Transcript 高血脂治疗进展（2012更新）

北京大学深圳医院
吴淳
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Intraduction-- European Guidelines,HPS
In low risk of vascular disease
Neuroprotective Effects
Atrial Fibrillation After CABG
Renal function and CKD
Systolic HF
Atherosclerosis (Atorvastatin Versus Rosuvastatin)
Residual Vascular Risk
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combination (sitagliptin /ezetimibe)
Discontinuation was side effects(62%)
New-Onset Diabetes, Muscular side effects
Non-every day statin administration
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A Sex-Based Meta-analysis
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Early statin therapy for ACS
Recommendations on management of hyperlipidaemia
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Increased plasma cholesterol and LDL cholesterol are
among the main risk factors for CVD.
Hypertriglyceridaemia and low HDL cholesterol are
independent CVD risk factors.
Statin therapy has a beneficial effect on atherosclerotic
CVD outcomes.
European Heart Journal doi:10.1093/eurheartj/ehs092
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In a population at 2% average coronary event risk per
year, cholesterol, apolipoprotein, and particle
measures of LDL were strongly correlated and had
similar predictive values for incident major occlusive
vascular events.
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It is unclear whether the associations between HDL
particle numbers and other cardiac events represent a
causal or reverse-causal effect.
此项为期5.3年的随访性随机辛伐他汀-安慰剂心脏
保护试验入组了20,000例患者，共计5,000项血管
事件
(Circulation. 2012;125:2469-2478.)
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Statin reduced the risk of major vascular events
irrespective of age, sex, baseline LDL cholesterol or
previous vascular disease
No evidence that reduction of LDL cholesterol with a
statin increased cancer incidence, cancer mortality,
or other non-vascular mortality.
Each 1 mmol/L reduction in LDL cholesterol
produced an absolute reduction in major vascular
events of about 11 per 1000 over 5 years.。
meta-analysis of individual data from 27 randomised trials Cholesterol Treatment
Trialists’ (CTT) Collaborators Published Online May 17, 2012
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Our recommendation would be start a statin as soon as the patient
passes a dysphagia screen.
Based on the results of the Heart Protection Study and the
SPARCL trial, either simvastatin 40 mg or atorvastatin 80 mg are
appropriate alternatives.
Clinical trials are needed to demonstrate unequivocal efficacy of
improved outcome and to determine if lower doses may have this
effect.
Additionally,improved outcome needs to be established in
cardioembolic stroke patients before routine use of statins in this
stroke subtype can be recommended.
Current Treatment Options in Cardiovascular Medicine (2012) 14:252–259
Current Treatment Options in Cardiovascular
Medicine (2012) 14:252–259
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12,689 patients with ischemic stroke over a 7-year
period at 17 hospitals
Statin use is strongly associated with improved
discharge disposition after ischemic stroke.
Neurology 2012;78:1678–1683
Neurology 2012;78:1678–1683
Neurology 2012;78:1678–1683
Studied 1,839 consecutive patients (1,177 men
[73.2%]) who underwent CABG
 Atorvastatin pretreatment significantly
reduced the occurrence of AF after bypass
grafting;
 The difference between the beneficial effects
of intensive and routine atorvastatin
treatments was not significant.
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International Journal of Cardiology xxx (2012) xxx–xxx
International Journal of Cardiology xxx (2012) xxx–xxx
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Cholesterol reduction is very important in people with
GFR values >15 ml/min who are not on dialysis.
In the PREVEND- IT trial, subjects with
microalbuminuria were treated with pravastatin No
effect on the rate of cardiovascular events
The 4D study and AURORA trial did not differ in the
resultant rates of cardiovascular events.
