PDF 410 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pharmacoepidemiology Research Lab, Division of Clinical Pharmacy, Faculty of Medicine, School of Pharmacy, Institute for Drug Researchthe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Department of Epidemiology, Biostatistics, and Occupational Health, Centre for Clinical Epidemiology, Jewish General HospitalLady Davis InstituteMontrealCanada
  3. 3.Gerald Bronfman Department of OncologyMcGill UniversityMontrealCanada
  4. 4.Hadassah Braun School of Public and Community MedicineThe Hebrew University of JerusalemJerusalemIsrael
  5. 5.Department of MedicineHadassah University Hospital Mt. ScopusJerusalemIsrael

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