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Rasheed Ibdah,1,* Omar Obeidat,1,* Yousef Khader,2 Jowan Al-Nusair,1 Obada Abusurrah,1 Abedallah Obeidat,1 Ali Obeidat,1 Sukaina Rawashdeh,1 Nasr Alrabadi,3 Abdelrahman F Obiedat,4 Naseem N Alnadi,4 Ayman Hammoudeh4 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Community Medicine, Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science & Technology, Irbid, 22110, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Cardiology, Istishari Hospital, Amman, Jordan*These authors contributed equally to this workCorrespondence: Rasheed Ibdah, Division of Cardiology, Department of Internal Medicine, Jordan University for Science and Technology, Irbid, 22110, Jordan, Email rkibdah@just.edu.joBackground and Purpose: CHA2DS2-VASc score is one of the most widely used scoring systems to assess the risk of systemic embolization and stroke in patients suffering from atrial fibrillation (Afib); furthermore, it is important in guiding their treatment. This study aimed to evaluate the predictivity of this score in the Jordanian population, build a deeper understanding of patients’ demographic and risk factors, and assess the usefulness of anticoagulation as a preventive measure.Methods: A total of 2020 patients with Afib registered in the Jordanian Atrial Fibrillation (JoFib) registry were enrolled in this study. All patients were followed up for 1 year to assess their susceptibility to develop cerebrovascular accident (CVA) and systemic embolism (SE). The association between CHA2DS2-VASc score and risk of development of stroke or systemic embolization was analyzed based on bivariate and adjusted multivariate analyses. The ROC curve was used to assess the predictivity of the CHA2DS2-VASc score.Results: The mean age of the study population was 67.8 years; 45.8% were males, and 81.8% were on anticoagulants. And, 71.8% had a CHA2DS2-VASc score of ≥ 3. During the follow-up period of 1 year; 69 developed new CVA (mean age, 72.8 years), and 9 developed SE. A total of 276 patients died; 18 patients died (6.5% out of all deceased)% from CVA. A moderate predictive power of the CHA2DS2-VASc score was demonstrated through ROC curve analysis with C statistics of 0.689 CI (0.634 to 0.744) for predicting the development of SE or CVA at 1 year.Conclusion: CHA2DS2-VASc showed a moderate predictivity of stroke, SE, and all-cause mortality at 1 year. The study suggested disregarding gender differences in deciding to initiate anticoagulant therapy.Keywords: atrial fibrillation, Jordan, CHA2DS2-VASc, stroke, risk

Mahasen Al-Najar,1 Mohammed Al-Nusair,2 Nasr Alrabadi,3 Ibrahim Alawaisheh,4 Tuqa Alawaisheh,4 Mohamad Jarrah,5 Karem H Alzoubi,6,7 Sumaya Njem,3 Ayman Hamoudeh8 1Department of Radiology, Faculty of Medicine, The University of Jordan, Amman, Jordan; 2Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Faculty of Medicine, The University of Jordan, Amman, Jordan; 5Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 6Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; 7Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 8Cardiology Department, Istishari Hospital, Amman, JordanCorrespondence: Mohamad Jarrah; Nasr Alrabadi, Correspondence: Tel +962795994247, Email jarrahmohammad16@gmail.com; nnalrabadi@just.edu.joAim: The risks of thromboembolism and major bleeding in atrial fibrillation (AF) patients were assessed according to the “Evaluated Heartvalves, Rheumatic or Artificial” (EHRA) classification. Additionally, the safety and efficacy of vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) were compared in AF patients with EHRA type 2 valvular heart disease (VHD) versus those with no VHD.Methods: AF patients enrolled in the “Jordan Atrial Fibrillation (JoFib)” study were followed up for thromboembolic events and major bleeding at 30, 180, and 365 days. Patients in the EHRA type 2 VHD and non-VHD groups were sub-grouped to compare different OACs.Results: 2020 AF patients were recruited. The thromboembolic risk was higher in EHRA type 2 VHD patients compared to non-VHD controls. Major bleeding also occurred at higher rates in EHRA type 2 patients. In addition, NOACs were more effective in preventing thromboembolic events than VKAs and non-anticoagulation in EHRA type 2 VHD patients. Furthermore, EHRA type 2 VHD patients taking rivaroxaban had significantly less thromboembolic risk than their non-anticoagulated counterparts. At the same time, apixaban and warfarin did not significantly lower the risk of thromboembolism compared to non-anticoagulation.Conclusion: AF patients with EHRA type 2 VHD are at significant risk of thromboembolism and major bleeding. Furthermore, NOACs were more effective than VKAs in preventing thromboembolic events in this group of patients without conferring an added risk of major bleeding. Moreover, rivaroxaban appears to be particularly efficacious.Keywords: thromboembolism, bleeding, atrial fibrillation, EHRA type 2 valvular heart disease, Jordan

