American Journal of Cardiovascular Drugs最新文献

Objective

To evaluate the comparative effects of dapagliflozin versus placebo in patients with heart failure (HF), focusing on functional capacity, symptoms, and safety outcomes.

Background

Despite advancements in heart failure (HF) therapy, HF is still a significant cause of recurrent hospitalization and death worldwide. Dapagliflozin has demonstrated potential in lowering hospitalizations and mortality associated with heart failure; however, its impact on functional capacity, particularly the 6-min walk distance (6MWD), and the comprehensive assessment of safety outcomes in diverse HF populations, including those with preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), requires further investigation.

Methods

PubMed, Web of Science, Cochrane Library, and Scopus databases were comprehensively searched to identify randomized controlled trials (RCTs) investigating the efficacy of dapagliflozin in comparison with control interventions for heart failure. The primary outcome was a change in the 6MWD, KCCQ score, and safety measures included hospitalization, all-cause mortality, and adverse events.

Results

In our meta-analysis of ten studies involving 12,695 patients with heart failure, dapagliflozin showed significantly improved Kansas City Cardiomyopathy Questionnaire (KCCQ) scores [risk ratio (RR) of 2.75, 95% confidence interval (CI) (1.95–3.569), p < 0.00001] and no significant differences in 6-min walk distance [6MWD; RR of 3.59, 95% CI (− 1.44 to 8.63), p = 0.16]. Dapagliflozin demonstrated a notable reduction in hospitalization for heart failure [RR of 0.76, 95% CI (0.68–0.84), p < 0.00001], significant overall reduction on the effect of any cause mortality [RR of 0.90, 95% CI (0.83–0.99), p = 0.03). There was, however, no significant effect on adverse events [RR of 0.96, 95% CI (0.98–1.03), p = 0.39).

Conclusions

Our meta-analysis of ten trials concluded that dapagliflozin significantly improved KCCQ scores in both HFrEF and HFpEF. The improvement in 6MWD was not statistically significant but trended toward dapagliflozin. Dapagliflozin also showed a mortality benefit in patients with reduced ejection fraction; however, in patients with preserved ejection fraction, the result was not statistically significant. There was also a statistically significant reduction in heart failure hospitalizations across all classes.

Background

Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs’ effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE.

Method

A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis.

Results

A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69–0.85), major bleeding (HR 0.77, 95% CI 0.72–0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77–0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68–0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83–1.10).

Conclusion

This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin.

Graphical Abstract

Background

In patients with atrial fibrillation (AF), the association between cancer and cardioembolic or bleeding risk during oral anticoagulant therapy still remains unclear.

Purpose

We aimed to assess the impact of cancer present at baseline (CB) or diagnosed during follow-up (CFU) on bleeding events in patients treated with direct oral anticoagulants (DOACs) for non-valvular AF (NVAF) compared with patients without CB or CFU, respectively.

Methods

All consecutive patients with NVAF treated with DOACs for stroke prevention were enrolled between January 2017 and March 2019. Primary outcomes were bleeding events or cardiovascular death, non-fatal stroke and non-fatal myocardial infarction, and the composite endpoint between patients with and without CB and between patients with and without CB.

Results

The study population comprised 1170 patients who were followed for a mean time of 21.6 ± 9.5 months. Overall, 81 patients (6.9%) were affected by CB, while 81 (6.9%) were diagnosed with CFU. Patients with CFU were associated with a higher risk of bleeding events and major bleeding compared with patients without CFU. Such an association was not observed between the CB and no CB populations. In multivariate analysis adjusted for anemia, age, creatinine, CB and CFU, CFU but not CB remained an independent predictor of overall and major bleeding (hazard ratio [HR] 2.67, 95% confidence interval [CI] 1.8–3.89, p < 0.001; HR 3.02, 95% CI 1.6–3.81, p = 0.001, respectively).

Conclusion

During follow-up, newly diagnosed primitive or metastatic cancer in patients with NVAF taking DOACs is a strong predictor of major bleeding regardless of baseline hemorrhagic risk assessment. In contrast, such an association is not observed with malignancy at baseline. Appropriate diagnosis and treatment could therefore reduce the risk of cancer-related bleeding.

