Systematic Review and Meta-Analysis in Randomized Controlled Trials of Anti-Hypertensive Drugs and the Risk of Cancer
Main Article Content
Abstract
This paper evaluates the potential carcinogenicity of anti-hypertensive medications by performing a meta-analysis on the risk of cancer associated with their use. The analysis incorporated data from 12 studies, encompassing a total of 16,711,997 observations, and focused on randomized controlled trials of anti-hypertensive drugs. The primary objective was to compare the cancer risk across different classes of these medications while considering their blood pressure-lowering effects. The meta-analysis employed a random-effects model to synthesize the results. The mean effect size was found to be 1.178, with a 95% confidence interval ranging from 1.027 to 1.351. A Z-test conducted to test the null hypothesis that the mean effect size equals 1 yielded a Z-value of 2.343 and a p-value of less than 0.019, leading to the rejection of the null hypothesis. This indicates a statistically significant association between the use of anti-hypertensive drugs and an increased risk of cancer. The heterogeneity among the included studies was significant, as evidenced by a Q-statistic of 85.118 with 11 degrees of freedom and a p-value of less than 0.001. The I-squared statistic was 87%, suggesting that 87% of the variance in observed effects was due to differences in true effects rather than sampling error. The tau-squared value, representing the variance of true effect sizes, was 0.040 in log units, while tau, the standard deviation of true effect sizes, was 0.201 in log units. Assuming a normal distribution of true effects, the prediction interval for the true effect size was estimated to be between 0.733 and 1.894, meaning that the true effect size in 95% of all studies would fall within this range. Overall, the findings suggest a potential risk of cancer associated with anti-hypertensive drugs, which warrants careful consideration when weighing their benefits and risks. The computations for the analysis were conducted using Comprehensive Meta-Analysis.
Article Details
Copyright (c) 2024 Audi Najib Isyaku, Mary U. Adehi, Nweze Obini Nwaze, Bilkisu Maijama'a, Abdullahi Adamu Ja'e (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.
Audi Najib Isyaku, Department of Statistics, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi.
Department of Statistics,
Faculty of Natural and Applied Sciences,
Nasarawa State University, Keffi.
Mary U. Adehi, Department of Statistics, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi.
Department of Statistics,
Faculty of Natural and Applied Sciences,
Nasarawa State University, Keffi.
Nweze Obini Nwaze, Department of Statistics, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi.
Department of Statistics,
Faculty of Natural and Applied Sciences,
Nasarawa State University, Keffi.
Bilkisu Maijama'a, Department of Statistics, Faculty of Natural and Applied Sciences, Nasarawa State University, Keffi.
Department of Statistics,
Faculty of Natural and Applied Sciences,
Nasarawa State University, Keffi.
Abdullahi Adamu Ja'e, Department of Human Physiology, Faculty of Basic Medical Sciences, Federal University of Lafia.
Department of Human Physiology,
Faculty of Basic Medical Sciences,
Federal University of Lafia.
Bangalore, S., Kumar, S., Kjeldsen, S. E., Makani, H., Grossman, E., Wetterslev, J., Gupta, A. K., Sever, P. S., Gluud, C., & Messerli, F. H. (2011). Antihypertensive drugs and risk of cancer: Network meta-analyses and trial sequential analyses of 324,168 participants from randomized trials. The Lancet Oncology, 12(1), 65-82.
https://doi.org/10.1016/S1470-2045(10)70260-6 DOI: https://doi.org/10.1016/S1470-2045(10)70260-6
Chen, L., Smith, G. D., Harbord, R. M., & Lewis, S. J. (2008). Alcohol intake and blood pressure: A systematic review implementing a Mendelian randomization approach. PLoS Medicine, 5(3), e52.
https://doi.org/10.1371/journal.pmed.0050052 DOI: https://doi.org/10.1371/journal.pmed.0050052
Coory, M. D. (2010). Comment on: Heterogeneity in meta-analysis should be expected and appropriately quantified. International Journal of Epidemiology, 39(3), 932-933.
https://doi.org/10.1093/ije/dyp157 DOI: https://doi.org/10.1093/ije/dyp157
Copland, E., Canoy, D., Nazarzadeh, M., Bidel, Z., Ramakrishnan, R., Woodward, M., Chalmers, J., Teo, K. K., Pepine, C. J., Davis, B. R., Kjeldsen, S., Sundström, J., Rahimi, K., & Blood Pressure Lowering Treatment Trialists' Collaboration. (2021). Antihypertensive treatment and risk of cancer: An individual participant data meta-analysis. The Lancet Oncology, 22(4), 558-570.
https://doi.org/10.1016/S1470-2045(21)00033-4 DOI: https://doi.org/10.1016/S1470-2045(21)00033-4
DerSimonian, R., & Laird, N. (2015). Meta-analysis in clinical trials revisited. Contemporary Clinical Trials, 45(Pt A), 139-145. https://doi.org/10.1016/j.cct.2015.09.002 DOI: https://doi.org/10.1016/j.cct.2015.09.002
Deng, Y., & Xie, Y. (2022). Effects of antihypertensive drugs on risk and prognosis of colorectal cancer: A meta-analysis of 37 observational studies. Frontiers in Pharmacology, 10, 10.
