Journal of Cardiovascular Pharmacology最新文献

The number of patients living with chronic kidney diseases is increasing, and so are the patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT). While there is a common understanding that these patients face higher risks of fatal or non-fatal cardiovascular and cerebrovascular events, and mineralocorticoid receptor antagonists (MRA) have been an essential pillar in managing heart failure, their use in this subset of patients have been overshadowed due to concerns of hyperkalemia. ESRD patients under RRT have often been excluded from landmark trials. This meta-analysis was conducted based on the PRISMA guideline after registering the protocol with PROSPERO (CRD42024499835). A database search included articles until April 2024 and relevant data extracted from the included studies. Analysis was done using RevMan web (version 5.4). A total of 15 studies among 1086 studies were included in the final analysis. Our meta-analysis revealed MRA significantly reduced all-cause mortality (OR 0.35, CI 0.23- 0.54) and cardio-vascular mortality (OR 0.37, 0.21-0.65). With some possible increase in the risk of hyperkalemia (OR 1.56, CI 1.01-2.42), with no discernible difference in the occurrence of stroke (OR 0.57, CI 0.25-1.28) or MI (OR 0.63, CI 0.08-4.72). The utilization of MRA in patients with ESRD under dialysis is linked to improved mortality outcomes, albeit with slight concerns for hyperkalemia. While current evidence leans towards MRA usage, prospective randomized controlled trials involving a broader patient cohort are essential to establish robust guidance for MRA application in this subset of patients.

Large scale randomized trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors can reduce cardiovascular events in patients with cardiovascular disease or with increased risks of cardiovascular disease. However, the evidence from older patients is limited. To compare the efficacy of SGLT2 inhibitors among non-older and older patients we have searched PubMed, Cochrane Central, and Embase until February 2023 for randomized controlled trials (RCTs) investigating SGLT2 inhibitors in older (age ≥ 65 years) patients with diabetes mellitus, chronic kidney disease, and chronic heart failure. The primary outcome was a composite outcome of cardiovascular death, acute myocardial infarction, and stroke. The secondary outcomes were exacerbation of heart failure, kidney disease progression, and a composite of cardiovascular death and heart failure. Our search identified 11 RCTs with a total of 79,370 patients. SGLT2 inhibitors were associated with a reduced risk of the primary outcome in the total cohort (HR: 0.91; CI [0.84-0.99]) with concordant results in both non-older and older populations (HR: 0.96; CI [0.88-1.05], HR: 0.87; CI [0.75-1.01], respectively) without subgroup differences (p=0.23), and a reduced risk of developing the composite of cardiovascular death and heart failure exacerbation in both non-older and older populations (HR: 0.77; CI [0.67-0.87], HR: 0.76; CI [0.71-0.82], respectively) without subgroup differences (p=0.96). A meta-analysis could not be performed for the other outcomes. These results suggested that SGLT2 inhibitors were similarly associated with a reduced risks of cardiovascular events across the spectrum of non-older and older patients with risk factors for developing cardiovascular disease.

Loop diuretics are a fundamental cornerstone in management of hypervolemia encountered in acute decompensated heart failure. There is variation in literature describing relative potency of loop diuretic agents, and very limited available data specific to the heart failure population. In this retrospective cohort study, we aimed to compare the urine output response between intravenous furosemide and bumetanide in patients with acute decompensated heart failure. Patients were eligible for inclusion if they were admitted between July 1, 2021 and June 30, 2022, with acute decompensated heart failure and received intravenous bumetanide or furosemide within 48 hours of admission. Propensity matching was utilized to determine comparison groups. The primary outcome was total urine output for 24 hours following initiation of the diuretic regimen. A total of 120 patients (60 in each group) were matched after exclusion criteria were applied. The total urine output was similar between groups. The bumetanide group did demonstrate a greater urine output: furosemide equivalent response (52 ± 46 mL/mg versus 33 ± 25 mL/mg; p=0.007). Based on our analysis, similar urine output may be achieved with either intravenous bumetanide or furosemide in acute decompensated heart failure; however a higher dose of furosemide may be required than what has been previously established as an equivalent dose to bumetanide to achieve a similar diuretic effect. These results should warrant further investigation to better establish dose-response relationships with loop diuretics in the acute decompensate heart failure.

