1,720,985 research outputs found
Pharmacokinetics, pharmacodynamics and clinical efficacy of non-statin treatments for hypercholesterolemia
No full textINTRODUCTION: Hypercholesterolemia is the main modifiable risk factor for atherosclerosis progression and cardiovascular disease (CVD) development. Its pharmacological management is usually based on the prescription of statins, that in some cases are not however fully effective to reach the desired Low-Density-Lipoproteins cholesterol (LDL-C) target, or are not tolerated by patients due to side effects. Areas covered: This manuscript summarizes the basic properties of the emerging new classes of lipid-lowering drugs such as ezetimibe, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors, and Microsomal Triglyceride Transfer Protein (MTP) inhibitors, also citing new drugs in development. Our aim is to describe the main pharmacodynamic and pharmacokinetic characteristics, the available efficacy, tolerability and safety data obtained in randomized clinical trials where these drugs were tested. Expert opinion: Non-statin lipid-lowering drugs can be considered an excellent strategy to reduce the residual CV risk, also represented by non-target LDL-C values and high lipoprotein(a) serum levels. In particular, the approved PCSK9 inhibitors (Evolocumab and Alirocumab) have been very effective in optimizing plasma LDL-C values and reducing CV event risk
The Effect of Xanthine Oxidase Inhibitors on Blood Pressure and Renal Function
No full textSeveral epidemiological studies have demonstrated the existence of a correlation between high serum uric acid (SUA) levels, hypertension, and chronic kidney disease (CKD). Xantine oxidase inhibitors (XOI) are the most powerful uric acid lowering drugs, with presumed beneficial effects on cardiovascular and renal system. The multifactorial mechanism linking hyperuricemia with cardiovascular and renal diseases involves both the SUA level and the xanthine oxidase (XO) activity. In this context, the clinical research has been recently focused at assessing the efficacy of urate-lowering drugs active on XO in patients with abnormal blood pressure values and renal dysfunction. The mechanism of action responsible for the beneficial effect of XOI has not completely elucidated, and long-term studies involving large population samples are needed. In particular, XOI could play an important role in the management of hypertension and CKD, especially in patients not entirely controlled by conventional therapies. In the present review, we summarize the results of recent clinical trials that largely support a positive effect of allopurinol and febuxostat on blood pressure, glomerular filtration rate (GFR), and serum creatinine in different populations of patients. Will these drugs be considered a reliable choice or alternative to currently used drugs for the hypertension and kidney failure treatment? The debate is open, but much evidence is accumulating and supporting this role
An evidence-based review on urate-lowering treatments: implications for optimal treatment of chronic hyperuricemia
Full text linkSeveral studies suggest that chronic hyperuricemia, the main precursor of gout, is involved in the pathogenesis of different systemic disorders that affect cardiovascular and renal systems, such as hypertension, obesity, hypercholesterolemia, atherosclerosis, metabolic syndrome, chronic heart failure, and chronic kidney disease. Recent epidemiological evidence has shown an increasing trend in the prevalence of hyperuricemia and gout in the Western world: a number of population-based studies estimate a prevalence of up to 21% for hyperuricemia and 1%-4% for gout. As such, early detection and careful management of this pathological condition is required, starting from lifestyle changes (mainly based on a diet low in red meat, sugars, and alcoholic beverages, with increased intake of vegetables, water, and vitamin C sources), adding specific drugs to lead serum uric acid (SUA) levels under the target value of 7 mg/dL. In particular, nonselective and selective XO inhibitors (allopurinol, oxypurinol, febuxostat) reduce SUA levels and the overproduction of reactive oxygen species, mainly related to XO overactivity that often causes inflammatory damage to the vascular endothelium. The effect of lowering SUA levels via XO inhibition includes an attenuation of oxidative stress and related endothelial dysfunction that largely contribute to the pathophysiology of metabolic syndrome and cardiovascular diseases. Therefore, the inhibition of XO overactivation seems to be an excellent therapeutic option to limit the harmful effects of excess UA and reactive oxygen species. In conclusion, rapid diagnosis and correct therapy for hyperuricemia may also improve the prevention and/or treatment of serious and multifactorial diseases. The available evidence supports the importance of promoting new experimental clinical trials to confirm the emerging antioxidant role of XO inhibitors, which could effectively contribute to cardiovascular and chronic kidney disease prevention
Optimizing Lipid Pattern by Adding a Combined Nutraceutical or Pravastatin to Fenofibrate Treatment in Hypertriglyceridemic Subjects: Single Site, Randomized, Open-Label, Post-Market Clinical Investigation
No full textIntroduction: Fenofibrate is an effective and safe treatment for hypertriglyceridemia. However, after TG reduction a residual dyslipidemia could appear and require further treatment.
Aim: To comparatively evaluate the short-term tolerability and efficacy of a combined lipid-lowering nutraceutical and pravastatin 40 mg in fenofibrate treated patients.
