Comparative Genitourinary Safety of In-class Sodium-Glucose Cotransporter-2 Inhibitors among Patients with Heart Failure with Preserved Ejection Fraction: A Cohort Study.

PURPOSE: The American Heart Association recommended sodium-glucose cotransporter-2 inhibitors (SGLT2i) for the management of heart failure with preserved ejection fraction (HFpEF). However, little is known about their real-world in-class comparative safety in patients with HFpEF. We aimed to assess the comparative safety of SGLT2i in the risk of urinary tract infection (UTI) or genital infection separately or as a composite outcome among patients with HFpEF. METHODS: This cohort study using MarketScan® Commercial and Medicare supplemental databases (2012-2020) included patients aged ≥ 18 years with a diagnosis of HFpEF who initiated SGLT2i therapy. Three pairwise comparison groups were established: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. After stabilized inverse probability treatment weighting, Cox proportional hazards regression was used to compare the risk of UTI or genital infection separately or as a composite outcome in each cohort. RESULTS: The risk of the composite outcome did not significantly differ between canagliflozin and dapagliflozin (adjusted hazard ratio [aHR] 0.64; 95% confidence interval [CI] 0.36-1.14) or between empagliflozin and canagliflozin (aHR 1.25; 95% CI 0.77-2.05). Similarly, there was no evidence of difference between dapagliflozin and empagliflozin in this risk (aHR 0.76; 95% CI 0.48-1.21). The results of analyses separately assessing UTI or genital infection were similar. CONCLUSIONS: There was no significant difference in the risk of UTI or genital infection among patients with HFpEF who initiated canagliflozin, dapagliflozin, or empagliflozin.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are used for the management of heart failure with preserved ejection fraction (HFpEF). It is important to assess their comparative risk of urinary tract infection (UTI) or genital infection among patients with HFpEF. We compared patients with HFpEF using SGLT2i in three pairwise groups: cohort 1, dapagliflozin versus canagliflozin; cohort 2, empagliflozin versus canagliflozin; and cohort 3, dapagliflozin versus empagliflozin. We found that there was no significant difference in the risk of genitourinary infections including UTI or genital infections among dapagliflozin, empagliflozin, and canagliflozin.

Comparative Safety of Long-Acting vs. Short-Acting Erythropoiesis-Stimulating Agents Among Patients Undergoing Hemodialysis.

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.

Comparative effectiveness of sacubitril/valsartan versus angiotensin receptor blockers in patients with heart failure with preserved ejection fraction: A real-world study.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Sacubitril/valsartan (SAC/VAL) or angiotensin receptor blockers (ARBs) are recommended therapy for heart failure with preserved ejection fraction (HFpEF), but little is known about their real-world comparative effectiveness among patients with HFpEF. The objective of this study was to determine the comparative effectiveness of SAC/VAL vs ARBs in preventing HF-related hospitalization or all-cause hospitalization among patients with HFpEF. METHODS: We conducted a cohort study using IBM MarketScan commercial and Medicare supplemental databases to identify patients aged 18 years or older with a diagnosis of HFpEF and initiation of SAC/VAL (2015-2020) or ARB (2009-2014) therapy. The index date was the date of the first SAC/VAL or ARB prescription fill. After propensity score (PS) matching with a ratio of 1 up to 3, Cox proportional hazards regression was used with robust variance estimators to compare the risks of HF-related hospitalization and all-cause hospitalization between the 2 therapies. Several subgroup and sensitivity analyses were conducted to check the robustness of the main analysis. RESULTS: After PS matching, 2,520 patients (846 receiving SAC/VAL and 1,674 receiving an ARB) were included in the final analyses. After controlling for covariates, there was no difference in the risk of HF-related hospitalization between SAC/VAL and ARB recipients (adjusted hazard ratio [aHR], 1.33; 95% confidence interval [CI], 0.99-1.77). There was also no difference in the risk of all-cause hospitalization between SAC/VAL and ARB recipients (aHR, 1.06; 95% CI, 0.91-1.24). CONCLUSION: Among individuals with private or Medicare Advantage insurance plans, there was no significant difference in the risk of HF-related hospitalization or all-cause hospitalization between adults with HFpEF who received SAC/VAL and those who received ARB therapy.

Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors among patients with heart failure with preserved ejection fraction.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are recommended by the American Heart Association for management of heart failure with preserved ejection fraction (HFpEF), but little is known about their in-class comparative effectiveness in real-world settings. OBJECTIVES: To assess the in-class comparative effectiveness of SGLT2i for preventing HF-related and all-cause hospitalizations among patients with HFpEF. METHODS: Using MarketScan® Commercial and Medicare Supplemental research databases (2012-2020), this cohort study included adults with HFpEF treated with SGLT2i. Stabilized inverse probability treatment weighted Cox proportional hazards regression was used to compare HF-related and all-cause hospitalizations in three pairwise comparisons: dapagliflozin versus canagliflozin, empagliflozin versus canagliflozin, and dapagliflozin versus empagliflozin. Subgroup and sensitivity analyses were conducted to assess robustness of the main analysis. RESULTS: In total, 3629 SGLT2i users (881 dapagliflozin, 1120 canagliflozin, and 1628 empagliflozin) were included. Compared with canagliflozin, dapagliflozin was associated with decreased risk of HF-related hospitalization (adjusted hazard ratio [aHR], 0.75; 95% confidence interval [CI], 0.56-1.01) and all-cause hospitalization (aHR, 0.84; 95% CI 0.73-0.97). Compared with canagliflozin, empagliflozin was associated with 55% decreased risk of HF-related hospitalization (aHR, 0.45; 95% CI 0.34-0.59) and 18% decreased risk of all-cause hospitalization (aHR, 0.82; 95% CI 0.73-0.93). Compared with empagliflozin, dapagliflozin was associated with 50% increased risk of HF-related hospitalization (aHR, 1.50; 95% CI 1.09-2.07) and a statistically nonsignificant increase in the risk of all-cause hospitalization (aHR, 1.05; 95% CI 0.92-1.20). CONCLUSIONS: Compared with canagliflozin or dapagliflozin use, empagliflozin use was associated with decreased risk of HF-related and all-cause hospitalizations. Compared with canagliflozin, dapagliflozin was associated with a reduced risk of HF-related and all-cause hospitalizations.

Hepatitis C Cascade of Care in the Direct-Acting Antivirals Era: A Meta-Analysis.

INTRODUCTION: The hepatitis C virus (HCV) epidemic remains a public health problem worldwide. A systematic review and meta-analysis were conducted to provide evidence of outcomes attained across the HCV care cascade in the era of direct-acting antivirals. METHODS: Studies from North America, Europe, and Australia (January 2014 through March 2021) reporting on HCV care cascade outcomes (screening to cure) were included. When calculating the proportions of individuals completing each step, the numerator for Steps 1-8 was the number of individuals completing each step; the denominator was the number of individuals completing the previous step for Steps 1-3 and Step 3 for Steps 4-8. In 2022, random effects meta-analyses were conducted to estimate pooled proportions with 95% CIs. RESULTS: Sixty-five studies comprising 7,402,185 individuals were identified. Among individuals with positive HCV ribonucleic acid test results, 62% (95% CI=55%, 70%) attended their first care appointment, 41% (95% CI=37%, 45%) initiated treatment, 38% (95% CI=29%, 48%) completed treatment, and 29% (95% CI=25%, 33%) achieved cure. HCV screening rates were 43% (95% CI=22%, 66%) in prisons or jails and 20% (95% CI=11%, 31%) in emergency departments. Linkage to care rates were 62% (95% CI=46%, 75%) for homeless individuals and 26% (95% CI=22%, 31%) for individuals diagnosed in emergency departments. Cure rates were 51% (95% CI=30%, 73%) in individuals with substance use disorder and 17% (95% CI=17%, 17%) in homeless individuals. Cure rates were lowest in the U.S. DISCUSSION: Despite the availability of effective all-oral direct-acting antiviral therapies, persistent gaps remain across the HCV care cascade, especially among traditionally marginalized populations. Public health interventions targeting identified priority areas (e.g., emergency departments) may improve screening and healthcare retention of vulnerable populations with HCV infection (e.g., substance use disorder populations).

Trends in pharmacotherapy utilization among patients with heart failure with preserved ejection fraction.

