Effect of bempedoic acid on mortality and cardiovascular events in primary and secondary prevention: A post-hoc analysis of the CLEAR-outcomes trial.

BACKGROUND: The effects of bempedoic acid on mortality in the secondary prevention setting have not been examined. METHODS: We used data from the overall and primary prevention reports of CLEAR - Outcomes to reconstruct data for the secondary prevention population. A Bayesian analyses was employed to calculate the posterior probability of benefit or harm for the outcomes of all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Relative effect sizes are presented as risk ratios (RR) with 95% credible intervals (CrI), which represent the intervals that true effect sizes are expected to fall in with 95% probability, given the priors and model. RESULTS: In primary prevention, the posterior probability of bempedoic acid decreasing all-cause and cardiovascular mortality was 99.4% (RR: 0.70; 95% CrI: 0.51 to 0.92) and 99.7% (RR: 0.58; 95% CrI: 0.38 to 0.86) respectively. In secondary prevention, the posterior probability of bempedoic acid increasing all-cause and cardiovascular mortality was 96.6% (RR: 1.15; 95% CrI: 0.99 to 1.33) and 97.2% (RR: 1.21; 95% CrI: 1.00 to 1.45) respectively. The probability of bemepdoic acid reducing MACE in the primary and secondary prevention settings was 99.9% (RR: 0.70; 95% CrI: 0.54 to 0.88) and 95.8% (RR: 0.92; 95% CrI: 0.84 to 1.01) respectively. CONCLUSION: In contrast to its effect in the primary prevention subgroup of CLEAR - Outcomes, bempedoic acid resulted in a more modest MACE reduction and a potential increase in mortality in the secondary prevention subgroup. Whether these findings represent true treatment effect heterogeneity or the play of chance requires further evidence.

Effect of statin use for the primary prevention of cardiovascular disease among older adults: a cautionary tale concerning target trials emulation.

OBJECTIVES: Evidence concerning the effect of statins in primary prevention of cardiovascular disease (CVD) among older adults is lacking. Using Quebec population-wide administrative data, we emulated a hypothetical randomized trial including older adults >65 years on April 1, 2013, with no CVD history and no statin use in the previous year. STUDY DESIGN AND SETTING: We included individuals who initiated statins and classified them as exposed if they were using statin at least 3 months after initiation and nonexposed otherwise. We followed them until March 31, 2018. The primary outcome was the composite endpoint of coronary events (myocardial infarction, coronary bypass, and percutaneous coronary intervention), stroke, and all-cause mortality. The intention-to-treat (ITT) effect was estimated with adjusted Cox models and per-protocol effect with inverse probability of censoring weighting. RESULTS: A total of 65,096 individuals were included (mean age = 71.0 ± 5.5, female = 55.0%) and 93.7% were exposed. Whereas we observed a reduction in the composite outcome (ITT-hazard ratio (HR) = 0.75; 95% CI: 0.68-0.83) and mortality (ITT-HR = 0.69; 95% CI: 0.61-0.77) among exposed, coronary events increased (ITT-HR = 1.46; 95% CI: 1.09-1.94). All multibias E-values were low indicating that the results were not robust to unmeasured confounding, selection, and misclassification biases simultaneously. CONCLUSION: We cannot conclude on the effectiveness of statins in primary prevention of CVD among older adults. We caution that an in-depth reflection on sources of biases and careful interpretation of results are always required in observational studies.

Thiazide Diuretics and Risk of Colorectal Cancer: A Population-Based Cohort Study.