Method: We prospectively enrolled 40 patients well-tolerating treatment with micronized fenofibrate 145 mg/day and with residual dyslipidemia (LDL-C > 115 mg/dL and TG > 150 mg/dL). Exclusion criteria have been type 2 diabetes, Familial Hypercholesterolemia, previous cardiovascular diseases and severe chronic kidney disease. Then, we have randomly assigned the patients to treatment with pravastatin 40 mg or a combined lipid-lowering nutraceutical (Armolipid Plus®, containing monacolin 3 mg and berberine 500 mg).
Results: After 8 weeks of treatment, 80% of pravastatin treated patients (N. 16/20) and 75% of those treated with Armolipid Plus® (N. 15/20) reached the desired LDL-C target, while 50% of pravastatin treated patients (N. 10/20) and 80% of the Armolipid Plus® treated ones reached the desired TG target (N. 16/20). No one adverse event has been registered during Armolipid Plus®, while 1 patient claimed myalgia and 1 reported significant increase of CPK (> 3 ULN) during pravastatin treatment. Both patients were then treated with Armolipid Plus® with resolution of symptoms and CPK increase, respectively.
Conclusion: In hypertriglyceridemic patients treated with fenofibrate, the association with a combined lipid lowering nutraceutical seem to be more effective in optimizing residual hypertriglyceridemia than pravastatin 40 mg, while being more tolerable and having similar effect on LDL-C plasma level
Additional therapy for cholesterol lowering in ezetimibe-treated, statin-intolerant patients in clinical practice: results from an internal audit of a university lipid clinic
No full textObjective: The aim of our study was to evaluate the tolerability and efficacy of alternative approaches to improve cholesterolemia control in patients with statin-related myalgia treated with ezetimibe. Research design and methods: We retrospectively evaluated 3534 Clinical Report Forms (CRFs) filled in the period June 2012–June 2015 for first visits to the lipid clinic of the University of Bologna. For this study, we selected 252 CRFs based on the following criteria: statin-related myalgia, previous failed treatment with at least two low-dosed statins, well tolerated treatment with ezetimibe. Then, the following lipid-lowering treatments were added in order to improve the ezetimibe low density lipoprotein cholesterol (LDL-C) lowering efficacy, based on clinical judgment: fenofibrate 145 mg, rosuvastatin 5 mg 1 tablet/week, rosuvastatin 5 mg 2 tablets/week, red yeast rice (standardized in monacolin K 3 mg) + berberine 500 mg, berberine 500 mg b.i.d., phytosterols 900 mg + psyllium fiber 3.5 g b.i.d. Patients continuing to claim a tolerable myalgia were then treated with coenzyme Q10 nanoemulsions 200 mg/day. Results: The treatment with standard lipid-lowering diet plus ezetimibe alone was associated with a mean LDL-C reduction of 17 ± 2%. The additive LDL-lowering effect with the various tested treatment was: −16 ± 2% with fenofibrate 145 mg/day, −13 ± 1% with rosuvastatin 5 mg 1 tablet/week, −17 ± 3% with rosuvastatin 5 mg 2 tablets/week, −19 ± 4% with red yeast rice + berberine, −17 ± 4% with berberine b.i.d. and −10 ± 3% with phytosterols + psyllium b.i.d.; 11% of the patients treated with fenofibrate required treatment modification because of myalgia recurrence, while the percentage was negligible for the other tested treatments. In patients with residual tolerable myalgia, treatment with coenzyme Q10 for 8 weeks was associated with a mean improvement of the graduated myalgia score from 4.8 ± 1.9 to 2.9 ± 1.3 (p = 0.013). Conclusions: Some alternative treatments seems to be effective and well tolerated, thus improving the ezetimibe effect on cholesterolemia
Is it Possible to Significantly Modify Blood Pressure with a Combined Nutraceutical on Top of a Healthy Diet? The Results of a Pilot Clinical Trial
No full textIntroduction: Beyond the well-known effects on blood pressure (BP) of the dietary approaches to stop hypertension (DASH) and the Mediterranean diets associated to a correct lifestyle, often a lifestyle change is not simple and can show only long-time results: in this sense, a possible support might be derived from the use of some anti-hypertensive supplements or nutraceuticals, which may provide a significant reduction in blood pressure. Aim: We conducted a randomized, double-blind, placebo-controlled clinical trial in a group of 36 pre-hypertensive and first-degree hypertensive patients. Methods: The treatment period with a mix of bioactive substances (BPLN®, containing a donor of nitric oxide, magnesium, and vitamins) or placebo was 16-week long and was preceded by 4 weeks of diet stabilization. Results: At the end of the intervention, patients treated with the nutraceutical product showed a significant reduction of all morning pressure parameters and of evening systolic blood pressure, both versus the baseline and versus the group treated with placebo. These effects were maintained even after the first 16 weeks of treatment, confirming that the preliminary results were not due to simple changes in volume and do not lead to adaptation/tachyphylaxis. No patient complained of any side effects while taking the active treatment and placebo. Conclusions: The tested nutraceutical composite reduces systolic and diastolic blood pressure in the medium term, leading to a significant reduction in the estimated cardiovascular risk in a sample of patients with pre-hypertension or first-degree hypertension