The SHARP trial， there was a significant 17% risk
reduction for the primary outcome of a major
atherosclerotic event， Of 3,023 study patients on
dialysis, there were no differences
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23 trials enrolling 29,147 participants were included
A significant reduction in GFR was detected in placebo-treated
No significant difference in GFR was detected in 5 head-to-head studies
In 9 studies, R treatment significantly increased the risk of proteinuria
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A and R show similar reno-protective effects in
patients at high cardiovascular risk, with comparable
rates of new onset proteinuria when commonly used
doses are considered
Contrib Nephrol. Basel, Karger, 2012, vol 178, pp 100–105
International Journal of Cardiology xxx (2012) xxx–xxx
International Journal of Cardiology xxx (2012) xxx–xxx
International Journal of Cardiology xxx (2012) xxx–xxx
International Journal of Cardiology xxx (2012) xxx–xxx
Atorvastatin and rosuvastatin comparably
reduce the decline of renal function in patients
at high cardiovascular risk without chronic
kidney disease
Atorvastatin improves renal function in high-risk
patients with chronic kidney disease.
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International Journal of Cardiology xxx (2012) xxx–xxx
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Of 10,001 TNT participants, 9,376 had estimated
glomerular filtration rate (eGFR) measurements at
baseline and 1 year.
Little change in eGFR occurred over 1 year in the
atorvastatin 10-mg group, whereas eGFR improved in the
80-mg group by 1.48 ml/min/1.73 m2
This suggests that improvement in kidney function may
be related to the beneficial effect of high-dose
atorvastatin on HF hospitalization.(大剂量阿托伐他汀
的使用改善了肾脏功能从而使得心衰住院率下降。)
)
(Am J Cardiol 2012;109:1761–1766
Patients with systolic HF of ischaemic aetiology
who have galectin-3 values <19.0 ng/mL may
benefit from rosuvastatin treatment.
 However, the data from this post hoc analysis
should be interpreted with caution since the
overall results of the CORONA study did not
show a significant effect on the primary
endpoint
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European Heart Journal Advance Access published May 7, 2012
European Heart Journal Advance Access published May 7, 2012
European Heart Journal Advance Access published May 7, 2012
Atherosclerosis
Atorvastatin Versus Rosuvastatin
ARTMAP Trial Am J Cardiol 2012;109:1700–1704)
ARTMAP Trial Am J Cardiol 2012;109:1700–1704)
Atherosclerosis
Atorvastatin Versus Rosuvastatin
p<0.0001
p<0.0001
p<0.028
p=0.01
p<0.0001
N=1039
J Am Coll Cardiol. 2012; 59 (13) Suppl Sxxx
P=0.01
SATURN研究分析：降脂幅度与斑
SATURN研究分析：降脂幅度与斑块逆转
整个队列的TAV变化与各项血脂生化指标之间的关联度
指标
r（相关系数）
p
LDL-C
0.11
0.0007
non-HDL-C
0.1
0.002
LDL-C/HDL-C
0.09
0.002
Apo B
0.09
0.004
Apo B/A-I
0.07
0.03
HDL-C
-0.01
0.79
Apo A-I
0.02
0.55
“与具有保护性的脂质相比，致动脉粥样硬化性的脂质水平对斑块体积变化更密切。
这一发现让我们洞见了为什么瑞舒伐他汀组实现了更佳的斑块逆转。
Achieved levels of atherogenic lipid levels associate more closely with changes in atheroma volume compared
with changes in protective lipid variables. These findings provide mechanistic insight into the greater degree
of regression observed in rosuvastatin-treated patients.“
——Stephen J. Nicholls
J Am Coll Cardiol. 2012; 59 (13) Suppl Sxxx
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In this primary prevention trial of nondiabetic
individuals with low LDL-C and elevated highsensitivity C-reactive protein,on-treatment LDL-C
was as valuable as non–HDL-C, apolipoprotein B,
or ratios in predicting residual risk.
In contrast, on-treatment triglycerides showed no
association with CVD
(JUPITER—Crestor 20mg Versus Placebo in Prevention of
Cardiovascular [CV] Events; NCT00239681)
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(J Am Coll Cardiol 2012;59:1521–8)
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Recent clinical trials with statins have confirmed that
reducing LDL cholesterol to low levels results in
improved outcomes in both primary and secondary
prevention.
Trials with fibrates, omega-3 fatty acids, niacin, ezetimibe,
and CETP inhibitors additionally have sought to reduce
residual cardiovascular risk beyond the effects of statin
therapy.
