American Journal of Cardiovascular Drugs最新文献

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are breakthrough agents for the treatment of type 2 diabetes mellitus (T2DM) and heart failure (HF). However, among patients with HF and T2DM, some uncertainty remains about individual comparisons, including dosing.

Objectives

We aimed to make a real-life individual comparison of SGLT2is among patients with HF and T2DM.

Methods

This was a subgroup analysis of the Turkish Ministry of Health’s National Electronic Database for adult patients with HF (TRends-HF). All-cause mortality (ACM) data up to 7 years were evaluated. Patients with HF and T2DM who were prescribed an SGLT2i were identified, and individual doses of empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg were compared. For individual comparisons, propensity score-matching analysis was generated as 1:1:1, and disease-modifying therapies (DMTs) for HF were considered.

Results

In the triple-matched cohort, 1-, 5-, and 7-year survival rates were 95%, 81%, and 76% versus 94%, 78%, and 72% versus 94%, 80%, and 75% for empagliflozin 25 mg, empagliflozin 10 mg, and dapagliflozin 10 mg, respectively. Among patients who were on triple DMT for HF, 1-, 5-, and 7-year survival rates were 95%, 78%, and 70% for empagliflozin 25 mg, 95%, 74%, and 66% for empagliflozin 10 mg, and 94%, 77%, and 69% for dapagliflozin, respectively. Annual emergency department visits were slightly lower with empagliflozin 10 mg and dapagliflozin 10 mg than with empagliflozin 25 mg. A greater proportion of patients on dapagliflozin 10 mg did not experience hospitalization during the 7-year follow-up compared with both doses of empagliflozin, albeit with a small effect size.

Conclusion

Among patients with HF and T2DM, SGLT2is are instrumental, and empagliflozin 10 mg remains significantly inferior to dapagliflozin 10 mg and empagliflozin 25 mg in terms of 5- and 7-year ACM.

Atrial fibrillation (AF) is the most common type of chronic arrythmia, with a lifetime prevalence of one in every three to five individuals above the age of 45 years. The higher heart rate, abnormal rhythm and inflammation caused by AF lead to changes in the function and structure of the heart. This, over time, can culminate in heart failure. In patients with AF, the lifetime prevalence of new-onset heart failure is twice that of stroke. The development of new-onset heart failure in AF is associated with high mortality. Despite the emphasis that AF guidelines put on preventing cardiovascular comorbidities, there is limited evidence regarding pharmacological therapies to prevent incident heart failure in individuals with AF. Specifically, the association between the use of rate control agents and incident heart failure in this population is unknown. Whilst rhythm control may reduce the risk of heart failure, the comparative effect of each pharmacological agent is not clear. In select subgroups of patients with AF, the choice of direct-acting oral anticoagulants and their optimal dosing has been attributed to a lower risk of new-onset heart failure. Future research is needed to identify an evidence-based approach to minimizing the development of heart failure in patients with AF.

Background

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with substantial morbidity and mortality. Current international guidelines recommend antiarrhythmic drugs or catheter ablation (CA) as rhythm-control strategies for AF. This study aimed to comprehensively assess economic evaluations (EEs) of the treatment of AF by country income level.

Methods

Seven electronic databases were systematically searched for EE literature until March 30, 2024, with no constraints on time or language. Two independent reviewers selected the studies, extracted the data, and assessed the quality of the data. Full EEs comparing CA with antiarrhythmic drugs for rhythm-control treatment were included; surgical or rate-control treatments were excluded. The quality of the included articles was assessed using the ECOBIAS checklist. Costs were converted to purchasing power parity US dollars for 2023. A random-effects meta-analysis was applied to pool incremental net benefit (INB) based on a heterogeneity test and its degree (I² > 25% or Cochran’s Q test < 0.1). We also explored heterogeneity and potential publication bias and conducted sensitivity and subgroup analyses.

Results

In total, 27 studies across nine countries were eligible, predominantly from high-income countries (n = 25), with a smaller subset from upper-middle-income countries (n = 2). Because of the heterogeneity among the studies, a random-effects model was selected over a fixed-effects model to pool INBs. Most studies (n = 21) favored CA as the cost-effective intervention, yielding an INB of $US23,796 (95% confidence interval [CI] 15,341–32,251) in high-income countries. However, heterogeneity was substantial (I² = 99.67%). In upper-middle-income countries, the estimated INB was $US18,330 (95% CI − 11,900–48,526). The publication bias results showed no evidence of asymmetrical funnel plots.

Conclusion

In this meta-analysis, CA emerged as a cost-effective rhythm-control treatment for AF when compared with antiarrhythmic drugs, particularly in high-income countries. However, economic evidence for upper-middle-income countries is lacking, and no primary evaluations were found for low-middle-income and low-income countries. Further EEs are necessary to expand the understanding of AF treatment globally.

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.

Graphical Abstract

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.