Aspirin for Primary Prevention in Patients With Elevated Coronary Artery Calcium Score: A Systematic Review of Current Evidences.

The 2019 American College of Cardiology and American Heart Association guidelines regarding low-dose aspirin in the primary prevention of atherosclerotic cardiovascular disease (ASCVD) indicate an increased risk of bleeding without a net benefit. The coronary artery calcium (CAC) score could be used to guide aspirin therapy in high-risk patients without an increased risk of bleeding. With this systematic review, we aimed to analyze studies that have investigated the role of CAC in primary prevention with aspirin. A total of 4 relevant studies were identified and the primary outcomes of interest were bleeding events and major adverse cardiac events. The outcomes of interest were stratified into 3 groups based on CAC scoring: 0, 1 to 99, and ≥100. A study concluded from 2,191 patients that with a low bleeding risk, CAC ≥100, and ASCVD risk ≥5% aspirin confers a net benefit, whereas patients with a high bleeding risk would experience a net harm, irrespective of ASCVD risk or CAC. All other studies demonstrated net benefit in patients with CAC ≥100 with a clear benefit. CAC scores correspond to calcified plaque in coronary vessels and are associated with graded increase in adverse cardiovascular events. Our review has found that in the absence of a significant bleeding risk, increased ASCVD risk and CAC score corelate with increased benefit from aspirin. A study demonstrated a decrease in the odds of myocardial infarction from 3 to 0.56 in patients on aspirin. The major drawback of aspirin for primary prevention is the bleeding complication. At present, there is no widely validated tool to predict the bleeding risk with aspirin, which creates difficulties in accurately delineating risk. Barring some discrepancy between studies, evidence shows a net harm for the use of aspirin in low ASCVD risk (<5%), irrespective of CAC score.

Takotsubo cardiomyopathy and psychiatric illness- insight from National Inpatient Sample (NIS) and National Re-admission Database (NRD) 2016 to 2018.

BACKGROUND: Emotional stress is a common precipitating cause of takotsubo cardiomyopathy (TC). Preexisting psychiatric disorder (PD) was linked to worsening outcomes in patients with TC1,2. However, there is limited data in literature to support this. This study aimed to determine the differences in outcomes in TC patients with and without PD. METHODS: We identified all patients with a diagnosis of TC using the National Inpatient Sample (NIS) and the National Readmission Database (NRD) data from 2016 to 2018. The patients were separated into TC with PD group and TC without PD group. Multiple variable logistic regression was then performed. RESULTS: Using NIS 2016-2018, we identified 23,220 patients with TC, and 43.11% had PD. The mean age was 66.73 ± 12.74 years, with 90.42% being female sex. The TC with PD group had a higher 30-readmission rate 1.25 (95% CI:1.06-1.47), Cardiogenic shock [aOR = 7.3 (95%CI 3.97-13.6), Mechanical ventilation [aOR = 4.2 (95%CI 2.4-7.5), Cardiac arrest [aOR = 2.6 (95%CI 1.1-6.3), than TC without PD group. CONCLUSION: Psychiatric disorders were found in up to 43% of patients with TC. The concomitant PD in TC patients was not associated with increased mortality, AKI, but had higher rates of cardiogenic shock, use of mechanical ventilation and cardiac arrest. The TC group with PD was also associated with increased 30-day readmission, LOS and total charges compared to TC patients without PD.

Bicuspid Aortic Valve Disease: Classifications, Treatments, and Emerging Transcatheter Paradigms.

Bicuspid aortic valve (BAV) is a common congenital valvular malformation, which may lead to early aortic valve disease and bicuspid-associated aortopathy. A novel BAV classification system was recently proposed to coincide with transcatheter aortic valve replacement being increasingly considered in younger patients with symptomatic BAV, with good clinical results, yet without randomized trial evidence. Procedural technique, along with clinical outcomes, have considerably improved in BAV patients compared with tricuspid aortic stenosis patients undergoing transcatheter aortic valve replacement. The present review summarizes the novel BAV classification systems and examines contemporary surgical and transcatheter approaches.

Impact of Repeated Reimbursement Penalties on Hospital Total Quality Scores.