Evidence from clinical trials and observational studies on the association between thiazide diuretics and colorectal cancer risk is conflicting. We aimed to determine whether thiazide diuretics are associated with an increased colorectal cancer risk compared with dihydropyridine calcium channel blockers (dCCBs). A population-based, new-user cohort was assembled using the UK Clinical Practice Research Datalink. Between 1990-2018, we compared thiazide diuretic initiators with dCCB initiators and estimated hazard ratios (HR) with 95% confidence intervals (CIs) of colorectal cancer using Cox proportional hazard models. Models were weighted using standardized morbidity ratio weights generated from calendar time-specific propensity scores. The cohort included 377,760 thiazide diuretic initiators and 364,300 dCCB initiators, generating 3,619,883 person-years of follow-up. Compared with dCCBs, thiazide diuretics were not associated with colorectal cancer (weighted HR = 0.97, 95% CI: 0.90, 1.04). Secondary analyses yielded similar results, although an increased risk was observed among patients with inflammatory bowel disease (weighted HR = 2.45, 95% CI: 1.13, 5.35) and potentially polyps (weighted HR = 1.46, 95% CI: 0.93, 2.30). Compared with dCCBs, thiazide diuretics were not associated with an overall increased colorectal cancer risk. While these findings provide some reassurance, research is needed to corroborate the elevated risks observed among patients with inflammatory bowel disease and history of polyps.

In symptomatic AF with end-stage HF, adding catheter ablation to medical therapy improved clinical outcomes at 18 mo.

SOURCE CITATION: Sohns C, Fox H, Marrouche NF, et al; CASTLE HTx Investigators. Catheter ablation in end-stage heart failure with atrial fibrillation. N Engl J Med. 2023;389:1380-1389. 37634135.

Marginal structural models with latent class growth analysis of treatment trajectories: Statins for primary prevention among older adults.

Latent class growth analysis is increasingly proposed as a solution to summarize the observed longitudinal treatment into a few distinct groups. When latent class growth analysis is combined with standard approaches like Cox proportional hazards models, confounding bias is not properly addressed because of time-varying covariates that have a double role of confounders and mediators. We propose to use latent class growth analysis to classify individuals into a few latent classes based on their medication adherence pattern, then choose a working marginal structural model that relates the outcome to these groups. The parameter of interest is defined as a projection of the true marginal structural model onto the chosen working model. Simulation studies are used to illustrate our approach and compare it with unadjusted, baseline covariates adjusted, time-varying covariates adjusted, and inverse probability of trajectory groups weighted adjusted models. Our proposed approach yielded estimators with little or no bias and appropriate coverage of confidence intervals in these simulations. We applied our latent class growth analysis and marginal structural model approach to a database comprising information on 52,790 individuals from the province of Quebec, Canada, aged more than 65 and who were statin initiators to estimate the effect of statin-usage trajectories on a first cardiovascular event.

SGLT-2 inhibitors improve cardiovascular and renal outcomes in patients with CKD: a systematic review and meta-analysis.

The effect of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized control trials (RCTs) with SGLT-2 inhibitors in patients with and without CKD. We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of SGLT-2 inhibitors versus active or placebo control in patients with and without diabetes from inception to November 2022. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 (PROSPERO registration CRD4202016054). The primary outcome was cardiovascular death. Secondary outcomes included hospitalization for heart failure, major adverse cardiovascular events, CKD progression, all-cause mortality, treatment discontinuation, and acute kidney injury (AKI). The relative risk (RR) was estimated using a random-effects model. Twelve RCTs were included in this meta-analysis (89,191 patients, including 38,949 with eGFR < 60 ml/min/1.73m2). Use of an SGLT-2 inhibitor in patients with CKD was associated with a lower incidence of cardiovascular death (RR 0.87; 95% CI 0.79-0.95) and of heart failure (RR 0.67; 95% CI 0.61-0.75), compared with placebo. Heart failure risk reduction with SGLT-2 inhibitors was larger among patients with CKD compared with patients without CKD (RR for the interaction 0.87, 95% CI 0.75-1.02, and p-value for interaction 0.08). SGLT-2 inhibitors were associated with a lower incidence of CKD progression among patients with pre-existing CKD: RR 0.77 (95% CI 0.68-0.88), compared with placebo. Among patients with CKD, a lower risk of AKI (RR 0.82; 95% CI 0.72-0.93) and treatment discontinuation was seen with SGLT-2 inhibitors compared with placebo. SGLT-2 inhibitors offer substantial protection against cardiovascular and renal outcomes in patients with CKD. These results strongly advocate in favor of using them in patients with CKD and keeping them as kidney function declines.

Beta-Blockers, Digoxin, or Both Following an Incident Diagnosis of Atrial Fibrillation: A Prospective Cohort Study.