Type 2 diabetes mellitus (T2DM) is associated with a heightened risk of cardiovascular and renal complications. While glycemic control remains essential, newer therapeutic options, such as SGLT2 inhibitors, offer additional benefits beyond glucose reduction. This review delves into the mechanisms underlying the cardio-renal protective effects of SGLT2 inhibitors. By inducing relative hypoglycemia, these agents promote ketogenesis, optimize myocardial energy metabolism, and reduce lipotoxicity. Additionally, SGLT2 inhibitors exert renoprotective actions by enhancing renal perfusion, attenuating inflammation, and improving iron metabolism. These pleiotropic effects, including modulation of blood pressure, reduction of uric acid, and improved endothelial function, collectively contribute to the cardiovascular and renal benefits observed with SGLT2 inhibitor therapy. This review will provide clinicians with essential knowledge, understanding, and a clear recollection of this pharmacological group’s mechanism of action.

Background

For symptomatic obstructive hypertrophic cardiomyopathy (oHCM), limited evidence exists on healthcare resource utilization (HRU) and cost for patients with symptomatic oHCM by treatment categories. We evaluated whether HRU and costs vary by initial treatment in symptomatic oHCM.

Methods

This is a retrospective study of medical and pharmacy claims from 2016 to 2021 to identify (per International Classification of Disease Tenth Revision diagnosis codes) adult patients in the USA with symptomatic oHCM. Patients included in the study cohort were required to be treatment naïve (≥ 12 months’ activity before first treatment) and symptomatic (fatigue, chest pain, syncope, dyspnea, heart failure, or palpitations within 3 months of index date). Patients were grouped by first index treatment [beta blocker (BB), calcium channel blockers (CCB), disopyramide, combination therapy], and HRU and costs [per person per year (PPPY), in USD] by initial treatment were reported.

Results

Among 7334 patients with symptomatic oHCM, initial treatment included BB (65.8%), CCB (21.1%), disopyramide (1.2%), or BB + CCB (11.9%). Overall, 87.2% were prescribed monotherapy. Outpatient visits were the main driver of all-cause HRU (mean 11.5 PPPY), and varied by initial treatment (BB: 11.0, CCB: 10.5, disopyramide: 7.2, combination therapy: 12.1). All-cause urgent care visits were more frequent than inpatient visits (means: 5.4 and 0.83 PPPY, respectively). All-cause incurred costs were $46,628 PPPY overall and varied by treatment (BB: $47,029, CCB: $42,124, disopyramide: $27,007, combination therapy: $54,024).

Conclusions

In this large, US-based cohort of patients with symptomatic oHCM, initial therapy was most commonly BB and CCB monotherapy. Costs and HRU were high for most patients, but greater for those treated initially with combination therapy.

Background

Mavacamten is a first-in-class cardiac myosin inhibitor approved by the US Food and Drug Administration (FDA) for symptomatic obstructive hypertrophic cardiomyopathy (HCM). This pharmacovigilance study aimed to assess mavacamten-related adverse drug reactions (ADRs) in the real world as reported in the FDA Adverse Event Reporting System (FAERS).

Methods

We conducted disproportionality analyses with four signal detection algorithms—reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and the multi-item gamma Poisson shrinker to identify mavacamten-related ADRs.

Results

Out of 4,500,131 reports from the FAERS database, 1004 mavacamten-related ADRs were identified from 1 January 2022 to 30 September 2023. A total of 26 significant disproportionality preferred terms (PTs) conforming to the four signal detection algorithms were noted. Some of the statistically significant cardiac ADRs at PT level include decreased ejection fraction (EF) [ROR 33.60 (95% confidence interval, CI 21.79–51.82), PRR 32.86 (χ² 615.96), information component (IC) 5.03, IC025 4.61, empirical Bayesian geometric mean (EBGM) 32.77, EBGM05 21.25], cardiac failure [ROR 9.39 (95% CI 6.49–13.60), PRR 9.13 (χ² 202.42), IC 3.19, IC025 2.83, EBGM 9.12, EBGM05 6.30], and atrial fibrillation [ROR 16.63 (95% CI 12.72–21.75), PRR 15.66 (χ² 769.93), IC 3.97, IC025 3.71, EBGM 15.64, EBGM05 11.96].

Conclusions

The results of our study were consistent with the safety data of clinical trials, including reduced ejection fraction, atrial fibrillation, dyspnea, and syncope. We also found potential new and unexpected ADR signals, such as urinary tract infection, gout, and peripheral edema.