Mohamad Jarrah,1 Nasr Alrabadi,2 Nashmi Al-Nusair,1 Karem H Alzoubi,3,4 Qasim Mhaidat,1 Mahasen Al-Najar,5 Ayman Hammoudeh6 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 2Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 3Department of Pharmacy Practice and Pharmacotherapeutics, University of Sharjah, Sharjah, United Arab Emirates; 4Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Radiology, Faculty of Medicine, The University of Jordan, Amman, Jordan; 6Cardiology Department, Istishari Hospital, Amman, JordanCorrespondence: Mohamad Jarrah; Nasr Alrabadi, Tel +962795994247, Email jarrahmohammad16@gmail.com; nnalrabadi@just.edu.joBackground: Diabetes mellitus (DM) is considered a risk and prognostic factor for elderly patients with the acute coronary syndrome (ACS). However, less is known about the characteristics of this relationship among younger patients in the Middle Eastern population.Objective: To explore the Clinical outcomes of cardiovascular-related events in young DM patients (≤ 50 years of age) during hospitalization and up to one year of follow-up.Methods: We compared the clinical features, in-hospital and one-year outcomes in young ACS diabetic patients with young ACS non-diabetic patients in 12 tertiary care centers in Jordan.Results: A total of 3517 ACS patients were included initially, 1031 of whom (29.3%) were < 50-year-old. Of those, 385 (37.3%) had DM. Compared with young non-diabetic patients, young diabetic patients were more likely to have a worse clinical baseline profile, which includes hypertension (53.2% vs 26.0%, p < 0.001), dyslipidemia (32.5% vs 19.5%, p < 0.001), and multivessel coronary artery disease (40.9% vs 32.0%, p = 0.03). Furthermore, the diabetic group had more females than males (14.0% vs 5.9%, p < 0.001) and a higher mean body mass index (28.8+4.7 kg/m 2 vs 27.9+4.0 kg/m2, p < 0.001). There were no differences between the two groups in the mortality rates during index hospitalization (0.39% vs 0.28%, p = 0.63) or at one-year follow-up (1.6% vs 0.6%, p = 0.41). Also, no significant differences were observed in the rates of stent thrombosis (1.95% vs 1.97%, p = 0.78) or readmission for ACS or coronary revascularization (10.8% vs 7.6%, p = 0.14).Conclusion: Despite a worse baseline clinical profile, young diabetic ACS patients did not have higher risks for in-hospital or one-year adverse cardiovascular events compared with the young non-diabetic ACS patients.Keywords: diabetes mellitus, acute coronary syndrome, cardiovascular events, in-hospital complications, one-year follow-up

