Therapeutic Advances in Cardiovascular Disease最新文献

In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience. We will review the phase III evidence for each of the available NOACs in different antithrombotic indications, including atrial fibrillation (in the absence of significant mitral stenosis or mechanical heart valves); prophylaxis of venous thromboembolism (VTE) in patients undergoing orthopedic surgery; and acute and long-term treatment of VTE. Further, we will illustrate scenarios in which the evidence is stronger for a particular agent in the context of the overall positive safety and efficacy profile of NOACs in general. Limitations of the factor Xa inhibitors include the lack of a specific antidote in case of a bleeding emergency (an approved agent is available for reversing the effect of the direct thrombin inhibitor). We discuss the options for mitigating bleeding and describe the ongoing developments towards specific reversal agents. In conclusion, the available data for efficacy and safety, together with reliable pharmacokinetics obviating the need for regular monitoring, indicate that NOACs may offer substantial benefits for patients with nonvalvular atrial fibrillation or VTE.

Background:: There have been significant advances in the treatment of patients with cardiomyopathy with reduced ejection fraction (EF < 40%). However, there is a dearth of information in the treatment of patients with cardiomyopathy and midrange EF (40-50%). Current guidelines state to treat these patients similarly to patients with cardiomyopathy and preserved EF. Data from the Prevention of Events with Angiotensin-Converting Enzyme Inhibition (PEACE) trial were used to elucidate whether angiotensin-converting enzyme (ACE) inhibitors improve clinical outcomes in patients with ischemic cardiomyopathy and midrange EF.

Methods:: A post hoc subgroup analysis of the PEACE trial was conducted to evaluate the effect of ACE inhibitors in a subgroup of patients with ischemic cardiomyopathy and midrange EF (40-50%). A Chi-square test and a Student's t-test were used to examine and compare the binary and continuous variables of baseline characteristics and outcomes between experimental and comparison groups.

Results:: We studied a subgroup of patients from the PEACE trial with ischemic cardiomyopathy and midrange EF ( n = 2512 of 8290 total patients). Patients were assigned to either the interventional group ( n = 1247) or the placebo group ( n = 1265). There were no significant differences in baseline demographic and health characteristics between the two groups. During a total of 7 years (mean 4.7 years) of follow up, the risk of composite outcomes [all-cause mortality, nonfatal myocardial infarction, and stroke; relative risk (RR) 0.79, 95% confidence interval (CI) 0.63-0.98; p = 0.03] and all-cause mortality (RR 0.85, 95% CI 0.73-0.99; p = 0.03) was reduced in patients treated with trandolapril.

Conclusion:: This study revealed the benefit of ACE inhibitors among patients with ischemic cardiomyopathy and midrange EF.

Background:: There is still much controversy about whether meteorological conditions influence the occurrence of acute aortic dissection (AAD). The aim of the present study was to investigate the possible correlation between atmospheric pressure, temperature, lunar cycle and the event of aortic dissection in our patient population.

Methods:: The clinical data for 348 patients with AAD (73% type Stanford A) were confronted with the meteorological data provided by the Cologne weather station over the same period.

Results:: There were no statistically significant differences between meteorological parameters on days of AAD events compared with control days. A logistic regression model showed that air pressure (odds ratio [OR] 1.004, 95% confidence interval [CI] 0.991-1.017, p = 0.542), air temperature (OR 0.978, 95% CI 0.949-1.008, p = 0.145), season ( p = 0.918) and month of the event ( p = 0.175) as well as presence of full moon (OR 1.579, 95% CI 0.763-3.270, p = 0.219) were not able to predict AAD events. Also, no predictive power of meteorological data and season was found on analysing their impact on different types of AAD events.

Conclusions:: Our study did not reveal any dependence of atmospheric pressure, air temperature or the presence of full moon on the incidence of different types of AAD.

Background:: Over the past decade, prehospital and in-hospital treatment for out-of-hospital cardiac arrest (OHCA) has improved considerably. There are sparse data on the long-term outcome, especially in elderly patients. We studied whether elderly patients benefit to the same extent compared with younger patients and at long-term follow up as compared with the general population.

Methods:: Between 2001 and 2010, data from all patients presented to our hospital after OHCA were recorded. Elderly patients (⩾75 years) were compared with younger patients. Neurological outcome was classified as cerebral performance category (CPC) at hospital discharge and long-term survival was compared with younger patients and predicted survival rates of the general population.

