American Journal of Cardiovascular Drugs最新文献

Background

Sex, age, medical history, treatment, tobacco use, and race (SAMe-TT₂R₂) score helps detect patients at risk of suboptimal anticoagulation control. A score above two suggests poor control; however, non-Caucasian status being assigned two points might hinder the recognition of poor control in patients of other races.

Objective

To evaluate the SAMe-TT₂R₂ score’s ability to predict poor anticoagulation control [defined as time in therapeutic range (TTR) < 60–70%] in Asian and non-Asian populations on vitamin K antagonists (VKAs).

Methods

We searched PubMed, Cochrane Library, Scopus, SpringerLink, and Web of Science using the keyword “SAMe-TT₂R₂.” Articles published before April 2022 were screened. We gathered mean TTR and diagnostic accuracy data for different SAMe-TT₂R₂ thresholds and conducted meta-analyses using random-effects models.

Results

A total of 30 studies were included (N = 36,690). The overall mean TTR differences were − 4.88 and − 6.41 for the cutoffs of ≥ 3 and ≥ 4, respectively. For non-Asian patients, the mean TTR differences were − 3.86, − 5.12, and − 8.09 for the cutoffs ≥ 2, ≥ 3, and ≥ 4, respectively. For Asian patients, the mean TTR differences were − 3.99 and − 4.07 for the cut-offs ≥ 3 and ≥ 4, respectively. The highest positive likelihood ratio (LR+) for the Asian subgroup was 1.17 [95% confidence interval (CI): 1.06–1.28; I² = 0%, p heterogeneity = 0.500] at cutoff ≥ 4 and for the non-Asian subgroup, at cut-off ≥ 3, the LR+ was 1.24 (95% CI 1.14–1.34; I² = 0% p heterogeneity = 0.455). The lowest LR− was found at a lower cutoff for both races (at cutoff ≥ 3 and ≥ 2 for Asian and non-Asian subgroups, respectively). The pooled results of other accuracy parameters were modest at all cutoffs, except for the sensitivity at cutoff ≥ 3 in the Asian subgroup (83.05%).

Conclusion

Our study results suggest that a higher SAMe-TT₂R₂ score resulted in a greater reduction of TTR among Asian and all races. The accuracy parameters showed the highest sensitivity for poor TTR at the SAMe-TT₂R₂ cutoff of ≥ 3 for Asian patients. However, the ability to identify patients likely to have poor TTR was limited. Further research is needed to enhance the risk assessment for poor anticoagulation control with VKAs.

Registration

The protocol of this systematic review was registered in the International Prospective Register of Scientific Reviews: PROSPERO, registration number CRD42021291865.

Graphical Abstract

Background

Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors (PCSK9i) have a beneficial effect on various domains of patients’ lipid profiles and cardiovascular and mortality outcomes. Here, we aim to further investigate the efficacy and safety of PCSK9i in patients with ACS or who experienced recent episodes.

Methods

We comprehensively searched PubMed, Scopus, Web of Science and Cochrane CENTRAL to identify all randomized controlled trials comparing PCSK9i versus placebo. Data were extracted and analysed using Stata/MP version 17.0.

Results

Eleven studies (n = 24,732) were included in this meta-analysis. In terms of efficacy outcomes, compared with the control group, PCSK9i significantly decreased levels of LDL-C, TC, TG, Lp (a) and Apo-B, with the following values, respectively: Cohen’s d of − 1.25, 95% confidence interval (CI − 1.64 to − 0.87); Cohen’s d of − 1.32, 95% CI (− 1.83 to − 0.81); Cohen’s d of − 0.26, 95% CI (− 0.37 to − 0.14); Cohen’s d of − 0.70, 95% CI (− 1.15 to − 0.26); and Cohen’s d of − 1.46, 95% CI (− 1.97 to − 0.94). The levels of HDL-C and Apo-A1 increased by: Cohen’s d 0.27, 95% CI (0.16–0.39) and Cohen’s d of 0.30, 95% CI (0.17–0.42), respectively. Regarding safety outcomes, PCSK9i was associated with lower odds of myocardial infarction (MI) and cerebrovascular events with the following values, respectively: OR = 0.87, 95% CI (0.78–0.97) and OR = 0.71, 95% CI (0.52–0.98).

Conclusions

PCSK9i was associated with better lipid profile and quality of life of patients and can be recommended as an optimal treatment strategy. Further trials should study combinations of PCSK9i with other lipid-lowering drugs.

