Blood pressure-lowering agents response- a systematic review and genome wide study

In spite of the vast amount of evidence on the benefits of blood pressure (BP) lowering that has accumulated to date, hypertension (HTN) remains the leading risk factor for disease and disability worldwide. Since the first BP-lowering agents became available in the 1950s, their effects have been tested thoroughly by means of the best evidence-providing approach, namely, large randomised controlled trials (RCTs). In the same way, the pharmacogenomics of HTN have the potential to identify genetic biomarkers that predict the response of BP-lowering agents through genome-wide association studies (GWAS), which analyse quantitative traits at millions of markers across the genome to identify genetic variations that could contribute to HTN. For the most part, computational approaches and software tools have played a significant role in translating RCTs and GWAS findings. This thesis aims first to systematically review the BP responses of main BPlowering agents, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), diuretics (DIs) and beta-blockers (BBs) in RCTs, and second to identify the single nucleotide polymorphisms (SNPs) associated with the BP-lowering responses of CCBs and BBs on Nordic Diltiazem (NORDIL) subjects using GWAS. Description of the research results: Following the Population Intervention Comparison Outcome Study (PICOS) design framework, a literature search of multiple sources resulted in the identification of 10,577 publications, with 5,568 unique records identified after duplicates were excluded. In total, 184 studies were identified as potentially eligible, of which 82 RCTs with a total of 197,684 participants were selected for quantitative synthesis. With regard to BP-lowering strategies, 13 studies with 41,886 participants focused on lowering BP intentionally, while the remaining 69 studies (155,798 participants) were classified as unintentional BP-lowering studies. Risk of bias in included studies: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework, all included studies were described as RCTs; however, most studies did not address how treatment randomization occurred or how allocation of treatment was concealed. All included studies also stated that they were double-blind studies, but again, most did not describe how the double blinding was ensured throughout the studies. The risk of attrition bias was avoided as all randomized participants were included in the analysis. All of the studies had a low risk for reporting bias. BP-lowering agents were added to randomly allocated treatment to control high BP; consequently, one potentially unclear source of bias was present in 13 of the 82 studies. The overall quality was rated to be acceptable to high. In all, 48 studies were rated to be high-quality studies, and 34 studies were rated as acceptable quality. Effect of intervention: After a systematic search and selection process, 56 studies were included in the analysis of delta BP response, 37 studies were included in the analysis of single-measure BP response and 20 studies were included in the analysis of repeated measures. A number of BP-lowering agents showed a significantly (P<0.05) superior BP response in comparison with other agents included in the review; however, the level of BP response was still small. CCBs were superior to ACEIs in lowering both systolic BP (SBP) and diastolic BP (DBP). DIs were superior to ACEIs and CCBs in lowering SBP. ARBs were superior to BBs in lowering SBP. CCBs and DIs were significantly superior to placebos in lowering both SBP and DBP. Genome-wide study: Following NORDIL quality control standards, a final set of 3,850 samples and 500,905 SNPs was available for analysis. In total, 51 SNPs showed a significant (P<1X10-5) association with BP response. The top discordant signals identified in NORDIL included five SNPs for SBP on BB arm, seven SNPs for DBP on BB arm, 12 SNPs for SBP on CCB arm and nine SNPs for DBP on CCB arm. Discordant SNPs from the NORDIL were replicated, based on the interests of five collaborative RCTs; including 11 SNPs for SBP on BB arm, 22 SNPs for DBP on BB arm, 23 SNPs for SBP on CCB arm and 18 SNPs for DBP on CCB arm. However, no SNP achieved a genome-wide significance of (P<5x10-8). Future recommendations: Further systematic reviews of RCTs comparing different BP-lowering agents are required to provide evidence of the options for BP-lowering medication. Specifically, there is a need to study BP response as an outcome by itself, taking into account different BP-lowering agent combinations,including classes and sub-classes, along with co-morbidities such as type 2 diabetes mellitus, coronary heart disease and chronic renal failure. Regarding the genome-wide study, further studies are needed to clarify the potential contribution of plausible SNPs in relation to CCB and BB response in HTN. These studies should include comprehensive sequencing of the candidate interval, genotyping of variants in many population samples, testing for association, functional studies and investigation of interactions with other genes or environmental factors. Furthermore, genome-wide studies need to identify directionally discordant signals between SNP and BP response for BB and CCB and confirm the validity of a SNP BP response by analysing the SNP effect on mortality

Potential applications of artificial intelligence (AI) in managing polypharmacy in Saudi Arabia: a narrative review

Prescribing medications is a fundamental practice in the management of illnesses that necessitates in-depth knowledge of clinical pharmacology. Polypharmacy, or the concurrent use of multiple medications by individuals with complex health conditions, poses significant challenges, including an increased risk of drug interactions and adverse reactions. The Saudi Vision 2030 prioritises enhancing healthcare quality and safety, including addressing polypharmacy. Artificial intelligence (AI) offers promising tools to optimise medication plans, predict adverse drug reactions and ensure drug safety. This review explores AI’s potential to revolutionise polypharmacy management in Saudi Arabia, highlighting practical applications, challenges and the path forward for the integration of AI solutions into healthcare practices

