Systematic Review: Side Efffects of Ramipril and Spironolactone Drug Combination in Cardiovascular Patients
DOI:
https://doi.org/10.37287/ijghr.v7i6.1141Keywords:
cardiovascular disease, heart failure, hyperkalemia, spironolactone, ramiprilAbstract
Cardiovascular disease is one of the leading causes of death worldwide, especially in developing countries. Combination therapy of ramipril, an ACE inhibitor, and spironolactone, an aldosterone antagonist, is widely used in hypertension and heart failure patients, offering clinical benefits such as blood pressure control and organ protection, but it also poses risks of hyperkalemia and renal dysfunction. This systematic review aimed to evaluate and identify the adverse effects of ramipril–spironolactone combination therapy. A systematic search was conducted in Google Scholar and PubMed NIH Central for articles published between 2020–2024 using the keywords “Ramipril” AND “Spironolactone” AND “Adverse Effect” and “Combination Therapy” AND “Cardiovascular Disease.” From an initial 1,026 articles, 38 were screened, 37 remained after duplicate removal, and 3 studies (2 from Google Scholar and 1 from PubMed) met the inclusion criteria. Article selection followed PRISMA 2020 guidelines, and data were extracted on study design, population, interventions, outcomes, and adverse effects. The results indicate that although ramipril–spironolactone combination therapy provides significant cardiovascular benefits, it is consistently associated with hyperkalemia, hypotension, and renal dysfunction; therefore, close monitoring of potassium levels, renal function, and blood pressure is strongly recommended to minimize adverse outcomes.
References
Abbas, S., Ihle, P., Harder, S., & Schubert, I. (2015). Risk of hyperkalemia and combined use of spironolactone and long-term ACE inhibitor/angiotensin receptor blocker therapy in heart failure using real-life data: A population- and insurance-based cohort. Pharmacoepidemiology and Drug Safety, 24(4), 406–413. https://doi.org/10.1002/pds.3748
Coffman, M., Guillot, E., Blondel, T., Garelli-Paar, C., Feng, S., Heartsill, S., & Atkins, C. E. (2021). Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST). Journal of Veterinary Internal Medicine, 35(4), 1673–1687. https://doi.org/10.1111/jvim.16155
Dipiro, J. T., Yee, G. C., Posey, L. M., Haines, S. T., Nolin, T. D., & Ellingrod, V. L. (2020). Pharmacotherapy A Pathophysiologic Approach (P. E. Hayes, G. R. Matzke, R. L. Talbert, & B. G. Wells, Eds.; Eleventh Edition). McGraw Hill.
Handler, J., & Permanente, K. (2008). Well Tolerated Spironolactone-Related Hyponatremia. In JOurNaL Of CLiNiCaL HypErTENsiON (Vol. 10, Issue 4). www.lejacq.com
Leong, X. F., Ng, C. Y., & Jaarin, K. (2015). Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis. In BioMed Research International (Vol. 2015). Hindawi Publishing Corporation. https://doi.org/10.1155/2015/528757
Lexicomp. (2023). Lexicomp Drug Interactions Title Angiotensin-Converting Enzyme Inhibitors / Potassium-Sparing Diuretics. https://www.uptodate.com/drug-interactions/?source=responsive_home#di-document
Li, N., Lin, M., Heizhati, M., Wang, L., Luo, Q., Li, Y., Yili, J., Hong, J., Yao, X., & Zhu, Q. (2020). Effect of spironolactone on cardiovascular morbidity and mortality in patients with hypertension and glucose metabolism disorders (ESCAM): A study protocol for a pragmatic randomised controlled trial. BMJ Open, 10(11). https://doi.org/10.1136/bmjopen-2020-038694
Messerli, F. H., Bangalore, S., Bavishi, C., & Rimoldi, S. F. (2018). Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use? In Journal of the American College of Cardiology (Vol. 71, Issue 13, pp. 1474–1482). Elsevier USA. https://doi.org/10.1016/j.jacc.2018.01.058
Patibandla, S., Heaton, J., & Kyaw, H. (2022). Spironolactone. https://www.ncbi.nlm.nih.gov/books/NBK554421/
Rahmawati, C., & Nurwahyuni, A. (2017). Analisis Minimalisasi Biaya Obat Antihipertensi antara Kombinasi Ramipril-Spironolakton dengan Valsartan pada Pasien Gagal Jantung Kongestif di Rumah Sakit Pemerintah XY di Jakarta Tahun 2014. Jurnal Ekonomi Kesehatan Indonesia, 1(4). https://doi.org/10.7454/eki.v1i4.1802
Rosendorff, C., Lackland, D. T., Allison, M., Aronow, W. S., Black, H. R., Blumenthal, R. S., Cannon, C. P., De Lemos, J. A., Elliott, W. J., Findeiss, L., Gersh, B. J., Gore, J. M., Levy, D., Long, J. B., O’Connor, C. M., O’Gara, P. T., Ogedegbe, O., Oparil, S., & White, W. B. (2015). Treatment of hypertension in patients with coronary artery disease: A scientific statement from the American Heart Association, American College of Cardiology, and American Society of Hypertension. Journal of the American Society of Hypertension, 9(6), 453–498. https://doi.org/10.1016/j.jash.2015.03.002
Rubel, D., Zhang, Y., Sowa, N., Girgert, R., & Gross, O. (2021). Organoprotective effects of spironolactone on top of ramipril therapy in a mouse model for alport syndrome. Journal of Clinical Medicine, 10(13). https://doi.org/10.3390/jcm10132958
Shah, A., Gandhi, D., Srivastava, S., Shah, K. J., & Mansukhani, R. (2017). Heart Failure: A Class Review of Pharmacotherapy. Journal Riview, 42(7), 464–472.
Tiara, U. I. (2020). Hubungan Obesitas Dengan Kejadian Hipertensi. Journal of Health Science and Physiotherapy, 2(2), 167–171. https://doi.org/10.35893/jhsp.v2i2.51
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