Sulfonylureas and the Risk of Ventricular Arrhythmias Among People with Type 2 Diabetes: A Systematic Review of Observational Studies.

Previous studies have suggested an association between sulfonylureas and an increased risk of cardiovascular death among patients with type 2 diabetes. A potential mechanism involves sulfonylurea-induced ventricular arrhythmias (VAs). We conducted a systematic review of observational studies to determine whether the use of sulfonylureas, compared with the use of other antihyperglycemic drugs, is associated with the risk of VA (ventricular tachycardia, ventricular fibrillation, and premature ventricular complexes), cardiac arrest, and sudden cardiac death among patients with type 2 diabetes. Two independent reviewers searched MEDLINE, EMBASE, CINAHL Plus, CENTRAL, and ClinicalTrials.gov from inception to July 2021 for observational studies comparing sulfonylureas vs. other antihyperglycemic therapies or intraclass comparisons of sulfonylureas. Our systematic review included 17 studies (1,607,612 patients). Per Risk Of Bias In Non-randomized Studies of Interventions (ROBINS)-I, there were few high-quality studies (2 studies at moderate risk of bias; 4 at serious risk; and 11 at critical risk). All studies at a moderate or serious risk of bias reporting comparisons with other therapies were consistent with an increased risk of VA. Sulfonylureas were associated with a higher risk of arrhythmia vs. dipeptidyl peptidase-4 inhibitors (adjusted hazard ratio (aHR): 1.52, 95% confidence interval (CI): 1.27-1.80) and of VA vs. metformin (aHR: 1.52, 95% CI: 1.10-2.13). One moderate quality study reported inconsistent results for a composite of cardiac arrest/VA in analyses of US Medicaid claims and Optum claims data. Our systematic review suggests that, among higher-quality observational studies, sulfonylureas are associated with an increased risk of VA. However, we identified few methodologically rigorous studies, underscoring the need for additional real-world studies.

Cardiovascular Disease-Related Morbidity and Mortality in Women With a History of Pregnancy Complications.

BACKGROUND: Women with a history of certain pregnancy complications are at higher risk for cardiovascular (CVD) disease. However, most clinical guidelines only recommend postpartum follow-up of those with a history of preeclampsia, gestational diabetes mellitus, or preterm birth. This systematic review was undertaken to determine if there is an association between a broader array of pregnancy complications and the future risk of CVD. METHODS: We systematically searched PubMed, MEDLINE and EMBASE (via Ovid), CINAHL, and the Cochrane Library from inception to September 22, 2017, for observational studies of the association between the hypertensive disorders of pregnancy, placental abruption, preterm birth, gestational diabetes mellitus, low birth weight, small-for-gestational-age birth, stillbirth, and miscarriage and subsequent CVD. Likelihood ratio meta-analyses were performed to generate pooled odds ratios (OR) and 95% intrinsic confidence intervals (ICI). RESULTS: Our systematic review included 84 studies (28 993 438 patients). Sample sizes varied from 250 to 2 000 000, with a median follow-up of 7.5 years postpartum. The risk of CVD was highest in women with gestational hypertension (OR 1.7; 95% ICI, 1.3-2.2), preeclampsia (OR 2.7; 95% ICI, 2.5-3.0), placental abruption (OR 1.8; 95% ICI, 1.4-2.3), preterm birth (OR 1.6; 95% ICI, 1.4-1.9), gestational diabetes mellitus (OR 1.7; 95% ICI, 1.1-2.5), and stillbirth (OR 1.5; 95% ICI, 1.1-2.1). A consistent trend was seen for low birth weight and small-for-gestational-age birth weight but not for miscarriage. CONCLUSIONS: Women with a broader array of pregnancy complications, including placental abruption and stillbirth, are at increased risk of future CVD. The findings support the need for assessment and risk factor management beyond the postpartum period.

Global, Regional, and Country-Specific Lifetime Risks of Stroke, 1990 and 2016.

BACKGROUND: The lifetime risk of stroke has been calculated in a limited number of selected populations. We sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. METHODS: We used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. Estimates of the lifetime risks in the years 1990 and 2016 were compared. Countries were categorized into quintiles of the sociodemographic index (SDI) used in the GBD Study, and the risks were compared across quintiles. Comparisons were made with the use of point estimates and uncertainty intervals representing the 2.5th and 97.5th percentiles around the estimate. RESULTS: The estimated global lifetime risk of stroke from the age of 25 years onward was 24.9% (95% uncertainty interval, 23.5 to 26.2); the risk among men was 24.7% (95% uncertainty interval, 23.3 to 26.0), and the risk among women was 25.1% (95% uncertainty interval, 23.7 to 26.5). The risk of ischemic stroke was 18.3%, and the risk of hemorrhagic stroke was 8.2%. In high-SDI, high-middle-SDI, and low-SDI countries, the estimated lifetime risk of stroke was 23.5%, 31.1% (highest risk), and 13.2% (lowest risk), respectively; the 95% uncertainty intervals did not overlap between these categories. The highest estimated lifetime risks of stroke according to GBD region were in East Asia (38.8%), Central Europe (31.7%), and Eastern Europe (31.6%), and the lowest risk was in eastern sub-Saharan Africa (11.8%). The mean global lifetime risk of stroke increased from 22.8% in 1990 to 24.9% in 2016, a relative increase of 8.9% (95% uncertainty interval, 6.2 to 11.5); the competing risk of death from any cause other than stroke was considered in this calculation. CONCLUSIONS: In 2016, the global lifetime risk of stroke from the age of 25 years onward was approximately 25% among both men and women. There was geographic variation in the lifetime risk of stroke, with the highest risks in East Asia, Central Europe, and Eastern Europe. (Funded by the Bill and Melinda Gates Foundation.).