The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Hyperlipidemia

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of circulating levels of low-density lipoprotein (LDL) particles. PCSK9 acts mainly by enhancing degradation of the LDL receptor in the liver. Several gain-of-function and loss-of-function mutations in the PCSK9 gene have been identified and linked to hypercholesterolemia and hypocholesterolemia, respectively. Since the loss-of-function mutations in humans are associated with protection against coronary heart disease, and with no apparent deleterious effects, PCSK9 inhibition is becoming attractive as a new strategy for lowering LDL cholesterol (LDL-C) levels, particularly in combination with statins. Candidate patient populations for PCSK9 inhibition include those with familial hypercholesterolemia, patients at high risk of cardiovascular disease not controlled by statin therapy, and patients with poor tolerance or total intolerance to statin therapy. PCSK9 inhibition represents a very promising target for reducing LDL-C levels and decreasing the risk of atherosclerotic cardiovascular diseases, but human clinical trials will be crucial to assess the potency and safety of PCSK9 inhibitors.     

Statins and coronary artery bypass graft surgery: preoperative and postoperative efficacy and safety

Background: In patients with native coronary artery disease, strong evidence supports the use of statins to reduce the risk of recurrent cardiovascular events and improve survival. However, for patients undergoing coronary artery bypass graft surgery (CABG), statins appear to be underutilized, and concerns have been raised regarding their perioperative safety. Objective: The goal of this systematic review is to evaluate the safety and efficacy of statin therapy before and after coronary surgical revascularization. Methods: A systematic review was performed to retrieve relevant articles from the Medline database published between 1987 and January 2009. Results: Administered before CABG, statins have been demonstrated to reduce perioperative mortality, stroke and atrial fibrillation. Preoperative statin therapy also reduces the systemic inflammatory response associated with cardiopulmonary bypass. Following CABG, statins inhibit saphenous vein graft disease and the progression of atherosclerosis in native coronary arteries. In addition, postoperative statins reduce the recurrence of cardiovascular events and improve all-cause mortality. High-intensity lipid reduction to achieve low-density lipoprotein levels to 70 mg/dl may benefit post-CABG patients, but this has yet to be evaluated prospectively. Adverse effects related to perioperative statin therapy seem to be extremely rare, and little data are available to support the practice of withholding statin therapy before or after surgery. Conclusion: Numerous studies have demonstrated that statins improve the outcomes of patients undergoing CABG. The benefits seem to outweigh the risks associated with their use, both in the preoperative and postoperative period. In the absence of contraindications, essentially all CABG patients are candidates for life-long statin therapy that ideally should be started before surgery. The optimal postoperative statin regimen remains unknown and should be the subject of future study.     

Impact of C-reactive protein on treatment of patients with cardiovascular disease.

PURPOSE: The impact of C-reactive protein (CRP) on the treatment of patients with cardiovascular disease is described. SUMMARY: CRP is a marker of coronary heart disease and other disease states. Its release from the liver activates endothelial dysfunction and contributes to atherothrombosis. In healthy persons, CRP was found to be an independent risk marker for cardiovascular disease when compared with low-density-lipoprotein (LDL) cholesterol. In 2003, the Centers for Disease Control and Prevention and the American Heart Association published a statement regarding CRP's use in clinical practice and public health. In a primary prevention study, statins were shown to reduce CRP, and patients with a low concentration of LDL cholesterol and high CRP may benefit from statin therapy. The results of a secondary prevention study confirmed that CRP reduction was not related to the lipid-lowering effects of the statins and that pravastatin reduced coronary events regardless of inflammation status designated by the CRP value. Another study demonstrated that intensive pharmacotherapy was more effective than moderate therapy in reducing CRP, but it found no difference in clinical outcomes among statin regimens once the goal CRP value was attained. In atheroma ultrasound studies, a reduced CRP level was related to reductions in atheroma volume regardless of the statin regimen used. CONCLUSION: The correct use of CRP in pharmacotherapeutic monitoring of statins has not been fully elucidated. Until more data regarding CRP and statin use are available, pharmacists must continue to focus on risk factors other than CRP, such as cholesterol levels, medical history, social history, and lifestyle characteristics, when making clinical decisions regarding statin therapy.     