Nabil Al-Zoubi,1 Nasr Alrabadi,2 Khalid Kheirallah,3 Ahmad Alqudah4 1Department of General Surgery/Vascular Surgery, Jordan University of Science and Technology, Irbid, 22110, Jordan; 2Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan; 3Department of Public Health and Community Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Laboratories/Jordan University of Science and Technology, Irbid, 22110, JordanCorrespondence: Nabil Al-ZoubiAssociate Professor of Vascular Surgery and Endovascular Therapy, Department of Surgery, Faculty of Medicine, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, JordanTel + 962 79-5577-4637Email nazoubi@just.edu.joBackground: FV, MTHFR, II, and PAI-I are the most common genes associated with thrombophilia genetic variants, which vary among different populations and ethnic groups. Little is known about the prevalence and multiplicity of these variants in Jordan. The aim of this study was to estimate the prevalence and multiplicity of the FV G1691A, FV H1299R, MTHFR 1298A>C, MTHFR 677C>T, II 20210G>A, and PAI-I 675 4G/5G variants among healthy Jordanians.Methods: This cross-sectional study was conducted on randomly selected healthy Jordanian participants. Non-Jordanians and those with a history of arterial/venous thrombosis, atherosclerosis, or a history of recurrent abortions were excluded from the study. PCR was used to detect variants in DNA extracted from participants’ blood samples.Results: A total of 300 subjects were screened: 170 (56.7%) females with an average age of 27.78± 9.32 years and 130 (43.3%) males with an average age of 29.88± 8.55 years. Genetic variants (at least one) were found in 75% of the subjects (81.2% among females and 66.9% among men), while 64.7%, 52%, and 12% were found to have at least two, three, and four variants, respectively. Overall, 21%, 29%, 54.3%, 27.3%, 7.7%, and 66% of participants were found to have FV G1691A, FV H1299R, MTHFR 1298A>C, MTHFR 677C>T, II 20210G>A, and PAI-I 675 4G/5G gene variants, respectively.Conclusion: Three-quarters of our population had at least one of the thrombophilia genetic variants, and most had more than one variant. The most common variants detected were associated with MTHFR, followed by PAI-I, FV, and then II. We observed that females had higher prevalence estimates than males. However, multiplicity among males was significantly higher than females. Our findings indicated noticeable differences in prevalence estimates compared with other populations.Keywords: thrombophilia, gene mutations, factor V Leiden, FV, MTHFR, factorII, PAI-I

Majed M Masadeh,1 Karem H Alzoubi,2 Bashar M Al-Taani,1 Majd M Masadeh,1 Zainah O Aburashed,1,2 Nasr Alrabadi3 1Department of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, JordanCorrespondence: Majed M MasadehDepartment of Pharmaceutical Technology, Jordan University of Science and Technology, Irbid 22110, JordanEmail mmmasadeh@just.edu.joBackground: Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains.Methods: The bacterial strains that were used include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of E. Coli cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation.Results: Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D.Conclusion: Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.Keywords: fluoroquinolones, vitamins, MIC, zones of inhibition, antimicrobial susceptibility, oxidative stress

Nasr Alrabadi,1 Hanin Makhlouf,2 Omar F Khabour,2 Karem H Alzoubi3 1Department of Pharmacology, Faculty Of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Nasr AlrabadiDepartment Of Pharmacology, Faculty Of Medicine, Jordan University Of Science And Technology, Irbid 22110, JordanTel +962795994247Email nnalrabadi@just.edu.joIntroduction: The informed consent process is an integral step in biomedical research. However, the emergence of biobanks and the need for open consent (also called “broad” or “blanket” consent) create challenges to this process.Aims and methodology: A survey was used to examine Jordanians’ perspectives on open consent and reuse of stored samples in future research.Results: The majority of participants had positive perceptions of informed consent and its importance. In addition, they appreciated the challenges that are associated with multiple uses of their biospecimens. About 55% agreed to provide open consent for reuse of their donated biospecimens. Participants (75–80%) also agreed that issues such as the possibility of sharing samples with international research centers, storage duration, and use of biospecimens after their death should be clarified as part of open consent. The inconvenience of the re-contact process, trust in the research team, and the importance of biobanks were all associated with participants’ willingness to provide open consent (P

