The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease

Abstract Background hyperlipidemia is one of the most important cardiovascular risk factors. Statins at high doses are commonly prescribed to lower LDL-cholesterol, but are often poorly tolerated. In particular, muscle pain and increase of creatine phosphokinase are frequent side effects. The purpose of this study was to assess whether the addition of a nutraceutical to simvastatin may result in the achievement of the therapeutic target (LDL-cholesterol less than 70mg/dL) without side effects in patients with ischemic heart disease. Methods Sixty-four patients with ischemic heart disease treated with simvastatin 20mg who had not achieved the therapeutic target were enrolled. Patients were randomised 1:1. Patients of group A (n=32) were given simvastatin 40mg per day and patients of group B (n=32) were given simvastatin 20mg plus 2 tablets of a nutraceutical composed of bergamot, phytosterols, artichoke, vitamin C. Results After 3months, patients in both groups showed a significant reduction from baseline in total cholesterol, LDL-c and tryglicerides. However, in group A, 4 patients reported myalgia (9,7%) with an increase in creatine phosphokinase; whereas no adverse events occurred in group B. Conclusions The association of a nutraceutical and simvastatin 20mg may be a valid therapeutic option for the treatment of hyperlipidemia in patients with ischemic heart disease intolerant to statin at high doses, in the absence of side effects. Further studies are needed to clarify the mechanisms of action of nutraceuticals

Additive effects of nutraceuticals to non-pharmacologic intervention to improve lipid profile in the real world clinical practice in European countries — The PIN (Portugal Italy Nutraceutical) Study

PEARL trial. Patientswere randomly assigned to atorvastatin (20 mg day, N= 50) or rosuvastatin (10 mg day, N= 50) for 30 days. After another 1-week wash-out period to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days. Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the point-of-care VerifyNow assay [Accumetrics, San Diego, California]) was measured before and at the end of each 30-day treatment period. High platelet reactivity after clopidogrel was defined as a PRU value N 208. Results: After the 30-day treatment with atorvastatin, platelet reactivity did not significantly change as compared with baseline, pre-treatment evaluation (119 ± 66 vs 136 ± 59 PRU, NS), with 2 patients only showing a PRU N 208. Similarly, after 30-day treatment with rosuvastatin, platelet reactivity was unchanged as compared with baseline (135 ± 46 vs 128 ± 62 PRU, NS), with PRU N 208 occurring in 3 patients. Conclusion: Atorvastatin does not negatively affect DAPT as compared with rosuvastatin when is given to stable CAD patients with baseline normal platelet reactivity while on DAPT. (ClinicalTrials.gov Identifier: NCT01567774)

Ranolazine reduces symptoms of palpitations and documented arrhythmias in patients with ischemic heart disease — The RYPPLE randomized cross-over trial

Background: Ranolazine decreases the frequency of arrhythmias during the acute phases of ischemic heart disease (IHD), but it remains unknown if it has similar effects in the chronic phase of the disease. We performed a prospective, randomized, cross-over pilot trial to test the hypothesis that chronic treatment with ranolazine can reduce the incidence of documented arrhythmias and the related symptoms of palpitation in stable patients with IHD. Methods: We randomized 105 patients with stable IHD and symptoms of angina and palpitations already on therapy with betablockers and/or calcium antagonists to ranolazine (750 mg bid, N = 53) or placebo (N = 52) for 30 days (until T-1). After a washout period to avoid any carryover effect, cross-over was performed,and patients were switched to the other drug which was continued for 30 days (until T-2). All patients underwent symptomlimited exercise stress testing and 48-hour ECG Holter monitoring at T1 and T2. During the study period, patients were told to use a OmronN® portable ECG monitor HCG-801 device in case of symptoms of palpitations. Results: Ranolazine reduced the number of anginal episodes more commonly than placebo (5 ± 8 episodes/30 days vs. 21 ± 24 episodes/30 day, p = 0.001) and increased exercise durations at 1 mm ST-segment depression (514 ± 211 s vs. 402 ± 287 s, p = 0.025) and at onset of angina (614 ± 199 s vs. 519 ± 151 s, p = 0.007) at stress testing. These effects were coupled by significant decreases with ranolazine as compared with placebo treatment periods in the occurrence of frequent (N1000 beats) supraventricular arrhythmias (33% vs 52%, p = 0.01) and complex ventricular arrhythmias (17% vs 30%, p = 0.045). Complete resolution of symptoms of palpitations was significantly more common with ranolazine than placebo (31/53 vs 16/52 patients, p = 0.008). Also, portable ECG recordings showed that arrhythmias were less common during ranolazine vs. placebo, with significant decreases in number (7 ± 10 episodes/30 days vs. 23 ± 29 episodes/30 day, p = 0.001) and duration (10 ± 18 min/ 30 days vs. 19 ± 21 min/30 day, p = 0.021) of symptomatic arrhythmic episodes. No severe side effects were recorded during the trial period. Conclusion: The antianginal and antiischemic properties of ranolazine are paralleled by significant decreases in the occurrence of both arrhythmias and the related symptoms of palpitations in stable patients with IHD. (ClinicalTrials.gov identifier: NCT01495520)