Results:: Of the 810 patients admitted after OHCA, a total of 551 patients (68%) achieved return of spontaneous circulation, including 125 (23%) elderly patients with a mean age of 81 ± 5 years. In-hospital survival was lower in elderly patients compared with younger patients with rates of 33% versus 57% ( p < 0.001). A CPC of 1 was present in 73% of the elderly patients versus 86% of the younger patients ( p = 0.031). In 7.3% of the elderly patients, a CPC >2 was observed versus 2.5% of their younger counterparts ( p = 0.103). Elderly patients had a median survival of 6.5 [95% confidence interval (CI) 2.0-7.9] years compared with 7.7 (95% CI 7.5-7.9) years of the general population ( p = 0.019).

Conclusions:: The survival rate after OHCA in elderly patients is approximately half that of younger patients. Elderly patients who survive to discharge frequently have favorable neurological outcomes and a long-term survival that approximates that of the general population.

Background: The aim of the present study was to determine whether raised preoperative serum creatinine affected the long-term outcome in patients undergoing surgical aortic repair for Stanford A acute aortic dissection (AAD).

Methods: A total of 240 patients diagnosed with Stanford A AAD underwent surgical repair from January 2006 to April 2015. A propensity score matching was applied, resulting in 73 pairs consisting of one group with normal and one group with preoperative elevated creatinine levels. The cohorts were well balanced for baseline and preoperative clinical characteristics. Both groups were compared regarding their early postoperative variables, as well as estimated survival with up to 9-year follow up. Also, the impact of acute postoperative kidney injury and its severity on long-term survival was analyzed.

Results: The proportion of patients suffering Stanford A AAD with raised creatinine levels was 31.3% ( n = 75). After propensity matching, there were no statistically significant differences regarding demographics, comorbidities, preoperative baseline and clinical characteristics. Postoperatively matched patients with elevated creatinine had longer intensive care unit ( p < 0.001) and total hospital stay ( p = 0.002), prolonged intubation times ( p = 0.014), higher need for hemofiltration ( p < 0.001), higher incidence of temporary neurological disorders ( p = 0.16), infection ( p = 0.005), and trend toward higher incidence of sepsis ( p = 0.097). However, there were no significant differences regarding 30-day mortality (20.5% versus 20.5%, p = 1.000) and long-term overall survival. Further, neither the incidence nor the different stages of acute kidney injury according to the Acute Kidney Injury Network showed any statistically significant differences in terms of long-term survival for both groups [log rank p = 0.636, Breslow (generalized Wilcoxon) p = 0.470, Tarone-Ware p = 0.558].

Conclusions: Patients with elevated creatinine levels undergoing surgical repair for Stanford A AAD demonstrate higher rate of early postoperative complications. However, 30-day mortality and long-term survival in this patient cohort is not significantly impaired.

Background: The aim of this study was to evaluate endovascular treatment for enlarged Stanford type B chronic aneurysmal aortic dissection (CAAD). The conventional treatment for CAAD is open repair; however, the operative mortality is high in extensive prosthetic graft replacements.

Methods: A retrospective single-center study was conducted on 74 consecutive patients who underwent endovascular treatment for CAAD in the past 8.5 years. In the partial exclusion (PE) group, entry sites in close proximity to the maximum diameter of CAAD were closed using a stent graft and reentry sites were left without closure. In the complete exclusion (CE) group, we attempted to close all entry and reentry sites.

Results: A total of 43 patients (PE group) and 31 patients (CE group) were included with mean ages of 59 and 63 years, respectively. Operative mortalities of 2.3% and 0% were observed in the PE and CE groups, respectively. Complete tear closure was successful in 17 of 31 patients (54.8%) in the CE group. In the PE group, complete thrombosis of the false lumen was achieved in only one case (2.3%). Freedom rates from reentry closure were 90.2%, 86.9%, and 78.2% at 1, 3, and 5 years, respectively. The diameter of the true lumen/aorta changed from 16.9/62.9 mm to 30.2/53.6 mm and from 13.7/55.1 mm to 25.8/51.0 mm in the aortic arch and descending thoracic aorta, respectively. The freedom rates from secondary intervention in successful and unsuccessful CE cases were 92.9% and 69.1%, respectively, at 1 year and 92.9% and 53.7%, respectively, at 3 years.

Conclusion: Endovascular treatment for CAAD had favorable early and midterm outcomes.

