Pharmacogenomic Profiling Of The Saudi Population And Its Implications For Personalized Dosing Of Anticoagulants

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Anticoagulant therapy (n=500). Intervention: VKORC1 and CYP2C9 variant alleles vs. Wild-type alleles. Primary outcome: Mean weekly warfarin dose requirement (CYP2C9 *2 and *3 vs *1/*1) (p=<0.001).

Q: What does this research mean for the field?

Carriers of VKORC1 GA/AA and CYP2C9 variant alleles require significantly lower warfarin doses than wild-type carriers in the Saudi population. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Maisoon Humood Alobaidallah, Mohammed Khalaf M. Alanazi, Fahad Abdulrahman Mohammed, Fadheel Mutlaq Fadheel Alshammari, Faisal Hulaylan Khulaif Albanaqi, Hind Fahad Alhamdan; Hind Abdullah Al-Matroodi, Yasser Aali Ali Alharbi, Noura Ali Ahmed Alkhlaiwi, Hana Ali Sulaiman Alhudaif, Hejji Dakhil Al-Anzi, Fahad Awadh Alanazi

doi:10.70082/actjqe60

November 15, 2024The Review of Diabetic StudiesOpen Access

Pharmacogenomic Profiling Of The Saudi Population And Its Implications For Personalized Dosing Of Anticoagulants

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Why the study?

Population-specific pharmacogenomic data affecting anticoagulant therapy are limited in Saudi Arabia, necessitating characterization of key variants and their clinical implications.

Does genotype-guided dosing based on VKORC1 and CYP2C9 profiling improve therapeutic control and safety in Saudi patients receiving anticoagulants?

Key Points

To characterize key pharmacogenomic variants affecting anticoagulant therapy in a Saudi cohort and evaluate their impact on individualized dosing and clinical outcomes.
Genotyped 500 Saudi patients receiving anticoagulant therapy for VKORC1, CYP2C9, and CYP4F2 variants.
Analyzed associations between specific genotypes and weekly warfarin maintenance dose requirements using multivariate regression.
Evaluated time to target international normalized ratio (INR) stabilization and adverse events under genotype-guided dosing, alongside semi-structured interviews with 35 healthcare providers.
Carriers of VKORC1 AA or GA required significantly lower weekly warfarin doses than GG carriers (24.6 mg vs 31.2 mg, p < 0.001), and CYP2C9 *2 and *3 carriers required lower doses than *1/*1 carriers (22.8 mg vs 30.5 mg, p < 0.001).
A multivariate model incorporating genetic, demographic, and clinical factors explained approximately 68% of the variability in warfarin dosing.
Under genotype-guided protocols, 82% of patients reached target INR values within three weeks, with a major bleeding rate of 3% and thromboembolic events occurring in 2%.

Study Design

Type

Cross-Sectional (n=500)

Multicenter

Yes

Structured PICO

Does genotype-guided dosing based on VKORC1 and CYP2C9 profiling improve therapeutic control and safety in Saudi patients receiving anticoagulants?

P

Population

500 Saudi adults (mean age 52.4 years, 45.5% female) receiving anticoagulant therapy for at least three months across multiple healthcare facilities.

E

Exposure

Genotype-guided dosing of anticoagulants based on VKORC1, CYP2C9, and CYP4F2 pharmacogenomic profiling

O

Outcome

Warfarin dose requirements and clinical outcomes (INR stabilization, major bleeding, and thromboembolic events)

Main Result

Absolute Event Rate: 22.8% vs 30.5%

p-value: p=<0.001

Limitations

Cross-sectional design may limit causal inferences
Restriction of the sample to patients attending participating healthcare facilities may affect generalizability
Cross-sectional design, which may limit causal inferences
Restriction of the sample to patients attending participating healthcare facilities, which may affect generalizability

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Implication

Pharmacogenomic profiling in a Saudi population reveals significant genetic variability in VKORC1 and CYP2C9, and genotype-guided dosing improves INR stabilization and reduces adverse events.

Abstract

Background: Variability in anticoagulant response, particularly to warfarin, is strongly influenced by genetic factors. Population-specific pharmacogenomic data are limited in Saudi Arabia. Objective: To characterize key pharmacogenomic variants affecting anticoagulant therapy in a Saudi population and assess their implications for personalized dosing and clinical outcomes. Methods: A total of 500 Saudi patients receiving anticoagulant therapy were genotyped for VKORC1, CYP2C9, and CYP4F2. Associations between genotypes and warfarin dose requirements were analyzed, and clinical outcomes under genotype-guided dosing were evaluated. Healthcare provider perspectives on pharmacogenomic implementation were also assessed. Results: Significant variability in VKORC1 and CYP2C9 genotypes was observed. Carriers of VKORC1 GA/AA and CYP2C9 variant alleles required significantly lower warfarin doses than wild-type carriers (p < 0.001). A multivariate model explained 68% of dose variability. Genotype-guided dosing resulted in rapid INR stabilization (82% within three weeks) and low rates of bleeding (3%) and thromboembolic events (2%). Conclusion: Pharmacogenomic profiling revealed clinically meaningful genetic variability in the Saudi population. Genotype-guided anticoagulant dosing improved therapeutic control and supports the integration of pharmacogenomics into personalized anticoagulant management in Saudi Arabia.

Discussion

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Cite This Study

Alhamdan et al. (2024) conducted a cross-sectional in Anticoagulant therapy (n=500). VKORC1 and CYP2C9 variant alleles vs. Wild-type alleles was evaluated on Mean weekly warfarin dose requirement (CYP2C9 *2 and *3 vs *1/*1) (p=<0.001).

synapsesocial.com/papers/6ac19d70aeea5716e8c6c60c https://doi.org/10.70082/actjqe60

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Pharmacogenomic Profiling Of The Saudi Population And Its Implications For Personalized Dosing Of Anticoagulants

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Pharmacogenomic Profiling Of The Saudi Population And Its Implications For Personalized Dosing Of Anticoagulants

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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