Ongoing research will help clarify the specific roles of
inflammation, HDL cholesterol, and triglycerides
(J Am Coll Cardiol 2012;59:1521–8)
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In CARDS, atorvastatin has proven its remarkable efficacy in
improving lipid profile and reducing CVD events in patients
with T2DM.
some recent data suggested that atorvastatin, like other
statins, may slightly deteriorate glucose control and increase
new-onset diabetes.
DPP-4 inhibitors (gliptins) improve fasting and postprandial
glucose levels, without promoting hypoglycemia or weight
gain (two adverse events that may increase the CVD risk).
Atorvastatin and sitagliptin are not prone to PK drug—drug
interactions.
Expert Opin. Drug Metab. Toxicol. (2012) 8(6)
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A total of 136 patients Undergoing Elective Vascular
Surgery assigned to RSV and 126 to RSV/EZT
completed the study protocol.
Our findings indicate that statin therapy intensified by
ezetimibe may reduce the incidence of cardiovascular
events within the first 12 months after vascular surgery.
Nonetheless, whether the use of ezetimibe as an add-on
therapy to reduce cardiovascular risk in these patients
needs to be tested in larger future studies.
J CARDIOVASC PHARMACOL THER published online 9 May 2012
J CARDIOVASC PHARMACOL THER published online 9 May 2012
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Participants (mean age 61 years) were predominantly white
(92%), female (61%), of middle, and had health insurance
(93%).
The primary reason for switching by current users was cost
(32%) and the primary reason for discontinuation was side
effects(62%).
Although70% reported that their physicians had explained the
importance of cholesterol levels for their heart health former
users were less satisfied with the discussions(65% vs. 83%, P
<05)
Journal of Clinical Lipidology (2012) 6, 208–215
Nutrition, Metabolism & Cardiovascular Diseases (2012) xx, 1
Nutrition, Metabolism & Cardiovascular Diseases (2012) xx, 1e5
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A survey in real life, 10,409 French subjects.
Muscular symptoms were reported by 104 (10%) statin
treated patients and led to discontinuation in 30% of the
symptomatic patients.
Approximately 38% of patients reported that their symptoms
prevented even moderate exertion, while 42% of patients
suffered major disruption to their everyday life.
Muscular symptoms have a greater impact than
usually thought
Nutrition, Metabolism & Cardiovascular Diseases (2012) xx, 1e5
Nutrition, Metabolism & Cardiovascular Diseases (2012) xx, 1e5
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Alternate day regimens An LDL-C level <100 mg/dl was
achieved by 57.6% of diabetic patients treated with a mean dose
of 5.6 mg atorvastatin,while 70% achieved with rosuvastatin at
a mean dose of 10 mg
Twice weekly regimens
 Once a week regimens
 Non-every day statins combined with other
lipid-lowering agent regimens
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European Journal of Internal Medicine 23 (2012) 474–478
European Journal of Internal Medicine 23 (2012) 474–478
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阿托伐他汀与瑞舒伐他汀隔日治疗可被对于他汀治疗不耐受的
病患。
但是，这些治疗方法对于心血管事件是由有效仍不清楚。
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European Journal of Internal Medicine 23 (2012) 474–478
Eleven trials representing 43 193 patients were
included in the analysis.
 Statin therapy is an effective intervention in the
secondary prevention of cardiovascular events
in both sexes.
 But there is no benefit on stroke and all cause
mortality in women.