Background: We analyzed the adequacy of the myocardial protection achieved with a single dose of retrograde crystalloid Celsior®, compared with an accepted standard (microplegia), in on-pump coronary artery bypass grafting surgery (CABG).

Methods: This was a retrospective comparative clinical study conducted in a single institution that included all the patients operated on who had elective isolated on-pump CABG, from March 2006 to June 2014. We evaluated maximum postoperative troponin T (TnT) as a marker of myocardial damage, adjusted for possible confounders using propensity score matching. We also analyzed markers of recovery of myocardial function, and the safety of the intravenous use of Celsior®.

Results: During the study period, 261 patients were included, divided in two groups: (a) continuous retrograde blood-based microplegia (114 patients); (b) retrograde single-dose crystalloid Celsior® (147 patients). The propensity score adjusted maximum TnT was significantly lower in the Celsior group [average treatment effect = -0.55 ng/dl; 95% confidence interval (CI) -1.10 to -0.1 ng/dl; p = 0.048]. There were no differences in the postoperative use of intra-aortic balloon of counterpulsation or in the requirements of high-dose inotropic medications. In-hospital mortality was equivalent in both study groups ( p = 0.73); surgical re-exploration because of bleeding was equivalent ( p = 0.37). There were no differences in prolonged mechanical ventilation ( p = 0.65) and intensive care unit length of stay ( p = 0.87).

Conclusion: An isolated single dose of retrograde Celsior® may be an effective and safe myocardial protection strategy in on-pump CABG.

Background: To review data from the pivotal phase III trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), and to summarize the major findings with regards to patient subgroups that are at an increased risk for stroke or bleeding.

Methods: A PubMed literature search (January 2009 to January 2017) was performed using the terms 'dabigatran', 'rivaroxaban', 'apixaban', 'edoxaban', 'atrial fibrillation', 'RE-LY', 'ROCKET AF', 'ARISTOTLE', and 'ENGAGE AF-TIMI 48'. All primary publications and secondary analyses in special populations at increased risk of stroke or bleeding from the pivotal phase III clinical trials were evaluated.

Results: Available secondary analyses indicate no treatment interactions with regards to stroke or systemic embolic event (SEE) prevention for any of the DOACs in the patient subgroups, including patients with advanced age, impaired renal function, diabetes, prior stroke, concomitant antiplatelet therapy, heart failure, prior stroke, history of hypertension, myocardial infarction (MI), coronary artery disease, and peripheral artery disease (PAD). Although higher bleeding incidence was reported with dabigatran and rivaroxaban in patients aged 75 years and over with apixaban in patients with diabetes, and with rivaroxaban in patients with previous MI or PAD, no changes in dosing are recommended.

Conclusions: Overall, results of secondary analyses indicate that the recommended dosing strategy for each of the DOACs produces a consistent anticoagulant effect across a diverse patient population, including those at increased risk of stroke or bleeding.

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia ( ClinicalTrials.gov identifier: NCT03068585). The objective of this follow-up study was to evaluate the long-term safety and efficacy of gene therapy in patients with limb ischemia of atherosclerotic genesis.

Aims: To evaluate the long-term safety and efficacy of the therapeutic angiogenesis, 36 patients in the treatment group (pl- VEGF165) and 12 patients in the control group participated in a 5-year follow-up study. Planned examinations were carried out annually for 5 years after pl- VEGF165 administration.

Results: Differences in the frequency of major cardiovascular events (pl- VEGF165 5/36 versus control 2/12; p = 0.85), malignancies (pl- VEGF165 1/36 versus control 0/12; p = 0.38) and impaired vision (there was none in either group) over the 5-year follow-up period did not achieve statistical significance. The target limb salvage was 95% ( n = 36) and 67% ( n = 12) in the pl- VEGF165 and control groups, respectively. The pain-free walking distance value increased by 288% from 105.7 ± 16.5 m to 384 ± 39 m in the treatment group by the end of the fifth year, with a peak of 410.6 ± 86.1 m achieved by the end of the third year. The ankle-brachial index (ABI) increased from 0.47 ± 0.01 to 0.56 ± 0.02 by the end of the first year, with a subsequent slight decrease to 0.51 ± 0.02 by the fifth year. The maximum increment of transcutaneous oximetry test (tcoO₂) by 36%, from 66.6 ± 3.7 mm Hg to 90.7 ± 4.9 mm Hg, was observed by the end of the second year.

Conclusion: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.