American Journal of Cardiovascular Drugs最新文献

Background and objectives: Cilostazol improves ischemic symptoms and prevents recurrence following cerebral infarction, and rosuvastatin reduces cholesterol levels. However, no reports exist on the pharmacokinetic interactions between these two drugs in healthy adults. This study evaluated the pharmacokinetic (PK) interactions and safety of cilostazol and rosuvastatin when co-administered to healthy male participants.

Methods: A randomized, open-label, multiple-dosing, two-arm, two-period study was conducted. Arm A had 30 participants receiving 200 mg cilostazol daily and arm B had 27 participants receiving 20 mg rosuvastatin daily for 7 days. In period 2, both arms received a combination of 200 mg cilostazol and 20 mg rosuvastatin daily for 7 days following a 7-day washout period. Plasma concentrations of cilostazol, its metabolites, and rosuvastatin were quantified using liquid chromatography-tandem mass spectrometry.

Results: Fifty-seven participants were randomized, and 44 completed the study. The geometric mean ratio (GMR) and 90% confidence intervals (CI) for maximum plasma concentration at steady state (C_max,ss) and area under the plasma concentration-time curve during the dosing interval at steady state (AUC_tau,ss) indicated no significant interaction between cilostazol and rosuvastatin. Safety assessments showed comparable profiles to individual drug administration, with no significant adverse events.

Conclusion: The repeated co-administration of cilostazol and rosuvastatin in healthy male participants resulted in minor PK interactions and exhibited a safety and tolerability profile similar to those of the individual drugs. This suggested that the combined regimen is well tolerated and does not necessitate dose adjustments.

Registration: ClinicalTrials.Gov identifier no. NCT06568133.

Thromboembolic events and atrial fibrillation are common among kidney transplant recipients (KTRs), and these conditions typically require anticoagulation. Traditionally, vitamin K antagonists were used for management, but the use of direct oral anticoagulants (DOACs) has increased in KTRs. In the general population, DOACs are recommended over warfarin, but the applicability of these recommendations to KTRs is unclear because of risk-benefit concerns. There is some hesitancy to use DOACs in KTRs because of their dependence on renal clearance for elimination, potential drug-drug interactions, and limited data. To date, studies of DOACs in KTRs have demonstrated that they are efficient in thromboembolic events, major bleeding is rare, and drug-drug interactions appear rare. However, no guidance yet exists about the use of DOACs, reversal of DOAC action, and the pre- and post-kidney transplant management of DOACs in KTRs, and the evidence base is scarce. Thus, decisions on DOAC use in KTRs are based on expert opinion and the resources and experiences of individual transplant centers. This review summarizes 10 published studies on the use of DOACs in 741 KTRs, evaluating the side effects, efficacy, drug-drug interactions, and perioperative management compared with those of 1320 KTRs using vitamin K antagonists. Although current data are limited, DOACs appear to be relatively safe and effective in KTRs, with some studies suggesting lower bleeding rates and better kidney function than with vitamin K antagonists. However, more research with larger patient groups is needed to draw definitive conclusions.

Introduction: In patients with atrial fibrillation (AF) who have undergone catheter ablation, the comparative effectiveness of sacubitril-valsartan (SV) versus ACE inhibitors (ACEi) or angiotensin-receptor blockers (ARB) in preventing AF recurrence remains unclear. The purpose of the present systematic review and meta-analysis is to determine whether SV offers superior outcomes in this clinical setting.

Methods: This study systematically reviewed PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and propensity-matched cohorts (PMC), evaluating SV's efficacy in preventing AF recurrence after catheter ablation. Outcomes included AF recurrence and structural remodeling assessed via left ventricular ejection fraction (LVEF) and left atrial volume index (LAVi), with statistical analyses performed using Review Manager 5.1.7 and heterogeneity assessed via I² statistics.

Results: The analysis comprised 642 patients from three RCTs and one PMC (319 SV-treated). SV significantly reduced AF recurrence [risk ratios (RR) 0.54; 95% confidence intervals (CI) 0.41-0.70; p < 0.00001; I² = 0%), a trend also observed when considering RCTs exclusively (RR 0.58; 95% CI 0.41-0.84; p = 0.004; I² = 0%). Moreover, SV demonstrated a notable reduction in LAVi [mean deviation (MD) -5.34 mL/m²; 95% CI -8.77 to -1.91; p = 0.002; I² = 57%] compared with ARB, alongside a significant improvement in LVEF (MD 1.83%; 95% CI 1.35-2.32; p < 0.00001; I² = 0%). Subgroup analyses among patients with hypertension and LVEF < 50% also indicated lower AF recurrence with SV.

Conclusion: SV therapy exhibited superior efficacy in reducing AF recurrence compared with ACEi or ARB and demonstrated superior outcomes in attenuating atrial structural remodeling after catheter ablation. These findings underscore the potential of SV as a therapeutic option for patients with AF undergoing catheter ablation, highlighting its efficacy in mitigating AF recurrence and structural remodeling.

Registration: PROSPERO identifier number CRD42024497958.

Background: Warfarin interacts with antibacterials to prolong the prothrombin time international normalized ratio (PT-INR) and increase the risk of bleeding. Patients initiating warfarin therapy often undergo precise dosage adjustments; however, the clinical implications of these interactions with antibacterials remain unclear. This study aimed to clarify the effect of antibacterials on PT-INR during the warfarin induction phase.

