Trends in Oral Anticoagulant Use and Individual Expenditures Across the United States from 2014 to 2020.

BACKGROUND: Landmark clinical trials have expended the indications for the direct oral anticoagulants (DOACs), but contemporary data on usage and expenditure patterns are lacking. OBJECTIVE: This study aimed to assess annual trends in oral anticoagulant (OAC) utilization and expenditure across the United States (US) from 2014 to 2020. METHODS: We utilized the Medical Expenditure Panel Survey (MEPS) to study the trends of use and expenditures of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban between 2014 and 2020 in the US. Survey respondents reported OAC use within the past year, which was verified against pharmacy records. Payment information was obtained from the respondent's pharmacy and was categorized as third-party or self/out-of-pocket. Potential indications and medical conditions of interest for OAC therapy were identified from respondent-reported medical conditions. We estimated the national number of OAC users and total expenditures across age, sex, race, ethnicity, insurance, and medical condition subgroups. Trends of OAC users' characteristics, expenditure, and number of prescriptions were evaluated using the Mann-Kendall test for trends. RESULTS: Between 2014 and 2020, the number of warfarin users decreased from 3.8 million (70% of all OAC users) to 2.2 million (p = 0.007) [29% of all OAC users], while the number of DOAC users increased from 1.6 million (30% of all OAC users) to 5.4 million (p = 0.003) [70% of all OAC users]. The total expenditure of OACs in the US increased from $3.4 billion in 2014 to $17.8 billion in 2020 (p = 0.003), which was driven by the increase in DOAC expenditures (p = 0.003). CONCLUSIONS: DOACs have replaced warfarin as the preferred OAC in the US. The increased costs associated with DOAC use may decline when generic formulations are approved.

Research barriers in Saudi pharmacy residency training programs.

Background: The aim of this study is to identify potential barriers to conducting and publishing pharmacy residency research. Methods: A cross-sectional study surveyed pharmacy residents in Saudi Arabia from August to September 2020. The online survey assesses residents' characteristics, residency research experience, barriers to completion, and challenges in publishing. A Likert scale assessed factors and barriers to conducting and publishing research during residency. Descriptive statistics were performed for binary variables, with Likert scale responses visualized using Gannt charts. Results: A total of 69 residents completed the survey, of whom 63.5 percent were female, and the median age was 28 years. More than half of the residents were in R2 (56.5 %), followed by R1 (24.6 %) and R3 (4.4 %). Half of residents had prior research experience, while 84.1 % had prior research training in workshops or courses. Cohort study design was the most common type of residency research project conducted. According to residents, the main barriers to conducting research were a lack of allocated time for research during rotations (81.7 %) and a lack of a realistic timeline determined by the SCFHS to finish the research project (66.2 %). Regarding barriers to publishing research, the majority of residents reported lack of time to work on the publication process (78.6 %), lack of previous publication experience (60 %), and lack of guidance from mentors (55.7 %) as the most important barriers. Conclusion: Pharmacy residents face barriers to conducting research during their residency program, including limited allocated time during rotations, a lack of realistic timelines, and data collection limitations. Additionally, they face challenges in publishing their research due to a lack of experience, mentorship, and guidance. Future research should consider seeking the perspective of residency program directors and preceptors on research barriers and evaluating the publication rate of residents' projects.

Metformin use among obese patients with prediabetes in Qassim, Saudi Arabia: An observational study.

Background and aims: The high prevalence of prediabetes and diabetes mellitus and its secondary complications in Saudi Arabia is a major healthcare concern. Evidence suggests that despite evidence-based efficacy and safety, metformin is underutilized in prediabetic obese patients. Thus, the aim of this study was to investigate the use of metformin in prediabetic obese patients in the Qassim region of Saudi Arabia. Methods: Prediabetic patients' electronic health records were accessed and screened from 2017 to 2021. The inclusion criteria were patients with obesity (BMI ≥ 35) diagnosed with prediabetes, and who received metformin. Patients with chronic kidney disease and those using metformin for other diseases were excluded. The first major endpoint of this study was the rate of metformin use among obese, prediabetic individuals. The second major endpoint was the factors associated with metformin prescribing in our cohort. Descriptive statistics were used to report the primary and secondary outcomes. Data are presented as percentages, means, standard deviations (SDs), medians, and interquartile ranges, as appropriate. All analyses were conducted using Stata version 16.1. Results: A total of 304 prediabetic patients were included in this study after screening the records of 1,789 patients. The average age was found to be 40, and the majority were female (72%). The average BMI was found to be 39.4 kg/m2, while the average HbA1c was 5.8%. In the entire sample, only 25 (8.22%) obese patients received metformin for diabetes prevention. Among obese patients with a BMI ≥ 30, 19 patients (8.7%) received metformin. Metformin users had higher odds of being on statins (OR 2.72, 95% CI 1.01 to 7.36; p = 0.049). Conclusion: According to the study, metformin is not frequently prescribed to prediabetic obese individuals in the Qassim region of Saudi Arabia. This prevention strategy is a missed opportunity in the management of prediabetes in high-risk patients. Future studies are needed to investigate the root causes of the underuse of metformin and potential interventions to promote evidence-based practice in Saudi Arabia.

