American Journal of Cardiovascular Drugs最新文献

Background

It remains controversial whether exercise training (EX) improves vascular endothelial function (VEF) independent of lipoprotein changes even though these are therapeutic goals for coronary artery disease (CAD).

Objective

The purpose of this study was to systematically review the effects of EX on VEF and blood lipid variables in patients with CAD.

Methods

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched five electronic databases (CINAHL, Embase, PubMed, SportDiscus, and Web of Science) until March 2024 for studies that met the following criteria: (i) patients with CAD aged ≥ 18 years; (ii) structured EX for ≥ 1 week in randomized or nonrandomized controlled studies; and (iii) measured brachial artery flow-mediated dilation (FMD) with or without blood lipid variables. We calculated effect sizes (ESs) and 95% confidence intervals (CIs) using a random-effects model and conducted subgroup analyses to identify the effect of training factors (duration, intensity, and weekly volume) on outcomes.

Results

In total, 11 studies with 19 trials (629 patients, 60 ± 9 years) met the inclusion criteria. We conducted a separate meta-analysis for each of the four outcome measures: FMD (13 ESs), high-density lipoprotein-cholesterol (HDL-C; eight ESs), low-density lipoprotein cholesterol (LDL-C; eight ESs), and triglycerides (TGs; eight ESs). EX significantly increased FMD (mean ES 0.57; 95% CI 0.44–0.70; P < 0.001) and HDL-C levels (mean ES 0.25; 95% CI 0.12–0.39; P < 0.001) but had no effect on LDL-C and TG. Subgroup analyses for FMD found no significant variation in effect by training factor (duration, intensity, and weekly volume).

Conclusion

EX improves VEF with increased HDL-C, but we found no changes in LDL-C and TG in patients with CAD, suggesting that HDL-C is preferentially associated with exercise-induced VEF improvement.

Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) have demonstrated promising effects in lowering cardiovascular incidents among patients with acute coronary syndrome. However, their influence on early platelet reactivity after primary percutaneous coronary intervention (PPCI) remains unclear.

Objectives

This research sought to investigate the effects of entirely human anti-PCSK9 antibodies on platelet function as measured by thrombelastography and 12-month postoperative results in patients receiving PPCI and treated with ticagrelor-based dual antiplatelet therapy.

Methods

This single-center prospective study was conducted at Zhongshan Hospital, Fudan University, China, between January 2021 and June 2023. Patients were divided into two groups: those receiving standard statin therapy (statin-only group) and those receiving additional PCSK9 mAbs (either evolocumab 140 mg or alirocumab 75 mg, subcutaneously, every 2 weeks; PCSK9 mAb group). A total of 1250 eligible patients were enrolled. To equalize baseline characteristics, propensity score matching was conducted in a 1:1 ratio, resulting in 310 patients per group. Platelet activity was measured using thrombelastography 5 days after PPCI, presented as adenosine diphosphate-induced maximal amplitude (MA_ADP). The primary clinical outcome was the occurrence of major adverse cardiovascular events, which included cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization, measured over a 12-month period.

Results

At 5 days after PPCI, the PCSK9 mAb group exhibited levels of MA_ADP that were significantly lower than those in the statin-only group (17.10 ± 9.52 mm vs. 20.73 ± 12.07 mm, P < 0.001). The use of PCSK9 mAbs was significantly correlated with reduced MA_ADP (β − 0.166, P < 0.001). The occurrence of major adverse cardiovascular events in the PCSK9 mAb group was significantly lower than in the statin-only group. Furthermore, individuals in the top MA_ADP tertile (MA_ADP > 21.7 mm) plus statin-only subgroup exhibited the lowest rate of cumulative event-free survival.

Conclusion

Incorporating PCSK9 mAbs into ticagrelor-based dual antiplatelet therapy significantly reduced platelet reactivity and correlated with better cardiovascular results over a 12-month period. These findings support the use of PCSK9 mAbs as an effective adjunctive therapy in the management of acute coronary syndrome.

Around one-quarter of all patients undergoing cardiac procedures, particularly those on cardiopulmonary bypass, develop cardiac surgery-associated acute kidney injury (CSA-AKI). This complication increases the risk of several serious morbidities and of mortality, representing a significant burden for both patients and the healthcare system. Patients with diminished kidney function before surgery, such as those with chronic kidney disease, are at heightened risk of developing CSA-AKI and have poorer outcomes than patients without preexisting kidney injury who develop CSA-AKI. Several mechanisms are involved in the development of CSA-AKI; injury is primarily thought to result from an amplification loop of inflammation and cell death, with complement and immune system activation, cardiopulmonary bypass, and ischemia-reperfusion injury all contributing to pathogenesis. At present there are no effective, targeted pharmacological therapies for the prevention or treatment of CSA-AKI, although several preclinical trials have shown promise, and clinical trials are under way. Progress in the understanding of the complex pathophysiology of CSA-AKI is needed to improve the development of successful strategies for its prevention, management, and treatment. In this review, we outline our current understanding of CSA-AKI development and management strategies and discuss potential future therapeutic targets under investigation.

