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[APCC2011]非诺贝特可显著降低剩留风险——意大利帕多瓦大学Paola Fioretto教授专访

作者:国际循环网   日期:2011/9/27 11:43:35

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以LDL-C为靶标的他汀治疗是公认的心血管疾病(CVD)一级预防和二级预防的基石,但荟萃分析显示,患者他汀治疗后仍残存77%的CV剩留风险。剩留风险已经成为心血管疾病治疗面临的新挑战和亟需解决的医学难题,而高TG、低HDL-C则是产生剩留风险的根源,是降低剩留风险的新策略。

  International Circulation: The topic of the association between serum triglyceride levels and cardiovascular disease has been controversial. Data from recent studies supports the conclusion that hypertriglyceridemia is an independent risk factor for cardiovascular disease so can we make a definite conclusion on this issue?
  Prof. Fioretto: There is a lot of discussion of this issue and the role of triglycerides in conferring risk for cardiovascular disease has been known for a long time. More recent studies have clearly confirmed that there is a strong association between both fasting and postprandial triglycerides and risk of developing both myocardial infarction and ischemic stroke. There is a very important study from Denmark on a very large number of subjects and the follow-up was 26 years and it made a conclusive statement on the role of postprandial triglycerides. Also, several days ago the European Atherosclerosis Society provided some clinical recommendations that are a type of guideline, which was published online only. They focus on high triglycerides and low HDL-C and the fact that patients, despite being at target for LDL-C, can still have very high cardiovascular risk. Therefore, the recommendations are very clear and in a nice analysis they recognized the role of high triglycerides and triglyceride-rich particles in conferring cardiovascular risk and they recommended treatment when the levels of triglycerides above 150 mg/dl. Also, very similar recommendations came out recently from the American Diabetes Association so I think there is agreement now that you must treat triglycerides when they exceed 150 mg/dl. Furthermore, I am aware from my interaction with colleagues here that in Asia, especially in China, that the prevalence of hypertriglyceridemia is very high. Consequently, it is a big problem in these countries and even more so than having elevated LDL-C.
  International Circulation: Is measuring fasting or postprandial triglycerides more valuable for clinicians?
  Prof. Fioretto: In clinical practice it is better to use fasting triglycerides because it is more standardized. Postprandial levels are more closely associated with cardiovascular risk because it somehow measures the remnant articles that are more atherogenic but this needs to be standardized and for the time being I think we are better off measuring fasting triglycerides. In any case, there is evidence that those fasting levels are also predictive of cardiovascular risk.
  International Circulation: Are there any new or emerging parameters that we can use to measure triglycerides?
  Prof. Fioretto: No, I think we can use routine measurement of fasting triglycerides.
  International Circulation: Many clinicians may have their patient on a statin and the LDL-C levels are low but the HDL-C is not good and they want to use a fibrate for treatment. If a clinician sees a rise in serum creatinine should they be concerned?
  Prof. Fioretto: This is something we always worried about because when we start therapy with a fibrate we have an increase in serum creatinine but if you keep checking serum creatinine it remains stable. We have the same phenomenon when we start an ACEI but we do not worry about it because we know that in the long term it is nephroprotective and it is not damaging the kidney. We have some recent publication from the FIELD trial where fenofibrate was used that is quite reassuring in that regard. This paper was focused on renal function in these patients and what it showed is that there is a rapid increase in creatinine when you start treatment and then creatinine remains stable. If you calculate estimated GFR (eGFR), which is the best measure of renal function you derive from creatinine, from randomization patients receiving fenofibrate lose less renal function compared to placebo. That is very reassuring and the other reassuring observation is that if you stop the drug then serum creatinine goes back to baseline values suggesting that it is not an expression of renal damage and it is some functional effect.
  International Circulation: So if anything it may have a renal protective effect?
  Prof. Fioretto: It looks like it may have a renal protective effect in terms of albuminuria and loss of GFR but it needs to be confirmed. We should feel reassured that we are not damaging the kidney. Of course, as part of your routine management of the patient you need to sometimes check serum creatinine but that is something that you need to do with many other drugs as well.
  International Circulation: What are the cutpoints for initiating triglyceride lowering therapy for patients, particularly if there are comorbities such as coronary heart disease or T2DM?
  Prof. Fioretto: The guidelines are very clear. When you have a patient at goal for LDL-C but with high triglycerides or low HDL-C you should treat them when triglyceride levels exceed 150 mg/dl.
  中文概要:以LDL-C为靶标的他汀治疗是公认的心血管疾病(CVD)一级预防和二级预防的基石,但荟萃分析显示,患者他汀治疗后仍残存77%的CV剩留风险。剩留风险已经成为心血管疾病治疗面临的新挑战和亟需解决的医学难题,而高TG、低HDL-C则是产生剩留风险的根源,是降低剩留风险的新策略。贝特类药物则毋庸置疑地成为该策略实施的有力武器。ACCORD、FIELD、HHS、BIP及VA-HIT等研究的荟萃分析,研究证实了非诺贝特的大血管剩留风险获益; FIELD则进一步证实了非诺贝特的微血管剩留风险获益。增加血肌酐浓度曾一度成为非诺贝特广泛应用的绊脚石,但非诺贝特治疗具有长期的安全性。血肌酐浓度仅在应用非诺贝特后的短期内增加,此后则将长期保持稳定状态。同时FIELD研究发现,非诺贝特组患者的eGFR下降幅度低于安慰剂组,非诺贝特治疗可显著延缓蛋白尿的进展,提示非诺贝特可能具有肾功能保护效应。此外,非诺贝特与辛伐他汀联合应用并不增加肌痛、肌溶解等不良反应的发生率,打消了人们对非诺贝特与他汀联合应用、共同优化血脂控制的安全性的顾虑,为非诺贝特在优化血脂控制中发挥更为重要的作用提供了理论依据。

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