OBJECTIVES: The incidence of hospital-acquired conditions (HACs) is a serious public health issue with implications ranging from patient morbidity and mortality to negative financial impacts on patients and health care systems. Despite substantial efforts to address and reduce HACs, research into the effect of quality improvement programs is inconclusive. This study seeks to better understand the relationship between repeated reimbursement penalties and improvement in HAC quality scores. METHODS: A quantitative comparative analysis of U.S. health care data was conducted. Data on quality outcomes and hospital characteristics were sourced from the Hospital-Acquired Condition Reduction Program from fiscal years 2018 and 2019 and the Centers for Medicare & Medicaid Services Inpatient Prospective Payment System impact files, respectively. RESULTS: In total, 3123 U.S. hospitals were analyzed to compare differences between total HAC scores of hospitals with and without penalties in consecutive years. Hospitals with repeated penalties had significantly greater improvement in scores ( t497.262 = -13.00, P < 0.001), and the impact was greatest in small hospitals (<100 beds). Repeated penalties had a smaller impact on disproportionate share hospitals (Cohen d = 0.73). Among all hospitals, the effect of repeated penalties was large (Cohen d = 0.75). CONCLUSIONS: This study suggests that repeated penalties can improve quality scores in U.S. hospitals. However, the effect may be exaggerated for smaller hospitals and those that serve patient populations with a relatively higher socioeconomic status. The reason disproportionate share hospitals did not show as much improvement as nondisproportionate hospitals may be because hospitals serving vulnerable populations often have fewer resources.

Trends in cardiac implantable electronic device utilization in adults with congenital heart disease: a US nationwide analysis.

BACKGROUND: Adults with congenital heart disease (ACHD) have increased risk of arrhythmias warranting implantation of cardiac implantable electronic devices (CIEDs), which may parallel the observed increase in survival of ACHD patients over the past few decades. We sought to characterize the trends and outcomes of CIED implantation in the inpatient ACHD population across US from 2005 to 2019. METHODS: A retrospective analysis of the Nationwide Inpatient Sample (NIS) identified 1,599,519 unique inpatient ACHD admissions (stratified as simple (85.1%), moderate (11.5%), and complex (3.4%)) using the International Classification of Diseases 9/10-CM codes. Hospitalizations for CIED implantation (pacemaker, ICD, CRT-p/CRT-d) were identified and the trends analyzed using regression analysis (2-tailed p < 0.05 was considered significant). RESULTS: A significant decrease in the hospitalizations for CIED implantation across the study period [3.3 (2.9-3.8)% in 2005 vs 2.4 (2.1-2.6)% in 2019, p < 0.001] was observed across all types of devices and CHD severities. Pacemaker implantation increased with each age decade, whereas ICD implantation rates decreased over 70 years of age. Complex ACHD patients receiving CIED were younger with a lower prevalence of age-related comorbidities, however, had a greater prevalence of atrial/ventricular tachyarrhythmias and complete heart block. The observed inpatient mortality rate was 1.2%. CONCLUSIONS: In a nationwide analysis, we report a significant decline in CIED implantation between 2005 and 2019 in ACHD patients. This may either be due to a greater proportion of hospitalizations resulting from other complications of ACHD or reflect a declining need for CIED due to advances in medical/surgical therapies. Future prospective studies are needed to elucidate this trend further.

Impact of preexisting coronary artery and peripheral artery disease on outcomes in diabetic patients after kidney transplant.

BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. METHODS: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. RESULTS: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. CONCLUSIONS: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.

Prognostic Value of Hospital Frailty Risk Score and Clinical Outcomes in Patients Undergoing Revascularization for Critical Limb-Threatening Ischemia.