Abstract: Patients with atrial fibrillation (AF) taking antithrombotic (AT) therapy are at an increased risk of gastrointestinal bleeding (GIB). The comparative effect of a combination of anticoagulant (AC) and antiplatelet (AP) versus AC monotherapy on clinical outcomes in patients with AF presenting with GIB is not well characterized. This study compares outcomes in AF patients with GIB on AC alone with those on combination AP and AC therapy, as part of a larger prospective study from 2013 to 2023. One hundred and thirty-seven patients diagnosed with AF who presented with overt GIB were evaluated during their hospitalization, at 1 month and 1 year postdischarge and then annually. The median follow-up of patients was 57 months. Patients in the combination AP + AC therapy group had a higher prevalence of coronary artery disease, myocardial infarction, and coronary/vascular stent placement compared with the AC monotherapy group. No statistically significant differences were noted between the 2 groups in terms of end-of-follow-up mortality, in-hospital mortality, major bleeding, rebleeding, and length of hospital stay. Cox regression analysis revealed chronic kidney disease [hazard ratio (HR) 2.05, 95% confidence interval (1.04-4.05) ( P = 0.038)] and warfarin use [HR 4.94, 95% confidence interval (1.11-22.09) ( P = 0.037)] to be independent predictors of mortality at 12 months. Antithrombotic therapy in patients with AF who experience GIB should be mainly directed by their cardiovascular needs. Health care providers may explore non-vitamin K antagonist oral anticoagulants as alternatives to warfarin for AF patients at risk of GIB, and efforts must be maximized to prevent bleeding in patients with chronic kidney disease.

Abstract: In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an interleukin-1 blocker, significantly reduced systemic inflammation, measured as the area under the curve (AUC) for high-sensitivity C reactive protein at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical end points at 1 year. Patients received a single administration of goflikicept 80 mg (n = 34), goflikicept 160 mg (n = 34), or placebo (n = 34). Both doses of goflikicept significantly reduced the AUC for high-sensitivity C reactive protein at 28 days compared with placebo, without statistically significant differences between the doses. There were no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg, and 160 mg groups in deaths (2.9%, 2.9%, and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, interleukin-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.

Abstract: Extracorporeal membrane oxygenation (ECMO) is a mechanical support treatment modality used in patients with refractory cardiac and/or pulmonary failure. Bleeding and thrombotic complications associated with ECMO are inherent concerns that require careful management. Anticoagulation optimization may help mitigate these risks by providing more adequate therapeutic anticoagulation and lessen the bleed risk. Heparin, the most used anticoagulant, carries concerns for heparin-induced thrombocytopenia and possible resistance given its dependence on cofactors and circulating proteins to exert its pharmacologic effect. In contrast, bivalirudin, a direct thrombin inhibitor, exerts its effect independent of cofactors or plasma proteins, and possesses thrombin-binding and metabolism features that may confer advantages in ECMO management. This review of the evidence for bivalirudin utilization in ECMO suggests favorable outcomes in circuit-related thrombosis, bleeding, and dosing reliability. In addition, blood product utilization, circuit interventions, and success in ECMO decannulation and survival were positive findings associated with bivalirudin that merit consideration. Common questions and concerns relative to bivalirudin utilization, including laboratory monitoring, utilization in low-flow states, dosing considerations in renal replacement therapy, reversibility, and cost are also discussed in this review. Moreover, this review suggests that bivalirudin utilization presents the opportunity for ECMO management simplification.

Abstract: Malnutrition is known to worsen the prognosis of chronic heart failure (HF). To gain information that may be helpful in establishing appropriate nutritional interventions for chronic HF, this study was performed to investigate the efficacy of nutritional management with 2 enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat HF model. After being fed a standard rodent feed (MF) containing 8% NaCl (high salt-MF [HS-MF]) from 6 to 11 weeks of age, rats were assigned to freeze-dried EH or ER diets with an NaCl concentration of 8% (HS-ER or HS-EH) until 18 weeks of age. Serum albumin was significantly higher at 14 and 17 weeks of age in rats fed the HS-ER and HS-EH diets compared with those remaining on the HS-MF diet. Body weight was also significantly higher at 14 and 17 weeks of age in animals fed the HS-ER diet, showing that nutritional deterioration was prevented. In addition, heart weight was significantly lower at 18 weeks of age in the HS-ER group than that in the HS-MF group, suggesting that cardiac hypertrophy was prevented. This study demonstrated improved nutritional status in a HF model in Dahl rats presumably owing to differences in nutritional composition in the diets. Future studies are needed to explore optimal nutritional management with enteral formulas in patients with chronic HF.

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided into two groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios (HR), and tested interactions between subgroups. All three CAD complexity scores (SYNTAX, SYNTAX II and Gensini) were associated with an increased risk of adverse events (HR 1.02 to 1.06, all p-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multi-vessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all p-values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.