Polypharmacy among patients with hypertension attending primary healthcare centres

Introduction: Saudi Arabia has several hypertensive patients who require close attention and specialised care for their medications. Polypharmacy is one of the reasons for the failure of patient compliance with antihypertensive medications. Therefore, this study aims to gain a better perspective on polypharmacy in hypertensive patients attending primary healthcare (PHC) centres in Makkah, Saudi Arabia. Methods: This was an observational, cross-sectional, descriptive study of hypertensive patients followed up at 10 PHC centres in Makkah, Saudi Arabia, from 1 July 2019 to 30 June 2022. Frequencies and percentages were used to present categorical data, and Pearson’s χ2 test was used to measure differences. A P value less than 0.05 was considered statistically significant. Results: A total of 506 patients were included in this study. The mean age of the patients was 60 years, and more than half (69%) were females. Regarding antihypertensive medication use, 64% were on antihypertensive combination therapy, 76% on dual therapy, 21% on triple therapy, and 3% on quadruple therapy. Moreover, 21% of the hypertensive patients were exposed to polypharmacy. There was a significant relationship (P&lt;0.001) between the overall number of chronic medications used per day and the duration of hypertension. Conclusion: More clinical research is needed to identify the impact of polypharmacy on the quality of healthcare in PHC centres in general and hypertensive patients specifically in different regions of Saudi Arabia

Efficacy and safety of empagliflozin in type 2 diabetes mellitus Saudi patients as add-on to antidiabetic therapy: a prospective, open-label, observational study

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m2 [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT &gt; AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy

A new vision of teaching clinical pharmacology and therapeutics for undergraduate medical students

For many years, clinical pharmacology (CP) has been taught at schools of medicine via traditional methods including classic lectures and experimental sessions. The explosion of scientific knowledge and the availability of many treatment options have necessitated the development of new strategies for pharmacology teaching and learning. Applying information learnt in real-life situations has become more important than finding information that is readily available in many places. The newly implemented reformed curriculum at Umm Al Qura University – Faculty of Medicine (UQUMED) is a student-centred, competency-based curriculum with enhanced integration across the disciplines. Teachers and students have a great responsibility in updating the curriculum. The “Use of Medicine” (UofM) vertical module is part of this reformed curriculum that focuses on key principles, a core list of medications, the vertical and horizontal integration of subjects, the knowledge application to real case situations, enhanced critical thinking and self-learning. It emphasizes rational prescribing, safe medical practice and excellence in teaching CP and therapeutics. The adoption of newer and innovative teaching and assessment methods and the training of faculty/staff can help to refresh CP education. One challenge in CP education is that teachers are shifting from acting as information providers to acting as facilitators so that students become life-long learners. The assessment of our reformed curriculum uses several valid reliable tools to evaluate the achieved skills and competencies. This manuscript describes the transformational changes in CP education at UQU up to the development and implementation of the UofM vertical module as part of the reformed UQUMED curriculum. Continuous updates in CP education are critical for rational, safe, and affordable medication prescribing for better patient care

Antihypertensive Drugs and Risk of Cancer: A Systematic Review and Meta-Analysis of 391, 790 Patients

Introduction: The potential risk of cancer associated with antihypertensive drugs has been disputed for decades as additional outcomes from randomized controlled trials (RCTs), observational studies, and meta-analyses showed conflicting results. Objective: To assess the risk of cancer in patients exposed to major antihypertensive drug classes. Methods: We searched bibliographic databases for RCTs published between 1950 to December 2015 studying angiotensin-receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers (BB), calcium channel blockers (CCB), and thiazide diuretics (TZ). RCTs with at least one year duration of planned active treatment and a minimum of 100 participants per treatment arm were eligible. Main Outcome Measures: Cancer and cancer-related deaths from the RCTs. Both fixed-effect and random-effects models were conducted and results were expressed as odds ratio (OR). Results: We identified 91 RCTs enrolling 391, 790 participants with an average follow-up of 3.4 years. There was no evidence of excess risk for cancer with ARB, ACEi, BB, and TZ (refer Fig.1). For CCBs, there was an increased risk of cancer (OR 1.07 95%CI 1.02, 1.1) with minimal heterogeneity (I2=13%). Subgroup analysis did not differ significantly between dihydropyridines (DHP) and non-dihiydropyridines subclasses. There was no statistically significant association between antihypertensive drug classes and risk of cancer deaths. Conclusions: Our results suggest that ARB, ACEi, BB, and TZ are not associated with increased risk of cancer. CCB therapy shows an increased risk of cancer. Further investigation on the risk of cancer with CCB is warranted

Risk of Polypharmacy and Its Outcome in Terms of Drug Interaction in an Elderly Population: A Retrospective Cross-Sectional Study

