Therapeutic Advances in Cardiovascular Disease最新文献

Background: Despite well established empiric dose adjustments for drug and disease-state interactions, the impact of body mass index (BM) on warfarin remains unclear. The objective of this study is to evaluate warfarin requirements in hospitalized patients, stratified by BMI.

Methods: This retrospective review included two cohorts of patients: cohort A (patients admitted with a therapeutic international normalized ratio (INR)) and cohort B (newly initiated on warfarin during hospitalization). Exclusion criteria included: age under 18 years, pregnancy, INR (goal 2.5-3.5), and warfarin thromboprophylaxis post orthopedic surgery. The primary outcome was mean total weekly dose (TWD) of warfarin based on weight classification: underweight (BMI <18 kg/m²), normal/overweight (BMI 18-29.9 kg/m²), obese (BMI 30-39.9 kg/m²), and morbidly obese (BMI ⩾ 40 kg/m²). Data were extracted from two community hospitals in reverse chronologic order during July 2015-June 2013 until both study institutions evaluated 100 patients per cohort in each BMI classification or until all patients had been evaluated within the prespecified timeframe.

Results: A total of 585 patients were included in cohort A (26 underweight, 200 normal/overweight, 200 obese, 159 morbidly obese). There was a statistically significant difference in TWD as determined by one-way analysis of variance ( p < 0.05). A Tukey post hoc test revealed a statistically significantly higher TWD in morbidly obese (41.5 mg) compared with underweight (25.6 mg, p < 0.05), normal/overweight (28.8 mg, p < 0.05) and obese patients (32.4 mg, p < 0.05). In cohort B, 379 patients were evaluated (9 underweight, 166 normal/overweight, 152 obese, 52 morbidly obese). Overall, 191 patients had a therapeutic INR on discharge (88.9% underweight, 52.4% normal/overweight, 44.1% obese, 55.8% morbidly obese, p = 0.035). Of those, there was a statistically significant difference in TWD ( p = 0.021) with a higher TWD in the morbidly obese (41 mg) compared with underweight patients (24.4 mg, p = 0.017).

Conclusions: Based on the results of this study, morbidly obese patients may require higher TWD to obtain and maintain a therapeutic INR.

Cardiovascular (CV) disease is a major cause of morbidity and mortality in the developing and the developed world. Mortality from CV disease had plateaued in the recent years raising concerning alarms about the sustained efficacy of available preventive and treatment options. Heart failure (HF) is among the major contributors to the CV-related health care burden, a persisting concern despite the use of clinically proven guideline-directed therapies. A requirement for more efficient medical therapies coupled with recent advances in bio-innovation led to the creation of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), which demonstrated substantial CV benefit when compared with the standard of care, enalapril, in patients with HF and reduced ejection fraction. Further investigations of this novel combination ARNI at the tissue level shed light into the anti-remodeling and cardioprotective effects of sacubitril/valsartan, while clinical studies in the phenotypes of HF with preserved ejection fraction, hypertension and subsets, coronary outcomes, postmyocardial infarction, and renal disease suggested that this combination could be beneficial across a wide spectrum of CV disease. Sacubitril/valsartan is a much-needed therapeutic advance in the avenue of CV disease.

Cardiovascular disease is currently not adequately managed and has become one of the main causes of morbidity and mortality worldwide. Current therapies are inadequate in terms of preventing its progression. There are several limitations, such as poor oral bioavailability, side effects, low adherence to treatment, and high dosage frequency of formulations due to the short half-life of the active ingredients used, among others. This review aims to highlight the most relevant aspects of the relationship between the cardiovascular system and the endocannabinoid system, with special attention to the possible translational effect of the use of anandamide in cardiovascular health. The deep and detailed knowledge of this interaction, not always beneficial, and that for years has gone unnoticed, is essential for the development of new therapies. We discuss the most recent and representative results obtained in the field of basic research, referring to the aforementioned subject, emphasizing fundamentally the main role of nitric oxide, renal physiology and its deregulation in pathological processes.