Methods: This was a retrospective, observational study. Patients who were newly treated with warfarin after cardiovascular surgery were included. The primary endpoint was the comparison of the maximum PT-INR and time in therapeutic range (TTR) after warfarin initiation between the antibacterial-treated (ABx) and non-treated (non-ABx) groups.

Results: The maximum PT-INR was significantly higher in the ABx group (which included β-lactams, glycopeptides, quinolones, tetracyclines, and aminoglycosides) than in the non-ABx group (median [interquartile range] 2.37 [2.03-2.71] vs. 2.08 [1.93-2.33]; P = 0.005); however, the TTR did not differ significantly (65% [44-76] vs. 71% [43-85]; P = 0.150). The odds ratio for maximum PT-INR > 2.6 with antimicrobial therapy was 2.51 (95% confidence interval 1.21-5.21).

Discussion: Antibacterial therapy was a risk factor for a maximum PT-INR >2.6. However, there was no association with the TTR, which is a marker of good outcomes. This was due to the strict warfarin dosing regimen according to the algorithm, which immediately and appropriately adjusted for PT-INR overexpansion.

Conclusions: Antibacterials have been suggested to increase PT-INR during the induction phase of warfarin. However, with strict dose adjustments, the clinical impact on the PT-INR and TTR is likely limited.

This report illustrates the Food and Drug Administration (FDA) approval of first-in-its-class activin A receptor IIA inhibitor, sotatercept (Winrevair™), for the treatment of pulmonary arterial hypertension (PAH). Sotatercept is used to increase exercise capacity, improve WHO functional class, and decrease the risk of clinical worsening events in adults with PAH. One phase 2 trial, one phase 3 trial, and an ongoing open-label extension study is described in detail within the current text. Sotatercept significantly improved the 6-min walk distance in patients with PAH after 24 weeks with a mean change increase of 40.1 meters in the experimental group versus 1.4 meters decrease in the placebo group. Epistaxis, telangiectasia, increased hemoglobin, hematocrit, red blood cell levels, and dizziness were adverse events more frequently observed in the sotatercept group than in the placebo group. Sotatercept has shown significant benefits in the reduction of pulmonary vascular resistance and N-terminal pro b-type natriuretic peptide in patients with PAH. However, more studies are needed to evaluate the reduction in mortality. Limitations in practice include high cost and unknown long-term effects.

Background: Colchicine has been shown to reduce adverse cardiovascular events (ACE) and stroke among patients with coronary artery disease. However, its efficacy with short- and long-term use and risk of stroke has not been well studied, with conflicting results to date.

Objective: We sought to evaluate the efficacy of colchicine for the prevention of stroke and other cardiovascular outcomes and to evaluate the effect of short- and long-term use.

Methods: We performed a systematic literature search on PubMed, EMBASE, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until July 20th, 2024. Odds ratios (ORs) were pooled using a random-effect model, and a p value of < 0.05 was considered statistically significant.

Results: A total of 16 RCTs with 24,967 patients were included (12,538 in colchicine group and 12,429 in the control group) in the analysis. Pooled analysis of primary outcomes showed that risk of incidence of stroke was comparable between colchicine and placebo groups (OR 0.78, 95% confidence interval [CI] 0.59-1.02, p = 0.07). Pooled analysis of secondary outcomes showed that colchicine significantly reduced the risk of incidence of ACE by 33% (OR 0.67, 95% CI 0.54-0.82, p < 0.001), and myocardial infarction by 21% (OR 0.79, 95% CI 0.65-0.95, p = 0.01) compared with placebo. However, the risk of all-cause mortality (OR 0.98, 95% CI 0.79-1.21, p = 0.83) and cardiovascular mortality (OR 0.78, 95% CI 0.56-1.08, p = 0.14) were comparable between both groups of patients.

Conclusion: Colchicine was associated with an overall reduction in the risk of incidence of ACE and MI; however, no such effect was observed with mortality and stroke.

Background: This study examines the effects of levosimendan in patients refractory to dobutamine weaning.

Methods: This retrospective study included patients with cardiogenic shock refractory to dobutamine weaning failure admitted between 2010 and 2022. Patients treated with another type of dobutamine alone were compared with those treated with levosimendan in combination with dobutamine. Successful inotrope withdrawal was defined as survival without catecholamine support, transplant, or definitive ventricular assist device at 30 days. Secondary outcomes included all-cause mortality at 30 and 90 days.

Results: Among 349 patients with cardiogenic shock and failure to withdraw from dobutamine, levosimendan was administered in combination with dobutamine in 114 patients, and another type of dobutamine alone was administered in 235 patients. At 30 days, successful inotrope withdrawal occurred in 46 (43.4%) patients taking levosimendan plus dobutamine versus 24 (10.5%) patients in the dobutamine-only group (weighted odds ratio [OR] 4.99, 95% confidence interval [CI] 2.65-9.38; p < 0.001), with similar results at 90 days (weighted OR 6.16, 95% CI 3.22-11.78; p < 0.001). Levosimendan + dobutamine was associated with lower 30-day mortality (weighted OR 0.47, 95% CI 0.26-0.84; p = 0.01), with no difference at 90 days (weighted OR 0.67, 95% CI 0.39-1.14; p = 0.14).

Conclusion: Adding levosimendan to dobutamine may improve inotrope withdrawal success and reduce 30-day mortality in patients with initial weaning failure.

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.