The simultaneous use of multiple drugs—termed ‘polypharmacy’—is often required to manage multiple physiological and biological changes and the interplay between chronic disorders that are expected to increase in association with ageing. However, by increasing the number of medications consumed, the risk of undesirable medication reactions and drug interactions also increases exponentially. Hence, knowledge of the prevalence of polypharmacy and the risk of potentially serious drug–drug interactions (DDIs) in elderly patients should be considered a key topic of interest for public health and health care professionals. Methods: Prescription and demographic data were collected from the electronic files of patients who were aged ≥ 65 years and attended Al-Noor Hospital in Makkah, Saudi Arabia, between 2015 and 2022. The Lexicomp® electronic DDI-checking platform was used to evaluate the patients’ medication regimens for any potential drug interactions. Results: A total of 259 patients were included in the study. The prevalence of polypharmacy among the cohort was 97.2%: 16 (6.2%) had minor polypharmacy, 35 (13.5%) had moderate polypharmacy, and 201 (77.6%) had major polypharmacy. Of the 259 patients who were taking two or more medications simultaneously, 221 (85.3%) had at least one potential DDI (pDDI). The most frequently reported pDDI under category X that should be avoided was the interaction between clopidogrel and esomeprazole and was found in 23 patients (18%). The most frequently reported pDDI under category D that required therapeutic modification was the interaction between enoxaparin and aspirin, which was found in 28 patients (12%). Conclusions: It is often necessary for elderly patients to take several medications simultaneously to manage chronic diseases. Clinicians should distinguish between suitable, appropriate and unsuitable, inappropriate polypharmacy, and this criterion should be closely examined when establishing a therapeutic plan

Over-the-Counter Medication Use among Parents in Saudi Arabia

Introduction: Self-medication is a growing public health concern worldwide. Studies have shown a gap between best practice and the current practice of using over-the-counter (OTC) medications. Despite being a well-recognised problem in Saudi Arabia, few studies have investigated OTC medication use in Saudi Arabia. Therefore, this study aimed to investigate the attitudes and knowledge of parents regarding OTC medication use in the Jeddah region, Saudi Arabia. Method: A cross-sectional study was carried out via an electronic questionnaire sent randomly to parents over four months, from 1 January to 30 April 2022. The participants’ characteristics and categorical variables were represented descriptively by frequency and percentage. A Chi-square test was used to test the relationship between the variables. Results: In total, 211 questionnaires were included in this study. Females represented 54.5% of the participants included in the study. Parents belonging to the 18-to-30-year-old group comprised the highest percentage (37.9%), and most of the parents (72.9%) had received an undergraduate education. Family physicians were the most common source (37.3%) of information about OTC medications, whereas more than half of parents purchased OTC medications from the community pharmacy (58.8%). While almost half of the parents (52.1%) visited a family physician when side effects of OTC medications appeared in their children, only (33.6%) stopped giving their children the OTC medicine. The relationship between the sociodemographic characteristics (including educational level, marital status, and employment status) and OTC drug consumption was significant (p < 0.001). Conclusion: Educational campaigns are needed to guide patients about the proper use of OTC medications. Studies on OTC medication use are lacking in Saudi Arabia in terms of its frequency, reasons for use, type of self-medication, and contributing factors

Reported Cases of Alcohol Consumption and Poisoning for the Years 2015 to 2022 in Hail, Saudi Arabia

This study aimed to determine the pattern of alcohol consumption and its poisoning among the Saudi population in the city of Hail, KSA. Data from a retrospective cohort were collected qualitatively at King Khalid Hospital (KKH) and Hail General Hospital (HGH), covering 550 participants from 2015 to 2022. Two groups were formed comprising patients admitted to the emergency room (ER) and community members; their ages ranged from 19 to 75 years. Group 1 contained 400 participants, of which 250 were patients (244 males, six females) who came to the (ER) with a suspected alcohol overdose or poisoning, and 150 were patients (128 males and 22 females) who were discharged from the (ER) with minimal complaints because of their drinking. Group 2 comprised 150 participants (128 males, 22 females) who were community members, who were surveyed using a questionnaire or interview. In Group 1, 30% of patients reported an altered state of consciousness as a major complaint, 28.8% of patients exhibited abnormal liver function tests (LFTs), 27% had abnormal renal function tests (RFT) with decreased glomerular filtration rates (GFR) and elevated levels of urea and creatinine or low levels of electrolytes or calcium, and 35.6% patients showed elevated levels of pancreatic enzymes. One death was reported due to high alcohol consumption. In Group 2, the community participants reported that they started drinking alcohol due to the influence of other people (29%), stress (11%), depression (10.8%), curiosity (4.4%), and boredom (4%). In addition, 77% of participants were frequent alcohol drinkers and 20% consumed it daily. Further, 68.7% claimed to drink alcohol for more than one hour at a time, while 83.3% experienced blackouts and 70% had problems related to their liver. Moreover, 72.7% of the participants ended up in the hospital and 34.6% suffered from multiple chronic diseases. It is concluded that social influences and stress contributed to the initiation of alcohol use. Despite data gaps, the findings of this study provide a practical understanding of alcohol consumption among the Saudi population and guidance for policymakers