Cardiac contraction and relaxation require a substantial amount of energy provided by the mitochondria. The failing heart is adenosine triphosphate (ATP)- and creatine-depleted. Studies have found iron is involved in almost every aspect of mitochondrial function, and previous studies have shown myocardial iron deficiency in heart failure (HF). Many clinicians advocated intravenous iron repletion for HF patients meeting the conventional criteria for systemic iron deficiency. While clinical trials showed improved quality of life, iron repletion failed to significantly impact survival or significant cardiovascular adverse events. There is evidence that in HF, labile iron is trapped inside the mitochondria causing oxidative stress and lipid peroxidation. There is also compelling preclinical evidence demonstrating the detrimental effects of both iron overload and depletion on cardiomyocyte function. We reviewed the mechanisms governing myocardial and mitochondrial iron content. Mitochondrial dynamics (i.e., fusion, fission, mitophagy) and the role of iron were also investigated. Ferroptosis, as an important regulated cell death mechanism involved in cardiomyocyte loss, was reviewed along with agents used to manipulate it. The membrane stability and iron content of mitochondria can be altered by many agents. Some studies are showing promising improvement in the cardiomyocyte function after iron chelation by deferiprone; however, whether the in vitro and in vivo findings will be reflected on on clinical grounds is still unclear. Finally, we briefly reviewed the clinical trials on intravenous iron repletion. There is a need for more well-simulated animal studies to shed light on the safety and efficacy of chelation agents and pave the road for clinical studies.

Background

Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know.

Methods

US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate.

Results

The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower.

Conclusion

Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA.

COMPASS ClinicalTrials.gov identifier: NCT01776424.

Introduction

Infection may induce thrombotic and hemorrhagic events; however, it is currently unclear whether the inflammatory response affects the coagulation function and the clinical efficacy and safety of rivaroxaban in older patients with non-valvular atrial fibrillation (NVAF).

Objective

This project aimed to assess the effectiveness and safety of the non-vitamin K antagonist oral anticoagulant rivaroxaban in older patients with NVAF complicated by infection, and to provide a basis for possible drug dose adjustment.

Methods

A total of 152 NVAF patients aged ≥ 65 years admitted to the Fifth People’s Hospital of Shanghai from June 2020 to May 2022 were included in this prospective, observational study. The changes in steady-state plasma concentration of rivaroxaban and FXa inhibition rate were compared between patients with and without infection, and the impact on the occurrence of infection, thrombotic events, and bleeding events was compared through 1-year follow-up.

Results

Our results showed that patients in the infection group had abnormal inflammation markers, as well as an increased occurrence of bleeding and thrombotic events during hospitalization and follow-up. The high incidence of bleeding events in patients was closely related to the occurrence of infection, lymphocyte reduction, and increased neutrophil-lymphocyte ratio. The increase in thrombotic events was related to a decrease in rivaroxaban plasma concentration. Bleeding events in patients taking anticoagulant drugs are not necessarily due to drug accumulation.

Conclusions

Timely control of infection, assessment of bleeding and thrombotic risks, and selection of appropriate anticoagulation treatment strategies should be made in older NVAF patients who develop pulmonary infection.

Clinical Trials Registration

Chinese Clinical Trial Registry Number ChiCTR2000033144.

Introduction

Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with the oral P2Y12 inhibition, clopidogrel, or placebo in acute coronary syndromes.

Methods

This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, minor bleeding, and the need for blood transfusion.

Results

The analysis was comprised of 6 studies including 26,444 patients treated with cangrelor, clopidogrel, or placebo. There were no statistically significant differences in the incidence of all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or major bleeding. Cangrelor was associated with a higher risk of minor bleeding than clopidogrel or placebo, with no difference in requiring blood transfusion.

Conclusion

Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.

Introduction

Diabetes and coronary artery disease are two common conditions that often co-exist. In recent years, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide significant cardioprotective benefits, especially among patients with heart failure.

Objective

In this systematic review, we look to identify the outcomes SGLT2i use in patients undergoing coronary revascularization.

Methods

Pubmed and Embase were systematically searched for articles describing the outcomes of patients taking SGLT2i and undergoing coronary revascularization. 834 titles and abstracts were screened, 42 full texts were reviewed, and 18 studies were found to meet the inclusion criteria and were included in this review.

Results

For patients undergoing coronary artery bypass grafting and percutaneous coronary intervention, the use of SGLT2i resulted in reductions in mortality, hospitalization for heart failure, and improved blood glucose; however, these benefits were not consistently reported in the literature. Reduced inflammatory markers and positive cardiac remodeling were identified among patients taking SGLT2i.

Conclusions

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide benefits for patients with heart failure along with a host of positive modulatory effects on the cardiovascular system, including reductions in inflammatory properties, hypertension, and left ventricular volume load. Given the clear benefit provided by SGLT2i to patients with cardiovascular disease and a host of positive properties that are expected to be protective for patients with ischemic heart disease, future investigation into the relationship between SGLT2i and outcomes for patients undergoing revascularization is imperative.

Background

Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients’ symptoms and reversing pulmonary vascular pathology.

Method

We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results

Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging.

Conclusion

Metformin and sotatercept appear as promising therapeutic drugs for PAH.

Clinical Trials Registration

This work was registered in PROSPERO (CDR42022340658).