Hanin Makhlouf,1 Nasr Alrabadi,2 Omar F Khabour,1 Karem H Alzoubi,3 Wael Al-Delaimy4 1Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Division of Global Health, Department of Family and Preventive Medicine, University of California at San Diego, San Diego, CA, USA Background: Biobanks (biorepositories) were established to compile collected bio-specimens for future research and usage. The collection/storage of bio-specimens triggers several social, legal, and ethical implications where public attitudes can represent the core measurement/parameter in defining the most acceptable practices and ethical approaches when dealing with biobanks. Aim: The aim of this study was to explore and understand population’s perspectives, expectations, and concerns toward biobanks in Jordan. Methods: A cross-sectional survey that included closed-ended questions was distributed among Jordanians. A total of 500 participants who are representative of the Jordanian population were included in this study. Results: There was overwhelming support (>85%) for the establishment of biobanks in Jordan, and most of the participants agreed on the importance of biobanks and samples’ donation for promoting medical research. Enthusiasm in biobanking participation was associated with the sociodemographic characteristics of participants including age, educational level, and previous knowledge of biobanks. Moreover, considering sample donation as a religiously good deed appeared to have the strongest positive correlation with willingness to donate bio-specimens for future research. Also, participants’ trust in medical and research services, especially the protection of their privacy and confidentiality, was the most critical concern when they decided to participate in biobanks. Conclusion: Population’s attitude toward biobanks in Jordan was positive and promising, and can encourage the future establishment of different biobanks. It is also necessary to take into consideration certain sociodemographic characteristics when discussing specific information with potential biobanks’ donors. Keywords: biorepositories, sample storage, sample donation, sample reuse, ethics

Mohamad I Jarrah,1 Nasr Alrabadi,2 Karem H Alzoubi3 1Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Background: The safety and efficacy of drug-eluting coronary stenting have been established for various degrees of severity of coronary artery disease. The DESyne is a contemporary cobalt–chromium thin-strut stent which has been studied in low-risk patients so far. Aim: The aim of this study was to evaluate the safety, efficacy and performance of the DESyne stent in patients with an indication for coronary stent implantation at the King Abdullah University Hospital (KAUH), Jordan. Patients and methods: Hospital records for all patients implanted with DESyne stent were retrospectively reviewed. Specific clinical events were recorded for all cases, and their incidence rates were estimated by the Kaplan–Meier method. A total of 715 patients (79.3% males and 58.3% with diabetes) with a mean age of 57.8±10.3 years were enrolled in this study. An acute coronary syndrome was the most frequent indication for stenting in 86.3% of the patients (unstable angina 72.0%, myocardial infarction [MI] 14.3%). A total of 849 lesions (1.2 lesions/patient) were treated with the DESyne stent. Results: After 1 year of follow-up, the death rates from cardiac or noncardiac causes were 0.6% and 1.1%, respectively. MI was observed in 0.9% of the cases, and an ischemia-driven revascularization was performed in 0.8% of them. The definite/probable stent thrombosis rate was 1.1%. Conclusion: Favorable clinical event rates including cardiac death, MI and stent thrombosis were observed for the DESyne stent in ischemic heart patients especially those with high prevalence of diabetes mellitus and acute coronary syndrome. Keywords: coronary stent system, DESyne stent, ischemic heart disease

Mohamad I Jarrah,1 Nizar M Mhaidat,2 Karem H Alzoubi,2 Nasr Alrabadi,3 Enas Alsatari,2 Yousef Khader,4 Moath F Bataineh5 1Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Public Health and Community Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Sport Rehabilitation, Faculty of Physical Education and Sport Sciences, Hashemite University, Zarqa, Jordan Background: Decreased levels of vitamin D were associated with increased risk of multiple diseases, including cardiovascular diseases. However, there seem to be some discrepancies among the results obtained from different studies. The aim of the present study was to explore the importance of having sufficient serum levels of vitamin D in reducing the incidence and the progression of coronary artery stenosis and ischemic heart disease (IHD). Methods: Serum levels of vitamin D were measured using radioimmunoassay in 186 Jordanian patients who underwent investigative coronary catheterization. Of these patients, 133 were suffering from coronary artery stenosis. The association between vitamin D levels, coronary stenosis and many risk factors was determined using SPSS software. Results and conclusions: Interestingly, the current results did not show an association between vitamin D abnormalities and the incidence or the reoccurrence of coronary artery stenosis. Moreover, significant differences were detected in the prevalence of vitamin D abnormalities based on the patient’s gender, and there was a significant association between vitamin D abnormalities and both body mass index and dyslipidemia. However, current results did not show any significant association with other risk factors for IHD. For instance, no association was found with smoking, hypertension, diabetes mellitus, stable and unstable angina or with acute recent myocardial infarction. Keywords: vitamin D, ischemic heart disease, IHD, coronary artery stenosis, cardiovascular system