Effect of combined lipid-lowering and antioxidant nutraceutical on plasma lipids, endothelial function, and estimated cardiovascular disease risk in moderately hypercholesterolemic patients: a double-blind, placebo-controlled randomized clinical trial
No full textIntroduction: Nutraceuticals are a good means to lower cardiovascular risk. Having established a reasonable pharmacological background, a new nutraceutical combination should be tested in clinical trials. Material and methods: This double-blind, placebo-controlled randomized clinical trial aims to evaluate the modulating effect, in a setting of controlled nutritional habits, of a combined food supplement with DIF1STAT (based on red yeast rice with a very low content of monacolins, linear aliphatic alcohols and niacin) and Olea europaea on plasma lipids and endothelial function, in a group of 40 healthy, moderately hypercholesterolemic patients in primary cardiovascular prevention. Results: After 8 weeks of treatment, when compared to the placebo group, the active treated patients experienced significant improvements of different metabolic parameters and endothelial reactivity compared to placebo. The treated patients showed a statistically significant percentage change in total cholesterol (-12.25 delta% vs. -1.8%, p < 0.01), low-density lipoprotein (LDL) cholesterol (-28.7 delta% vs. -1.1%, p < 0.01), high-density lipoprotein (HDL) cholesterol (+4.99% vs. +0.9%, p < 0.05), non-HDL cholesterol (-16.02 delta% vs. -1.5%, p < 0.01), SUA (-12.96 delta%, p < 0.05) and endothelial reactivity (+6.73% vs. -1.4%, p < 0.01). In both groups, there was no case of intolerance and the safety parameters were unchanged. Conclusions: The tested nutraceutical association is able to significantly improve different lipid parameters compared to placebo, and endothelial reactivity compared to baseline. Even if the study power appears to be adequate for the primary endpoints, the effect on endothelial function needs confirmation in a longer clinical trial
LDL-oxidation, serum uric acid and pulse-wave velocity relationship in chronic kidney disease: Data from the Brisighella heart study cohort
No full textAim.The aim of our study was to evaluate the relationship between oxidized LDL (oxLDL), elevated Serum Uric Acid (SUA) and arterial stiffness in subjects with normal renal function compared with subjects with mild or moderate chronic kidney disease (CKD).Methods:We selected from the database of the Brisighella Heart Study 205 adult non-smokers subjects, in primary prevention for cardiovascular disease, with normal renal function (M: 99, F: 106), 118 age-matched subjects with mild CKD (M: 55; F: 63) and 94 with moderate CKD (M: 44; F: 50), all visited during the 2012 population survey. All subjects under-
went a medical visit including the determination of LDL oxidative sus- ceptibility, oxLDL levels and arterial stiffness parameters such as Augmentation Index (AI) and Pulse Wave Velocity (PWV). Results: An univariate analysis revealed a direct correlation of PWV with t he main anthropometric, haemodynamic and laboratory values usually associated to higher arterial stiffness and a significant inverse correlation with LDL-C lag phase, HDL-C and apoAI (p<0.05), either in subjects with normal renal function, or with mild or moderate CKD. In a stepwise multiple regression model we observed that in normal renal function and
mild CKD groups the main predictors of PWV were age, Systolic Blood Pressure (SBP), ox-LDL, apoB and SUA (p<0.05), while in moderate CKD group the main predictors were age, SBP and apoB, only (p<0.05).Conclusions:In our population sample, SUA and oxLDL are signifcantly related to PWV in subjects with normal renal functions and with mild CKD, but not in subjects with more advanced CKD
Serum uric acid change and modification of blood pressure and fasting plasma glucose in an overall healthy population sample: data from the Brisighella heart study
No full textBackground: Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. It is less clear if changes in SUA are associated to different incidence in these main cardiovascular risk factors. Methods: From the cohort of the Brisighella Heart Study, we selected non-diabetic subjects that in 2008 were untreated with SUA-lowering drugs nor antihypertensive ones. Then we divided the subjects in four main groups: the ones that maintained their SUA level unchanged during the next 4 years, the ones that increased it >1 mg/dL without treatment, the ones that reduced it >1 mg/dL without drug treatment and the ones that reduced it >1 mg/dL with the continuous use of allopurinol. Results: Compared with 2008, SBP significantly increased in subjects with worsened (and untreated) SUA level, while improved in subjects treated with allopurinol (p < 0.05). In 2012, subjects with worsened (and untreated) SUA level had a significantly higher SBP compared with subjects with unchanged SUA and those with SUA improved after allopurinol treatment (p < 0.05). An identical trend has been observed as it regards FPG. Conclusion: It seems that SUA improvement could positively influence the age-related worsening of SBP and FPG in general population.Key messages Serum uric acid (SUA) is an emerging risk factor for incident hypertension and type 2 diabetes. SUA improvement could positively influence the age-related worsening of SBP and FPG in general population
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