Background The comparative effectiveness of sulfonylureas and metformin on cardiovascular disease (CVD) outcomes in type 2 diabetes are not well characterized. Objective To compare the effectiveness of sulfonylureas and metformin on the outcome of CVD (acute myocardial infarction, stroke) or death Design Retrospective cohort study Setting National Veterans Health Administration (VHA) databases linked to Medicare files Patients Veterans who initiated metformin or sulfonylureas for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. Measurements Composite outcome of hospitalizations for acute myocardial infarction, stroke, or death. Cox regression analyses compared the incidence of the composite outcome between groups, adjusting for baseline demographics, medications, cholesterol, glycated hemoglobin, creatinine, blood pressure, body mass index, healthcare utilization and co-morbidities. Results Among 253,690 patients (98,665 sulfonylurea and 155,025 metformin initiators) the crude outcome rates were 18.2 and 10.4 per 1000 person-years in sulfonylurea and metformin users, respectively (adjusted hazard ratio [aHR] 1.21, 95% Confidence Intervals [CI] 1.13, 1.30). Results were consistent for both glyburide (aHR 1.26, 95% CI 1.16, 1.37) and glipizide (aHR 1.15, 95% CI 1.06, 1.26) as well as for those with prior history of CVD (aHR 1.25, 95% CI 1.13, 1.55) and without history of CVD (aHR: 1.16, 95% CI: 1.06, 1.29). Results were also consistent in a propensity score-matched analysis. For patients initiating sulfonylureas rather than metformin, we estimated an excess of 1 and 4 CVD events per 1000 person-years for those without and with a CVD history, respectively. Limitations Data on women and minorities is limited but reflective of the VHA population. Conclusions Use of sulfonylureas compared to metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death.

Objective To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. Design Observational cohort study. Setting Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. Participants All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. Main outcome measures The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. Results Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. Conclusions Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

The time course of cardiovascular disease (CVD) risk after smoking cessation is unclear. Risk calculators consider former smokers to be at risk for only 5 years. OBJECTIVE To evaluate the association between years since quitting smoking and incident CVD. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of prospectively collected data from Framingham Heart Study participants without baseline CVD (original cohort: attending their fourth examination in 1954-1958; offspring cohort: attending their first examination in 1971-1975) who were followed up through December 2015. EXPOSURES Time-updated self-reported smoking status, years since quitting, and cumulative pack-years. MAIN OUTCOMES AND MEASURES Incident CVD (myocardial infarction, stroke, heart failure, or cardiovascular death). Primary analyses included both cohorts (pooled) and were restricted to heavy ever smokers (Ն20 pack-years). RESULTS The study population included 8770 individuals (original cohort: n = 3805; offspring cohort: n = 4965) with a mean age of 42.2 (SD, 11.8) years and 45% male. There were 5308 ever smokers with a median 17.2 (interquartile range, 7-30) baseline pack-years, including 2371 heavy ever smokers (406 [17%] former and 1965 [83%] current). Over 26.4 median follow-up years, 2435 first CVD events occurred (original cohort: n = 1612 [n = 665 among heavy smokers]; offspring cohort: n = 823 [n = 430 among heavy smokers]). In the pooled cohort, compared with current smoking, quitting within 5 years was associated with significantly lower rates of incident CVD (incidence rates per 1000 person-years: current smoking, 11.56 [95% CI, 10.30-12.98]; quitting within 5 years, 6.94 [95% CI, 5.61-8.59]; difference, −4.51 [95% CI, −5.90 to −2.77]) and lower risk of incident CVD (hazard ratio, 0.61; 95% CI, 0.49-0.76). Compared with never smoking, quitting smoking ceased to be significantly associated with greater CVD risk between 10 and 15 years after cessation in the pooled cohort (incidence rates per 1000 person-years: never smoking, 5.09 [95% CI, 4.52-5.74]; quitting within 10 to <15 years, 6.31 [95% CI, 4.93-8.09]; difference, 1.27 [95% CI, −0.10 to 3.05]; hazard ratio, 1.25 [95% CI, 0.98-1.60]). CONCLUSIONS AND RELEVANCE Among heavy smokers, smoking cessation was associated with significantly lower risk of CVD within 5 years relative to current smokers. However, relative to never smokers, former smokers' CVD risk remained significantly elevated beyond 5 years after smoking cessation.