冠心病住院患者调脂药物应用情况调查

目的 调查冠心病住院患者中调脂药物的应用情况。方法 对347例确诊的冠心病患者在住院期间应用他汀类及贝特类调脂药物的使用情况进行调查，并对不同水平的LDL—C中他汀类药物的应用进行调查。结果 在347例患者中有221例的LDL—C＞2.6mmol/L，占63．69％，但仅有160例使用他汀类药物，使用率为46．1％；而使用贝特类药物的患者只有22例，使用率为6．3％。结论 在冠心病住院患者中存在着他汀类药物量使用不足的现象。     

新型代谢综合征治疗药物的设计、合成及生物活性评价

目的 设计合成新型代谢综合征治疗药物.方法 以具有降脂活性的阿昔莫司做为基本结构单元,与贝特类药物的"苯氧脂酸类"药效团有机结合,设计了一类新型的苯氧脂肪酸酯类化合物,以对羟基苯胺、对羟基苄胺以及对羟基苯乙胺为原料,首先将氨基保护,然后与相应的卤代脂肪链羧酸酯成醚,然后脱除Boc保护基得到相应的胺类中间体,最后与阿昔莫司成酰胺得目标化合物,并考察了目标化合物对Triton WR-1339所致急性高脂血症小鼠血清甘油三酯和总胆固醇的影响.结果和结论 合成目标化合物5个,均经1H NMR和ESI-MS确证结构正确.初步活性评价结果表明,所合成化合物均具有一定的降脂活性,其中化合物4c的调脂活性与阳性对照苯扎贝特接近,对于新型代谢综合征药物的发现具有积极意义.     

调脂药物的联合应用及安全性监测

血脂异常是动脉粥样硬化性心脑血管疾病的重要危险因素。他汀类药物通过降低低密度脂蛋白胆固醇水平,使心血管事件明显减少。但是即使采用大剂量的他汀类药物仍难以达到指南要求的血脂水平标准,因此针对合并糖尿病、代谢综合征等心血管高危人群,他汀类药物联合贝特类、烟酸类、胆固醇吸收抑制药等药物成为临床上的重要选择。     

Lipid and other management to improve arterial disease and survival in end stage renal disease

Introduction: Arterial disease is common in advancing renal failure, culminating in myocardial infarction with cardiac failure, strokes and peripheral and renal artery disease. Attention to cardiac and arterial disease may slow deterioration of renal function. Management of risk factors can reduce these sequelae.

Areas covered: Modifiable risk factors for arterial disease and relevant pharmacotherapies.

Expert opinion: Cardiovascular disease is the biggest killer in renal failure. Statins are viewed as essential in symptomatic coronary disease and have been shown in non-renal patients to improve survival after myocardial infarction. Cochrane recommends statins in renal failure but not in end stage renal disease or transplant patients. Large well powered clinical trials focussed specifically on renal patients failed to demonstrate cardiovascular outcome or mortality benefits of statins when compared to placebo. Other lipid lowering pharmacotherapies are weaker and adverse effects may account for the absence of net clinical benefit in non-renal patients in published clinical trials. Patients should be started on a statin after myocardial infarction, regardless of lipid levels, but the risk of adverse effects in advanced renal failure with its comorbidities predicates employing only essential doses. Optimal antihypertensive and antithrombotic pharmacotherapy are also priorities.     

PPAR agonists for the treatment of cardiovascular disease in patients with diabetes

Diabetes is a complex disease defined by hyperglycaemia; however, strong associations with abdominal obesity, hypertension and dyslipidaemia contribute to the high risk of cardiovascular disease. Although aggressive glycaemic control reduces microvascular complications, the evidence for macrovascular complications is less certain. The theoretical benefits of the mode of action of peroxisome proliferator-activated receptor (PPAR) agonists are clear. In clinical practice, PPAR-α agonists such as fibrates improve dyslipidaemia, while PPAR-γ agonists such as thiazolidinediones improve insulin resistance and diabetes control. However, although these agents are traditionally classed according to their target, they have different and sometimes conflicting clinical benefit and adverse event profiles. It is speculated that this is because of differing properties and specificities for the PPAR receptors (each of which targets specific genes). This is most obvious in the impact on cardiovascular outcomes-in clinical trials pioglitazone appeared to reduce cardiovascular events, whereas rosiglitazone potentially increased the risk of myocardial infarction. The development of a dual PPAR-α/γ agonist may prove beneficial in effectively managing glycaemic control and improving dyslipidaemia in patients with type 2 diabetes. Yet, development of agents such as muraglitazar and tesaglitazar has been hindered by various serious adverse events. Aleglitazar, a balanced dual PPAR-α/γ agonist, is currently the most advanced in clinical development and has shown promising results in phase II clinical trials with beneficial effects on glucose and lipid variables. A phase III study, ALECARDIO, is ongoing and will establish whether improvements in laboratory test profiles translate into an improvement in cardiovascular outcomes.     