Background The impact of medical record-based frailty assessment on clinical outcomes in patients undergoing revascularization for critical limb-threatening ischemia (CLTI) is unknown. Methods and Results This study included patients with CLTI aged ≥18 years from the nationwide readmissions database 2016 to 2018 who underwent endovascular revascularization (ER) or surgical revascularization (SR). The hospital frailty risk score, a previously validated International Classification of Diseases, Tenth Edition, Clinical Modification (ICD-10-CM) claims-based score, was used to categorize patients into low- (<5), intermediate- (5-15), and high-risk (>15) frailty categories. Primary outcomes were in-hospital mortality and major amputation at 6 months. A total of 64 338 patients were identified who underwent ER (82.3%) or SR (17.7%) for CLTI. The mean (SD) age of the cohort was 69.3 (11.8) years, and 63% of patients were male. This study found a nonlinear association between hospital frailty risk score and in-hospital mortality and 6-month major amputation. In both ER and SR cohorts, the intermediate- and high-risk groups were associated with a significantly higher risk of in-hospital mortality (high-risk group: ER: odds ratio [OR], 7.2 [95% CI, 4.4-11.6], P<0.001; SR: OR, 28.6 [95% CI, 3.4-237.6], P=0.002) and major amputation at 6 months (high-risk group: ER: hazard ratio [HR], 1.6 [95% CI, 1.5-1.7], P<0.001; SR: HR, 1.7 [95% CI, 1.4-2.2], P<0.001) compared with the low-risk group. Conclusions The hospital frailty risk score, generated from the medical record, can identify frailty and predict in-hospital mortality and 6-month major amputation in patients undergoing ER or SR for CLTI. Further studies are needed to assess if this score can be incorporated into clinical decision-making in patients undergoing revascularization for CLTI.

Causes and Predictors of 30-Day Readmission in Patients With COVID-19 and ST-Segment-Elevation Myocardial Infarction in the United States: A Nationwide Readmission Database Analysis.

Background Rates, causes, and predictors of readmission in patients with ST-segment-elevation myocardial infarction (STEMI) during COVID-19 pandemic are unknown. Methods and Results All hospitalizations for STEMI were selected from the US Nationwide Readmissions Database 2020 and were stratified by the presence of COVID-19. Primary outcome was 30-day readmission. Multivariable hierarchical generalized logistic regression analysis was performed to compare 30-day readmission between patients with STEMI with and without COVID-19 and to identify the predictors of 30-day readmissions in patients with STEMI and COVID-19. The rate of 30-day all-cause readmission was 11.4% in patients with STEMI who had COVID-19 and 10.6% in those without COVID-19, with the adjusted odds ratio (OR) not being significantly different between the two groups (OR, 0.88 [95% CI, 0.73-1.07], P=0.200). Of all 30-day readmissions in patients with STEMI and COVID-19, 41% were for cardiac causes. Among the cardiac causes, 56% were secondary to acute coronary syndrome, while among the noncardiac causes, infections were the most prevalent. Among the causes of 30-day readmissions, infectious causes were significantly higher for patients with STEMI who had COVID-19 compared with those without COVID-19 (29.9% versus 11.3%, P=0.001). In a multivariable model, congestive heart failure, chronic kidney disease, low median household income, and length of stay ≥5 days were found to be associated with an increased risk of 30-day readmission. Conclusions Post-STEMI, 30-day readmission rates were similar between patients with and without COVID-19. Cardiac causes were the most common causes for 30-day readmissions, and infections were the most prevalent noncardiac causes.

Impact of Gender, Race, and Insurance Status on Inhospital Management and Outcomes in Patients With COVID-19 and ST-Elevation Myocardial Infarction (a Nationwide Analysis).

There is a paucity of data exploring the impact of gender, race, and insurance status on invasive management and inhospital mortality in patients with COVID-19 with ST-elevation myocardial infarction (STEMI) in the United States. The National Inpatient Sample database for the year 2020 was queried to identify all adult hospitalizations with STEMI and concurrent COVID-19. A total of 5,990 patients with COVID-19 with STEMI were identified. Women had 31% lower odds of invasive management and 32% lower odds of coronary revascularization than men. Black patients had lower odds of invasive management (odds ratio [OR] 0.61, 95% confidence interval [CI] 0.43 to 0.85, p = 0.004) than White patients. Black and Asian patients had lower odds of percutaneous coronary intervention (Black: OR 0.55, 95% CI 0.38 to 0.80, p = 0.002; Asian: OR 0.39, 95% CI 0.18 to 0.85, p = 0.018) than White patients. Uninsured patients had higher odds of getting percutaneous coronary intervention (OR 1.78, 95% CI 1.05 to 2.98, p = 0.031) and lower odds of inhospital mortality (OR 0.41, 95% CI 0.19 to 0.89, p = 0.023) than privately insured patients. Patients with out-of-hospital STEMI had 19 times higher odds of invasive management and 80% lower odds of inhospital mortality than inhospital STEMI. In conclusion, we note important gender and racial disparities in invasive management of patients with COVID-19 with STEMI. Surprisingly, uninsured patients had higher revascularization rates and lower mortality than privately insured patients.