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials.

Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2 , or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.

Systolic Blood Pressure Time in Target Range and Major Adverse Kidney and Cardiovascular Events.

BACKGROUND: Whether time-in-target range (TTR) for systolic blood pressure (SBP) associates with adverse kidney and cardiovascular events remains incompletely understood. METHODS: This study included participants in 2 clinical trials that compared intensive (<120 mm Hg) and standard (<140 mm Hg) SBP lowering. SBP-TTR for months 0 to 3 was calculated using therapeutic ranges of 110 to 130 mm Hg and 120 to 140 mm Hg for the intensive and standard arms, respectively. Adverse kidney events included the composite of dialysis, kidney transplant, serum creatinine >3.3 mg/dL, sustained eGFR <15 mL/(min·1.73 m2), or sustained eGFR decline >40%. Adverse cardiovascular events included myocardial infarction, stroke, heart failure, and cardiovascular death. Adjusted Cox proportional hazards regression models were used to estimate the association between SBP-TTR and kidney and cardiovascular events. RESULTS: Participants with higher TTR were younger and less likely to have preexisting cardiovascular disease. Compared with participants with TTR of 0%, the risk of adverse kidney events was lower for participants with TTR of >0% to 43% (hazard ratio [95% CI], 0.57 [0.42-0.76]; P<0.001), 43% to <70% (0.57 [0.42-0.78]; P=0.001), 70% to <100% (0.53 [0.38-0.74]; P<0.001), and 100% (0.33 [0.20-0.57]; P<0.001) in fully adjusted models. The risk of major adverse cardiovascular events was lower for participants with TTR of >0% to 43% (0.66 [0.52-0.83]; P=0.001), 43% to <70% (0.70 [0.55-0.90]; P=0.005), 70% to <100% (0.65 [0.50-0.84]; P=0.001), or 100% (0.56 [0.39-0.80]; P=0.001) compared with those with TTR of 0%. CONCLUSIONS: Higher SBP-TTR associates with lower risks of adverse kidney and cardiovascular events in adults with hypertension. SBP-TTR may be a potential therapeutic target and quality metric.

Economic analysis of glucagon like peptide-1 receptor agonists from the Saudi Arabia payer perspective.

Objectives: To perform a cost of control analysis of glucagon like peptide-1 receptor agonists (GLP1RA) in Saudi Arabia (SA) and determine the economic impact of adopting GLP1RAs. Methods: A budget impact model that captures the cost of control model was constructed to simulate hypothetical patient on six treatment options: a current mix of 60% liraglutide and 40% dulaglutide, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide. We estimated the relative amounts of SAR spend to achieve HbA1c targets (≤6.5% or < 7.0%). For each treatment option, annual treatment cost, proportion of patients achieving HbA1c targets, and cost to treat major adverse cardiovascular events (MACE) were aggregated to estimate the cost of control per patient per year (CCPPPY) over 5-year horizon (2021-2025). Probabilistic sensitivity analysis (PSA) was performed as a confirmatory analysis. Results: The CCPPPY to achieve HbA1c ≤ 6.5%/<7.0% using current mix, semaglutide, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 17,097/SAR 14,113, SAR 12,889/SAR 11,123, SAR 15,594/SAR 12,892, SAR 19,184/SAR 15,940, SAR 580,211/SAR 380,936, and SAR 246,570/SAR 143,759, respectively. The relative amounts of SAR spend to achieve HbA1c ≤ 6.5%/<7.0% relative to 1 SAR on semaglutide in case of adopting current mix, liraglutide, dulaglutide, exenatide, and lixisenatide were SAR 1.42/SAR 1.18, SAR 1.30/SAR 1.07, SAR 1.60/SAR 1.33, SAR 48.33/SAR 31.73, and SAR 20.54/SAR 11.97, respectively. These results were confirmed in the PSA. Conclusions: Semaglutide 1 mg once weekly was the most economically favorable GLP1RA; associated with the least CCPPPY, and amount of SAR spent to achieve HbA1c of ≤6.50%/<7.00% versus all other GLP1RAs.