BACKGROUND: Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rate control strategy remains uncertain. METHODS: A retrospective cohort claims database study of patients with an incident hospital discharge diagnosis of atrial fibrillation between 2011 and 2015. The exposure variables were a discharge prescription for beta-blockers, digoxin, or both. The primary outcome was a composite of total in-hospital mortality or a repeat cardiovascular (CV) hospitalization. Baseline confounding was controlled with propensity score inverse probability weighting using a entropy balancing algorithm and the prespecified estimand was the average treatment effect among the treated. Treatment effects for the weighted samples were calculated from a Cox proportional hazards model. RESULTS: A total of 12,723 patients were discharged on beta-blockers alone, 406 on digoxin alone, and 1499 discharged on combined beta-blocker and digoxin therapy with a median follow-up time of 356 days. After baseline covariate adjustment, the digoxin alone (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.85-1.81) and the combined group (HR, 1.09; 95% CI, 0.90-1.31) were not associated with increased risk for the composite endpoint compared with the beta- blocker-alone group. These results were robust to sensitivity analyses. CONCLUSIONS: Patients hospitalized for incident atrial fibrillation and discharged on digoxin alone or the combination of digoxin and a beta-blocker were not associated with an increase in the composite outcome of recurrent CV hospitalizations and death compared with those discharged on isolated beta-blocker therapy. However, additional studies are required to refine the precision of these estimates.

Imaging Utilization Patterns in the Follow-Up of Extremity Soft Tissue Sarcomas in the United States.

This study aimed to describe patterns of imaging utilization after resection of extremity soft tissue sarcoma in the United States, assess for potential disparities, and evaluate temporal trends. A retrospective cohort study using a national database of private payer claims data was performed to determine the utilization rate of extremity and chest imaging in a 5-year postoperative follow-up period for patients with extremity soft tissue sarcoma treated between 2007 and 2019. Imaging utilization was assessed according to patient demographics (age, sex, race and ethnicity, and region of residency), calendar year of surgery, and postoperative year. Associations of demographic variables with imaging use were assessed using chi-square tests, trends in imaging use were analyzed using the Cochran-Armitage trend test or linear regression, and associations of postoperative year with imaging use were evaluated with the Pearson Correlation coefficient. A total of 3707 patients were included. Most patients received at least 1 chest (74%) and extremity (53%) imaging examination during their follow-up period. The presence of surveillance imaging was significantly associated with age (P < 0.0001) and region (P = 0.0029). Over the study period, there was an increase in use of extremity MRI (P < 0.05) and ultrasound (P < 0.01) and chest CT (P < 0.0001) and a decrease in use of chest radiographs (P < 0.0001). Imaging use declined over postoperative years (decrease by 85%-92% from year 1-5). In conclusion, the use of surveillance imaging varied according to patient demographics and has increased for extremity MRI and ultrasound and chest CT over the study period.

Hydrochlorothiazide use and risk of keratinocyte carcinoma and melanoma: A multisite population-based cohort study.

BACKGROUND: The association between hydrochlorothiazide (HCTZ) and skin cancer remains controversial. OBJECTIVE: To determine whether HCTZ is associated with an increased risk of skin cancer compared with angiotensin-converting enzyme inhibitors and calcium channel blockers. METHODS: Two new-user, active comparator cohorts were assembled using 6 Canadian databases. Site-specific hazard ratios (HRs) with 95% CIs were estimated using standardized morbidity ratio weighted Cox proportional hazard models and pooled using random-effects meta-analysis. RESULTS: HCTZ was not associated with an overall increased risk of keratinocyte carcinoma compared with angiotensin-converting enzyme inhibitors or calcium channel blockers, although increased risks were observed with longer durations (≥10 years; HR: 1.12; 95% CI: 1.03-1.21) and higher cumulative doses (≥100,000 mg; HR: 1.49; 95% CI: 1.27-1.76). For melanoma, there was no association with angiotensin-converting enzyme inhibitors, but a 32% increased risk with calcium channel blockers (crude incidence rates: 64.2 vs 58.4 per 100,000 person-years; HR: 1.32; 95% CI: 1.19-1.46; estimated number needed to harm at 5 years of follow-up: 1627 patients), with increased risks with longer durations and cumulative doses. LIMITATIONS: Residual confounding due to the observational design. CONCLUSIONS: Increased risks of keratinocyte carcinoma and melanoma were observed with longer durations of use and higher cumulative doses of HCTZ.

