Journal of Cardiovascular Pharmacology and Therapeutics最新文献

Background: Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model.

Methods: Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured.

Results: At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both p < 0.001), with no difference in sBP between vehicle and SZC (p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC (p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle (p < 0.01); urine sodium increased with SZC (p < 0.01); and urine calcium increased with patiromer (p < 0.01). Urine phosphorus decreased with patiromer (p < 0.01) but increased with SZC (p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017).

Conclusions: After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP.

Patients with pulmonary arterial hypertension (PAH) who are admitted to the hospital pose a challenge to the multidisciplinary healthcare team due to the complexity of the pathophysiology of their disease state and PAH-specific medication considerations. Pulmonary arterial hypertension is a progressive disease that may lead to death as a result of right ventricular (RV) failure. During acute on chronic RV failure it is critical to decrease the pulmonary vascular resistance with the goal of improving RV function and prognosis; therefore, aggressive PAH-treatment based on disease risk stratification is essential. Pulmonary arterial hypertension treatment for acute on chronic RV failure can be impacted by end-organ damage, hemodynamic instability, drug interactions, and PAH medications dosage and delivery. Sotatercept, a first in class activin signaling inhibitor that works on the bone morphogenetic protein/activin pathway is on track for Food and Drug Administration approval for the treatment of PAH based on results of recent trials in where the medication led to clinical and hemodynamic improvements, even when added to traditional PAH-specific therapies. The purpose of this review is to highlight important considerations when starting or continuing sotatercept in patients admitted to the hospital with PAH.

Current guidelines recommend anticoagulation alone for low-risk pulmonary embolism (PE) with the addition of systemic thrombolysis for high-risk PE. However, treatment recommendations for intermediate-risk PE are not well-defined. Due to bleeding risks associated with systemic thrombolysis, ultrasound-assisted catheter-directed thrombolysis (USAT) has evolved as a promising treatment modality. USAT is thought to decrease the rate of major bleeding by using localized delivery with lower thrombolytic dosages. Currently, there is little guidance on the implementation of USAT in the real-world clinical setting. This study was designed to evaluate our experience with USAT at this single community hospital with a newly initiated Pulmonary Embolism Response Team (PERT). All patients identified by the PERT with an acute PE diagnosed by a computed tomography (CT) scan from January 2021 to January 2023 were included. During the study period, there were 89 PERT activations with 40 patients (1 high-risk and 37 intermediate-risk PE) receiving USAT with alteplase administered at a fixed rate of 1 mg/h per catheter for 6 h. The primary efficacy outcome was the change in Pulmonary Embolism Severity Index (PESI) score within 48 h after USAT. The primary safety outcome was major bleeding within 72 h. The mean age was 57.4 ± 17.4 years and 50% (n = 20) were male, 17.5% (n = 7) had active malignancy, and 20% (n = 8) had a history of prior deep vein thrombosis (DVT) or PE. The mean PESI score decreased from baseline to 48 h post-USAT (84.7 vs 74.9; p = 0.025) and there were no major bleeding events. The overall hospital length of stay was 7.5 ± 9.8 days and ICU length of stay was 2.2 ± 2.8 days. This study outlined our experience at this single community hospital which resulted in an improvement in PESI scores and no major bleeding events observed.

Background: Moxonidine, an imidazoline I₁ receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic.

Aims: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes.

Methods: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment.

Results: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters.

Conclusion: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

Objective: This study evaluates the 3-year clinical outcomes of high Killip grade (III/IV) acute myocardial infarction (AMI) patients treated with either β-blockers (BB) and angiotensin-converting enzyme inhibitors (ACEI) or BB and angiotensin receptor blockers (ARB).

Methods: A total of 13,105 patients were registered at the Korea Acute Myocardial Infarction Registry at the National Institute of Health (KAMIR-NIH). Among them, 871 patients with high Killip classification AMI were divided into the BB + ACEI group (n = 489) and the BB + ARB group (n = 381). Following propensity score matching, 343 patients were selected in each group. All patients completed a 3-year follow-up period.