Characteristics of the ideal clinical pharmacy residency candidate: A survey of residency program directors and preceptors in Saudi Arabia.

OBJECTIVE: Residency positions are highly competitive. Pharmacy students who are familiar with the ideal qualities of residency candidates and the expectations of residency programs may be more likely to obtain one of these coveted positions. This study identifies the characteristics that residency program directors (RPDs) and preceptors use to define an ideal residency candidate. METHODS: This is a cross-sectional, descriptive study that surveyed pharmacy RPDs and preceptors across the Kingdom of Saudi Arabia. The questionnaires are comprised of two sections: demographic information and characteristics of the residency candidates. Over a five-month period (May 1, 2020 - September 30, 2020), the survey was sent electronically to the participants. RESULTS: Of the 78 surveys returned, 68 surveys were included (RPDs: 36, Preceptors: 32) and 12 surveys (15.17%) were excluded due to incompleteness. Number of RPDs responded to the survey represents (65%) of the total RPDs in Saudi Arabia. The mean response scores from the results of the Likert scale [strongly agree (1) - strongly disagree (5)] - suggest that a candidate's performance during the interview (mean score = 1.5), their professional appearance (1.5), an alignment between a candidate's interests and the program focus (1.6), and previous hospital experience (1.8) mattered most. While being from the same region (3.4), having an advanced degree (2.8) and the cumulative Grade Point Average (2.7) mattered the least. We find that previous hospital experience (29%), familiarity with the program (16%), research experience (15%), Saudi Commission for Health Specialists aggregate score (10%), and letters of recommendation (4%) are considered the top five factors. CONCLUSION: Residency candidates should focus on training in clinical settings. Offering mock interviews and Saudi Pharmacist Licensure Examination practice tests and involving pharmacy students in clinical research may increase their chance in securing a residency position.

Heart failure outcomes and glucagon-like peptide-1 receptor agonists: A systematic review of observational studies.

AIM/OBJECTIVE: Recently, the glucagon-like peptide-1 receptor agonists (GLP-1RA) class showed a significant reduction in heart failure (HF) hospitalization in several meta-analyses of cardiovascular outcome trials (CVOTs). The objective of this systematic review is to summarize the real-world evidence regarding HF outcomes of GLP-1RAs. METHODS: We searched the PubMed and EMBASE databases for observational studies that investigated HF outcomes of GLP-1RAs. RESULTS: Our search yielded 10 observational studies. Of those, 7 were cohort studies, and 3 were nested case-control studies. The risk of HF was the outcome in four cohort studies. One study that compared exenatide and exenatide combined with insulin to insulin showed a reduction in HF risk in the exenatide and exenatide plus insulin groups (HR 0.34, 95% CI 0.22-0.52, p-value <0.001 and HR 0.40, 95% CI 0.32-0.50, p-value <0.001, respectively). The other three cohort studies did not show a statistically significant result. In the three cohort studies that investigated HF hospitalization as an outcome, two showed a lower rate of HF hospitalization [48 (16.7%) vs. 76 (28%), p-value <0.05 and HR 0.51, 95% CI 0.34-0.77, p = 0.002] in the GLP-1RA groups. Conversely, the remaining study showed a reduction of 14% in HF hospitalization in the dipeptidyl peptidase-4 inhibitors (DPP-4i) group compared to the GLP-1RA group (HR 0.86, 95% CI 0.83-0.90). In contrast to the cohort studies, the three nested case-control studies showed similar results of no association of GLP-1RA use and HF hospitalization with OR 0.67 (95% CI 0.32-1.42), HR 0.95 (95% CI 0.83-1.10), and OR 0.84 (95% CI 0.48-1.47), respectively. CONCLUSION: The real-world evidence regarding the reduction in HF risk and hospitalization in GLP-1RA users is conflicting. Further well-designed, large multicenter, observational studies are needed to show clearer evidence.

Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis.

BACKGROUND: The cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA). METHODS: Medline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA). RESULTS: A total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events. CONCLUSION: The GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.