The Role of SGLT2 Inhibitors on Heart Failure Outcomes in Nondiabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure (HF). However, studies examining their benefits exclusively in nondiabetic patients on various HF outcomes are limited. By conducting a MEDLINE and ClinicalTrials.gov search for randomized controlled trials, we identified 4 studies on SGLT2i with data on HF outcomes in nondiabetic patients and performed a meta-analysis. There were 10.638 nondiabetic patients, with 5316 patients in the SGLT2i group and 5322 in the placebo group included in this meta-analysis. The composite of worsening HF (hospitalization for HF or urgent visit for HF) or cardiovascular death had 726 events (13.66%) in the SGLT2i group and 907 (17.04%) in the placebo group, with a hazard ratio (HR) of 0.78 and 95% confidence interval (CI) of 0.71-0.86 ( P < 0.0001). There were 551 events (10.36%) of hospitalization for HF in the SGLT2i group, compared with 751 (14.11%) in the placebo group with an HR of 0.71 (95% CI, 0.62-0.81; P < 0.0001). Cardiovascular death occurred in 396 patients (7.45%) in the SGLT2i group and 452 (8.49%) in the placebo group, with an HR of 0.88 (95% CI, 0.77-1.00; P = 0.059). All-cause mortality occurred in 552 patients (10.38%) in the SGLT2i group and 586 (11.01%) in the placebo group, with an HR of 0.95 (95% CI, 0.84-1.07; P = 0.37). This study showed that in patients with HF without diabetes mellitus, SGLT2i improve HF outcomes, including a significant decrease in hospitalizations for HF and a favorable response for the outcome of cardiovascular death.

The Efficacy and Safety of Sacubitril/Valsartan Compared to Valsartan in Patients with Heart Failure and Mildly Reduced and Preserved Ejection Fractions: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Sacubitril/valsartan improves heart failure (HF) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, randomized controlled trials (RCTs) in patients with heart failure and mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) have shown inconsistent results. We conducted this meta-analysis to comprehensively evaluate the efficacy and safety of sacubitril/valsartan compared to valsartan within this specific patient population. Methods: We searched the MEDLINE database and ClinicalTrials.gov and identified four RCTs that could be included in our analysis, with 3375 patients in the sacubitril/valsartan group and 3362 in the valsartan group. Results: Our study shows that, in patients with HFmrEF and HFpEF, sacubitril/valsartan was superior to valsartan in some of the key HF outcomes, such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), with a small but significant mean difference of 1.13 (95% confidence interval or CI of 0.15 to 2.11, p-value 0.024), an improvement in the New York Heart Association (NYHA) class (odds ratio or OR of 1.32, 95% CI 1.11 to 1.58, p-value 0.002), and the composite outcome of hospitalizations for HF and cardiovascular death, with a relative risk (RR) of 0.86 (95% CI 0.75 to 0.99, p-value 0.04). However, there was no additional benefit with sacubitril/valsartan compared to valsartan for the outcomes of cardiovascular death and all-cause mortality. In terms of side effects, sacubitril/valsartan was associated with a higher risk of hypotension when compared to valsartan (OR 1.67, 95% CI 1.27 to 2.19, p-value < 0.0001), but did not show an increased risk of hyperkalemia or worsening renal function. Conclusions: In individuals with HFmrEF or HFpEF, sacubitril/valsartan can result in improvements in the HF outcomes of the KCCQ CSS, the NYHA class, and the composite outcome of hospitalization for HF and cardiovascular death when compared to valsartan. While there was a higher risk of hypotension with sacubitril/valsartan compared to valsartan, there was no corresponding increase in the risk of hyperkalemia or worsening renal function.

Subclinical Atrial Fibrillation: To Anticoagulate or Not?

Atrial fibrillation (AF) carries a stroke risk, often necessitating anticoagulation, especially in patients with risk factors. With the advent of implantable and wearable heart monitors, episodes of short bouts of atrial arrhythmias called atrial high-rate episodes (AHREs) or subclinical AF (SCAF) are commonly identified. The necessity of anticoagulation in patients with SCAF is unclear. However, recent randomized controlled trials, the NOAH-AFNET 6 and ARTESIA, have offered insights into this matter. Furthermore, a study-level meta-analysis combining data from both these trials has provided more detailed information. Reviewing the information thus far, we can conclude that DOACs can result in a notable reduction in the risk of ischemic stroke and can potentially decrease the risk of debilitating stroke, albeit with an increased risk of major bleeding. Thus, informed, shared decision-making is essential, weighing the potential benefits of stroke prevention against the risk of major bleeding when considering anticoagulation in this patient population.

Efficacy and safety of once-weekly subcutaneous semaglutide on weight loss in patients with overweight or obesity without diabetes mellitus-A systematic review and meta-analysis of randomized controlled trials.

