Journal of Cardiovascular Pharmacology and Therapeutics最新文献

Acute heart failure, advanced cardiac failure, cardiac surgery, and sepsis are conditions that require simultaneous treatment to stimulate contractility and/or reduce systemic vascular resistance, with levosimendan and milrinone being treatment options. This research's aim is to review the current indications and evidence for these medications across various scenarios. Evidence suggests that levosimendan is a non-inferior alternative to dobutamine and superior to milrinone in treating low cardiac output syndrome following cardiac surgery. In cases of septic shock, levosimendan has been linked to lower mortality rates compared to placebo, while milrinone's efficacy remains inconclusive. Furthermore, postoperative patients undergoing correction for congenital heart disease have shown reduced mechanical ventilation time and intensive care unit stays when treated with levosimendan, although differences exist between the populations assigned to each intervention. In conclusion, levosimendan, compared to milrinone, appears to offer better hemodynamic favorability in patients undergoing cardiac surgery. However, additional research is necessary to further understand its impact on hemodynamic outcomes, mortality, intensive care unit, and hospital stays in patients with cardiogenic shock of both ischemic and non-ischemic etiologies, as well as septic shock.

The dawn of cardioprotection by infarct size reduction originated from the idea to favourably alter the oxygen demand-supply balance of the ischaemic/infarcting myocardium by reducing the contractile determinants of its oxygen consumption. This idea is probably not correct, since the ischaemic/infarcting myocardium does not contract anyway. None of the successful initial preclinical attempts of infarct size reduction translated into clinical practice, except for timely reperfusion which has become and still is the backbone of all clinical infarct therapy up today. The idea of cardioprotection gained momentum again with the recognition of ischaemic conditioning, and a myriad of preclinical studies have identified molecules and mechanisms of such self-defence mechanism. Although there are positive clinical proof-of-concept studies, ischaemic conditioning strategies and drugs related to its signal transduction have not translated into clinical practice. We are currently trying to understand the obstacles to translation from successful preclinical studies on cardioprotection to clinical practice, but are also waiting for an innovative mechanistic breakthrough.

Purpose: The molecular etiology of atrial fibrillation (AF) and its treatment are poorly understood. AF involves both electrical and structural features. Vericiguat can ameliorate cardiac remodeling in heart failure. The effects of vericiguat on AF, however, are unclear. Here, the actions of vericiguat on atrial structural and electrical remodeling in AF and its possible mechanisms were investigated. Methods and Results: Thirty-six rabbits were randomly allocated to four groups, namely, sham, RAP (pacing with 600 beats/min over three weeks), vericiguat-treated (three weeks' pacing plus daily oral dose of 1.5 mg/kg of vericiguat), and vericiguat-treated only. HL-1 cells received rapid pacing with or without vericiguat. Parameters including electrophysiology, echocardiography, histology, Ca²⁺ levels, and I_CaL density, as well as levels of TRPC6, CaN, NFAT4, p-NFAT4, Cav1.2, collagen I, collagen III, and ST2 were measured. Significant changes of above proteins expression level, circulating biochemical indices, Ca²⁺ concentrations, and I_CaL density in both animals and cell models, these effects were significantly restored by vericiguat. Vericiguat also reversed the enlarged atrium and significantly reduced myocardial fibrosis, together with preventing reduced atrial effective refractory periods (AERPs) and AF induction rate. Conclusion: Vericiguat thus ameliorated AF-associated structural and electrical remodeling. These findings suggest the potential of vericiguat for treating AF.