Combination drug therapy for hyperlipidemia

Low-dose combination hypolipidemic therapy may be the best approach to achieve the stringent target low-density lipoprotein cholesterol (LDL-C) levels recommended by the latest National Cholesterol Education Program guidelines in patients with multiple risk factors or existing coronary heart disease. Three randomized, double-blind clinical trials have investigated the efficacy and safety of low-dose fluvastatin, a new, wholly synthetic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, in combination with bile acid sequestrants, fibric acid derivatives, and niacin, respectively. Low-dose fluvastatin coupled with low-dose cholestyramine proved to be significantly more effective than higher doses of either agent alone in reducing LDL-C levels in patients with hypercholesterolemia. The combination was well tolerated, with most adverse events attributable to the gastrointestinal effects of cholestyramine. In patients with heterozygous familial hypercholesterolemia and severely elevated LDL-C and triglyceride (TG) levels, the combination of fluvastatin with bezafibrate was equivalent to fluvastatin plus cholestyramine in lowering LDL-C levels but was superior in raising high-density lipoprotein cholesterol (HDL-C) levels and reducing TG levels. Bezafibrate was considerably better tolerated than cholestyramine. Neither regimen was associated with untoward elevations in hepatic transaminase or creatine phosphokinase levels. Combination therapy with fluvastatin and niacin reduced LDL-C levels by more than 30% in 90% of hypercholesterolemic subjects studied and decreased these levels by more than 40% in 60% of these subjects. The combination also increased HDL-C levels by 36.4%, decreased TG levels by 32%, and reduced lipoprotein (a) levels by 37%. These modifications were achieved without adverse hepatic or myopathic effects. In summary, low-dose fluvastatin can be safely and effective combined with either bile acids, fibrates, or niacin to achie greater reductions in LDL-C than standard monotherapy.     

Urinary incontinence—pharmacotherapy options

Abstract

Inflammatory changes are responsible for maintenance of the atherosclerotic process and may underlie some of the most feared vascular complications. Among the multiple mechanisms of inflammation, the arterial deposition of lipids and particularly of cholesterol crystals is the one responsible for the activation of inflammasome NLRP3, followed by the rise of circulating markers, mainly C-reactive protein (CRP). Elevation of lipoproteins, LDL but also VLDL and remnants, associates with increased inflammatory changes and coronary risk. Lipid lowering medications can reduce cholesterolemia and CRP: patients with elevations of both are at greatest cardiovascular (CV) risk and receive maximum benefit from therapy. Evaluation of the major drug series indicates that statins exert the largest LDL and CRP reduction, accompanied by reduced CV events. Other drugs, mainly active on the triglyceride/HDL axis, for example, PPAR agonists, may improve CRP and the lipid pattern, especially in patients with metabolic syndrome. PCSK9 antagonists, the newest most potent medications, do not induce significant changes in inflammatory markers, but patients with the highest baseline CRP levels show the best CV risk reduction. Parallel evaluation of lipids and inflammatory changes clearly indicates a significant link, both guiding to patients at highest risk, and to the best pharmacological approach.

• Key messages

• Lipid lowering agents with “pleiotropic” effects provide a more effective approach to CV prevention

• In CANTOS study, patients achieving on-treatment hsCRP concentrations ≤2?mg/L had a higher benefit in terms of reduction in major CV events

• The anti-inflammatory activity of PCSK9 antagonists appears to be of a minimal extent

     

Comparison of effects of fibrates in patients with hypertriglyceridemia

It has long been known that antihyperlipidemic agents categorized as fibrates are capable of reducing triglyceride concentrations, although the superiority of one over another remains questionable. In the present study, investigators compared treatment results from various fibrates. In all, 60 patients aged 54.1+/-12 y with hypertriglyceridemia were included in the study. Patients who had increased values on liver function tests, had been given a diagnosis of hypothyroidism or chronic renal failure, and who needed statin medication were excluded. Patients were divided into 4 groups according to the medication given; treatments consisted of Lipanthyl 1 x 1, Lipofentrade mark 1 x 1, Lopid 1 x 1, and Lopid 2 x 1. Biochemical and hematologic parameters of patients were recorded at the first visit and at the end of the 2-mo treatment period. A total of 18 patients (30%) were given Lipanthyl 1 x 1, 14 (23.3%) received Lipofen 1 x 1, 16 (26.7%) were treated with Lopid 1 x 1, and 12 (20%) were given Lopid 2 x 1. Effects on triglyceride values were assessed in all groups. Lopid 1 x 1 and Lopid 2 x 1 produced significant decreases in triglyceride values. Most adverse effects were reported in the group given Lopid 2 x 1. In the treatment of hypertriglyceridemia, fibrates have similar effects on tolerability and reliability. However, study findings indicated that Lopid 1 x 1 and 2 x 1 treatments have greater efficacy.