Prevalence, trends, and outcomes of cardiovascular diseases in pregnant patients in the USA: 2010-19.

AIMS: Contemporary data on the prevalence, trends, and outcomes of cardiovascular diseases (CVDs) in pregnant patients are limited. This study aimed to analyse the prevalence, trends, and outcomes of CVD and their subtypes in hospitalized pregnant patients in the USA. METHODS AND RESULTS: This retrospective population-based cohort study used the Nationwide Readmission Database to identify all hospitalized pregnant patients from 1 January 2010, to 31 December 2019. Data analyses were conducted from January to February 2022. Pregnancy-associated hospitalizations were identified. The main outcomes were the prevalence and trend of CVD in pregnant patients. 39 212 104 hospitalized pregnant patients were identified: 4 409 924 with CVD (11.3%) and 34 802 180 without CVD (88.8%). The annual age-adjusted CVD prevalence increased from 9.2% in 2010 to 14.8% in 2019 (P < 0.001). Hypertensive disorder of pregnancy (1069/10 000) was the most common, and aortic dissection (0.1/10 000) was the least common CVD. The trends of all CVD subtypes increased; however, the trend of valvular heart disease decreased. Age-adjusted in-hospital all-cause mortality was 8.2/10 000 in CVD, but its trend decreased from 8.1/10 000 in 2010 to 6.5/10 000 in 2019 (P < 0.001). CVD was associated with 15.51 times higher odds of in-hospital all-cause mortality compared with non-CVD patients [odds ratio (OR): 15.51, 95% confidence interval (CI)13.22-18.20, P < 0.001]. CVD was associated with higher 6-week postpartum readmission (OR: 1.97, 95% CI: 1.95-1.99), myocardial infarction (OR: 3.04, 95% CI: 2.57-3.59), and stroke (OR: 2.66, 95% CI: 2.41-2.94)(P < 0.001 for all). CONCLUSION: There is an increasing age-adjusted trend in overall CVD and its subtypes among pregnant patients in the USA from 2010 to 2019. Pregnant patients with CVD had higher odds of in-hospital mortality than those without CVD. However, in-hospital all-cause mortality among patients with and without CVD has decreased over the past 10 years. CVD was associated with higher 6-week postpartum all-cause readmission, myocardial infarction, and stroke rates.

Outcomes and Readmission in Patients With Retinal Artery Occlusion (from the Nationwide Readmission Database).

Retinal artery occlusion (RAO) is an ophthalmologic emergency, leading to sudden vision loss. Understanding its risk factors and garnering information on the incidence of adverse events can provide helpful information on the cost-effective evaluation of patients and secondary prevention. In this retrospective cohort study, we used the Nationwide Readmission Database from 2016 to 2018 and queried the database to identify patients with RAO. The clinical outcomes were cumulative incidence of myocardial infarction (MI), stroke, death (in-hospital and 6 months after discharge), resource utilization, all-cause readmission at 6 months, and reasons for all-cause readmission. We identified a total of 14,527 patients with RAO. The mean age of patients with RAO was 69 ± 13 years. Hypertension (11,839, 82%), hyperlipidemia (8,868, 61%), ischemic cardiomyopathy (4,826, 33%), smoking (4,772, 33%), and diabetes (4,588, 32%) were common co-morbidities in patients with RAO. Of 14,527 patients with RAO, 308 patients (2.1%) died, 1,577 (10.9%) developed stroke, and 615 (4.2%) developed MI within 6 months. A total of 2,841 patients (24.9%) were readmitted within 6 months of discharge. Carotid artery stenosis (386, 10.8%) was the most common cause of readmission. History of stroke or transient ischemic attack and Elixhauser co-morbidity index ≥3 were predictors of stroke. Female gender, ischemic cardiomyopathy, carotid artery disease, heart failure, chronic kidney disease, and cancer were predictors of MI. Cancer, chronic kidney disease, Elixhauser co-morbidity index ≥3, Medicare/Medicaid payer status, nonelective index admission, atrial fibrillation, and carotid artery disease were predictors of 6-month all-cause readmission. In conclusion, patients with RAO have a significant burden of co-morbidities, death, stroke, MI, and readmission. RAO may be used as a clinical marker of future stroke and MI, and should trigger screening for acute vascular ischemic events.

