American Journal of Cardiovascular Drugs最新文献

Purpose: Apixaban, a direct oral anticoagulant is administered for stroke prevention in atrial fibrillation patients. Dosing adjustment is guided by renal function, age, and body weight. However, no data exist on its pharmacokinetics in patients with a body mass index (BMI) ≥ 35 kg/m². The aim was to investigate the effects of BMI ≥ 35 kg/m² on trough plasma concentrations of apixaban in patients with atrial fibrillation.

Methods: This prospective study compared steady-state trough concentrations of apixaban in patients with a BMI ≥ 35 kg/m² and patients with a BMI < 35 kg/m².

Results: Sixty patients were included. In patients receiving 5 mg apixaban twice daily, the median trough plasma concentration was 29% lower in patients with a BMI ≥ 35 kg/m² than in those with a BMI < 35 kg/m² (148.9 ng/ml, interquartile range [IQR] 94.5-205.6, compared to 209.1 ng/ml, IQR 167-266.8 ng/ml, respectively; P = 0.044). However, median trough concentrations fell within the manufacturer's predicted range for effective steady-state apixaban exposure. A similar trend was observed with 2.5 mg apixaban twice daily, although statistical significance was not reached. Multivariate analysis revealed no correlation between BMI values and trough concentrations.

Conclusion: BMI ≥ 35 kg/m² patients exhibited lower apixaban trough concentrations, while remaining within the manufacturer's established range for effective steady-state apixaban, suggesting that dose adjustment is unnecessary for this specific patient group.

Background: Cardiovascular disease is on the rise globally, with ischemic heart disease being the leading cause of mortality and morbidity. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular outcomes in patients with heart failure, evidence is limited in guiding initiation in post-acute myocardial infarction (post-AMI) patients. Hence, this study aimed to appraise the current literature on the effect of SGLT2i on the clinical outcomes of post-AMI patients.

Methods: A comprehensive search of PubMed, EMBASE, SCOPUS, and ClinicalTrials.gov was conducted up to 1 May 2024. Only randomized controlled trials studying the use of SGLT2i in post-AMI patients were included. We included adult patients aged 18 years old and older diagnosed with AMI and initiated on SGLT2i in the acute post-AMI setting. SGLT2i studies solely in heart failure settings were excluded.

Results: Eight clinical trials were included in the systematic review, comprising 11,436 patients. Compared with placebo, SGLT2i initiation in post-AMI patients significantly reduced total number of heart failure hospitalizations (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.62-0.90) and was associated with a lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (- 26.67 pg/ml, 95% CI - 41.74 to - 11.59). There was no difference in all-cause mortality (RR 1.02, 95% CI 0.81-1.28), cardiovascular mortality (RR 1.03, 95% CI 0.83-1.28), change in left ventricular ejection fraction, and glycated hemoglobin (HbA1c), as compared with placebo.

Conclusion: SGLT2i use in patients with AMI was associated with a reduction in heart failure hospitalizations and a decrease in NT-proBNP. There were no significant differences in mortality outcomes.

Registration: PROSPERO identifier number CRD42024540843.

Uncontrolled hyperglycemia in people with diabetes is an established risk of premature cardiovascular disease. Repeated hypoglycemic events are also associated with increased cardiovascular mortality. Both hyperglycemia and hypoglycemia induce cellular stress, notably endoplasmic reticulum (ER) stress, a known promoter of cardiovascular disease. Contemporary anti-hyperglycemic drugs such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors simultaneously inhibit oxidative stress and ER stress in human coronary artery endothelial cells. Similarly, other known cardioprotective drugs, such as statins and inhibitors of the renin-angiotensin-aldosterone system (RAAS) share a common pleiotropic effect of reducing cellular stress. Antioxidants reduce oxidative stress but may aggravate ER stress. This dichotomy of antioxidant effects may underline the unfavorable outcomes of clinical trials with antioxidant vitamin use. The aim of this review is to highlight the potential role of cellular stress reduction in cardioprotective effects of contemporary diabetes drugs. Future clinical trials are needed to test the hypothesis that cellular stress is the fundamental culprit in cardiovascular disease.

Introduction: Contrast-induced acute kidney injury (CI-AKI) is a common complication of iodinated contrast administration during coronary procedures, especially in patients with diabetes mellitus (DM). Besides periprocedural hydration and statins, there are no other pharmacological strategies with consistent results to prevent CI-AKI up to date. This study aims to evaluate the efficacy of chronic use of sodium-glucose co-transporter 2 (SGLT2) inhibitors on the prevention of CI-AKI in patients with type 2 DM following coronary procedures.

