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All Journal Bioscientia Medicina : Journal of Biomedicine and Translational Research Bioscientia Medicina : Journal of Biomedicine and Translational Research
Taufik Rizkian Asir
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Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology Neuroscience

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The Impact of RNA Interference on Atherosclerotic Plaque Progression: A Meta-Analysis of Preclinical Studies R. Ifan Arief Fahrurozi; Akmal M Hanif; Taufik Rizkian Asir; Wahyudi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i1.1161

Abstract

Background: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of plaque within arteries, remains a leading cause of cardiovascular morbidity and mortality. RNA interference (RNAi) has emerged as a promising therapeutic strategy for atherosclerosis by targeting genes involved in plaque formation and progression. This meta-analysis aimed to evaluate the efficacy of RNAi in preclinical models of atherosclerosis. Methods: A systematic search of PubMed, Embase, and Web of Science databases was conducted from January 2013 to December 2023 to identify preclinical studies investigating the impact of RNAi on atherosclerotic plaque progression. Studies utilizing various RNAi modalities (siRNA, miRNA mimics/inhibitors, shRNA) targeting different genes involved in atherosclerosis were included. The primary outcome was plaque size reduction. Secondary outcomes included changes in plaque composition, lipid profiles, and inflammatory markers. A random-effects model was used to pool data and calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Seven preclinical studies met the inclusion criteria, encompassing a total of 210 animals. RNAi interventions significantly reduced atherosclerotic plaque size compared to controls (SMD -1.51; 95% CI -2.36 to -0.66; p<0.00001; I²=12%). Analysis of secondary outcomes revealed favorable effects of RNAi on plaque composition, with a significant decrease in lipid content and an increase in collagen content. Furthermore, RNAi significantly improved lipid profiles by reducing total cholesterol and LDL-cholesterol levels. A significant reduction in inflammatory markers, such as TNF-α and IL-6, was also observed. Conclusion: This meta-analysis provides compelling evidence supporting the therapeutic potential of RNAi in attenuating atherosclerotic plaque progression in preclinical models. RNAi effectively reduced plaque size, improved plaque stability, and modulated lipid metabolism and inflammation.
Beta-Blocker Therapy in Older (≥75 Years) and Frail Patients with Heart Failure: A Systematic Review and Meta-Analysis Nurhayani Fatimah; Wahyudi; Taufik Rizkian Asir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 11 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i11.1433

Abstract

Background: Beta-blockers are a cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF), but their efficacy and safety in the burgeoning population of very elderly and frail patients, particularly those with preserved ejection fraction (HFpEF), remain uncertain. This population is characterized by unique pathophysiological features, including altered pharmacokinetics, heightened inflammation, and autonomic dysregulation, which may modulate the treatment effect. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) and observational studies published between 2015-2025 that evaluated beta-blockers versus placebo or standard care in patients aged ≥75 years or defined as frail with heart failure. The primary efficacy outcome was all-cause mortality. The primary safety outcome was treatment discontinuation due to adverse events. Results: Eight studies (three RCTs, five observational) involving 8,512 patients were included. In the overall population, beta-blocker therapy was associated with a reduction in all-cause mortality (Hazard Ratio: 0.88; 95% CI: 0.79−0.98), but with significant heterogeneity (I2=68%). Subgroup analysis revealed this benefit was confined to patients with HFrEF (HR: 0.72; 95% CI: 0.63−0.83), with no benefit observed in HFpEF (HR: 1.09; 95% CI: 0.95−1.25). In frail patients with HFpEF, a trend towards harm was noted (HR: 1.21; 95% CI: 0.98−1.49). Beta-blockers significantly increased treatment discontinuation (Odds Ratio: 2.15; 95% CI: 1.55−2.98), driven primarily by bradycardia. Conclusion: Beta-blocker therapy reduces mortality in elderly patients with HFrEF, consistent with findings in younger populations. However, in elderly and frail patients with HFpEF, beta-blockers offer no mortality benefit and may be associated with harm, likely due to a pathophysiological mismatch between the drug's mechanism and the disease state.
Beta-Blocker Therapy in Older (≥75 Years) and Frail Patients with Heart Failure: A Systematic Review and Meta-Analysis Nurhayani Fatimah; Wahyudi; Taufik Rizkian Asir
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 11 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i11.1433