Effectiveness and hepatotoxicity of statins in men seropositive for hepatitis C virus

STUDY OBJECTIVE: To evaluate the effectiveness and hepatotoxicity of statins in patients who are seropositive for hepatitis C virus (HCV). DESIGN: Retrospective review of a registry of patients with HCV. SETTING: Veterans Affairs Medical Center. PATIENTS: One hundred forty-six male patients who were seropositive for HCV and had received statin therapy between January 1, 1995, and September 9, 2003. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were collected for each patient; lipid and alanine aminotransferase (ALT) levels at baseline (within 6 mo of starting a statin), at 3 and 6 months after starting a statin, and at long-term follow-up (mean 22 mo) were also recorded. The primary efficacy end point was a significant decrease from baseline to long-term follow-up low-density lipoprotein cholesterol (LDL) level; the primary safety end point was a significant increase from baseline in ALT level. The mean change in LDL level was a reduction of 22% (p<0.01). No significant increases in ALT levels were observed; only one patient discontinued therapy due to ALT level elevations greater than 3 times the upper limit of normal. CONCLUSION: In men seropositive for HCV, statins were effective in reducing LDL levels and did not result in significant increases in ALT levels from baseline. Thus, statin therapy should be considered for patients with HCV who are at risk for coronary heart disease and do not have significantly elevated serum transaminase levels at baseline.     

Combination therapy with statin and fibrate in patients with dyslipidemia associated with insulin resistance,metabolic syndrome and type 2 diabetes mellitus

Introduction: People with insulin resistance/metabolic syndrome (IR/MS) and/or type 2 diabetes mellitus (T2DM) have increased rates of cardiovascular disease (CVD) even when low-density lipoprotein cholesterol levels are at or near target levels. Contributors to this problem are the high triglyceride (TG) levels and low levels of high-density lipoprotein cholesterol (HDLC) that are commonly present in this population, even with statin therapy.

Areas covered: This review focuses on the use of a combination of statins with fibrates, which lower TG and raise HDLC concentrations and, therefore, have the potential to further lower rates of CVD more in people with IR/MS and/or T2DM. Treatment with this combination is uncommon because doctors and patients are fearful of muscle, liver and renal complications and because the evidence that the combination will actually reduce risk has been lacking. In this review, the authors examine the efficacy and safety of the statin–fibrate combination, particularly fenofibrate and simvastatin, the combination used in the ACCORD trial.

Expert opinion: The authors' opinion is that this combination of fenofibrate and statin is as safe as either drug alone and, in patients with significant dyslipidemia, is likely to reduce CVD. Concerns remain concerning fenofibrate-associated increases in serum creatinine levels and the significant heterogeneity in the reduction in CVD by the combination in women. A trial of statin + fenofibrate in people with IR/MS and/or T2DM who also have significant dyslipidemia is needed.     

Efficacy and safety evaluation of intensive statin therapy in older patients with coronary heart disease: a systematic review and meta-analysis

Purpose

To reveal and evaluate the efficacy and safety of intensive statin therapy in older patients (age ≥ 65 years) with coronary heart disease (CHD).

Methods

Electronic databases were searched for randomized controlled trials (RCTs) that involved intensive statin therapy use in older patients with CHD. Data was extracted and used to calculate risk ratios (RR) by software Revman 5.1.

Results

Five RCTs and 11,132 patients were included in. Compared with non-intensive statin therapy, intensive statin therapy had significant effect on reducing low density lipoprotein cholesterol (LDL-C) levels (55.4 %) and total cholesterol (TC) and triglyceride (Tg). Although the results showed that intensive statin therapy had no superior effect on reduction of mortality (both all-cause mortality [RR?=?0.97, p?=?0.65] and cardiac death [RR?=?0.95, p?=?0.57]) and cardiac arrest (RR?=?1.09, p?=?0.81), it possessed significant effects on prevention of nonfatal myocardial infarction (MI) (RR?=?0.78, p?=?0.008), stroke (RR?=?0.72, p?=?0.02) and coronary revascularization (RR?=?0.69, p?=?0.007). In terms of side effects, intensive statin therapy was associated with small absolute increase in incidence of drug discontinuation, due to adverse events (3.9 %) and liver enzymes abnormalities (1.7 %). And the occurrence rates of myopathy, rhabdomyolysis and creatine kinase (CK) elevation were very low.