Usefulness of MRI-Based Local Surveillance After Surgical Treatment of Musculoskeletal Soft-Tissue Sarcomas: A Systematic Review and Meta-Analysis.

BACKGROUND. The value of routine MRI follow-up after surgical treatment of musculoskeletal soft-tissue sarcoma (STS) is controversial. OBJECTIVE. The purpose of this study was to evaluate the usefulness of MRI-based surveillance for musculoskeletal STS represented by the proportion of local recurrences (LRs) discovered by MRI versus clinically, stratified by imaging surveillance intensity; the characteristics of LRs detected on imaging versus clinically; and the impact of imaging surveillance on survival. EVIDENCE ACQUISITION. Multiple electronic databases were searched systematically for articles published through November 28, 2022, about controlled trials and cohort studies on the usefulness of MRI-based surveillance for musculoskeletal STS. The risk of bias was assessed using an adapted Newcastle-Ottawa scale. Random-effects meta-analyses of the proportion of LRs discovered by MRI as opposed to clinically were conducted. The association of low- versus high-intensity surveillance with the proportion of LR detected on MRI was assessed with a chi-square test of subgroup differences; for this latter assessment, high intensity was defined as at least one local surveillance imaging examination for low-risk tumors and at least three imaging examinations for high-risk tumors during the first 2 posttreatment years. EVIDENCE SYNTHESIS. A total of 4821 titles and abstracts were identified, and 19 studies were included. All studies were retrospective cohorts. There was substantial variability in follow-up approaches. The risk of bias was moderate in 32% and high in 68% of studies. The pooled proportion of LRs detected on MRI was 53% (95% CI, 36-71%) with high-intensity surveillance and 6% (95% CI, 3-9%) with low-intensity surveillance (p < .01). Comparison of LR characteristics (LR size, depth, grade, location, resection margins) detected on imaging versus clinically identified inconsistent results between studies. Trends toward better survival for imaging-detected LRs or more frequent imaging use were noted in four studies. CONCLUSION. When used at a high intensity, MRI-based surveillance can detect many clinically occult LRs, although the studies are small, occasionally yielded conflicting results, and are often of poor quality. A survival benefit could be associated with imaging use, but further research is needed to evaluate the causality of any observed survival differences. CLINICAL IMPACT. MRI-based surveillance after surgical treatment of musculoskeletal STS is useful to detect clinically occult LRs and could improve patient outcomes.

Risk of Bias in Randomized Clinical Trials Comparing Transcatheter and Surgical Aortic Valve Replacement: A Systematic Review and Meta-analysis.

Importance: Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines highlighted some concerns about the randomized clinical trials (RCTs) comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. Quantification of these biases has not been previously performed. Objective: To assess whether randomization protects RCTs comparing TAVI and SAVR from biases other than nonrandom allocation. Data Sources: A systematic review of the literature between January 1, 2007, and June 6, 2022, on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was performed. Specialist websites were also checked for unpublished data. Study Selection: The study included RCTs with random allocation to TAVI or SAVR with a maximum 5-year follow-up. Data Extraction and Synthesis: Data extraction was performed by 2 independent investigators following the PRISMA guidelines. A random-effects meta-analysis was used for quantifying pooled rates and differential rates between treatments of deviation from random assigned treatment (DAT), loss to follow-up, and receipt of additional treatments. Main Outcomes and Measures: The primary outcomes were the proportion of DAT, loss to follow-up, and patients who were provided additional treatments and myocardial revascularization, together with their ratio between treatments. The measures were the pooled overall proportion of the primary outcomes and the risk ratio (RR) in the TAVI vs SAVR groups. Results: The search identified 8 eligible trials including 8849 participants randomly assigned to undergo TAVI (n = 4458) or SAVR (n = 4391). The pooled proportion of DAT among the sample was 4.2% (95% CI, 3.0%-5.6%), favoring TAVI (pooled RR vs SAVR, 0.16; 95% CI, 0.08-0.36; P < .001). The pooled proportion of loss to follow-up was 4.8% (95% CI, 2.7%-7.3%). Meta-regression showed a significant association between the proportion of participants lost to follow-up and follow-up time (slope, 0.042; 95% CI, 0.017-0.066; P < .001). There was an imbalance of loss to follow-up favoring TAVI (RR, 0.39; 95% CI, 0.28-0.55; P < .001). The pooled proportion of patients who had additional procedures was 10.4% (95% CI, 4.4%-18.5%): 4.6% (95% CI, 1.5%-9.3%) in the TAVI group and 16.5% (95% CI, 7.5%-28.1%) in the SAVR group (RR, 0.27; 95% CI, 0.15-0.50; P < .001). The imbalance between groups also favored TAVI for additional myocardial revascularization (RR, 0.40; 95% CI, 0.24-0.68; P < .001). Conclusions and Relevance: This study suggests that, in RCTs comparing TAVI vs SAVR, there are substantial proportions of DAT, loss to follow-up, and additional procedures together with systematic selective imbalance in the same direction characterized by significantly lower proportions of patients undergoing TAVI that might affect internal validity.