Results: The results indicate no significant differences between the BB + ACEI group and BB + ARB group in terms of cardiac death, recurrent myocardial infarction, and the rate of repeat percutaneous coronary intervention. However, the BB + ACEI group exhibited significantly lower risks in major adverse cardiac events (HR = 0.574, 95% CI: 0.421-0.783, p < .001), all-cause mortality (HR = 0.561, 95% CI: 0.404-0.778, p = .001), and non-cardiac death (HR = 0.365, 95% CI: 0.208-0.639, p < .001) compared to the BB + ARB group.

Conclusion: Our results suggest that BB + ACEI treatment is more beneficial than BB + ARB for high Killip grade AMI patients. Additionally, the BB + ACEI group has a superior preventative effect on mortality compared to the BB + ARB group.

Aims: In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis.

Methods and results: In this retrospective cohort study, we obtained de-identified health record data to extract anticoagulation strategy, comorbidities, prescriptions, lab values, and procedures for a cohort of patients with cirrhosis who develop AF. After selecting a propensity matched population to match patients with various anticoagulation strategies, we tracked data on outcomes for death, transfusion requirements, hospital and ICU admissions. After propensity score weighting and multivariable adjustment, anticoagulation strategy was associated with increased hospital admission count (OR = 1.74 per admission, P < .001), binary risk of hospital admission (OR = 1.54, P = .010) and risk of ICU admission (OR = 1.41, P = .047). We detected no significant differences in mortality, transfusion of blood products, or average length of stay. Direct oral anticoagulant (DOAC) prescriptions were associated with increased binary risk of hospital admission compared to warfarin prescriptions. In a third comparison, DOAC strategy alone was associated with increased hospital admission count (OR = 1.41 per admission, P < .001) and binary risk of hospital admission (OR = 1.52, P = .038) compared to no anticoagulation strategy.

Conclusion: Anticoagulation strategy in patients with cirrhosis and AF was associated with increased rate of hospital admission and ICU admission but not associated with increased risk of mortality or transfusion requirement.

Objective: Platelets are strongly associated with cardiovascular events due to their role in thrombotic processes. Reticulated platelets have higher prothrombotic potential. The aim of the study was to evaluate the effectiveness of immature platelet fraction (IPF) in predicting long-term clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This prospective, observational study enrolled patients with ACS treated with dual antiplatelet therapy comprising acetylsalicylic acid and clopidogrel or ticagrelor. The primary outcome was a composite endpoint defined as major adverse cardiovascular events (MACE): all-cause death, myocardial infarction (MI), ischemic stroke, or unplanned revascularization. IPF was determined using flow cytometry in the first 24 h of hospitalization. MACE were evaluated by 2 physicians based on electronic databases and source documentation including discharge letters received from patients upon telephone contact. Results: Overall, there were 140 ACS patients (mean age 65.1 ± 11.7, 37 females [26.4%]) included in this study. Of them, 22.9% had diabetes mellitus, 69.3% hyperlipidemia, 25% had a history of MI. The median IPF values were 2.85 [1.8-4.2] %. Clinical follow-up (median time: 57 months [interquartile range 55-59 months]) was available for 130 patients (92.9%). MACE occurred in 27 patients (20.8%). There were higher rates of MACE at higher IPF tertiles (3rd vs 1st tertile: HR = 5.341 95% CI: 1.546-18.454, P = .008). Cox regression analyses showed that IPF level was independently associated with MACE. Time-dependent receiver-operating characteristic curve analysis revealed area under the curve of 0.656 for 5-year outcome with an IPF cutoff point of 3.45% being 63.0% sensitive and 65.0% specific for MACE. Conclusions: The study showed IPF may be an independent predictor of long-term mortality and MACE (ClinicalTrials.gov number, NCT06177587).