Comparison of 6-Month Outcomes of Endovascular vs Surgical Revascularization for Patients With Critical Limb Ischemia.

Importance: The Bypass Versus Angioplasty for Severe Ischemia of the Leg randomized controlled trial showed comparable outcomes between endovascular revascularization (ER) and surgical revascularization (SR) for patients with critical limb ischemia (CLI). However, several observational studies showed mixed results. Most of these studies were conducted before advanced endovascular technologies were available. Objective: To compare ER and SR treatment strategies for 6-month outcomes among patients with CLI. Design, Setting, and Participants: This retrospective, population-based cohort study used the Nationwide Readmissions Database to identify 66 277 patients with CLI who underwent ER or SR from January 1, 2016, to December 31, 2018. Data analyses were conducted from January 1, 2022, to February 8, 2022. A propensity score with 1:1 matching was applied. Patients with CLI who underwent ER or SR were identified, and those with missing information on the length of stay and/or younger than 18 years were excluded. Exposures: Endovascular or surgical revascularization. Main Outcomes and Measures: The primary outcome was a major amputation at 6 months. Significant secondary outcomes were in-hospital and 6-month mortality and an in-hospital safety composite of acute kidney injury, major bleeding, and vascular complication. Subgroup analysis was conducted for major amputation in high-volume centers. Results: A total of 66 277 patients were identified between 2016 and 2018 who underwent ER or SR for CLI. The Nationwide Readmissions Database does not provide racial and ethnic categories. The mean (SD) age of the cohort was 69.3 (12) years, and 62.5% of patients were male. A total of 54 546 patients (82.3%) underwent ER and 11 731 (17.7%) underwent SR. After propensity score matching, 11 106 matched pairs were found. Endovascular revascularization was associated with an 18% higher risk of major amputation compared with SR (997 of 10 090 [9.9%] vs 869 of 10 318 [8.4%]; hazard ratio, 1.18; 95% CI, 1.08-1.29; P = .001). However, no difference was observed in major amputation risk when both procedures were performed in high-volume centers. Endovascular revascularization and SR had similar mortality rates (517 of 11 106 [4.7%] vs 490 of 11 106 [4.4%]; hazard ratio, 1.06; 95% CI, 0.93-1.20; P = .39). However, the ER group had a 17% lower risk of in-hospital safety outcomes compared with the SR group (2584 of 11 106 [23.3%] vs 2979 of 11 106 [26.8%]; odds ratio, 0.83; 95% CI, 0.78-0.88; P < .001). Conclusions and Relevance: The results of this study suggest that ER was safer, without any difference in mortality, but ER was associated with an increased risk of major amputation compared with SR. However, the risk of major amputation was similar when both procedures were performed at high-volume centers.

Analysis of Hospital Quality Measures and Web-Based Chargemasters, 2019: Cross-sectional Study.

BACKGROUND: The federal health care price transparency regulation from 2019 is aimed at bending the health care cost curve by increasing the availability of hospital pricing information for the public. OBJECTIVE: This study aims to examine the associations between publicly reported diagnosis-related group chargemaster prices on the internet and quality measures, process indicators, and patient-reported experience measures. METHODS: In this cross-sectional study, we collected and analyzed a random 5.02% (212/4221) stratified sample of US hospital prices in 2019 using descriptive statistics and multivariate analysis. RESULTS: We found extreme price variation in shoppable services and significantly greater price variation for medical versus surgical services (P=.006). In addition, we found that quality indicators were positively associated with standard charges, such as mortality (ß=.929; P<.001) and readmissions (ß=.514; P<.001). Other quality indicators, such as the effectiveness of care (ß=-.919; P<.001), efficient use of medical imaging (ß=-.458; P=.001), and patient recommendation scores (ß=-.414; P<.001), were negatively associated with standard charges. CONCLUSIONS: We found that hospital chargemasters display wide variations in prices for medical services and procedures and match variations in quality measures. Further work is required to investigate 100% of US hospital prices posted publicly on the internet and their relationship with quality measures.