Amiodarone vs Dronedarone for Atrial Fibrillation: A Retrospective Cohort Study.

Background: Atrial fibrillation is one of the most common arrhythmias, but the optimal drug choice for a rhythm-control strategy remains uncertain. Methods: This article reports on a retrospective cohort claims database study conducted using the Truven Health Market Scan Commercial Claims and Encounters and Medicare Supplemental databases. Patients with a new diagnosis of atrial fibrillation, and a discharge date between 2011 and 2015, were included. The exposure variables of interest were a discharge prescription for amiodarone or dronedarone. The average treatment effect for the composite of total mortality or a repeat cardiovascular (CV)-related hospitalization was the primary outcome. Sensitivity analyses with other treatment effect metrics were performed. Baseline covariate imbalances between the groups were adjusted using propensity-score methods with inverse probability weighting. Results: A total of 1735 patients were discharged on amiodarone, and 338 were discharged on dronedarone, with a median follow-up time of 357 days. A total of 43 (12.7%) CV-related hospitalizations occurred in the dronedarone group, and 146 (8.4%) occurred in the amiodarone group (risk difference 4.3%, 95% confidence interval [CI] 0.4%-8.3%, P = 0.02). A total of 4 (1.2%) deaths occurred in the dronedarone group, and 31 (1.8%) deaths occurred with amiodarone (risk difference -0.6%, 95% CI -2.1%-0.9%, P = 0.6). After adjusting for baseline covariates, the dronedarone hazard ratio for the composite endpoint was 1.47 (95% CI 1.01-2.12). This result was generally robust to sensitivity analyses. Conclusion: In this incident cohort of patients hospitalized for atrial fibrillation, compared to those discharged on amiodarone, patients who received a dronedarone discharge prescription had an increase in the composite endpoint of recurrent CV-related hospitalization and death, over a median 1-year follow-up period.