Semaglutide is found to be efficient for weight loss in patients with overweight or obesity with diabetes mellitus (DM). With a wide range of adverse events reported, the efficacy and safety of once-weekly subcutaneous semaglutide in individuals without DM, with overweight or obesity, is unclear. We conducted a comprehensive meta-analysis of randomized studies on once-weekly semaglutide in this patient population. We identified nine studies with 11,641 patients in the semaglutide group and 10,479 in the placebo group. We observed that semaglutide resulted in significant benefits, including change in body weight (%): mean difference (MD) of -11.49% (p < 0.0001), change in absolute body weight: MD of -11.74 kg (p < 0.0001), and change in waist circumference: MD of -9.06 cm (p < 0.0001). Gastrointestinal side effects are predominant including nausea: odds ratio (OR) of 4.06 (p < 0.0001), vomiting: OR of 4.43 (p < 0.0001), diarrhea: OR of 2.10 (p < 0.0001), constipation: OR of 2.43 (p < 0.0001), gallbladder disorders: OR of 1.26 (p = 0.010), and cholelithiasis: OR of 2.06 (p = 0.04). Serious adverse events were not statistically significant: OR of 1.06 (p = 0.82). However, the percentage of participants discontinuing due to adverse events and gastrointestinal side effects was statistically significant: ORs of 2.22 (p < 0.0001) and 3.77 (p < 0.0001), respectively. This study shows that in patients with overweight or obesity without DM, once-weekly subcutaneous semaglutide can significantly decrease body weight without risk of serious adverse events when compared with a placebo. However, gastrointestinal side effects are predominant with semaglutide, which can result in medication discontinuation.

Misleading Procalcitonin in Patients With Staphylococcus aureus Bacteremia: A Report of Two Cases.

Procalcitonin (PCT) is an important biomarker for bacterial infection with a high negative predictive value. It is almost always positive in patients who are bacteremic with pathogenic bacteria. Here, we report two cases of Staphylococcus aureus bacteremia, where PCT levels were unexpectedly negative. This uncommon occurrence challenges the assumption of PCT's infallibility as a diagnostic marker in patients with true bacteremia. The first case is a 55-year-old woman with no past medical issues who presented with one week of generalized weakness and two days of fever and chills. Though her white blood cell (WBC) count and c-reactive protein (CRP) were elevated, PCT was normal, with no apparent source of infection, and hence antibiotic differed. However, her blood cultures returned positive for methicillin-resistant Staphylococcus aureus (MRSA). The patient was started on vancomycin and discharged on daptomycin, she responded appropriately and improved. The second case is an intravenous (IV) drug user, a 40-year-old woman, who presented with septic arthritis and osteomyelitis involving the right hip. She had blood cultures positive for methicillin-susceptible Staphylococcus aureus (MSSA); however, a PCT check on the day of positive blood cultures and various occasions subsequently was normal. These two cases remind us that we cannot over-rely on one test to rule out bacterial infection and should consider the whole clinical picture. They highlight the need for vigilance among clinicians that PCT can rarely be negative in cases of true bacteremia in spite of its high negative predictive value. Physicians and antibiotic stewardship programs should be cautious and aware of this potential pitfall when utilizing PCT as a diagnostic tool.

The Effect of Colchicine on Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Colchicine is a potent anti-inflammatory agent whose benefits have been explored for various conditions, including atrial fibrillation (AF). In this article, we tried to understand why colchicine might be beneficial in AF and reviewed various studies that looked at the effect of colchicine against AF. We followed the PRISMA algorithm and undertook a literature search to identify studies with control groups that looked at the effect of colchicine against AF and conducted a meta-analysis. We identified six studies on post-cardiac surgical patients, three on post-pulmonary vein isolation (PVI)/ablation patients, and two on coronary artery disease. In patients who underwent cardiac surgery, we found that colchicine is beneficial against postoperative atrial fibrillation (POAF) with a relative risk (RR) of 0.70 (95% CI of 0.58 to 0.84) and a p-value of 0.0001. We also found that in patients who underwent PVI/ablation, colchicine is beneficial in decreasing AF recurrence over three months with an RR of 0.57 (95% CI of 0.39 to 0.83) and a p-value of 0.0032 and over 12 months follow-up with an RR of 0.58 (95% CI of 0.42 - 0.80) and a p-value of 0.0008. Our meta-analysis showed that in patients with coronary artery disease, colchicine had no significant benefit in decreasing the incidence of AF with a hazard ratio (HR) of 0.86 (95% CI of 0.69 - 1.06) and a p-value of 0.16. From this study, we conclude that colchicine may be beneficial for decreasing the incidence of AF in post-cardiac surgery patients and post-PVI/ablation patients. It may not decrease the incidence of AF in patients with coronary artery disease.

Atypical Guillain-Barre Syndrome With a Sensory Level and Hyper-Acute Presentation: A Case Report.

A 46-year-old man with a prior history of cervical spondylosis and myelopathy needing cervical spinal surgery three years back presented to the emergency department with acute onset areflexic flaccid weakness of both lower extremities, with a sensory level at T10. Magnetic resonance imaging studies (MRI) of the cervical, thoracic, and lumbar spine ruled out significant cord compression, spinal cord ischemia, spinal shock, or findings to suggest transverse myelitis. CSF analysis showed normal albumin and protein; however, with the features of paraplegia with flaccidity, areflexia, absence of bowel and bladder symptoms, and MRI ruling out other possibilities, a diagnosis of Guillain-Barre syndrome (GBS) was made. The patient was treated with intravenous immunoglobulin (IVIG) and showed a clinical response, with improvement in strength in both lower extremities. This case is rare and unique, as it exhibits atypical features for a GBS case, including a sensory level and hyper-acute presentation, with the onset of weakness to a nadir within an hour. This case highlights the importance of awareness of such atypical GBS presentations so that the diagnosis is not missed and is appropriately managed for favorable patient outcomes.