Background

Amiodarone is an effective anti-arrhythmic drug; however, it is frequently associated with thyroid dysfunction. The aim of this study was to investigate the incidence and risk factor of amiodarone-induced dysfunction in an iodine-sufficient area.

Methods

This retrospective cohort study included 27,023 consecutive patients treated with amiodarone for arrhythmia, using the Korean National Health Insurance database. A Cox regression analysis was performed to determine independent risk factors for amiodarone-induced thyroid dysfunction.

Results

During a mean follow-up period of 6.4 years, 1326 (4.9%) patients developed thyrotoxicosis and 3121 (11.5%) developed hypothyroidism. The incidence rate of amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) was 6.92 and 17.1 per 1000 person-years, respectively. In the multivariate analysis, chronic kidney disease (CKD) [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.06–1.99], and Hashimoto’s thyroiditis (HR 2.00, 95% CI 1.31–3.07) were associated with AIT, while female sex (HR 1.22, 95% CI 1.14–1.32), diabetes (HR 1.14, 95% CI 1.06–1.24), CKD (HR 1.18, 95% CI 1.05–1.34), and Hashimoto’s thyroiditis (HR 2.26, 95% CI 1.66–3.09) were associated with AIH.

Conclusions

The incidence of AIH was higher compared with AIT in an area with sufficient iodine intake. Several potential risk factors for AIT and AIH were identified. When amiodarone treatment is considered for patients, particularly those at a high risk of thyroid dysfunction, it is warranted to perform regular thyroid function assessments.

Patients with hypertension are at an increased risk of cardiovascular disease and death. Resistant hypertension, or hypertension that is unsuccessfully treated with multiple antihypertensive medications, further exacerbates the complications and negative outcomes for patients. A new pathway, via aldosterone synthesis inhibition, is currently being studied as a method to reduce blood pressure values in patients who are currently taking other antihypertensive medications. This review presents and discusses the current pharmacokinetic, pharmacodynamic, and clinical and scientific evidence pertaining to baxdrostat, a novel aldosterone synthase inhibitor.

Background and Objective

Left atrial strain (LAS) has prognostic value in patients with atrial fibrillation (AF). Consequently, therapies that improve LAS may help reduce AF-related adverse cardiac events. We aimed to compare how digoxin and bisoprolol modulate LAS in patients with AF being treated with rate control.

Methods

This was a bicentric randomized controlled trial. Patients with AF, naïve to beta-blockers and digoxin, and scheduled for treatment with a rate control strategy were randomized to receive oral bisoprolol 5–10 mg daily or digoxin 0.25 mg daily. The primary aim was to compare the change in peak LAS before and after 30 days of treatment between the two groups.

Results

A total of 60 patients, equally distributed between the two groups, completed the trial. By day 30, there was no significant difference in global peak LAS between the groups. However, when analyzed separately, the two-chamber view showed a significantly higher peak LAS in the digoxin group than in the BB group (mean 7.5 ± standard deviation 3.2% vs. 5.9 ± 3.4%; p = 0.004). Similarly, the four-chamber view also showed a higher peak LAS in the digoxin group (7.2 ± 3.6% vs. 6.4 ± 3.8%; p = 0.047). Considering the entire LAS curve rather than solely the peak value, digoxin significantly increased all LAS curves. In the global and four-chamber view, the digoxin maximum effect occurred significantly earlier than the peak of the LAS curve (p < 0.001). This effect remained constant over the cardiac cycle in the two-chamber curve (p < 0.001).

Conclusion

Our findings suggest that, in patients with rate-controlled AF, digoxin positively modulates LAS when compared with bisoprolol.

Clinical Trials Registration Number

NCT05540600, https://clinicaltrials.gov.