Contexte: La fibrillation auriculaire est l'une des arythmies les plus fréquentes, mais ce qui constitue un choix optimal en matière de médicament dans le cadre d'une stratégie de normalisation du rythme cardiaque demeure incertain. Méthodologie: Cet article présente une étude de cohorte rétro-spective menée à partir des renseignements accessibles dans les bases de données MarketScan Commercial Claims and Encounters et Medicare Supplemental de Truven Health Analytics à propos des réclamations. Les patients qui avaient reçu leur congé de l'hôpital entre 2011 et 2015 après un nouveau diagnostic de fibrillation auriculaire ont été inclus dans l'étude. La variable d'exposition d'intérêt était la prescription d'amiodarone ou de dronédarone à la sortie de l'hôpital. L'effet moyen du traitement sur la variable composite, soit la mortalité totale et la réhospitalisation d'origine cardiovasculaire (CV), constituait le paramètre d'évaluation principal. Des analyses de sensibilité fondées sur d'autres indicateurs de l'effet du traitement ont été effectuées. Les déséquilibres intergroupes touchant les covariables de base ont été corrigés par pondération de probabilité inverse selon l'indice de propension. Résultats: À leur sortie de l'hôpital, 1 735 patients s'étaient vu prescrire de l'amiodarone et 338, de la dronédarone. Le temps de suivi médian était de 357 jours. Le nombre total d'hospitalisations d'origine CV atteignait 43 (12,7 %) sous dronédarone et 146 (8,4 %) sous amiodarone (différence de risque : 4,3 %; intervalle de confiance [IC] à 95 % : 0,4-8,3 %, P = 0,02). Par ailleurs, le nombre total de décès était de quatre (1,2 %) sous dronédarone et de 31 (1,8 %) sous amiodarone (différence de risque : -0,6 %; IC à 95 % : -2,1 %-0,9 %, P = 0,6). Après correction en fonction des covariables de base, le rapport des risques instantanés s'établissait à 1,47 (IC à 95 % : 1,01-2,12) au regard de la variable composite chez les patients sous dronédarone, et ce résultat s'est généralement maintenu dans les analyses de sensibilité. Conclusion: Au sein de la cohorte incidente de patients hospitalisés pour cause de fibrillation auriculaire, une augmentation des cas de réhospitalisation d'origine CV et de la mortalité (variable composite à l'étude) a été notée au cours d'une période médiane de suivi de un an chez les patients qui s'étaient vu prescrire de la dronédarone plutôt que de l'amiodarone à leur sortie de l'hôpital.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES: To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES: PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA: Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS: Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS: Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS: All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS: Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.

Dihydropyridine Calcium Channel Blockers and Risk of Pancreatic Cancer: A Population-Based Cohort Study.

Background Recent studies have reported that dihydropyridine calcium channel blockers (dCCBs) may increase the risk of pancreatic cancer, but these studies had methodological limitations. We thus aimed to determine whether dCCBs are associated with an increased risk of pancreatic cancer compared with thiazide diuretics, a clinically relevant comparator. Methods and Results We conducted a new user, active comparator, population-based cohort study using the UK Clinical Practice Research Datalink. We identified new users of dCCBs and new users of thiazide diuretics between 1990 and 2018, with follow-up until 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs for pancreatic cancer, comparing dCCBs with thiazide diuretics. Models were weighted using standardized morbidity ratio weights based on calendar time-specific propensity scores. We also conducted secondary analyses by cumulative duration of use, time since initiation, and individual drugs and assessed for the presence of effect modification by age, sex, smoking status, body mass index, history of chronic pancreatitis, and diabetes. The cohort included 344 480 initiators of dCCBs and 357 968 initiators of thiazide diuretics, generating 3 360 745 person-years of follow-up. After a median follow-up of 4.5 years, the weighted incidence rate per 100 000 person-years was 37.2 (95% CI, 34.1-40.4) for dCCBs and 39.4 (95% CI, 36.1-42.9) for thiazide diuretics. Overall, dCCBs were not associated with an increased risk of pancreatic cancer (weighted HR, 0.93; 95% CI, 0.80-1.09). Similar results were observed in secondary analyses. Conclusions In this large, population-based cohort study, dCCBs were not associated with an increased risk of pancreatic cancer compared with thiazide diuretics. These findings provide reassurance regarding the long-term pancreatic cancer safety of these drugs.

In the general population, salt substitutes vs. regular salt reduce BP levels, CV outcomes, and mortality.

SOURCE CITATION: Yin X, Rodgers A, Perkovic A, et al. Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis. Heart. 2022;108:1608-15. 35945000.

Developing a cross-validation tool for evaluating economic evidence in rapid literature reviews.

Background: Rapid economic reviews efficiently summarize economic evidence. However, reporting main findings without assessing quality and credibility can be misleading. The objective of this study was to develop a rapid cross-validation screening tool to evaluate economic evidence when conducting rapid economic literature reviews. Methods: This article outlines our reasoning and the theoretical concepts for developing the screening tool. Results: This cross-validation tool is a qualitative approach under a Bayesian framework that uses prior health economic evidence to gauge the credibility of the rapid economic review's findings. This article describes an application of this tool and highlights practical considerations for its development and deployment. Conclusion: This tool can provide a valuable screening instrument to evaluate the quality and credibility of the economic evidence.