Atherosclerotic cardiovascular diseases (ASCVDs) are associated with a substantial mortality, physical morbidity, and mental disability. Elevated plasma low-density lipoprotein cholesterol (LDL-C) levels play a major role in the pathophysiology of ASCVDs. Statins have been shown to reduce ASCVD risk and associated events and are recommended as first-line therapy for treatment of hypercholesterolemia by current international guidelines. The key issue is to attain guideline-recommended LDL-C levels (below 70 mg/dl) for patients at very high cardiovascular risk. However, many high-risk and very-high-risk patients on statin therapy remain beyond treatment goals despite lifestyle modification and statins, and are exposed to a high risk of future cardiovascular events including myocardial infarction (MI), stroke, revascularization procedures, and death. This clearly emphasizes the urgent need for additional LDL-C reduction with new therapeutic strategies to target these highly atherogenic particles and to further reduce the burden of ASCVDs. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role as a key regulator of the hepatic LDL receptor recycling process. Developments over the past 15 years have demonstrated PCSK9 inhibition to be a novel therapeutic strategy to manage increased LDL-C levels. A number of clinical studies using humanized monoclonal antibody technology against PCSK9 have shown profound reductions of LDL-C levels when used either alone or in combination with statin therapy. Recently, the first cardiovascular outcome study demonstrated a significant reduction of ASCV events when evolocumab was added to a statin therapy. This review will discuss current knowledge about antibody-mediated PCSK9 inhibition as add-on therapy to statin and the clinical potential that may be expected.

Background The aim of this study was to evaluate the rheolytic effects of stenting a mid-shaft/distal left main coronary artery (LMCA) lesion with and without ostial coverage. Stenting of the LMCA has emerged as a valid alternative in place of traditional coronary bypass graft surgery. However, in case of mid-shaft/distal lesion, there is no consensus regarding the extension of the strut coverage up to the ostium or to stent only the culprit lesion. Methods We reconstructed a left main-left descending coronary artery (LM-LCA)-left circumflex (LCX) bifurcation after analysing 100 consecutive patients (mean age 71.4 ± 9.3, 49 males) with LM mid-shaft/distal disease. The mean diameter of proximal LM, left anterior descending (LAD) and LCX, evaluated with quantitative coronary angiography (QCA) was 4.62 ± 0.86 mm, 3.31 ± 0.92 mm, and 2.74 ± 0.93 mm, respectively. For the stent simulation, a third-generation, everolimus-eluting stent was virtually reconstructed. Results After virtual stenting, the net area averaged wall shear stress (WSS) of the model and the WSS at the LCA-LCX bifurcation resulted higher when the stent covered the culprit mid-shaft lesion only compared with the extension of the stent covering the ostium (3.68 versus 2.06 Pa, p = 0.01 and 3.97 versus 1.98 Pa, p < 0.001, respectively. Similarly, the static pressure and the Reynolds number were significantly higher after stent implantation covering up the ostium. At the ostium, the flow resulted more laminar when stenting only the mid-shaft lesion than including the ostium. Conclusions Although these findings cannot be translated directly into real practice our brief study suggests that stenting lesion 1:1 or extending the stent to cover the LM ostium impacts differently the rheolytic properties of LMCA bifurcation with potential insights for restenosis or thrombosis.

The simplification of fixed dose medications by using a single 'polypill' is an attractive strategy to improve adherence to medications which has shown benefit to cardiovascular risk factor control and cardiovascular disease prevention or delay in the progression of these diseases. We review the evidence obtained from a series of clinical trials demonstrating an improvement in adherence to the polypill compared to the use of each compound separately, and found similar or better control of the classical cardiovascular risk factors and a similar safety profile. These results suggest that the use of the polypill could have a beneficial impact in cardiovascular morbidity and mortality. Furthermore, the polypill has the potential to improve cost effectiveness and is simple to use. However, before recommending the implementation of the polypill in programs aimed at primary and secondary cardiovascular prevention, we are awaiting the results of several current clinical trials aimed at measuring the impact on the frequency of major cardiovascular outcomes, particularly in low-medium-income countries.