Pharmacokinetic and Pharmacodynamic Interactions between Food or Herbal Products and Oral Anticoagulants: Evidence Review, Practical Recommendations, and Knowledge Gaps.

Interactions between food and oral anticoagulants (OACs), particularly vitamin K antagonists such as warfarin, are widely recognized and may also be clinically relevant for direct OACs. Pharmacokinetic and pharmacodynamic interactions with food or herbs can lead to anticoagulation potentiation, increased risk of bleeding, or reduced drug efficacy, all compromising patient safety. We conducted a systematic search for randomized controlled trials (RCTs) on PubMed for assessments of interactions between OACs and various ingestants. Since the RCT evidence was slim, we also reviewed prospective longitudinal studies, case series, and case reports to identify possible associations between foods and anticoagulation therapy. We referred to basic or translational studies that shared putative explanations for such interactions, but we failed to identify high-quality evidence in most cases. The limited evidence, small sample size of the studies, conflicting results, and possible heterogeneity in the contents of herbal products prevent a conclusive assessment of these interactions. Existing evidence suggests that (1) cranberry juice consumption (up to 240 mL/d and probably even more) with warfarin is safe; (2) use of green leafy vegetables with a high daily content (more than 250 µg) of vitamin K should be cautioned for patients receiving warfarin, because it may decrease warfarin efficacy. It is also advisable for patients to maintain highly constant intake of green leafy vegetables to ensure stable warfarin effectiveness; (3) ginger, even in small quantities (excluding commercial ginger-flavored beverages, which contain only negligible amounts of ginger), and mango (more than one fruit) can both potentiate warfarin effects; (4) patients taking OACs should avoid St. John's wort due to diminished anticoagulant effect; and (5) consumption of less than 240 mL of grapefruit juice daily is unlikely to interact with OACs. Future longitudinal observational cohort studies and RCTs with larger sample sizes are needed to study specific interactions between food or herbal products and OACs.

Ivabradine Approved and Other Uses in Clinical Practice: A Systematic Review.

ABSTRACT: Heart rate (HR) stands as a prognostic indicator of cardiovascular disease and a modifiable risk factor in heart failure (HF). Medication intolerance can curtail the application of conventional HR-lowering ß-blockers to the optimum target dose. Ivabradine (IVA), a specific negative-chronotropic agent, selectively inhibits I f current in pacemaker cells of the sinoatrial node without depressing myocardial contractility or comprising hemodynamics. This review summarized ivabradine's clinical labeled and off-label uses and mechanism of action focusing on the clinical outcomes. PubMed was searched up to January 2024 using the main keywords of IVA, coronary artery disease (CAD), HF, postural tachycardia syndrome (POTS), and tachyarrhythmia. To comprehensively review IVA's clinical indications, mechanisms, and therapeutic effects, all studies investigating treatment with IVA in humans were included, comprising different types of studies such as randomized controlled trials and longitudinal prospective observational studies. After screening, 141 studies were included in our review. A large number of reviewed articles were allocated to heart failure with reduced ejection fraction and CAD, suggesting IVA as an alternative to ß-blockers in case of contraindications or intolerance. The beneficial effects of IVA as premedication for coronary computed tomography angiography, HR lowering in POTS, and inappropriate sinus tachycardia constituted most studies among off-label uses. The promising results have been reported on the efficacy of IVA in controlling HR, especially in patients with inappropriate sinus tachycardia or POTS. Owing to the unique mechanism of action, IVA has the potential to be used more frequently in future clinical practice.

Diagnostic accuracy of 3-item stroke scale for detection of cerebral large vessel occlusion: A systematic review and meta-analysis.

BACKGROUND: Prompt identification of large vessel occlusion (LVO) in acute ischemic stroke (AIS) is crucial for expedited endovascular therapy (EVT) and improved patient outcomes. Prehospital stroke scales, such as the 3-Item Stroke Scale (3I-SS), could be beneficial in detecting LVO in suspected patients. This meta-analysis evaluates the diagnostic accuracy of 3I-SS for LVO detection in AIS. METHODS: A systematic search was conducted in Medline, Embase, Scopus, and Web of Science databases until February 2024 with no time and language restrictions. Prehospital and in-hospital studies reporting diagnostic accuracy were included. Review articles, studies without reported 3I-SS cut-offs, and studies lacking the required data were excluded. Pooled effect sizes, including area under the curve (AUC), sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and NLR) with 95% confidence intervals (CI) were calculated. RESULTS: Twenty-two studies were included in the present meta-analysis. A 3I-SS score of 2 or higher demonstrated sensitivity of 76% (95% CI: 52%-90%) and specificity of 74% (95% CI: 57%-86%) as the optimal cut-off, with an AUC of 0.81 (95% CI: 0.78-0.84). DOR, PLR, and NLR, were 9 (95% CI: 5-15), 2.9 (95% CI: 2.0-4.3) and 0.32 (95% CI: 0.17-0.61), respectively. Sensitivity analysis confirmed the analyses' robustness in suspected to stroke patients, anterior circulation LVO, assessment by paramedics, and pre-hospital settings. Meta-regression analyses pinpointed LVO definition (anterior circulation, posterior circulation) and patient setting (suspected stroke, confirmed stroke) as potential sources of heterogeneity. CONCLUSION: 3I-SS demonstrates good diagnostic accuracy in identifying LVO stroke and may be valuable in the prompt identification of patients for direct transfer to comprehensive stroke centers.

Comparative analysis of treatment options for chronic heart failure and depression: a systematic review and Bayesian network meta-analysis.

Different interventions have been evaluated for the treatment of depression in heart failure (HF) patients. However, clear and established recommendations are lacking. PubMed, Scopus, and Web of Science databases were systematically searched for randomized controlled trials (RCT) evaluating the effect of various treatment options on depression scores in heart failure patients. The primary outcome was a change in depression scores presented as standardized mean difference (SMD). A Bayesian network for meta-analysis was constructed. Twenty-five RCTs were included, randomizing 6014 patients with confirmed heart failure and depression between 2003 and 2022. Compared to treatment as usual (TAU), only cognitive behavioral therapy (CBT) (SMD - 0.60, CI95% [- 1.0, - 0.17]) leads to a significant reduction in depression scores. Other interventions did not improve depression scores significantly. Our results show that for patients with HF and depression, CBT can significantly improve measures of depression, being the most efficacious treatment.