Introduction: Ventricular remodeling is a mal-adaptive process. Both angiotensin-converting enzyme inhibitors and sacubitril/valsartan have been shown to reverse remodeling in mostly uncontrolled observational studies. There is a lack of head-to-head studies. Methods: This cohort study compares the remodeling effects of angiotensin receptor blockers combined with a neprilysin inhibitor (ARNI) and perindopril in heart failure with reduced ejection fraction (HFrEF) patients between January 2017 and December 2020. Inclusion criteria: (i) age > 18 years, (ii) recent diagnosis of de-novo HFrEF (EF < 40%), (iii) baseline echocardiography performed not more than 2 months prior to treatment onset, and (iv) follow-up echocardiography performed not earlier than 6 months and not later than 18 months posttreatment onset. No prior treatment with renin-angiotensin-aldosterone system inhibitors was permitted in the ARNI group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) were analyzed. A two-way repeated measure ANOVA (for normally distributed) and generalized estimating equation test for nonnormally distributed interval dependent variables. Mean comparison between and within groups was performed using the Bonferroni test. Results: Following an average treatment period of 9 months, LVEF improved from 24.9% to 36.4% for ARNI and from 28.7% to 40.5% for perindopril, increments of 11.5% and 11.8% resp. (Bonferroni test [P ≤ .05]). LVEDV was reduced by 8.4 mL and 3.2 mL, and LVESV by 17.9 mL and 10.8 mL for ARNI and perindopril resp. Only the reduction of LVESV for ARNI was statistically significant (P = .007). Conclusion: Both ARNI and perindopril yielded a significant improvement in the LVEF within 9 months. The remodeling effect of ARNI seems stronger because of the greater improvements in left ventricular volumes.

Background: The effect of combined nicorandil and beta-adrenergic receptor blockers (BBs) compared with that of BBs alone on long-term clinical outcomes in patients with coronary artery disease (CAD) remains undetermined.

Methods: A multicenter retrospective cohort study was performed. Adult patients who had been hospitalized for CAD and treated for angina with a combination of nicorandil and BBs or BBs alone were included. The effect of different treatments on the cumulative incidence of major adverse cardiovascular event (MACE) and their components within a follow-up duration of 2.5 years were analyzed using Kaplan-Meier survival curves. An inverse probability of treatment weighting (IPTW) method was used to adjust for the possible effect of confounding factors.

Results: A total of 137,714 patients were screened, of whom 16,912 individuals (mean age: 61.5 years, men: 67.1%) were successfully enrolled. Among the enrolled participants, 4669 received the combined treatment of nicorandil and BBs, while 12,243 received BBs alone. After IPTW, the results demonstrated that the combined treatment was associated with a significantly reduced incidence of MACE (hazard ratio [HR] 0.79, 95% conidence interval [CI] 0.72-0.87) and stroke (HR 0.48, 95% CI 0.42-0.54) but not of MI (HR 1.03, 95% CI 0.92-1.15) or all-cause mortality (HR 0.93, 95% CI 0.64-1.37). Sensitivity analyses revealed similar results.

Conclusions: A combined antiangina treatment of nicorandil and BBs may be more effective than treatment of BBs alone in reducing the long-term incidence of MACE in patients with CAD.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n  =  55) and the control group (n  =  101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 μmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and β2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P  =  .043). Compared with the control group, Scr, uric acid, and β2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P  =  .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

Introduction: This study evaluated the efficacy and safety of a single-pill triple-combination of olmesartan/amlodipine/rosuvastatin (Olme/Amlo/Rosu) in comparison with a single-pill dual-combination of olmesartan/amlodipine (Olme/Amlo) in hypertensive patients with low-to-moderate cardiovascular risk.

Methods: This multicenter, active-control, randomized study included 106 hypertensive patients at low-to-moderate cardiovascular risk who were randomly assigned to receive either Olme/Amlo/Rosu 20/5/5 mg (Treatment 1), Olme/Amlo/Rosu 20/5/10 mg (Treatment 2), or Amlo/Olme 20/5 mg (Control) once daily for 8 weeks. The primary endpoint was the difference of the percent change in low-density lipoprotein cholesterol (LDL-C) level at 8 weeks from baseline in the 3 groups.

Results: The difference in the least square mean percent change (standard deviation) of LDL-C in the Treatment 1 and 2 groups compared with the Control group at 8 weeks was -32.6 (3.7) % and -45.9 (3.3) %, respectively (P < .001). The achievement rates of LDL-C level <100 mg/dL at 8 weeks were significantly different between the 3 groups (65.8%, 86.7%, and 6.3% for Treatment 1, 2, and Control groups, respectively, P < .001). The results of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein B/apolipoprotein A1 were superior in the Treatment 1 and 2 groups compared with the Control group. Serious adverse drug reaction did not occur in the 3 groups. Medication adherence rates were excellent in the 3 groups (98.0% for Treatment 1 group, 99.7% for Treatment 2 group, and 96.3% for the Control group, P > .05).