Methods: A systematic literature search of MEDLINE, Google Scholar, Embase, and Cochrane Library was performed. Relevant observational studies and randomized controlled studies (RCTs) were identified. Results were pooled using a random-effect model meta-analysis. Subgroup analyses were performed to evaluate the potential benefit of SGLT2 inhibitors on the prevention of CI-AKI in patients undergoing urgent or elective coronary angiography/percutaneous coronary interventions (CAG/PCI).

Results: Seven observational studies and one randomized controlled trial with 2740 patients were included. Chronic treatment (minimum duration 2 weeks to 6 months) with an SGLT2 inhibitor was associated with a significantly reduced risk of CI-AKI in diabetic patients undergoing coronary procedures compared with the control group [risk ratio (RR) 0.48; 95% confidence interval (CI) 0.39-0.59; p < 0.001). Results of subsequent subgroup analysis showed a significant reduction in the incidence of CI-AKI in diabetic patients undergoing both elective CAG/PCI (RR 0.49; 95% CI 0.35-0.68; p<0.001) and urgent CAG/PCI (RR 0.48; 95% Cl 0.35-0.66; p < 0.001).

Discussion: Chronic use of SGLT2 inhibitors may be preventative against the incidence of CI-AKI in patients with type 2 DM undergoing coronary interventions. Further RCTs are needed to confirm our findings.

Cardiac remodeling is a compensatory adaptive response to chronic heart failure (HF) altering the structure, function, and metabolism of the heart. Many nutritional and metabolic diseases can aggravate the pathophysiological development of cardiac remodeling. Vitamin D deficiency leads to cardiac remodeling by activating the renin-angiotensin-aldosterone system (RAAS), resulting in enhanced inflammation and directly promoting cardiac fibrosis and extracellular matrix deposition. Hyperparathyroidism upregulates protein kinase A or protein kinase C, enhances intracellular calcium influx, promotes oxidative stress, activates RAAS, and increases aldosterone levels, thereby aggravating cardiac remodeling. Besides, fibroblast growth factor 23 (FGF23) plays a direct role in the heart, resulting in ventricular hypertrophy and myocardial fibrosis. Vitamin D deficiency leads to hyperparathyroidism, which in turn increases the level of FGF23. Elevated levels of FGF23 further inhibit vitamin D synthesis. Evidence exists that vitamin D deficiency, hyperparathyroidism, and marked elevations in FGF23 concentration form a vicious cycle and are believed to contribute directly to cardiac remodeling. Therefore, the purpose of this article is to introduce the specific effects of the above substances on the heart and to explain the significance of understanding the vitamin D-parathyroid hormone-FGF23 axis in improving or even reversing cardiac remodeling, thus contributing to the treatment of patients with HF.

Background: Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients.

Methods: The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a post hoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years.

Results: Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p < 0.0001). The increased risk in the aspirin group was prominent within 3 years, and the hazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3 years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p = 0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group.

Conclusion: The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) are at high risk of major adverse cardiovascular events (MACE) and mortality. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), including monoclonal antibodies (alirocumab, evolocumab) and small interfering RNA (inclisiran), substantially reduce lipid levels. This meta-analysis aimed to evaluate the efficacy of both types of PCSK9i specifically in patients with HeFH.

Methods: A librarian-assisted systematic search of MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov was performed from 2013 to 2023. Randomized controlled trials of PCSK9i versus control in patients with HeFH were included. No language restrictions were applied. Cochrane Risk-of-Bias tool 2 was used to assess quality of evidence. Meta-analyses were performed using Cochrane ReviewManager. Outcomes included change in atherogenic lipids, MACE, and all-cause death.

Results: Seven trials were included (N = 2196). Overall risk of bias was mostly low or with some concerns. Median follow-up was 24 weeks. PCSK9i had an uncertain effect on MACE (odds ratio [OR] 1.25, 95% confidence interval [CI] 0.69-2.26) and all-cause death (OR 2.47, 95% CI 0.33-18.26) due to the low event rate and short follow-up. However, PCSK9i significantly reduced low-density lipoprotein cholesterol (LDL-C) by 54% (95% CI 49-58), apolipoprotein B by 43% (95% CI 37-49), and lipoprotein(a) by 20% (95% CI 13-28).

Conclusions: In patients with HeFH, PCSK9i significantly reduced atherogenic lipids (LDL-C, apolipoprotein B, and lipoprotein[a]). Despite this, the effect on MACE or all-cause death was unclear. Larger-scale randomized controlled trials of longer duration are needed to validate whether this short-term reduction in lipid levels translates into a reduction in clinically meaningful outcomes.