Effects of the Sodium-Glucose Cotransporter Inhibitors on Cardiovascular Death and All-Cause Mortality: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Clinical Trials.

BACKGROUND: Patients with diabetes mellitus are at an increased risk of cardiovascular morbidity and all-cause mortality. Heart failure and type 2 diabetes often occur concomitantly, and each disease independently increases the risk for the other. OBJECTIVE: Emerging data have revealed that some sodium-glucose cotransporter inhibitors (SGLTi) improve cardiovascular and renal outcomes, particularly in patients with type 2 diabetes. The magnitude of this effect in patients without any underlying condition remains unclear. As a result, we conducted a meta-analysis of the mortality outcomes of available SGLTi in patients with or without cardiovascular diseases, type 2 diabetes, cardiovascular risk factors, and heart failure. METHODS: We performed a systematic review and meta-analysis of randomized, placebo-controlled major cardiovascular outcome trials of SGLTi in patients regardless of their cardiovascular disease or risk status. PubMed, Cochrane, Google Scholar, MEDLINE, and EMBASE were searched for the relevant studies. Three reviewers extracted study data and three reviewers summarized the strength of the evidence. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of all-cause mortality, cardiovascular death, or hospitalization for heart failure. Odds ratios with 95% confidence intervals were pooled across trials to calculate the overall effect size. RESULTS: A total of 5043 all-cause mortality events were observed in the study groups. In 42,050 patients who received SGLTi, 2581 events were reported, and 2462 events were reported in 35,491 patients who received placebo (odds ratio = 0.86, 95% confidence interval 0.80-0.93, p = 0.0003). The use of SGLTi significantly reduced cardiovascular mortality compared with control across the patients' population (odds ratio = 0.86, 95% confidence interval 0.79-0.93, p = 0.0001). There was a consistent pattern of mortality beneficial estimates for all patients with different co-morbid conditions in the SGLTi-treated arm compared with the placebo-treated group. The presence or absence of significant cardiovascular disease risk factors (including a family history of premature coronary artery disease, baseline estimated glomerular filtration rate, dyslipidemia, hypertension, smoking, history of cardiovascular disease, and older age) did not affect the estimated mortality benefits. CONCLUSIONS: Sodium-glucose cotransporter inhibitors significantly reduced major adverse cardiovascular events, including hospitalization and all-cause mortality in patients with or without established atherosclerotic cardiovascular disease. We observed a beneficial trend in patients with heart failure with preserved ejection fraction, and no benefits in patients with stroke or myocardial infarction.

Patients with diabetes are at increased risk of cardiac illness and mortality. Heart failure (HF) and type II diabetes mellitus (DM II) often occur concurrently, and each disease independently increases the risk for the other. Evolving data have revealed that medications utilized for diabetes management, specifically, sodium-glucose cotransporter inhibitors (SGLTi) improve cardiac and renal health, particularly in patients with DM II. The impact of this effect in other patients remains unclear. Therefore, we conducted a comprehensive review of the mortality and other benefits of available SGLTi in patients with or without cardiac diseases, DM II, cardiac risk factors, and HF. A total of 5043 mortality events were observed in the study groups. The use of SGLTi significantly reduced cardiac death compared with placebo. There was a reduction in the number of deaths for patients with different conditions in the SGLTi treated arm compared with the placebo group. The presence or absence of cardiac disease, or risk factors did not affect mortality benefits. SGLTi significantly reduced major adverse cardiac events, including hospitalization and mortality in patients with or without cardiac disease.

The Impact of Anticoagulation on COVID-19 (SARS CoV-2) Patient Outcomes: A Systematic Review.

