PERSONALISASI TERAPI KARDIOVASKULAR: INTEGRASI FARMAKOGENOMIK DALAM PENGOBATAN PENYAKIT JANTUNG KORONER
Keywords:
Pharmacogenomics, genetic polymorphism, coronary artery diseaseAbstract
Coronary artery disease (CAD) is a leading cause of global mortality, including in Indonesia. Although cardiovascular therapies have advanced, individual treatment responses remain variable. This variability is largely influenced by genetic factors, particularly gene polymorphisms affecting drug metabolism and response. This article aims to systematically review the scientific evidence on the impact of genetic polymorphisms on cardiovascular drug responses and evaluate the potential of pharmacogenomics integration in personalized treatment for CAD. Methods: A systematic literature search was conducted through PubMed, ScienceDirect and Google Scholar for articles published between 2015 and 2024. Out of 32 articles identified and 7 were selected for in-depth analysis. Results: Genetic polymorphisms such as CYP2C19, SLCO1B1, VKORC1, and ABCB1 have been shown to influence the efficacy and safety of cardiovascular drugs like clopidogrel, statins, and warfarin. Furthermore, polygenic risk scores (PRS) are increasingly utilized to predict CAD risk. However, the clinical implementation of pharmacogenomics remains limited, especially in developing countries. Conclusion: Pharmacogenomic integration has the potential to enhance the effectiveness of CAD therapy through personalized medicine approaches. Further research in local populations and health policy support are needed to optimize its clinical application.
References
1. Kementerian Kesehatan RI. Hasil Utama Riskesdas 2018. Jakarta: Badan Penelitian dan Pengembangan Kesehatan; 2019.
2. Kementerian Kesehatan Republik Indonesia. Keputusan Menteri Kesehatan Republik Indonesia Nomor HK.01.07/MENKES/1419/2023 tentang Pedoman Nasional Pelayanan Kedokteran Tata Laksana Angina Pektoris Stabil. Jakarta: Kementerian Kesehatan RI; 2023.
3. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019. J Am Coll Cardiol. 2020;76(25):2982–3021.
4. Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, AlKatheeri R, et al. Global epidemiology of ischemic heart disease: results from the Global Burden of Disease Study. Cureus. 2020;12(7):e9349.
5. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;39(2):119–77.
6. Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP. Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies. PLoS One. 2009;4(12):e7960.
7. McDonough CW. Pharmacogenomics in cardiovascular diseases. Curr Protoc. 2021 Jul;1(7):e189. doi: 10.1002/cpz1.189. PMID: 34232575; PMCID: PMC8344365.
8. Sanghvi MM, Young WJ, Naderi H, Burns R, Ramírez J, Bell CG, Munroe PB. Using Genomics to Develop Personalized Cardiovascular Treatments. Arterioscler Thromb Vasc Biol. 2025 Jun;45(6):866–881. doi:10.1161/ATVBAHA.125.319221. PMID:40244646
9. Caudle KE, Dunnenberger HM, Freimuth RR, Peterson JF, Burlison JD, Whirl‐Carrillo M, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215–23.
10. Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet. 2018;50(9):1219–24.
11. Inouye M, Abraham G, Nelson CP, et al. Genomic risk prediction of coronary artery disease in 480,000 adults. J Am Coll Cardiol. 2018;72(16):1883–1893.
12. Sirugo G, Williams SM, Tishkoff SA. The missing diversity in human genetic studies. Cell. 2019;177(1):26–31.
13. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–62.
14. Link E, Parish S, Armitage J, Bowman L, Heath S, Matsuda F, et al. SLCO1B1 variants and statin-induced myopathy—A genomewide study. N Engl J Med. 2008;359(8):789–99.
15. Türkmen D, Singh K, Curtis D, Asselbergs FW, Schmidt AF. Sex differences in the effect of SLCO1B1 polymorphisms on statin discontinuation and adverse muscle effects: UK Biobank cohort study. PLoS Med. 2022;19(5):e1003999.
16. Dutch Pharmacogenetics Working Group (DPWG). Gene-drug interactions: SLCO1B1–statins. In: KNMP Pharmacogenetics Working Group Guidelines. The Hague: Royal Dutch Pharmacists Association; 2021.
17. Wadelius M, Chen LY, Downes K, Ghori J, Hunt S, Eriksson N, et al. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. N Engl J Med. 2005;352(22):2285–93.
18. Liu ZQ, Li X, Fu JY, Chen Y, Jin Y, Li W, et al. Relationship between ABCB1 polymorphism and clopidogrel resistance: a meta-analysis. Genet Mol Res. 2014;13(4):9521–31.
19. Wang Y, Liu H, Shao W, Zhang D, Zhang Q, Zhang Y. Association of ABCB1 C3435T polymorphism with major adverse cardiac events and clopidogrel resistance in coronary artery disease patients: A meta-analysis. PLoS One. 2016;11(10):e0165315.
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