Target Molekuler Dalam Farmakoterapi Gagal Jantung: Implikasi Terhadap Pengembangan Terapi Jantung Modern
DOI:
https://doi.org/10.51574/illea.v2i1.4675Keywords:
Gagal jantung, target molekuler, farmakoterapi, ARNI, Inhibitor SGLT2Abstract
Gagal jantung merupakan sindrom klinis kompleks yang melibatkan perubahan hemodinamik, seluler, dan molekuler, serta menjadi penyebab utama morbiditas dan mortalitas global. Perkembangan farmakoterapi modern menunjukkan pergeseran paradigma dari terapi simptomatik menuju terapi berbasis target molekuler. Artikel ini bertujuan untuk mengulas target molekuler utama dalam farmakoterapi gagal jantung dan implikasinya terhadap pengembangan terapi modern. Metode yang digunakan adalah tinjauan literatur naratif dengan analisis publikasi ilmiah dari tahun 2016–2026 melalui basis data PubMed, Scopus, dan Google Scholar. Hasil kajian menunjukkan bahwa jalur molekuler utama yang menjadi target terapi meliputi sistem renin–angiotensin–aldosterone (RAAS), sistem saraf simpatis, jalur natriuretic peptide, transporter glukosa SGLT2, serta jalur inflamasi dan fibrosis miokard. Terapi modern seperti ARNI dan inhibitor SGLT2 menunjukkan efek kardioprotektif melalui mekanisme pleiotropik, sementara biomarker molekuler dan farmakogenomik mendukung pendekatan precision medicine. Kesimpulannya, integrasi target molekuler dalam farmakoterapi gagal jantung memberikan peluang pengembangan terapi yang lebih efektif dan individualisasi terapi berbasis karakteristik molekuler pasien.
References
Bozkurt, B., Coats, A. J. S., & Tsutsui, H. (2021). Universal definition and classification of heart failure. Journal of Cardiac Failure, 27(4), 387–413. https://doi.org/10.1016/j.cardfail.2021.01.022
Braunwald, E. (2021). Heart failure. Journal of the American College of Cardiology, 77(14), 1785–1795. https://doi.org/10.1016/j.jacc.2021.02.010
Cappola, T. P., & Margulies, K. B. (2022). Genetics and genomics of heart failure. Circulation Research, 130(11), 1728–1750. https://doi.org/10.1161/CIRCRESAHA.122.320581
Greene, S. J., Fonarow, G. C., & Butler, J. (2020). Risk profiles in heart failure: Implications for prognosis and management. Circulation, 141(17), 1366–1379. https://doi.org/10.1161/CIRCULATIONAHA.119.040601
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., Fang, J. C., Fedson, S. E., Fonarow, G. C., Hayek, S. S., Hernandez, A. F., Khazanie, P., Kittleson, M. M., Lee, C. S., Link, M. S., Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure. Circulation, 145(18), e895–e1032.
https://doi.org/10.1161/CIR.0000000000001063
Johnson, K. W., Torres Soto, J., Glicksberg, B. S., Shameer, K., Miotto, R., Ali, M., Ashley, E., & Dudley, J. T. (2018). Artificial intelligence in cardiology. Journal of the American College of Cardiology, 71(23), 2668–2679. https://doi.org/10.1016/j.jacc.2018.03.521
Krittanawong, C., Johnson, K. W., Rosenson, R. S., Wang, Z., Aydar, M., & Bangalore, S. (2019). Deep learning for cardiovascular medicine. Journal of the American College of Cardiology, 73(25), 3158–3172. https://doi.org/10.1016/j.jacc.2019.04.017
Mann, D. L., & Bristow, M. R. (2021). Mechanisms and models in heart failure: The biomechanical model and beyond. Circulation, 143(15), 1463–1475.
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., Cleland, J. G. F., Coats, A. J. S., Crespo-Leiro, M. G., Farmakis, D., Gilard, M., Heymans, S., Hoes, A. W., Jaarsma, T., Jankowska, E. A., … Zamorano, J. L. (2021). 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal, 42(36), 3599–3726. https://doi.org/10.1093/eurheartj/ehab368
Murphy, S. P., Ibrahim, N. E., & Januzzi, J. L. (2020). Heart failure with reduced ejection fraction: A review. JAMA, 324(5), 488–504. https://doi.org/10.1001/jama.2020.10262
Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., Januzzi, J., Verma, S., Tsutsui, H., Brueckmann, M., Jamal, W., Kimura, K., Schnee, J., Zeller, C., Cotton, D., Bocchi, E., Böhm, M., Choi, D. J., Chopra, V., Zannad, F. (2020). Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine, 383(15), 1413–1424.
https://doi.org/10.1056/NEJMoa2022190
Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., Falk, V., González-Juanatey, J. R., Harjola, V. P., Jankowska, E. A., Jessup, M., Linde, C., Nihoyannopoulos, P., Parissis, J. T., Pieske, B., Riley, J. P., Rosano, G. M. C., Ruilope, L. M., Ruschitzka, F., & Rutten, F. H. (2016). 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal, 37(27), 2129–2200. https://doi.org/10.1093/eurheartj/ehw128
Poller, W., Dimmeler, S., & Buzás, E. I. (2020). RNA-based therapeutics in cardiovascular disease. Nature Reviews Cardiology, 17(9), 493–507. https://doi.org/10.1038/s41569-020-0351-9
Shah, S. J., Katz, D. H., Selvaraj, S., Burke, M. A., Yancy, C. W., Gheorghiade, M., & Margulies, K. B. (2021). Precision medicine for heart failure: Current and future perspectives. JACC: Heart Failure, 9(4), 246–260. https://doi.org/10.1016/j.jchf.2020.11.010
Sharma, A., Zhao, X., Hammill, B. G., Hernandez, A. F., & Peterson, E. D. (2021). Trends in heart failure outcomes and therapies. Journal of the American Heart Association, 10(5), e019233.
Tica, O., Antonescu, C., & Popescu, B. A. (2025). Pharmacogenomics in heart failure therapy. The Pharmacogenomics Journal, 25(2), 123–135.
Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., Elkind, M. S. V., Evenson, K. R., Eze-Nliam, C., Ferguson, J. F., Generoso, G., Ho, J. E., Kalani, R., Khan, S. S., Kissela, B. M., … Virani, S. S. (2023). Heart disease and stroke statistics—2023 update. Circulation, 147(8), e93–e621.
https://doi.org/10.1161/CIR.0000000000001123
Virani, S. S., Alonso, A., Aparicio, H. J., Benjamin, E. J., Bittencourt, M. S., Callaway, C. W., Carson, A. P., Chamberlain, A. M., Cheng, S., Delling, F. N., Elkind, M. S. V., Evenson, K. R., Ferguson, J. F., Gupta, D. K., Khan, S. S., Kissela, B. M., Knutson, K. L., Lee, C. D., Lewis, T. T., … American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. (2021). Heart disease and stroke statistics—2021 update. Circulation, 143(8), e254–e743. https://doi.org/10.1161/CIR.0000000000000950
Wilk, J. B., Larson, M. G., Vasan, R. S., & Levy, D. (2025). Genetic determinants and molecular pathways in heart failure. Nature Reviews Cardiology, 22(1), 45–60.
Zannad, F., Ferreira, J. P., Pocock, S. J., Anker, S. D., Butler, J., Filippatos, G., & Packer, M. (2022). SGLT2 inhibitors in heart failure. Nature Reviews Cardiology, 19(3), 173–186.