Conclusions

This results show that intensive statin therapy has excellent effects on reduction of serum lipid level including LDL-C, TC, Tg, and also on prevention of nonfatal MI, stroke and coronary revascularization with small absolute increased risk of side effects. Our analysis supports the use of intensive statin therapy in patients ≥?65 years old with CHD.     

Safety issues with statin therapy.

OBJECTIVE: To describe the most important potential adverse effects related to statin therapy, discuss mechanisms of toxicity and drug interactions, and suggest approaches for enhancing safety with statin therapy. DATA SOURCES: Large-scale clinical trials, government databases and papers, and recent studies of statin safety. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: The number of patients requiring intensive therapy with statins to achieve lipid goals is climbing, and as the number grows, so does the potential for adverse effects with these agents. The most detrimental adverse effects of statins are hepatotoxicity and myopathy. Liver dysfunction induced by statins is rare and usually mild, with asymptomatic transaminase elevation or acute cholecystitis. Progression to liver failure is exceedingly rare, and transaminase elevations is usually reversible with dose reduction. Statin-associated myopathy is generally a concern when patients have more than one risk factor for muscle syndromes, such as an elderly patient with poor renal function. Drug interactions represent an additional concern, especially for atorvastatin, lovastatin, and simvastatin, all of which are metabolized by the important 3A4 isoenzyme of the cytochrome P450 system of the liver. CONCLUSION: The benefits of all available statins for the treatment or prevention of cardiovascular disease outweigh any potential risks of therapy. For patient groups most susceptible to adverse effects, such as the elderly and those on multiple medications, clinicians should consider the use of statins that are least likely to interact with other medications.     

Combination therapy with statin and fibrate in patients with dyslipidemia associated with insulin resistance, metabolic syndrome and type 2 diabetes mellitus

INTRODUCTION: People with insulin resistance/metabolic syndrome (IR/MS) and/or type 2 diabetes mellitus (T2DM) have increased rates of cardiovascular disease (CVD) even when low-density lipoprotein cholesterol levels are at or near target levels. Contributors to this problem are the high triglyceride (TG) levels and low levels of high-density lipoprotein cholesterol (HDLC) that are commonly present in this population, even with statin therapy. AREAS COVERED: This review focuses on the use of a combination of statins with fibrates, which lower TG and raise HDLC concentrations and, therefore, have the potential to further lower rates of CVD more in people with IR/MS and/or T2DM. Treatment with this combination is uncommon because doctors and patients are fearful of muscle, liver and renal complications and because the evidence that the combination will actually reduce risk has been lacking. In this review, the authors examine the efficacy and safety of the statin-fibrate combination, particularly fenofibrate and simvastatin, the combination used in the ACCORD trial. EXPERT OPINION: The authors' opinion is that this combination of fenofibrate and statin is as safe as either drug alone and, in patients with significant dyslipidemia, is likely to reduce CVD. Concerns remain concerning fenofibrate-associated increases in serum creatinine levels and the significant heterogeneity in the reduction in CVD by the combination in women. A trial of statin + fenofibrate in people with IR/MS and/or T2DM who also have significant dyslipidemia is needed.     

Statin discontinuation in high-risk patients: a systematic review of the evidence

Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. Since the late 1980s, statins have emerged as effective lipid-lowering therapies and are now widely used to protect against and slow the progression of CVD and cerebrovascular disease. However, there is a significant gap between disease improvement in clinical trials and daily practice possibly attributable to poor adherence with statin therapy. High discontinuation rates were reported in primary and secondary prevention. This systematic review aims to summarize the current literature regarding the association between statin therapy discontinuation and cardiovascular and cerebrovascular events and all-cause mortality in high-risk patients. Available English literature was reviewed using Medline, Embase, Web of Sciences and the Cochrane Library; 39 studies were identified. In primary and secondary prevention, as well as perioperatively, non-adherence or discontinuation of statin therapy was associated with detrimental effects on cardiovascular and cerebrovascular outcomes, including disease severity and mortality. Importantly, some studies reported that very low adherence and discontinuation was associated with worse outcomes than never using statins. In conclusion, non-adherence and discontinuation of statin therapy significantly increased the incidence of cardiovascular and cerebrovascular events as well as all-cause mortality in high-risk patients. Patients would therefore benefit from closer adherence assessment and education programs aimed at increasing awareness of the risk associated with discontinuation of statin therapy.     

Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?

The 3-hydroxy-3-methyl coenzyme A (HMG-CoA) reductase inhibitors or statins, specifically inhibit the enzyme HMG-CoA in the liver, thereby inhibiting the rate limiting step in cholesterol biosynthesis and so reducing plasma cholesterol levels. Numerous studies have consistently demonstrated that cholesterol lowering with statin therapy reduces morbidity and mortality from coronary heart disease, whilst recent evidence has demonstrated that benefits of statin therapy may also extend into stroke prevention. Since hypercholesterolaemia is a chronic condition, the long-term safety and tolerability of these agents is an important issue. Numerous large-scale clinical trials have consistently demonstrated a positive safety and tolerability profile for statins. Hepatic, renal and muscular systems are rarely affected during statin therapy, with adverse reactions involving skeletal muscle being the most common, ranging from mild myopathy to myositis and occasionally to rhabdomyolysis and death. Postmarketing data supports the positive safety and tolerability profile of statins, with an overall adverse event frequency of less than 0.5% and a myotoxicity event rate of less than 0.1%. The recent withdrawal of cerivastatin from the world market due to deaths from rhabdomyolysis has, however, focused attention on the risk of adverse events and in particular myotoxicity associated with statins. Indeed, initial clinical trial data supports postmarketing data, demonstrating a higher incidence of myotoxicity associated with cerivastatin, particularly when used in combination with fibrates. The potential mechanisms underlying statin-induced myotoxicity are complex with no clear consensus of opinion. Candidate mechanisms include intracellular depletion of essential metabolites and destabilisation of cell membranes, resulting in increased cytotoxicity. Cytochrome P450 3A4 is the main isoenzyme involved in statin metabolism. Reduced activity of this enzyme due to either reduced expression or inhibition by other drugs prescribed concomitantly such as cyclosporin or itraconazole may increase drug bioavailability and the risk of myotoxicity. Such factors may partly account for the interindividual variability in susceptibility to statin-induced myotoxicity, although other as of yet unclarified, genetic factors may also be involved. The risk of rhabdomyolysis is increased with combination fibrate-statin therapy, with initial evidence suggesting that gemfibrozil-statin combination may particularly increase the risk of myotoxicity, with pharmacodynamic as well as pharmacokinetic mechanisms being involved.     

Safety and efficacy of fibrate–statin combination therapy compared to fibrate monotherapy in patients with dyslipidemia: A meta-analysis

BackgroundDyslipidemia is a major risk factor for the development of cardiovascular disease. Treatment with fibrate, statins, or other lipid-lowering drugs prevents primary or recurrent cardiovascular events. However, all lipid-lowering drugs have side effects, which may become more severe if combination therapy is prescribed.MethodsWe performed a meta-analysis of published data to compare the safety and efficacy of fibrates alone, compared to fibrate–statin combinations, in patients with dyslipidemia. Six articles were assessed in terms of the efficacy of therapy and nine from the viewpoint of therapeutic safety.ResultsIn terms of efficacy, fibrate–statin combinations afforded significantly greater reductions in the levels of total cholesterol (SE = −2.248; 95% CI 1.986–2.510), LDL cholesterol (SE = −2.274; 95% CI 2.015–2.533), and triglycerides (SE = −0.465; 95% CI 0.272–0.658) compared to fibrate alone. In terms of safety, treatment with fibrate alone was associated with a significant decrease in the number of kidney-related adverse events (RR = −0.547; 95% CI 0.368–0.812), compared to treatment with fibrate–statin combinations.ConclusionWe suggest that treatment with a fibrate–statin combination affords clinical benefits that are superior to treatment with fibrate alone, but increases the risk of side effects (particularly renal). Therapy should thus be carefully monitored.     