Nicotinamide adenine dinucleotide (NAD⁺) is a promising anti-aging molecule that plays a role in cellular energy metabolism and maintains redox homeostasis. Additionally, NAD⁺ is involved in regulating deacetylases, DNA repair enzymes, inflammation, and epigenetics, making it indispensable in maintaining the basic functions of cells. Research on NAD⁺ has become a hotspot, particularly regarding its potential in cardiovascular disease (CVD). Many studies have demonstrated that NAD⁺ plays a crucial role in the occurrence and development of CVD. This review summarizes the biosynthesis and consumption of NAD⁺, along with its precursors and their effects on raising NAD⁺ levels. We also discuss new mechanisms of NAD⁺ regulation in cardiovascular risk factors and its effects of NAD⁺ on atherosclerosis, aortic aneurysm, heart failure, hypertension, myocardial ischemia–reperfusion injury, diabetic cardiomyopathy, and dilated cardiomyopathy, elucidating different mechanisms and potential treatments. NAD⁺-centered therapy holds promising advantages and prospects in the field of CVD.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.

Background

Morphine is used to control pain in ST-elevation myocardial infarction but reduces P2Y12 inhibition. It is not known if this modulation of platelet inhibition appreciably affects clinical outcomes.

Methods

We screened 979 articles and identified seven studies that met the eligibility criteria for meta-analysis. Outcomes included 11 metrics across angiographic and clinical domains. A random effects model assessed heterogeneity between studies.

Results

The opiate group showed decreased achievement of postprocedural thrombolysis in myocardial infarction (TIMI) 2 flow relative to placebo [risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52–0.97, p = 0.03, I² = 0.0%]. All other metrics listed below showed no statistically significant difference between groups: infarct size, microvascular obstruction, microvascular/salvage index, absence of pre- percutaneous coronary intervention (PCI) TIMI 3 flow, postprocedural TIMI 2 flow, postprocedural TIMI 3 flow, all-cause mortality, stroke, repeat MI, unstable angina, and left ventricular ejection fraction. However, there were no statistically significant differences in infarct size [odds ratio (OR) − 0.12, 95% CI − 0.37 to 0.17, p = 0.42], microvascular obstruction [standard mean difference (SMD) = 0.02, 95% CI − 0.12 to 0.16, p = 0.82], microvascular obstruction/salvage index (SMD = − 0.05, 95% CI − 0.24 to 0.13, p = 0.57), absence of pre-PCI TIMI 3 flow (OR 0.98, 95% CI 0.79–1.22, p = 0.87), and postprocedural TIMI 3 flow (OR 1.23, 95% CI 0.84–1.79, p = 0.28) between the two groups.

Conclusions

In STEMI, opiates correlate with worse angiographic outcomes, specifically postprocedural TIMI 2 flow. However, this observation does not appear to be clinically consequential.

Background

CDK4/6 inhibitors are highly valued, but the incidence of cardiovascular adverse events (CVAEs) associated with CDK4/6 inhibitors is not clear.

Objective

Our aim was therefore to assess the risk of developing CVAEs associated with CDK4/6 inhibitors, by conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), along with a pharmacovigilance study of the FDA Adverse Event Reporting System (FAERS) database.

Methods

Eligible CVAEs were extracted from the ClinicalTrials.gov registry. A systematic search of electronic databases (PubMed, Embase, Cochrane Library, and important meetings) until 3 September 2023 was conducted. A disproportionality analysis was performed from the first quarter (Q1) of 2013 to Q1 of 2023 using data from the FAERS database. Study heterogeneity was assessed using the I² statistic. Using Peto odds ratio (Peto OR) and inverse variance methods to calculate the risk and incidence of CVAEs associated with CDK4/6 inhibitors.

Results

In total, 17 RCTs with 23,437 patients were included in our meta-analysis. During the follow-up period of 8.4–34.0 months, CDK4/6 inhibitors significantly increased the risk of CVAEs (Peto OR, 1.86, 95% confidence interval, 1.30–2.68, P < 0.01). The rates of hypertension and QT prolongation were 68.07 (62.87–73.27) and 57.15 (50.83–63.48) per 1000 patients, respectively. Moreover, we identified nine CVAEs that were not reported in RCTs. These included acute coronary syndrome, arrhythmia, lymphoedema, hot flush, vein rupture, thrombophlebitis migrans, embolism venous, angiopathy and intracardiac thrombus, which were found to be strongly correlated with CDK4/6 inhibitors. Furthermore, the risk of CVAEs varied depending on the specific CDK4/6 inhibitors used, its combination with different endocrine therapies, and the patient's treatment stage.

Conclusion

CDK4/6 inhibitors increase the risk of CVAEs, some of which may lead to serious consequences. Early recognition and management of CVAEs is of great importance in clinical practice.

Registration

PROSPERO registration number CRD42023462059.