Introduction

Despite the effect on blood lipid levels, the clinical benefits of intensive versus standard pharmacological lipid-lowering therapy remain unclear. Previous reviews have presented relative effects on the risk of clinical outcomes, but not the absolute risk reductions (ARRs) and the time gained to a clinical outcome, also called outcome postponement (OP). The aim of this study was to estimate the effect of intensive versus standard lipid-lowering therapy in terms of ARR and OP of major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, and all-cause mortality.

Methods

We searched PubMed, Embase, and prior reviews to identify trials comparing intensive versus standard lipid-lowering therapy for the risk of cardiovascular disease. We extracted the number of patients with MACE, MI, stroke, and all-cause mortality. Risk of bias was assessed according to the five domains of the Cochrane Risk of Bias Tool 2.0. We calculated ARRs and OPs to assess the clinical benefits of intensive versus standard therapy for each outcome. We conducted meta-analyses standardizing the results to 2 and 5 years of follow-up.

Results

We identified 11 double-blind, randomized, controlled trials (n = 101,357). The follow-up period ranged from 1.5 to 7.0 years, with an average follow-up duration of 3.7 years. Risk of bias was generally high. During an estimated 2 years of intensive versus standard lipid-lowering therapy, 1.1% (95% confidence interval [CI] 0.7–1.5) fewer patients had MACE and the OP of MACE was 4.1 days (95% CI 2.6–5.6). The effects were 0.7% (95% CI 0.4–0.8) and 2.5 days (95% CI 1.6–3.3) for MI, 0.2% (95% CI 0.1–0.3) and 0.9 days (95% CI 0.5–1.2) for stroke, and 0.2% (95% CI − 0.1 to 0.4) and 0.6 days (95% CI − 0.4 to 1.5) for all-cause death. During on average 5 years of intensive versus standard lipid-lowering therapy, 2.4% (95% CI 1.5–3.3) fewer patients had MACE and the time gained to MACE was 23.5 days (95% CI 14.9–32.0). The effects were 1.5% (95% CI 1.0–2.1) and 14.6 days (95% CI 9.3–20.0) for MI, 0.6% (95% CI 0.4–0.8) and 5.3 days (95% CI 3.3–7.4) for stroke, and 0.4% (95% CI −0.2 to 0.1) and 3.6 days (95% CI − 2.1 to 9.2) for all-cause death.

Conclusion

Intensive lipid-lowering therapy during 2 or 5 years did not lead to fewer deaths or lifetime gained, and the effects on MI and stroke were negligible. The largest effect was that MACE did not occur in two of 100 patients and was postponed 3–4 weeks after 5 years of intensive treatment. Given the small effect, patients should receive this information as part of shared decision making.

Background

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF).

Methods

A retrospective cohort study was conducted in individuals with established AF using data from Optum’s deidentified Clinformatics^® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke.

Results

A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82–0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87–2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33–4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (p value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71–2.62) and those not on OAC (HR 2.11; 95% CI 1.83–2.43).

Conclusion

In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack of timely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the “buy-and-bill” process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.

Chronic kidney disease (CKD) remains a significant global health issue and is a leading cause of mortality worldwide. Patients with CKD have an increased risk of developing atrial fibrillation (AF) and venous thromboembolism (VTE). While direct oral anticoagulants (DOACs) have become a standard of care for anticoagulation (AC) in patients with AF and VTE, the appropriate use of these agents in comorbid kidney impairment warrants detailed discussion. This scientific narrative review summarizes the effectiveness and safety of apixaban use in patients with renal dysfunction by assessing the current published pharmacokinetic, interventional, observational, and guideline data. Apixaban is a highly selective, orally active, direct inhibitor of factor Xa, with well-established pharmacokinetics and consistent clinical outcomes across a broad range of patient populations, including those with kidney impairment. Overall, the scientific literature has shown that apixaban has a favorable clinical efficacy and safety profile compared with vitamin K antagonists for patients with AF or VTE and comorbid kidney impairment. These data support the approved label dosing strategy of apixaban in reducing the risk of stroke/systemic embolism in patients with nonvalvular AF and in treating VTE across all ranges of kidney function. Both clinician experience and knowledge of patient-specific factors may be required in the management of comorbid patients with advanced CKD or those requiring dialysis, as data on these patients are limited.