Study objective: Half of patients with heart failure have preserved ejection fraction (HFpEF). Over the years, guidelines have recommended or advised against various therapies for HFpEF management. However, there is limited evidence on the trends in utilization of the various medications. The aim of this study was to examine the trends in the use of pharmacotherapies among patients with HFpEF from 2008 through 2020. Design: Retrospective cohort study of patients with HFpEF used MarketScan® Commercial and Medicare Supplemental Databases (2007-2020). Participants: Patients with HFpEF. Outcome measures: Utilization rates for angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), aldosterone receptor antagonists (ARAs), diuretics, ß-blockers, calcium channel blockers (CCBs), phosphodiesterase 5 inhibitors (PDE5Is), nitrates, digoxin, and sodium glucose cotransporter-2 inhibitors (SGLT2i) within 90 days of the first HFpEF diagnosis. Results: We identified 156,730 patients with HFpEF (mean [SD] age, 73 [13.4] years; 57 % females). From 2008 to 2020, we found increased utilization rates for ARNIs (0.02 % vs. 0.17 % of all patients, p < 0.01), ARBs (14.3 % vs. 18.6 %, p < 0.01), ARAs (7.0 % vs. 8.4 %, p < 0.01), CCBs (30.6 % vs. 33.4 %, p < 0.01), and SGLT2i (0.001 % vs. 0.021 %, p < 0.01). By contrast, the utilization of ACEIs (30.4 % vs. 20.5 %, p < 0.01), digoxin (9.5 % vs. 2.4 %, p < 0.01), nitrates (10.7 % vs. 4.9 %, p < 0.01), diuretics (54.1 % vs. 50.4 %, p = 0.20), and ß-blockers (52.6 % vs. 51.7 %, p < 0.01) decreased, while utilization rates of PDE5Is remained stable (1.5 % vs. 1.1 %, p = 0.90) . Conclusions: During the 13-year study period, the utilization of ARNIs, ARBs, ARAs, CCBs, and SGLT2i increased while the utilization of digoxin, nitrates, diuretics, and ß-blockers decreased among patients with HFpEF.

An Umbrella Review of the Cost Effectiveness of Human Papillomavirus Vaccines.

BACKGROUND AND OBJECTIVES: Although many systematic reviews for the human papillomavirus vaccines cost effectiveness have been published, they vary in perspectives, methods, and quality. We aimed to condense systematically such evidence to facilitate locating, processing, and learning, not only about the consensus of findings but also how models were built and their evolution over time and across settings. METHODS: We conducted an umbrella review of cost-effectiveness studies for human papillomavirus vaccines using three databases (PubMed, Embase, and Cochrane). Based on their objectives, we classified studies into three groups (human papillomavirus vaccines cost effectiveness, model characteristics, and all-type vaccines, including human papillomavirus vaccines). We used the AMTAR2 to assess the quality of the studies. Additionally, we provided a summary of study findings, discussions, and evidence gaps in the literature. RESULTS: Though most studies were critically low quality and had a low quality of reporting, the human papillomavirus vaccine was consistently cost effective in young girls and men who have sex with men. Stratified analyses by rated quality did not change the results. The quality assessment of the reviews did not necessarily reflect the quality assessment of underlying studies. The human papillomavirus vaccine models became more complex over time, capturing more realistic disease transmission with different human papillomavirus strains and herd immunities. CONCLUSIONS: Additional evidence is needed for vulnerable populations (e.g., childhood cancer survivors) who are at high risk for human papillomavirus vaccine-related cancers and, therefore, may be more cost effective when receiving human papillomavirus vaccines. Quantifying human papillomavirus vaccine cost effectiveness via meta-analyses is feasible if investigators can increase the homogeneity of their populations.

Effectiveness of sacubitril/valsartan versus aldosterone antagonists in heart failure with reduced ejection fraction: A retrospective cohort study.