Conclusion: Single-pill triple-combination of olmesartan/amlodipine/rosuvastatin was superior to the single-pill dual-combination of amlodipine/olmesartan in LDLC-lowering effects, with excellent safety profiles and adherence rates, in hypertensive patients at low-to-moderate cardiovascular risk.Trial Registration: CLinicalTrials.gov identifier NCT04120753.

Objective: To investigate the safety and effectiveness of catheter-based therapy (CBT) compared to conventional catheter-directed thrombosis (CDT) for non-oncological patients with inferior vena cava thrombosis (IVCT), as well to evaluate the differences between CBTs using AngioJet rheolytic thrombectomy (ART) and large lumen catheter aspiration (LLCA).

Methods: This retrospective single-center study included eligible patients with IVCT treated with CBTs coupled with/without CDT or CDT alone as the first-line treatment between January 3, 2015 and January 28, 2022. The baseline demographics, comorbidities, clinical characteristics, treatment details, course data were all reviewed.

Results: A total of 106 patients (128 limbs) were included, with 42 cases were treated with ART, 30 with LLCA, and 34 with CDT alone. Technical success rates were 100% (128/128), and 95.5% (84/88) limbs treated with CBT subsequently underwent CDT. The mean duration of CDT time and total infusion agent dosage in patients with CBTs were lower than those who underwent CDT alone (P < .05). Similarities were observed in ART compared to LLCA (P < .05). At the end of CDT, clinical success was achieved in 85.2% (75/88) of limbs treated with CBTs and 77.5% (31/40) of limbs with CDT alone, and 88.5% (46/52) in ART and 80.6% (29/36) in LLCA. The 12-month follow-up showed slightly lower incidences of recurrent thrombosis (7.7% vs 15.2%) and post-thrombotic syndrome (14.1% vs 21.2%), which persisted in patients who underwent ART compared to LLCA (4.3% vs 12.9% and 8.5% vs 22.6%). Patients who underwent CBTs tended to have lower minor complications (5.6% vs 17.6%) but were at higher risk of transient macroscopic hemoglobinuria (58.3% vs 0%) and recoverable acute kidney injury (11.1% vs 2.9%) compared to CDT alone. These findings were similar in ART compared to LLCA (2.4% vs 10.0%, 100% vs 0%, and 16.7% vs 3.3%, respectively). LLCA seemed to have more hemoglobin losses (10.50 ± 9.20 vs 5.57 ± 10. 42 g/L, P < .05).

Conclusion: CBTs coupled with/without CDT are safe and effective in patients with IVCT, reducing the clot burden in a moderate time, restoring blood flow rapidly, minimizing thrombolytic drug requirement and lowering minor bleeding complication compared to CDT alone. ART and LLCA have comparable outcomes but with different adverse event profiles.

Background: Heart failure (HF) is an important adverse outcome of diabetes mellitus (DM) with high rates of mortality and HF-related hospitalizations. The risk of HF is 2 times higher in patients with DM compared to those without DM. Due to under-recognition and underdiagnoses, HF is often a neglected outcome in the diabetic population. There is a dearth of data regarding the true prevalence of HF and the management protocols for diabetic patients at risk of HF in the UAE and the Middle East. This lacuna in the information has led to the inception of this "call to action" paper, which identifies the gaps in the true prevalence of HF and describes the importance of early diagnosis and appropriate management of HF in the Middle East.

Methodology: An advisory board meeting was convened and a group of key opinion leaders and experts in cardiology and endocrinology assembled to describe the prevalence, diagnosis, and management of HF in diabetes patients and to present a "call to action" in the UAE and Middle East scenario. After the group discussion, key expert opinions were formulated and "call to action" recommendations were proposed.

Conclusion: This "call to action" is mainly based on the available evidence from the literature and the experts' clinical experience. Based on the new evidence from various cardiovascular outcome trials, the "call to action" highlights a series of collaborative learning regarding the role of newer antidiabetic therapies like sodium-glucose cotransporter-2 inhibitors in the prevention and management of HF. This "call to action" intends to serve as a guide for physicians, including primary healthcare providers, in their management of diabetic patients with HF.