Enhancing quantum efficiency of thin-film silicon solar cells by Pareto optimality

We present a composite design methodology for the simulation and optimization of the solar cell performance. Our method is based on the synergy of different computational techniques and it is especially designed for the thin-film cell technology. In particular, we aim to efficiently simulate light trapping and plasmonic effects to enhance the light harvesting of the cell. The methodology is based on the sequential application of a hierarchy of approaches: (a) full Maxwell simulations are applied to derive the photon’s scattering probability in systems presenting textured interfaces; (b) calibrated Photonic Monte Carlo is used in junction with the scattering matrices method to evaluate coherent and scattered photon absorption in the full cell architectures; (c) the results of these advanced optical simulations are used as the pair generation terms in model implemented in an effective Technology Computer Aided Design tool for the derivation of the cell performance; (d) the models are investigated by qualitative and quantitative sensitivity analysis algorithms, to evaluate the importance of the design parameters considered on the models output and to get a first order descriptions of the objective space; (e) sensitivity analysis results are used to guide and simplify the optimization of the model achieved through both Single Objective Optimization (in order to fully maximize devices efficiency) and Multi Objective Optimization (in order to balance efficiency and cost); (f) Local, Global and “Glocal” robustness of optimal solutions found by the optimization algorithms are statistically evaluated; (g) data-based Identifiability Analysis is used to study the relationship between parameters. The results obtained show a noteworthy improvement with respect to the quantum efficiency of the reference cell demonstrating that the methodology presented is suitable for effective optimization of solar cell devices

Echocardiographic and Macroscopic Images Aortic Cusp Laceration

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Usefulness of nutraceuticals (armolipid plus) versus ezetimibe and combination in statin-intolerant patients with dyslipidemia with coronary heart disease

Statins are extensively used to treat dyslipidemia, but, because of their low tolerability profile, they are discontinued in a significant proportion of patients. Ezetimibe and nutraceuticals have been introduced as alternative therapies and have proved to be effective and well tolerated. A single-blind, single-center, randomized, prospective, and parallel group trial comparing a combination of nutraceuticals (red yeast rice, policosanol, berberine, folic acid, coenzyme Q10 and astaxanthin), called Armolipid Plus, and ezetimibe for 3 months in terms of efficacy and tolerability. Patients who did not achieve their therapeutic target (low-density lipoprotein cholesterol <100 mg/dl) could add the alternative treatment on top of randomized treatment for another 12 months: 100 patients who are dyslipidemic with ischemic heart disease treated with percutaneous coronary intervention were enrolled (ezetimibe n = 50, nutraceutical n = 50). Efficacy (lipid profile) and tolerability (adverse events, transaminases, and creatine kinase) were assessed after 3 and 12 months. After 3 months, 14 patients in the nutraceutical group achieved their therapeutic target, whereas none of the patients in the ezetimibe group did. At 1-year follow-up, 58 patients (72.5%) of the combined therapy group (n = 86) and 14 (100%) of the nutraceutical group reached the therapeutic goal. No patients experienced important undesirable effects. In conclusion, nutraceuticals alone or in combination with ezetimibe are well tolerated and improve the lipid profile in statin-intolerant patients with coronary heart disease. Further studies are needed to assess long-term effects of nutraceuticals on mortality