BACKGROUND: Emerging data suggest that coagulopathy, cytokine storm, and acute respiratory distress syndrome are associated with the 2019 coronavirus disease (COVID-19). The prevalence of hypercoagulable state in these patients is unknown, but appears to be higher compared to those with other critically ill patients. Elevated D-dimer, large blood vessels clots, deep vein thrombosis, pulmonary embolism and disseminated intravascular coagulation have been reported in patients diagnosed with COVID-19 either on admission or during hospitalization and may be predictors of poor outcomes. METHODS: We performed a comprehensive literature review using the search terms of COVID-19; severe acute respiratory syndrome coronavirus-2, coagulopathy, thrombosis and anticoagulation in PubMed, Ovid, google scholar, Medline and EMBASE databases from December 2019 to May 30, 2020. RESULTS: A total of 64 relevant studies were reviewed; of which, 4 studies met the inclusion criteria and were included for analysis. The majority of the studies were retrospective involving 525 critically ill COVID-19 patients. The most commonly studied anticoagulant administered was low molecular weight heparins. Anticoagulation dosing varied throughout the studies and may be classified as standard venous thromboembolism prophylaxis, intermediate dosing, or full dose anticoagulation. The most studied objective was improvement in coagulopathy. Significant reduction in D-dimer, improvement in coagulopathy markers such as Interlukin-6, fibrinogen degradation product level, as well as lymphocyte count were reported. CONCLUSION: Despite the limited quality of studies analyzed, prophylaxis and higher intensity dosed anticoagulation is associated with improved pulmonary oxygenation, decreased coagulopathy markers and decreased mortality in COVID-19 patients.

Impact of intravenous acetaminophen on reducing opioid use after hysterectomy.

STUDY OBJECTIVE: To examine the impact of intravenous acetaminophen on the total quantity of opioids (in morphine equivalents) administered within the first 48 hours postoperatively and perioperatively, while still affording patients adequate analgesia, in women who underwent total abdominal hysterectomies. DESIGN: Retrospective chart review. SETTING: Tertiary care community hospital. PATIENTS: One hundred women underwent total abdominal hysterectomies performed by a single surgeon: 50 patients received opioids only (fentanyl, morphine, hydromorphone, meperidine, or oxycodone), without the addition of any acetaminophen, between January 1 and March 28, 2011, and 50 patients received intravenous acetaminophen 1000 mg every 6 hours in addition to opioids (multimodal group) between May 1 and July 16, 2012 (time period coincided with the addition of intravenous acetaminophen to the hospital formulary). Patients in both groups were also given nonopioids (celecoxib, dexmedetomidine, aspirin, or tizanidine) perioperatively. MEASUREMENTS AND MAIN RESULTS: Patients in both groups had a mean age of 55 years (mean±SD 55±13 yrs in the multimodal group, 55±15 yrs in the opioids-only group), surgery time of ~2 hours (116±51 min in the multimodal group, 118±40 min in the opioids-only group), and an anesthesia time of ~3.5 hours (209±79 min in the multimodal group, 207±79 min in the opioids-only group). During postoperative days 1-2, intravenous acetaminophen reduced opioid use by 31% (mean±SD 47±24 mg in the multimodal group vs 68±37 mg in the opioids-only group, p=0.003) and by 26% during the total perioperative period, defined as preoperative, intraoperative, recovery room, and postoperative days 1-2 (73±24 mg in the multimodal group vs 99±39 mg in the opioids-only group, p=0.001). CONCLUSION: The multimodal approach to perioperative analgesic management, which includes concurrent administration of intravenous acetaminophen and opioids, is effective in reducing the total average amount of opioids administered on postoperative days 1-2 and perioperatively. Limitations of this study include its short duration, retrospective design, and single-site setting. These results may not be generalized to patients undergoing other types of obstetric-gynecologic surgeries.

Detoxification from high-dose zolpidem using diazepam.

OBJECTIVE: To report a rare case of physical and psychological addiction to an excessive dose of zolpidem and subsequent completed detoxification using diazepam. CASE SUMMARY: A 46-year-old white man with a history of polysubstance abuse received a prescription for zolpidem 2 years prior to his hospital detoxification. During that time, he gradually escalated the total dosage to an amount of 400 mg/day in divided doses. Upon hospitalization, he was detoxified using a standard benzodiazepine 7-day diazepam tapering regimen. DISCUSSION: Zolpidem is a nonbenzodiazepine medication approved for the short-term treatment of insomnia. Its mechanism is a selective benzodiazepine type 1 receptor agonist. The selectivity of the drug for the type 1 receptor may not be absolute and is inversely dose dependent. Compared with the benzodiazepines, zolpidem addiction is rare. However, at higher than recommended doses for extended periods of time, its addictive potential may be similar to that of the benzodiazepines. CONCLUSIONS: Given the similarities in receptor binding and pharmacologic activities of zolpidem and the benzodiazepines, we chose to use a standard benzodiazepine detoxification protocol to treat zolpidem withdrawal. Confirmation of this has been evidenced by successful zolpidem detoxification using a standard 7-day benzodiazepine/diazepam taper regimen.