Journal of Cardiovascular Pharmacology and Therapeutics最新文献

Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has been approved for the treatment of HF. At present, there have been few systematic and detailed reviews discussing the efficacy and safety of sacubitril/valsartan in HF. In this review, we first introduced the pharmacological mechanisms of sacubitril/valsartan, including the reduction in the degradation of natriuretic peptides in the natriuretic peptide system and inhibition of the renin-angiotensin system. Then, we summarized the efficacy of sacubitril/valsartan in HF patients with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) including the reduction in risks of mortality and hospitalization, reversal of cardiac remodeling, regulation of biomarkers of HF, improvement of the quality of life, antiarrhythmia, improving renal dysfunction and regulation of metabolism. Finally, we discussed the safety and tolerability of sacubitril/valsartan in the treatment of HFrEF or HFpEF. Compared with ACEIs/ARBs or placebo, sacubitril/valsartan showed good safety and tolerability, although the risk of hypotension might be high. In conclusion, the overwhelming majority of studies show that sacubitril/valsartan is effective and safe in the treatment of HFrEF patients but that it has little benefit in HFpEF patients. Sacubitril/valsartan will probably be a promising anti-HF drug in the near future.

Background: Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting.

Methods: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO.

Results: Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO.

Conclusion: The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

The obesity pandemic is accompanied by increased risk of developing metabolic syndrome (MetS) and related conditions: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular (CV) disease (CVD). Lifestyle, as well as an imbalance of energy intake/expenditure, genetic predisposition, and epigenetics could lead to a dysmetabolic milieu, which is the cornerstone for the development of cardiometabolic complications. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs promote positive effects on most components of the "cardiometabolic continuum" and consequently help reduce the need for polypharmacy. In this review, we highlight the main pathophysiological mechanisms and risk factors (RFs), that could be controlled by GLP-1 and dual GIP/GLP-1 RAs independently or through synergism or differences in their mode of action. We also address the evidence on the use of GLP-1 and dual GIP/GLP-1 RAs in the treatment of obesity, MetS and its related conditions (prediabetes, T2DM and NAFLD/NASH). In conclusion, GLP-1 RAs have already been established for the treatment of T2DM, obesity and cardioprotection in T2DM patients, while dual GIP/GLP-1 RAs appear to have the potential to possibly surpass them for the same indications. However, their use in the prevention of T2DM and the treatment of complex cardiometabolic metabolic diseases, such as NAFLD/NASH or other metabolic disorders, would benefit from more evidence and a thorough clinical patient-centered approach. There is a need to identify those patients in whom the metabolic component predominates, and whether the benefits outweigh any potential harm.

Peripheral artery disease (PAD) is a severe manifestation of atherosclerosis. Patients with PAD are at heightened risk for atherothrombotic complications, including myocardial infarction and stroke (MACE); however, there is also an equal or greater risk of major adverse limb events (MALE), such as acute limb ischemia (ALI) and major amputation. Therefore, there is a need for effective medical therapies to reduce the risk of both MACE and MALE. Recent trials have demonstrated the role of thrombin inhibition in reducing the risk of MACE and MALE in PAD patients. One such medical therapy, vorapaxar, is a potent inhibitor of protease activated receptor-1 which mediates the cellular effects of thrombin. Vorapaxar, used in addition to aspirin, has demonstrated robust reductions in MACE and MALE in PAD patients. In this article, we provide a contemporary review of the current state of PAD and the role of antithrombotic medications in the treatment of PAD, as well as the current clinical data on vorapaxar and strategies to integrate vorapaxar into contemporary medical management of peripheral artery disease.

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

Background and aims: Morphine use for patients presenting with NSTE-ACS is associated with excess mortality. However, the role of morphine in STE-ACS is ill characterized. We have recently confirmed direct prothrombotic effect of morphine using murine models. We sought to explore whether morphine use in STE-ACS patients, used to be scheduled for downstream P₂Y₁₂ blockers, is negatively associated with procedural and clinical outcomes.

Methods: A single-center, observational retrospective analysis enrolling 130 non-randomized stable patients sustaining STE-ACS as their first manifestation of coronary disease, who presented between December 2010 and June 2013. All were managed by early invasive approach. Of study patients, 55 were treated by morphine, and 75 were not. All were administered downstream P₂Y₁₂ blockers according to an already abandoned local policy. Outcomes evaluated included TIMI grade flow, thrombus burden, ST-segment resolution, myocardial function by echocardiography, and cardiovascular death.

Results: Morphine administration was associated with a significantly higher incidence of impaired final TIMI grade flow (TIMI < 3, 40% vs 4%, P < .05), lower incidence of ST-segment resolution >70% (40.7% vs 76.5%, P < .05), and a higher incidence of moderate or severe systolic dysfunction (48.1% vs 29.1%, P < .05) compared with morphine naive patients. Interestingly, the overall mortality rate was higher in the morphine-treated group (18% vs 5.3%, P < .05).

Conclusions and relevance: Morphine administration combined with the downstream P₂Y₁₂ blockers practice signify a group with a higher occurrence of impaired myocardial reperfusion and cardiovascular death despite established on-time primary angioplasty.

Introduction: Studies suggest that non-alcoholic fatty liver disease (NAFLD) is associated with an independent risk of cardiovascular disease (CVD). We utilized a large cohort of patients undergoing myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) to determine the association between alanine aminotransferase (ALT) as a surrogate marker for presumed NAFLD, and the presence of myocardial ischemia and mortality.

Methods: We retrospectively assessed SPECT-MPI results and medical records of individuals evaluated between 1997 and 2008. We excluded patients with known non-NAFLD liver diseases, ALT values <17 or >340 U/L and absent liver tests. Elevated ALT cases were classified as presumed NAFLD. The primary endpoint was abnormal SPECT-MPI. Secondary endpoints included cardiac death, acute myocardial infarction and all-cause mortality.

Results: Of 26,034 patients who underwent SPECT-MPI, 11,324 met inclusion criteria. 1635 (14.4%) patients had elevated ALT. SPECT-MPI results did not differ significantly between subjects with elevated ALT and controls. Elevated ALT was associated with increased risk for the composite endpoint of cardiac death or acute myocardial infarction at 5-year follow-up (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.01-1.67) and in all-cause mortality (HR 1.27, CI 1.02-1.58) but only in patients with normal SPECT-MPI.

Conclusions: The long-term mortality of patients with abnormal SPECT-MPI is not modulated by ALT, likely reflecting an already high risk and established CVD. However, patients with normal SPECT-MPI are at increased risk for a future cardiac event if they have an elevated ALT level, suggesting an important role for NAFLD in earlier stages of CVD.