Ezetimibe: a first-in-class, novel cholesterol absorption inhibitor

Significant numbers of patients at risk for coronary heart disease (CHD) fail to reach National Cholesterol Education Program (NCEP)-designated low density lipoprotein cholesterol (LDL-C) goals in spite of the wide range of currently available treatments, including combination therapies. Ezetimibe, the first in a class of novel cholesterol absorption inhibitors, demonstrated lipid-lowering and antiatherosclerotic activity in experimental and clinical hypercholesterolemia. Studies in hypercholesterolemic dogs showed that ezetimibe coadministered with statins caused greater lipid-lowering effects compared to either drug alone. These effects were confirmed in clinical studies of patients with primary hypercholesterolemia where initiation of treatment with ezetimibe plus a statin, or addition of ezetimibe to ongoing statin therapy, produced significant incremental reductions in LDL-C, as well as incremental increases in high-density lipoprotein cholesterol (HDL-C) and reductions in triglyceride levels. Combination therapy also significantly increased the number of patients attaining LDL-C goal at the end of treatment, compared to statin monotherapy. In studies using simvastatin, atorvastatin, pravastatin, and lovastatin, addition of ezetimibe to low dose statin was as effective as a 2- to 3-fold upward titration of the corresponding statin dose. Ezetimibe-statin combination therapy provided similar improvements in patients with primary hypercholesterolemia, as well as with heterozygous and homozygous familial hypercholesterolemia. Ezetimibe monotherapy effectively reduced plasma campesterol and sitosterol in patients with homozygous sitosterolemia. Clinical studies showed that ezetimibe was well tolerated, with a safety profile comparable to placebo when administered as monotherapy and comparable to statin alone when coadministered with a statin. These data provide strong evidence that, through their complementary lipid-lowering mechanisms, ezetimibe coadministered with a statin offers an effective combination treatment option for patients with hypercholesterolemia, including those with genetically inherited disease.     

Effects of statins on all-cause mortality at different low-density-lipoprotein cholesterol levels in Asian patients with type 2 diabetes

Objective: To investigate the effects of statins on all-cause mortality risk at different low-density lipoprotein cholesterol (LDL-C) levels, and to compare the mortality risk between statin users and non-users with identical LDL-C levels in a type 2 diabetes cohort.

Methods: In total, 10,582 outpatients aged ≥18 years with type 2 diabetes mellitus (T2DM) between 2009 and 2012 were enrolled in this retrospective cohort study in central Taiwan. All-cause mortality events were followed up until the end of 2014. According to the medical records during the follow-up period, the patients were classified into statin (+) and statin (?) groups. Patients were categorized into different LDL-C segments based on their mean LDL-C levels during the 2.8-year follow-up.

Results: Non-cardiovascular mortality accounted for more than half the deaths. Overall, statin therapy significantly reduced the all-cause mortality risk in both univariable and multivariable models (hazard ratios?=?0.39 and 0.38, respectively). Sub-group analyses showed that the lowest mortality risk occurred in the 80–89?mg/dL segment in the statin (?) group and in the 90–99?mg/dL segment in the statin (+) group. Statin therapy significantly reduced the mortality risk at all LDL-C levels except for low LDL-C (<60?mg/dL).

Conclusions: In addition to reducing LDL-C levels, statin therapy reduced all-cause mortality risk in Taiwanese patients with T2DM. Statins further reduced the mortality risk at most LDL levels. However, at low LDL-C levels, the positive effects of statins may have been nullified.     

Colesevelam: potential uses for the newest bile resin

Colesevelam is the newest bile resin with a unique chemical structure. It binds to bile acids with higher affinity than traditional bile acid sequestrants and has fewer gastrointestinal side effects and drug interactions. Colesevelam is safe and efficacious alone or in combination with HMG-CoA reductase inhibitors (statins) in reducing low-density lipoprotein cholesterol (LDL-C) levels. Despite this, the role of colesevelam in the treatment of hyperlipidemia remains limited, particularly in the face of new lipid lowering agents. As guidelines for cholesterol control become more stringent, the need to maximize therapeutic benefit through combination therapy will become increasingly more important. Colesevelam has a dose-sparing effect on statin therapy, potentially decreasing the risk of unwanted side effects or drug-drug interactions associated with statin use. This makes colesevelam a viable option for addition to a statin regimen when goal LDL-C levels cannot be achieved with a statin alone. Additionally, anecdotal reports indicate that colesevelam may have potential benefits in certain patient populations that cannot tolerate other lipid lowering therapies, including organ transplant recipients, cholestatic liver disesase, and end-stage renal disease. By recognizing the potential utility of colesevelam, clinicians can better manage those patients who are not able to tolerate first-line therapies.     