Abstract

Background: Beta-blockers are a cornerstone of therapy for heart failure with reduced ejection fraction (HFrEF), but their efficacy and safety in the burgeoning population of very elderly and frail patients, particularly those with preserved ejection fraction (HFpEF), remain uncertain. This population is characterized by unique pathophysiological features, including altered pharmacokinetics, heightened inflammation, and autonomic dysregulation, which may modulate the treatment effect. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (RCTs) and observational studies published between 2015-2025 that evaluated beta-blockers versus placebo or standard care in patients aged ≥75 years or defined as frail with heart failure. The primary efficacy outcome was all-cause mortality. The primary safety outcome was treatment discontinuation due to adverse events. Results: Eight studies (three RCTs, five observational) involving 8,512 patients were included. In the overall population, beta-blocker therapy was associated with a reduction in all-cause mortality (Hazard Ratio: 0.88; 95% CI: 0.79−0.98), but with significant heterogeneity (I2=68%). Subgroup analysis revealed this benefit was confined to patients with HFrEF (HR: 0.72; 95% CI: 0.63−0.83), with no benefit observed in HFpEF (HR: 1.09; 95% CI: 0.95−1.25). In frail patients with HFpEF, a trend towards harm was noted (HR: 1.21; 95% CI: 0.98−1.49). Beta-blockers significantly increased treatment discontinuation (Odds Ratio: 2.15; 95% CI: 1.55−2.98), driven primarily by bradycardia. Conclusion: Beta-blocker therapy reduces mortality in elderly patients with HFrEF, consistent with findings in younger populations. However, in elderly and frail patients with HFpEF, beta-blockers offer no mortality benefit and may be associated with harm, likely due to a pathophysiological mismatch between the drug's mechanism and the disease state.
The Impact of RNA Interference on Atherosclerotic Plaque Progression: A Meta-Analysis of Preclinical Studies R. Ifan Arief Fahrurozi; Akmal M Hanif; Taufik Rizkian Asir; Wahyudi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 1 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i1.1161

Abstract

Background: Atherosclerosis, a chronic inflammatory disease characterized by the buildup of plaque within arteries, remains a leading cause of cardiovascular morbidity and mortality. RNA interference (RNAi) has emerged as a promising therapeutic strategy for atherosclerosis by targeting genes involved in plaque formation and progression. This meta-analysis aimed to evaluate the efficacy of RNAi in preclinical models of atherosclerosis. Methods: A systematic search of PubMed, Embase, and Web of Science databases was conducted from January 2013 to December 2023 to identify preclinical studies investigating the impact of RNAi on atherosclerotic plaque progression. Studies utilizing various RNAi modalities (siRNA, miRNA mimics/inhibitors, shRNA) targeting different genes involved in atherosclerosis were included. The primary outcome was plaque size reduction. Secondary outcomes included changes in plaque composition, lipid profiles, and inflammatory markers. A random-effects model was used to pool data and calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Seven preclinical studies met the inclusion criteria, encompassing a total of 210 animals. RNAi interventions significantly reduced atherosclerotic plaque size compared to controls (SMD -1.51; 95% CI -2.36 to -0.66; p<0.00001; I²=12%). Analysis of secondary outcomes revealed favorable effects of RNAi on plaque composition, with a significant decrease in lipid content and an increase in collagen content. Furthermore, RNAi significantly improved lipid profiles by reducing total cholesterol and LDL-cholesterol levels. A significant reduction in inflammatory markers, such as TNF-α and IL-6, was also observed. Conclusion: This meta-analysis provides compelling evidence supporting the therapeutic potential of RNAi in attenuating atherosclerotic plaque progression in preclinical models. RNAi effectively reduced plaque size, improved plaque stability, and modulated lipid metabolism and inflammation.
Renal and Cardiovascular Outcomes of SGLT2 Inhibitors versus ARNI in Cardiorenal Syndrome: A Network Meta-Analysis of Randomized Controlled Trials Gladian Yanuriska; Taufik Rizkian Asir; Wahyudi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1591

