Current Vascular Pharmacology - Volume 23, Issue 6, 2025

Current guidelines and consensus statements advise caution in using direct oral anticoagulants (DOACs) for morbidly obese patients with body mass index (BMI) >40 kg/m², indicating warfarin as the most studied treatment.

We systematically searched databases from their inception to January 4, 2024, to identify studies that evaluated the effectiveness and safety of DOACs compared to warfarin in patients with BMI >40 kg/m² and atrial fibrillation (AF) or venous thromboembolism (VTE). The outcomes of all-cause mortality, major and minor bleeding, stroke/systematic embolism (SE), VTE, and their composite endpoint were analyzed using a random-effects model.

This meta-analysis included 24 studies and 119,960 morbidly obese patients with AF or VTE on oral anticoagulation therapy: 51,363 on DOACs (43%) vs. (57%) 68,597 on warfarin. DOAC use was significantly associated with lower all-cause mortality and major bleeding risk compared to warfarin. Although the risk of composite endpoint, stroke/SE, and VTE was lower in the DOAC group, no statistically significant difference was observed, indicating no superiority of warfarin compared to DOAC use. The risk of minor bleeding events, hemorrhagic stroke, and ischemic stroke was lower in the DOAC compared to the warfarin group. The same trend favoring DOACs over warfarin in all assessed endpoints was observed in the subgroup analysis based on anticoagulation indication (AF or VTE).

Our findings have documented a potentially more effective and safer profile of DOACs compared to warfarin in morbidly obese patients regardless of the indication for anticoagulation.

To describe clinical factors predictive of warfarin response in atrial fibrillation (AF) patients and to evaluate its association with adverse outcomes.

Patients in the Middle Eastern JoFib study, a prospective, multicenter registry of AF patients, using warfarin with at least one international normalized ratio (INR) reading, were enrolled. We used the most recent INR as a measure of warfarin control.

Out of the total 2020 patients, 544 (26.9%) were using warfarin. Multivariable logistic regression analysis demonstrated that heart failure (adjusted OR 0.55, 95%CI 0.36-0.86) and increasing HAS-BLED score (adjusted OR 0.73, 95%CI 0.58-0.92) decreased the odds of having a therapeutic INR. Chronic kidney disease (adjusted OR 3.11, 95%CI 1.46-6.62), heart failure (adjusted OR 2.37, 95%CI 1.4-4.01), and cancer (adjusted OR 2.48, 95%CI 1.03-6.01) were independently predictive of having INR less than 2.0. The first episode of AF was independently predictive of having INR above 3.0 (adjusted OR 2.48, 95%CI 1.39-4.42). Multivariable Cox regression analysis demonstrated that INR below the therapeutic range (aHR 4.36, 95%CI 2.19-8.68) and INR above the therapeutic range (aHR 3.03, 95%CI 1.33-6.92) were predictive of all-cause mortality. Below-range INR also predicted cardiovascular mortality (aHR 3.69, 95%CI 1.66-8.16).

Clinical factors predictive of sub-optimal INR in Middle Eastern AF patients using warfarin include chronic kidney disease, heart failure, cancer, high HAS-BLED score, and first episode of AF. Furthermore, sub-optimal INR is predictive of all-cause and cardiovascular mortality.

Complex coronary lesions have been an understudied aspect of coronary artery disease in elderly patients. Oxidative stress and inflammation may be implicated in the pathogenesis of complex coronary lesions.

The aim of this study is to investigate the complex interplay between pro-oxidative stress response, pro-inflammatory response, and complex coronary lesions in elderly patients.

Enzyme-linked immunosorbent assays for the detection of serum biomarkers [reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), superoxide dismutase (SOD) activity, total antioxidant capacity (TAC), transforming growth factor beta (TGF-β) and interleukin-4 (IL-4)] were performed in elderly patients with complex coronary lesions.

The levels of pro-oxidative stress and pro-inflammatory markers (ROS, MDA, TNF-α and IFN-γ) were increased in the complex coronary lesion group when compared with the non-complex coronary lesion group (P < 0.01) in elderly patients. Anti-oxidative stress and anti-inflammatory markers (SOD activity, TAC, TGF-β, and IL-4) were decreased in the complex coronary lesion group when compared with the non-complex coronary lesion group (P < 0.01) in elderly patients.

Our findings suggest that the pathogenesis of complex coronary lesions may involve pro-oxidant/anti-oxidant and pro-inflammation/anti-inflammation imbalance, as well as the interplay between oxidative stress and inflammation in elderly patients.

Diabetic nephropathy, a major contributor to chronic kidney disease, is closely associated with inflammatory responses.

This study aimed to evaluate the effectiveness of combination therapy with dapagliflozin and telmisartan in treating diabetic nephropathy and its effect on patient’s albuminuria levels.

We conducted a 12-week prospective observational study to assess diabetic nephropathy. Patients with diabetic nephropathy were treated with either dapagliflozin and telmisartan (n=92) or telmisartan alone (n=92). Measurements of waist-to-hip ratio, fasting blood glucose, hemoglobin A1c (HbA1c), blood pressure, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), uric acid, blood urea nitrogen, lipid profile, and inflammatory biomarkers, including C-C motif chemokine ligand 21 messenger RNA (CCL21 mRNA) and monocyte chemoattractant protein-1 (MCP-1), were obtained at baseline and following 12-weeks of treatment.

Dapagliflozin and telmisartan combination therapy demonstrated a significant decrease in UACR compared with baseline levels (p<0.001). After treatment, the dapagliflozin and telmisartan group had significantly lower waist-to-hip ratio, fasting blood glucose, HbA1c, uric acid, total cholesterol, and low-density lipoprotein compared with the monotherapy group (p<0.05). Additionally, inflammatory biomarkers, including CCL21 mRNA and MCP-1, were substantially lower in the combination therapy group than in the monotherapy group (p<0.05).

In comparison to monotherapy, combination therapy demonstrated more significant clinical effects in treating diabetic nephropathy. This combination therapy effectively controls blood glucose levels and UACR, reduces inflammatory responses, and improves kidney function recovery in diabetic nephropathy patients, thereby enhancing the overall clinical treatment outcomes for these patients.

The global COVID-19 vaccination campaign has significantly reduced severe illness and mortality; however, emerging evidence raises concerns regarding its potential cardiovascular effects, particularly myocardial infarction (MI).

This study investigates the relationship between COVID-19 vaccination and MI incidence among first-time MI patients in Saudi Arabia. Post-COVID-19 vaccination within six months post-vaccination accounted for potential confounding factors, such as pre-existing health conditions, age, and lifestyle. A total of 102 MI patients, with a male predominance of 60.8% and a significant correlation with middle age, were analysed. A+ blood group patients were the most prevalent (33.3%), followed by B+ (29.4%), while Rh-negative patients constituted only 7.8%. Elevated mean BNP (761.98 pg/ml), pulse rate (87.72 bpm), and systolic blood pressure (139.98 mmHg) indicated heightened cardiac stress (p < 0.01).

Significant elevations in AST (121.65 U/L) and ALT (133.63 U/L) levels suggested liver stress post-Covid-19 vaccination (p < 0.01). Males had higher AST, ALT, and bilirubin levels than females, with p-values of 0.02, 0.01, and 0.04, respectively, indicating hepatic differences. Elevated biomarkers like CK-MB (58.05 IU/L) and CPK (313.86 mcg/L) further affirmed significant myocardial damage post-vaccination (p < 0.05).

These findings suggest a link between vaccination and cardiovascular events and highlight the importance of considering individual health profiles in evaluating vaccine safety, cardiovascular health, and hepatic implications.