Background: More than half of melanoma patients taking first-line anti-PD-1 therapy either express transient or no response at all. The efficacy and safety of secondary treatments for these patients are still not well established. Here, we evaluate the efficacy and safety of different melanoma FDA-approved ICI modalities used in post-anti-PD-1 refractory settings. Materials and methods: We searched the PubMed database and the ASCO meetings library for studies on advanced melanoma patients with cancer progression on anti-PD-1 therapy and were then treated with ipilimumab, nivolumab/ipilimumab combination, or retreated with anti-PD-1. Primary and secondary endpoints were efficacy and toxicity, respectively. Pooled estimates for each treatment group were obtained using a random or fixed effects model according to detected heterogeneity. Results: Fourteen studies, of which 10 on ipilimumab, 2 on anti-PD-1 treatment, and 6 on combination therapies, were included, involving a total of 1460 patients. Twelve studies reported objective response rates (ORRs) and nine of them reported immune-related adverse events (irAEs). As for ORR, patients experienced a response that was inferior compared to the same therapy in treatment -naïve patients, with combination therapy having the best ORR of a pooled 23.08% (95% CI: 16.75% to 30.03%), followed by ipilimumab with a pooled ORR of 8.19% (95% CI: 5.78% to 10.92%). Survival data were also inferior in the ipilimumab cohort (mOS: 5.1 to 7.4 months) compared to ipilimumab in anti-PD-1 naive patients. As for grade 3/4 irAE occurrence, the ipilimumab cohort showed an estimate of 43.77% (95% CI 22.55% to 66.19%). Conclusion: Our findings provide the best current evidence that patients who progress on anti-PD-1 can still respond to different ICI modalities (ipilimumab with or without nivolumab, and retreatment or continuation beyond progression with anti-PD-1) with tolerable grade 3/4 irAEs. However, more prospective clinical trials are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Rasheed K Ibdah,1 Laith N AL-Eitan,2 Nasr N Alrabadi,3 Ayah Y Almasri,2 Adan H Alnaamneh,2 Rame H Khasawneh,4 Mansour A Alghamdi5,6 1Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Hematopathology, King Hussein Medical Center (KHMC), Jordan Royal Medical Services (RMS), Amman, Jordan; 5Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia; 6Genomics and Personalized Medicine Unit,College of Medicine, King Khalid University, Abha, Saudi ArabiaCorrespondence: Laith N AL-EitanDepartment of Biotechnology and Genetic Engineering, Jordan University of Science and Technology. P.O.Box 3030, Irbid 22110, JordanTel +962-2-7201000 Ext. 23464Fax +962-2-7201071Email lneitan@just.eduBackground: The main objective of this study is sought to determine the impacts of PCSK9, WDR12, CDKN2A, and CXCL12 polymorphisms on warfarin sensitivity and responsiveness in Jordanian cardiovascular patients during the initiation and stabilization phases of therapy.Methods: This study took place at the anticoagulation clinic at Queen Alia Heart Institute (QAHI) in Jordan. DNA samples were collected from 212 cardiovascular patients and 213 healthy controls. Genomic SNPs genotyping was conducted using the MassARRAY System at the Australian Genome Research Facility.Results: This study assessed 10 polymorphisms (rs11206510 within the PCSK9 gene, rs6725887 and rs7582720 within the WDR12 gene, rs4977574, rs10757278, and rs1333049 within the CDKN2A gene, rs2862116, rs7906426, rs1746048, and rs268322 within the CXCL12 gene) in 212 Jordanian cardiovascular patients. Carriers of CDKN2A rs1333049, rs10757278, and PCSK9 rs11206510 polymorphisms had an increased risk of resistance during the initiation phase of warfarin therapy compared to those who do not carry it, or those who are carrying one polymorphism only (P < 0.05), while carriers of CXCL12 rs7906426 polymorphism had similar increased risk but during the stabilization phase of warfarin therapy (P < 0.05).Conclusion: Carriers of CXCL12 rs2862116 polymorphism had an increased risk to be warfarin extensive responders compared to those with no or only one polymorphism (P = 0.01). However, the presence of PCSK9 rs11206510 polymorphism affects the warfarin maintenance doses (P ˃ 0.0001).Keywords: warfarin, cardiovascular disease, PCSK9, WDR12, CDKN2A, CXCL1