Transesophageal echocardiography through nasal way as a guide to percutaneous closure of patent foramen ovale

Percutaneous device closure of patent foramen ovale (PFO) has become an effective and safe alternative to medical or surgery treatment. Transesophageal echocardiography (TEE), as commonly used to guide this procedure, has the limitation to require general anesthesia. Recently, intracardiac echocardiography (ICE) with AcuNav probe was used to guide percutaneous PFO closure. We report a 42 year-old man with two previous cryptogenetic strokes in whom both diagnosis and guidance of PFO closure were performed by means of TEE using the AcuNav catheter introduced through nasal way (TEENW). This technique, that does not require general anesthesia, provided adequate and complete view of the Amplatzer procedure. TEENW might offer a feasible and equivalent echocardiographic alternative either to standard TEE or ICE as a guide to percutaneous PFO closure

Greater cardiovascular risk reduction with once-daily fixed combination of three antihypertensive agents and statin versus free-drug combination. the all-in-one trial

BACKGROUND: The ultimate goal of antihypertensive therapy is cardiovascular risk (CVR) reduction. The aim of this study was to compare the efficacy and safety of once-daily fixed combination (ODFC) versus free-drug combination (FDC) of 3antihypertensive agents and statin. METHODS: The ALL-IN-ONE trial was a 12-week randomized, prospective, multicenter trial. A total of 305 hypertensive patients were randomized 1:1. The "fixed group" was given an ODFC of perindropil 10mg plus indapamide 2.5mg plus amlodipine 5 or 10mg plus atorvastatin 20mg. The "free group" was given a FDC of the 3antihypertensive agents plus atorvastatin 20mg. Primary end-points were the differences in clinic BP, cholesterol levels and CVR risk between the 2 groups after treatments. Secondary end-points included intragroup differences in clinic BP. Safety and compliance were also assessed. RESULTS: At 12-weeks, the fixed group had lower systolic BP and similar diastolic BP compared to the free group. BP targets at week 12 were more commonly reached with fixed than free combination (89% and 80% respectively, p=0.048). For cholesterol serum in both groups there was a significant reduction of values. Also CVR reduction was greater in those taking ODF. Safety was not significantly different between the 2 groups. Conversely, compliance was significantly greater in the fixed-group vs. the free-group. CONCLUSION: This randomized trial shows that ODF combination of perindropil, indapamide and amlodipine is as safe as free combination of the 3 drugs, but is associated with a greater efficacy in BP control, compliance and, associated with statin, in cholesterol reduction. A better cardiovascular risk control is achieved with ODF combination than with a free administratio

Gender related differences in treatment and response to statins in primary and secondary cardiovascular prevention. The never-ending debate

Statins are a main curbstone in the prevention of cardiovascular disease (CVD), pandemic in 21st century. CVD displays evident sex and gender differences, not only in clinical manifestation and outcomes but also in pharmacological treatment. Whether statin therapy should be differentially prescribed according to sex is a matter of debate. Aside a different pharmacological action, statins are not proven to be less effective in one gender comparing to the other, nor to be less safe. Nevertheless, up to date evidence shows that statins have not been adequately tested in women, especially in primary prevention trials. Since data-lacking, making a treatment decision on women is potentially harmful, although female individuals represent the majority of the population and they have a greater lifetime CVD risk. Therefore, adequately powered randomized control trials with longer follow-up are warranted to establish if a benefit on CV events and mortality prevention exists in both sexes. The aim of the present review is to summarize the sex and gender differences in statin use: it raises concerns and updates perspectives towards an evidence-based and sex-tailored prevention of CVD management