新型调脂药ezetimibe--胆固醇吸收的选择性抑制剂

传统的树脂类、贝特类等药物因为不良反应大，降低胆固醇效果差而不易被病人接受。他汀类药物降低胆固醇效果好，但某些病人单用他汀类药物不能有效降低体内胆固醇水平。因此本文介绍了新近在美国上市的ezetimibe，一种新型胆固醇吸收的选择性抑制剂，在单用或与他汀类药物联用时，都能稳定降低血浆低密度脂蛋白胆固醇(LDL-C)水平，为临床治疗高脂血症提供了新的选择。     

Statins and stroke

Pharmacological studies highlighted pleiotropic effects of statins, that seem to influence atherogenesis not only by increasing atherosclerotic plaque stability but also by modulating endothelial function and inflammation and acting on platelet aggregation and thrombosis. Despite a strong association between increased levels of low-density lipoprotein cholesterol (LDL-C) and the incidence of coronary heart disease (CHD) has been well proven, it not yet established whether serum LDL-C levels are related to stroke incidence. The major aim of this paper is to perform a comprehensive up-to-date review of research papers, meta-analyses and randomized controlled clinical trials reporting the effects of statins in primary and secondary stroke prevention strategies. In addition, our work provides an overview on statin chemical structure, mechanism of action and pharmacological properties, investigating also most common adverse effects and relationship between statin therapy and haemorrhagic stroke risk, in order to assess drugs safety. Although studies are heterogeneous, our analysis shows that statins reduce the risk of stroke occurrence in high risk patients and seem also to reduce stroke recurrence. Moreover, the low incidence and reversibility of adverse effects, and the unclear association with hemorrhagic events, support the safe use of these drugs.     

Statins for primary prevention: at what coronary risk is safety assured?

AIMS: Increasingly HMG CoA reductase inhibitors (statins) are being used for primary prevention of vascular disease in patients with a raised cholesterol but at low absolute risk of coronary heart disease (CHD). This study uses clinical trial results to explore the limits of absolute safety for statin use in such patients. METHODS: The major placebo controlled statin outcome trials were identified by automated and manual literature searches. Principal results including all cause mortality in placebo and intervention groups and baseline values of standard coronary risk factors were abstracted for each trial. For the trials identified the reduction in overall mortality with statin treatment for each study was regressed against the underlying CHD risk of the population recruited into that trial using a statistically robust method. RESULTS: The regression line describing the relationship between mortality benefit and risk suggests that statin use could be associated with an increase in mortality of 1% in 10 years. This would be sufficiently large to negate statin's beneficial effect on CHD mortality in patients with a CHD event risk less than 13% over 10 years. CONCLUSIONS: Absolute safety of statins has not been demonstrated for patients at low risk of CHD. Patients absolute risk of CHD should be calculated before starting statin treatment for primary prevention. Extensions of such treatment to low risk patients should await further evidence of safety.     

他汀联合贝特类降脂药物临床试验进展

糖尿病患者典型的血脂异常表现为高甘油三酯(TG)、低高密度脂蛋白胆固醇(HDL-C)伴小而密型低密度脂蛋白(sdLDL)增多。他汀和贝特联用能更全面地改善糖尿病患者血脂谱,有可能使糖尿病患者的血管风险进一步减少。ACCORD-血脂试验是第一个比较在他汀基础上应用贝特类药物能否进一步降低2型糖尿病患者心血管风险的研究。结果显示,辛伐他汀联合非诺贝特治疗组与单用辛伐他汀组比较,主要临床终点事件、次要终点事件方面差异无统计学意义。但在血浆TG≥2.3 mmol.L-1(204 mg.dL-1)合并HDL-C≤0.88 mmol.L-1(34 mg.dL-1)的亚组中,辛伐他汀与非诺贝特合用可以减少剩留血管风险,使心血管事件减少31%。此外,研究还显示,非诺贝特能够改善微量白蛋白尿和大量白蛋白尿;与辛伐他汀合用具有良好的安全性。该研究为2型糖尿病患者的调脂治疗提供了新的循证医学证据。