Background: The ISCHEMIA trial postulated that patients with stable coronary artery disease (CAD) and moderate or severe ischemia would benefit from revascularization. We investigated the relationship between severity of CAD and that of ischemia and trial outcomes, overall and by management strategy. Methods: 5,179 patients with moderate or severe ischemia were randomized to an initial invasive or conservative management strategy. Blinded, core-laboratory-interpreted coronary CT angiography (CCTA) was used to assess anatomic eligibility for randomization. Extent and severity of CAD were classified using the modified Duke Prognostic Index (n=2,475, 48%). Ischemia severity was interpreted by independent core laboratories (nuclear, echocardiography, magnetic resonance imaging, exercise tolerance testing, n=5,105, 99%). We compared 4-year event rates across subgroups defined by severity of ischemia and CAD. The primary endpoint for this analysis was all-cause mortality. Secondary endpoints were myocardial infarction (MI), cardiovascular (CV) death or MI, and the trial primary endpoint (CV death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). Results: Relative to mild/no ischemia, neither moderate nor severe ischemia was associated with increased mortality (moderate ischemia hazard ratio (HR) 0.89, 95% confidence interval [CI] 0.61- 1.30, severe ischemia HR 0.83, 95% CI 0.57-1.21, p=0.33). Nonfatal MI rates increased with worsening ischemia severity (HR for moderate ischemia 1.20 (95% CI 0.86-1.69) vs. mild/no ischemia; HR for severe ischemia 1.37, 95% CI 0.98-1.91, p=0.04 for trend, p=NS after adjustment for CAD). Increasing CAD severity was associated with death (HR 2.27, 95% CI 1.37-3.75) and MI (HR 1.69, 95% CI 1.17-2.45) for the most vs. least severe CAD subgroup. Ischemia severity did not identify a subgroup with treatment benefit on mortality, MI, the trial primary endpoint, or CV death or MI. In the most severe CAD subgroup (n=659), the 4-year rate of CV death or MI was lower in the invasive strategy group (difference 6.3%, 95% CI 0.2%-12.4%), but 4-year all-cause mortality was similar. Conclusions: Ischemia severity was not associated with increased risk after adjustment for CAD severity. More severe CAD was associated with increased risk. Invasive management did not lower all-cause mortality at 4 years in any ischemia or CAD subgroup. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01471522
ImportanceRecent national guidelines recommend sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD); yet, there are limited data on the use of these agents in contemporary community practice.ObjectiveTo evaluate the use of SGLT2i and GLP-1 RA in adults with T2D and ASCVD across a diverse sample of health care systems in the US.Design, Setting, and ParticipantsThis multicenter, retrospective cohort study used electronic health record data from 88 US health care systems participating in Cerner Real World Data between January 2018 to March 2021. Adults with ASCVD and T2D taking at least 1 glucose-lowering medication, had end-stage kidney disease, or had stage 5 chronic kidney disease were excluded.Main Outcomes and MeasuresTreatment with SGLT2i or GLP-1 RA.ResultsA total of 321 304 patients were identified with T2D and ASCVD ASCVD (130 280 female [40.5%]; median [IQR] age, 70.9 [62.9-78.0] years) who were potentially eligible for SGLT2i and/or GLP-1 RA, including 37 754 Black individuals (11.8%), 51 522 Hispanic individuals (16.0%), and 256 008 White individuals (11.8%). From January 2018 to March 2021, the use of SGLT2i increased from 5.8% (11 285 of 194 264) to 12.9% (11 058 of 85 956), GLP-1 RA increased from 6.9% (13 402 of 194 264) to 13.8% (11 901 of 85 956), and use of either agent increased from 11.4% (22 069 of 194 264) to 23.2% (19 909 of 85 956). Those taking an SGLT2i or GLP-1 RA were younger, less frequently hospitalized in the year prior, and more likely to be taking additional secondary prevention medications. Treated and nontreated populations were similar in terms of race, ethnicity, and outpatient health care utilization. Sulfonylureas and dipeptidyl peptidase 4 inhibitors remained more commonly used than SGLT2i or GLP-1 RA through 2021.Conclusions and RelevanceIn this study, uptake of SGLT2i and GLP-1 RA in adults with T2D and ASCVD increased modestly after guideline recommendations, although less than a quarter of persons with ASCVD and T2D receiving medical therapy were taking either. Further efforts are necessary to maximize the potential population benefit of these therapies in this high-risk population.
BACKGROUND: Unanticipated respiratory compromise that lead to unplanned intubations is a known phenomenon in hospitalized patients. Most events occur in patients at high risk in wellmonitored units; less is known about the incidence, risk factors, and trajectory of patients thought at low risk on lightly monitored general care wards. The aims of our study were to quantify demographic and clinical characteristics associated with unplanned intubations on general care floors and to analyze the medications administered, monitoring strategies, and vitalsign trajectories before the event. METHODS: We performed a multicenter retrospective cohort study of hospitalized subjects on the general floor who had unanticipated, unplanned intubations on general care floors from August 2014 to February 2018. RESULTS: We identified 448 unplanned intubations. The incidence rate was 0.420 per 1,000 bed-days (95% CI 0.374-0.470) in the academic hospital and was 0.430 (95% CI 0.352-0.520) and 0.394 per 1,000 bed-days (95% CI 0.301-0.506) at our community hospitals. Extrapolating these rates to total hospital admissions in the United States, we estimate 64,000 events annually. The mortality rate was 49.1%. Within 12 h preceding the event, 35.3% of the subjects received opiates. All received vital-sign assessments. Most were monitored with pulse oximetry. In contrast, 2.5% were on cardiac telemetry, and only 4 subjects used capnography; 53.7% showed significant vital-sign changes in the 24 h before the event. However, 46.3% had no significant change in any vital signs. CONCLUSIONS: Our study showed unanticipated respiratory compromise that required an unplanned intubation of subjects on the general care floor, although not common, carried a high mortality. Besides pulse oximetry and routine vital-sign assessments, very little monitoring was in use. A significant portion of the subjects had no vital-sign abnormalities leading up to the event. Further research is needed to determine the phenotype of the different etiologies of unexpected acute respiratory failure to identify better risk stratification and monitoring strategies.
Background: Understanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies. Methods: Data from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20–39 years [median, 30 years] of age), early midlife (FOS, 40–59 years [median, 43] years of age), and late midlife (ARIC, 45–59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI). Results: Among 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08–3.27], 2.09 [95% CI, 1.83–2.40], and 2.11 [95% CI, 1.96–2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70–2.30], 1.64 [95% CI, 1.47–1.84], and 1.22 [95% CI, 1.15–1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70–0.78], 0.70 [95% CI, 0.67–0.72], and 0.72 [95% CI, 0.70–0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69–0.78], 0.66 [95% CI, 0.62–0.69], and 0.66 [95% CI, 0.64–0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001–0.05), 0.02 (95% CI, −0.002 to 0.037), and 0.002 (95% CI, −0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively. Conclusions: Despite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.
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