https://doi.org/10.3389/fphar.2021.670657 DOI: https://doi.org/10.3389/fphar.2021.670657
Egger, M., Davey Smith, G., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315(7109), 629-634.
https://doi.org/10.1136/bmj.315.7109.629 DOI: https://doi.org/10.1136/bmj.315.7109.629
Ferreira, J. S., & Rocha, A. R. (2010). Prevalência de hipertensão arterial em crianças e adolescentes obesos. Ciência & Saúde Coletiva, 15(Suppl. 1), 97-104.
https://doi.org/10.1590/S1413-81232010000100015 DOI: https://doi.org/10.1590/S1413-81232010000100015
Haghdoost, A. A., Sadeghirad, B., Hajarizadeh, B., & Mirzazadeh, A. (2007). The application of systematic review and meta-analysis concepts in summarizing the findings of observational studies. Iranian Journal of Psychiatry, 2, 132-136.
Heisel, A. G. U., Vuurboom, M. D., Daams, J. G., de Rie, M. A., Vogt, L., van den Born, B. H., & Olde Engberink, R. H. G. (2023). The use of specific antihypertensive medication and skin cancer risk: A systematic review of the literature and meta-analysis. Vascular Pharmacology, 150, 107173.
https://doi.org/10.1016/j.vph.2023.107173 DOI: https://doi.org/10.1016/j.vph.2023.107173
Higgins, J. P., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414), 557-560. https://doi.org/10.1136/bmj.327.7414.557
https://doi.org/10.1136/bmj.327.7414.557 DOI: https://doi.org/10.1136/bmj.327.7414.557
Mukete, B. N., Cassidy, M., Ferdinand, K. C., & Le Jemtel, T. H. (2015). Long-term anti-hypertensive therapy and stroke prevention: A meta-analysis. American Journal of Cardiovascular Drugs, 15(4), 243-257. https://doi.org/10.1007/s40256-015-0129-0
https://doi.org/10.1007/s40256-015-0129-0 DOI: https://doi.org/10.1007/s40256-015-0129-0
Muldoon, M. F., Manuck, S. B., Mendelsohn, A. B., Kaplan, J. R., & Belle, S. H. (2001). Cholesterol reduction and non-illness mortality: Meta-analysis of randomized clinical trials. BMJ, 322(7277), 11-15. https://doi.org/10.1136/bmj.322.7277.11
https://doi.org/10.1136/bmj.322.7277.11 DOI: https://doi.org/10.1136/bmj.322.7277.11
Pahor, M., Psaty, B. M., Alderman, M. H., Applegate, W. B., Williamson, J. D., Cavazzini, C., & Furberg, C. D. (2000). Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: A meta-analysis of randomized controlled trials. The Lancet, 356(9246), 1949-1954. https://doi.org/10.1016/S0140-6736(00)03306-7
https://doi.org/10.1016/S0140-6736(00)03306-7 DOI: https://doi.org/10.1016/S0140-6736(00)03306-7
Rotshild, V., Hirsh-Raccah, B., Miskin, I., Muszkat, M., & Matok, I. (2021). Comparing the clinical efficacy of COVID-19 vaccines: A systematic review and network meta-analysis. Scientific Reports, 11(1), 22777. https://doi.org/10.1038/s41598-021-02321-z
https://doi.org/10.1038/s41598-021-02321-z DOI: https://doi.org/10.1038/s41598-021-02321-z
Salem, M. A., Ezzat, S. M., Ahmed, K. A., Alseekh, S., Fernie, A. R., & Essam, R. M. (2022). A comparative study of the antihypertensive and cardioprotective potentials of hot and cold aqueous extracts of Hibiscus sabdariffa L. in relation to their metabolic profiles. Frontiers in Pharmacology, 13, 840478.
https://doi.org/10.3389/fphar.2022.840478 DOI: https://doi.org/10.3389/fphar.2022.840478
Wiranata, S., Anjani, I., Wulandari, P., Indrakusuma, A., Sadeva, K., Wisnawa, A., Fajar, J., Adiputra, P. A. T., Sudarsa, I. W., Lestari, A., Desak Made, W., & Supadmanaba, I. G. P. (2021). The risk of antihypertensive drug among breast cancer patients: A systematic review and meta-analysis. Open Access Macedonian Journal of Medical Sciences, 9, 327-334.
https://doi.org/10.3889/oamjms.2021.6841 DOI: https://doi.org/10.3889/oamjms.2021.6841
Xie, Y., Deng, Y., & Xi, Y. (2021). Association between antihypertensive medication use and breast cancer: A systematic review and meta-analysis. Frontiers in Pharmacology, 2, 10.
https://doi.org/10.3389/fphar.2021.609901 DOI: https://doi.org/10.3389/fphar.2021.609901
Zang, G. (2013). Antihypertensive drugs and the risk of fall injuries: A systematic review and meta-analysis. The Journal of International Medical Research, 41(5), 1408-1417.
https://doi.org/10.1177/0300060513497562 DOI: https://doi.org/10.1177/0300060513497562