Abstract

Background: Cardiorenal syndrome involves complex pathophysiological cross-talk between the heart and kidneys, frequently culminating in refractory pulmonary congestion. Two primary pharmacological pillars, Sodium-Glucose Cotransporter-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitors, independently provide profound cardiovascular and renal benefits. However, direct comparative efficacy remains unquantified, creating clinical dilemmas in therapeutic sequencing. Methods: A systematic review and network meta-analysis were conducted utilizing nine pivotal randomized controlled trials. A frequentist network meta-analysis approach utilizing random-effects models was employed. Time-to-event and continuous outcomes were harmonized and pooled utilizing Standardized Mean Differences to allow for indirect head-to-head comparisons between the two drug classes. Results: The network comprised 43,450 patients. Both therapies significantly reduced cardiovascular events compared to standard care. In indirect comparisons, Angiotensin Receptor-Neprilysin Inhibitors demonstrated a superior reduction in the risk of urgent heart failure hospitalizations (Standardized Mean Difference -0.14; 95 percent Confidence Interval, -0.27 to -0.01) compared to Sodium-Glucose Cotransporter-2 inhibitors. Conversely, regarding the primary composite renal outcome (estimated glomerular filtration rate decline, end-stage renal disease, or renal death), Sodium-Glucose Cotransporter-2 inhibitors exhibited overwhelming statistical superiority over Angiotensin Receptor-Neprilysin Inhibitors (Indirect Standardized Mean Difference -0.35; 95 percent Confidence Interval, -0.50 to -0.20; p<0.001). Conclusion: Both drug classes are indispensable for managing cardiorenal syndrome. Angiotensin Receptor-Neprilysin Inhibitors provide superior acute cardiovascular hemodynamic relief, whereas Sodium-Glucose Cotransporter-2 inhibitors offer unparalleled long-term structural protection of renal function. Tailored therapeutic sequencing must leverage these distinct physiological advantages.
Renal and Cardiovascular Outcomes of SGLT2 Inhibitors versus ARNI in Cardiorenal Syndrome: A Network Meta-Analysis of Randomized Controlled Trials Gladian Yanuriska; Taufik Rizkian Asir; Wahyudi
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 10 No. 5 (2026): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v10i5.1591

Abstract

Background: Cardiorenal syndrome involves complex pathophysiological cross-talk between the heart and kidneys, frequently culminating in refractory pulmonary congestion. Two primary pharmacological pillars, Sodium-Glucose Cotransporter-2 inhibitors and Angiotensin Receptor-Neprilysin Inhibitors, independently provide profound cardiovascular and renal benefits. However, direct comparative efficacy remains unquantified, creating clinical dilemmas in therapeutic sequencing. Methods: A systematic review and network meta-analysis were conducted utilizing nine pivotal randomized controlled trials. A frequentist network meta-analysis approach utilizing random-effects models was employed. Time-to-event and continuous outcomes were harmonized and pooled utilizing Standardized Mean Differences to allow for indirect head-to-head comparisons between the two drug classes. Results: The network comprised 43,450 patients. Both therapies significantly reduced cardiovascular events compared to standard care. In indirect comparisons, Angiotensin Receptor-Neprilysin Inhibitors demonstrated a superior reduction in the risk of urgent heart failure hospitalizations (Standardized Mean Difference -0.14; 95 percent Confidence Interval, -0.27 to -0.01) compared to Sodium-Glucose Cotransporter-2 inhibitors. Conversely, regarding the primary composite renal outcome (estimated glomerular filtration rate decline, end-stage renal disease, or renal death), Sodium-Glucose Cotransporter-2 inhibitors exhibited overwhelming statistical superiority over Angiotensin Receptor-Neprilysin Inhibitors (Indirect Standardized Mean Difference -0.35; 95 percent Confidence Interval, -0.50 to -0.20; p<0.001). Conclusion: Both drug classes are indispensable for managing cardiorenal syndrome. Angiotensin Receptor-Neprilysin Inhibitors provide superior acute cardiovascular hemodynamic relief, whereas Sodium-Glucose Cotransporter-2 inhibitors offer unparalleled long-term structural protection of renal function. Tailored therapeutic sequencing must leverage these distinct physiological advantages.
Co-Authors Akmal M Hanif Gladian Yanuriska Nurhayani Fatimah R. Ifan Arief Fahrurozi WAHYUDI