Dipeptidyl peptidase-4 inhibitors and cardiovascular events in patients with type 2 diabetes, without cardiovascular or renal disease.

BackgroundCardiovascular safety of dipeptidyl peptidase-IV inhibitors (DPP-4i) in patients without cardiovascular or renal disease, a majority of newly diagnosed patients with type 2 diabetes often excluded from clinical trials on this association, is poorly understood. Thus, we investigate the risk of major adverse cardiovascular events (MACE) associated with DPP-4i in low-risk patients with diabetes.MethodsUsing a new-user retrospective cohort derived from IBM MarketScan Commercial Claims and Encounters (2010-2015), we identified patients aged 35-65 with type 2 diabetes, without cardiovascular or renal disease, initiating DPP-4i, sulfonylureas, or metformin. Primary composite outcome of time to first MACE was defined as the first of any of the following: myocardial infarction, cardiac arrest, coronary artery bypass graft, coronary angioplasty, heart failure, and stroke. Secondary outcomes were time to first heart failure, acute myocardial infarction, and stroke. We compared outcomes for DPP-4i versus sulfonylurea and DPP-4i versus metformin using propensity score weighted Cox proportional hazards, adjusting for demographics, baseline comorbidities, concomitant medications, and cumulative exposure.ResultsOf 445,701 individuals, 236,431 (53.0%) were male, median age was 51 (interquartile range: [44, 57]), 30,267 (6.79%) initiated DPP-4i, 52,138 (11.70%) initiated sulfonylureas, and 367,908 (82.55%) initiated metformin. After adjustment, DPP-4i was associated with lower risk of MACE than sulfonylurea (adjusted hazard ratio (aHR) = 0.87; 95% confidence interval (CI): 0.78-0.98), and similar risk to metformin (aHR = 1.07; 95% CI: 0.97-1.18). Risk for acute myocardial infarction (aHR = 0.70; 95% CI: 0.51-0.96), stroke (aHR = 0.57; 95% CI: 0.41-0.79), and heart failure (aHR = 0.57; 95% CI: 0.41-0.79) with DPP-4i was lower compared to sulfonylureas.ConclusionOur findings show that for this cohort of low-risk patients newly treated for type 2 diabetes, DPP-4i exhibited 13% lower risk for MACE compared to sulfonylureas and similar risk for MACE compared to metformin, suggesting DPP-4i is a low cardiovascular risk option for low-risk patients initiating antihyperglycemic treatment

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial

BackgroundCoronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.MethodsWe evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm.ResultsAmong 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16).ConclusionsIn this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14.Clinical trials registrationNCT04373460

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial

BackgroundCoronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.MethodsWe evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm.ResultsAmong 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16).ConclusionsIn this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14.Clinical trials registrationNCT04373460

Symptom Duration and Resolution With Early Outpatient Treatment of Convalescent Plasma for Coronavirus Disease 2019: A Randomized Trial

Background Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients. Methods We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm. Results Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving control plasma were still symptomatic (P = .78) at day 14. Associations between CCP and symptom resolution by day 14 did not differ significantly from those in controls after adjustment for baseline characteristics (adjusted subdistribution hazard ratio, 0.99; P = .62). The most common cluster consisted of cough, fatigue, shortness of breath, and headache and was found in 308 (57.2%) and 325 (61.1%) of CCP and control plasma recipients, respectively (P = .16). Conclusions In this trial of outpatients with early COVID-19, CCP was not associated with faster resolution of symptoms compared with control. Overall, there were no differences by treatment in the prevalence of each symptom or symptom clusters at day 14. Early treatment with coronavirus disease 2019 convalescent plasma was not associated with faster symptom resolution than control treatment, in contrast with decreased hospitalization in the same population, suggesting that the timing antibody treatment may affect hospitalization and symptom progression differently

Search strategy in detail.

(PDF)</p

Posterior predictive check of primary outcomes by study.

Shown are observed outcome data (first row) and draws for the posterior predictive distribution (subsequent rows) of the ordinal outcome scale at day 28–35, plotted against the expected linear predictor for each individual. Each column corresponds to one study in our analysis. Data points have been jittered for clarity. (PDF)</p

Subgroup analysis of differences in ordinal scale at days 28–35.

Estimated proportional odds ratios comparing day 28–35 ordinal scale in HCQ/CQ versus control groups. Estimates are given for the pooled patient population and for subgroups. Blue circles represent model-standardized estimates; blue horizontal lines represent 95% credible intervals. Open grey circles represent plug-in estimates; grey horizontal lines represent 95% confidence intervals. Grey circle size represents the number of patients in the corresponding subgroup. Arrows indicate uncertainty intervals extending beyond plot limits. Study acronyms are explained in Fig 1. Two trials did not have study acronyms (only trial registration numbers). Abbreviations: 95% CrI, 95% credible intervals; HCQ/CQ, hydroxychloroquine or chloroquine; NA, not applicable; NIV, noninvasive ventilation (includes BiPAP/CPAP and/or high-flow oxygen); OR, odds ratio.</p

Primary, secondary, and safety outcomes, overall and by trial.

Primary, secondary, and safety outcomes, overall and by trial.</p