5-Fluorouracil Rechallenge After Cardiotoxicity.

BACKGROUND 5-Fluorouracil (5-FU) is a widely used intravenous chemotherapy agent that is highly effective in the treatment of a variety of solid malignancies. Cardiotoxicity related to 5-FU is a complex clinical entity associated with significant morbidity and mortality. Whether a patient who experienced a major cardiac side effect from 5-FU can be safely rechallenged with this drug is a clinical dilemma. CASE REPORT We present the case of a patient with stage III colorectal adenocarcinoma who experienced ventricular fibrillation during the first cycle of FOLFOX (5-FU, folinic acid, and oxaliplatin) regimen in the adjuvant setting. Post-resuscitation electrocardiogram revealed ST-elevation in the inferior leads with reciprocal changes. Coronary angiogram revealed no obstructive coronary artery disease. Cardiac workup led to the conclusion of probable fluorouracil-induced vasospasm as the cause of his cardiac arrest. He received implantable cardioverter defibrillator. The decision was made to hold 5-FU. At 3-month follow-up, there was evidence of progressive metastasis. After comprehensive risk-benefit discussions, the decision was made for palliative chemotherapy using 5-FU/leucovorin. A pre-treatment regimen including isosorbide dinitrate, diltiazem, and metoprolol was used. The patient tolerated 5-FU rechallenge without recurrent cardiovascular complication. CONCLUSIONS The cardiotoxicity profile of 5-FU can range from anginal chest pain to sudden cardiac death. When considering 5-FU rechallenge, clinicians should adopt a multidisciplinary approach, favor using prophylactic antianginal therapy, change to bolus dosing, and use continuous telemetry monitoring. Screening patients for dihydropyrimidine dehydrogenase deficiency prior to 5-FU administration may facilitate an individualized strategy for optimal dosing and safety.

Formulation design and characterization of an elementary osmotic pump tablet of flurbiprofen.

Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. The objective of the present study was to develop elementary osmotic pump tablets containing Flurbiprofen using an inclusion complex. Formation of complex was confirmed by Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy. A 3(2) factorial design was applied systematically; the amount of osmotic agent (X1) and size of delivery orifice (X2) were selected as independent variables. Batches were prepared by the direct compression method and evaluated for percent cumulative drug release (%CDR) at 9 h as dependent variables. The amount of osmotic agent and size of the delivery orifice had a significant effect on %CDR. The results of multiple linear regression analysis revealed that elementary osmotic pump tablets should be prepared using an optimum concentration of osmotic agent and size of delivery orifice to achieve a zero-order drug release. Contour plots as well as response surface plots were constructed to show the effects of X1 and X2 on %CDR. A model was validated for accurate prediction of %CDR by performing checkpoint analysis. The computer optimization process, contour plots, and response surface plots were predicted at the concentration of independent variables X1 and X2 (78.38 mg and 0.99 mm, respectively), for maximized response. The drug release from the developed formulation was found to be independent of pH and agitational intensity. The above optimized batch was also evaluated by different pharmacokinetic models like zero-order, first-order, Higuchi, Korsmeyer Peppas, and Hixson Crowell models. Stability study of the optimized batch was conducted at accelerated conditions for 6 months, and was found stable. This study strongly indicates application of osmotic tablets of Flurbiprofen for the treatment of rheumatoid arthritis, as well as osteoarthritis. LAY ABSTRACT: The aim of this study was to develop an elementary osmotic pump tablet of Flurbiprofen and to deliver the drug at a zero-order rate. Elementary osmotic pumps are well known for delivering moderately soluble drugs at a zero-order rate. Elementary osmotic pump tablets containing an inclusion complex of Flurbiprofen was prepared by the direct compression method. The amount of osmotic agent and size of delivery orifice were selected as independent variables. Percent cumulative drug release at 9 h was evaluated for all batches, and it was found that amount of osmotic agent and size of delivery orifice had a significant effect on percent cumulative drug release. The drug release from the developed formulation was found to be independent of pH and agitational intensity. It was also observed that the optimized formulation followed zero-order kinetics and was stable for 6 months at accelerated conditions.