STUDY OBJECTIVE: To assess the effectiveness of sacubitril/valsartan versus angiotensin receptor antagonist therapy for prevention of heart failure (HF)-related hospitalization and all-cause hospitalization in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF). DESIGN: Retrospective cohort study. DATA SOURCE: IBM® MarketScan® research databases (2014-2018). PATIENTS: Patients aged 18 years or older with their first HFrEF hospitalization on or after January 1, 2015, who initiated sacubitril/valsartan or angiotensin receptor antagonist after hospital discharge. INTERVENTION: Sacubitril/Valsartan versus Angiotensin receptor antagonist. MEASUREMENTS AND MAIN RESULTS: The index date was the first sacubitril/valsartan or angiotensin receptor antagonist fill date. After 1 up to 3 propensity score matching, Cox proportional hazards regression was used with robust variance estimators to compare HF-related and all-cause hospitalizations between treatments. Subgroup and sensitivity analyses were conducted to assess the robustness of the main analysis. After propensity score matching, 1,088 sacubitril/valsartan and 2,839 angiotensin receptor antagonist new users were included. The crude incidence of HF-related hospitalization was 13 per 100 person-years for sacubitril/valsartan users and 18 per 100 person-years for angiotensin receptor antagonist users. Compared with angiotensin receptor antagonist use, sacubitril/valsartan use was associated with 27% lower risk of HF-related hospitalization (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58-0.91; p = 0.006) and 31% lower risk of all-cause hospitalization (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.79; p < 0.001). Subgroup analyses revealed no significant heterogeneity, including subpopulations with chronic kidney disease or coronary artery disease. CONCLUSIONS: Compared with angiotensin receptor antagonists, sacubitril/valsartan was associated with lower risk of HF-related and all-cause hospitalizations. Our data suggest that, when added sequentially, sacubitril/valsartan should be the preferred initial agent over angiotensin receptor antagonists.

Association of Adverse Drug Events with Hospitalization Outcomes and Costs in Older Adults in the USA using the Nationwide Readmissions Database.

BACKGROUND: Adverse drug events (ADEs) are a primary cause of significant morbidity, mortality, and healthcare utilization in older adults. OBJECTIVE: The objective of this study was to evaluate the clinical outcomes and cost of ADEs during hospitalization in older adults. METHODS: Discharges for patients aged 65 years or older were identified in the 2014 Nationwide Readmissions Database. ADEs were selected based on a previously developed algorithm of 442 unique diagnoses and external causes of injury codes. Patients were categorized into ADE or non-ADE groups. Regression models were used for a multivariable analysis for each outcome metric, which included all-cause readmission, in-hospital mortality, length of stay, and costs. RESULTS: The study included 3,832,322 patients. Among these patients, 203,432 (5.3%) had at least one ADE during hospitalization. The majority of ADEs were related to broad categories of "medications affecting blood constituents" (22%) and "adverse effects of biological and medicinal substances in therapeutic use" (23%). In adjusted models, older adults with ADEs during hospitalization had a 25% (p < 0.0001) and 9% (p < 0.0001) higher odds of readmission and in-hospital mortality, respectively, as compared with those without ADEs. A 17% (p < 0.0001) increase in the length of stay was estimated in the ADE group and 1% point estimate (p > 0.05) rise in cost was observed in the ADE group when compared with the non-ADE group. CONCLUSIONS: ADEs have a substantial burden on in-patient care of older adults both clinically (increased readmission, in-hospital mortality, and length of stay) and financially. Targeted interventions can help to prevent ADEs and, consequently, the associated clinical and economic burden.

Cost effectiveness evaluation of hepatitis C therapy in Lahore.

Approximately 10 million Pakistan's of population is a victim of Hepatitis C virus. A comparative study of two treatments for Hepatitis C being provided in private clinics and government hospitals was conducted to evaluate the cost effectiveness of these treatments. The quality adjusted life years (QALYs) for each treatment plan was determined with the help of health utilities, using EQ-5D scores. A comprehensive data collection form aided in scrutinizing the cause and effect of each treatment on the patient's quality of life. The total sample size for this study is 200 total from the public and private sectors. For both the treatment strategies, values for quality adjusted life years (QALYs), incremental cost effective ratio (ICER) and cost effective analysis (CEA) were calculated. The Hepatitis C virus 3a and 3b genotypic patients who were treated with pegylated interferon α-2a and ribavirin combination (strategy 2) showed an increased quality adjusted life years (QALYs) of two years, as compared to those who received interferon α-2a and ribavirin regimen (strategy 1). An incremental cost effectiveness ratio (ICER) of Rs 144673.5 per quality adjusted life year (QALYs) was gained by patients treated with strategy 2. The therapy followed by the government sector (strategy 1) is relatively inexpensive accounting for Rs 654.5/quality adjusted life years (QALY) and therapy provided at the clinic sector (strategy 2) is relatively expensive Rs 5620.6/ quality adjusted life years (QALY). However, the cost effectiveness analysis for the pegylated interferon therapy is quite comparable with the other standard treatments; hence it can be called cost effective according to the quality adjusted life years (QALYs) gained and efficacy of the said therapy.