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Arch Intern Med. 2012;172(12):909-919
Arch Intern Med. 2012;172(12):909-919
Arch Intern Med. 2012;172(12):909-919
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对于男性以及女性，他汀对于心血管事件二级
预防有效，但他汀治疗对于女性卒中及全因死
亡并无益处。
Arch Intern Med. 2012;172(12):909-919
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Meta-analysis of 18 randomized trials involving over 14,000 Ps
Risk ratios for the combined endpoint of death, myocardial
infarction, and stroke of early statin therapy compared to
control were 0.93 (P=0.34) at 1 month and 0.93 (P=0.27) at 4
months
Unstable angina with a risk ratio of 0.76 ( P=0.02) at 4 months
International Journal of Cardiology 158 (2012)93–100
International Journal of Cardiology 158 (2012)93–100
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在ACS发病内14天使用他汀治疗能够获益，但
随后的4个月中，死亡率、心肌梗死率、卒中
并无明显下降，而不稳定型心绞痛发生率可以
降低。
International Journal of Cardiology 158 (2012)93–100
European Heart Journal (2012) 33, 1635–1701
European Heart Journal 2011;32:1769–1818
CV-1209-CR-0173
有效期至2013年9月
CV-1209-CR-0173
有效期至2013年9月
D A Wood. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402425
欧洲目前使用他汀的现状
-有多少真正需要他汀的人服用了他汀
欧洲人通常服用他汀6个月后，只有一半能坚持
Marazzi G. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402424
CV-1209-CR-0173
有效期至2013年9月
数据来源：美国中西部大学附属医院1998.1至2001.11共2544例一级预防、2258
例二级预防的患者。
终止治疗的中位时间
一级预防：3.4年
二级预防：3.7年
二级预防平均停药时间3.7年，一级预防平均停药时间3.4年
Marazzi G. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402424
CV-1209-CR-0173
有效期至2013年9月
EUROASPIRE III
22个国家，8966 名冠状动脉疾病患者关于
生活方式、危险因素、心血管药物治疗的调查
Netherlands
Finland
Russia
Ireland
UK
Latvia
Lithuania
Germany
Czech Republic
France
Croatia
Poland
Hungary
Belgium
Slovenia
Romania
Bulgaria
Greece
Spain
Italy
K Kotseva Eur J Cardiovasc Prev Rehabilitation 2009; 16:121-37
D A Wood. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402425
Turkey
Cyprus
CV-1209-CR-0173
有效期至2013年9月
EUROASPIRE III
通过滴定法，总胆固醇达到目标的比例*
55.7%
United Kingdom
Finland
Ireland
The Netherlands
Turkey
51.3%
49.7%
46.6%
45.9%
42.6%
Greece
France
Romania
Spain
Slovenia
Czech Republic
41.7%
35.6%
35.2%
34.6%
33.9%
33.8%
Croatia
Belgium
Hungary
Cyprus
Italy
Poland
Men 37.8% , Women 23.1%
31.1%
30.8%
29.5%
29.3%
Germany
Latvia
Bulgaria
Russian Federation
Lithuania
0%
All patients: 34.1%
31.8%
31.4%
22.9%
20.1%
16.3%
13.4%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
* Total cholesterol < 4 mmol/L among patients using lipid-lowering drugs
D A Wood. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402425
CV-1209-CR-0173
有效期至2013年9月
EUROASPIRE III- Primary Care（一级预防）
通过滴定法，总胆固醇达到目标的比例*
UK
24.9%
Slovenia
19.8%
Finland
17.9%
Spain
13.6%
Italy
12.1%
Belgium
9.1%
Croatia
8.2%
All patients: 13.2%
Germany
8.0%
Men 19.1% , Women 8.8%
Poland
7.8%
Bulgaria
7.7%
Romania
6.6%
Latvia
6.6%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
* Total cholesterol < 4 mmol/L among patients using lipid-lowering drugs
D A Wood. 2012 ESC presented. http://spo.escardio.org/SessionDetails.aspx?id=402425
CV-1209-CR-0173
有效期至2013年9月
中国46239成人的胆
固醇治疗的知晓率、
治疗率和控制率
Yang W.Y., et al. Circulation. 2012;125:2212-2221.
2012年中国门诊患者血脂达标率现况调查
REALITY-CHINA SURVEY
连续入选在
2011年3月至
12月期间，19
个省84家医院
心内科门诊，
共计12244例
患者
Zhou YJ, et al. 2012 ACC presented on March 26,2012，at Chicago
2012年中国门诊患者血脂达标率现况调查
REALITY-CHINA SURVEY
危险分层与LDL-C达标率
按照低危，中危，高危和极高危分层后，门诊患者的达标率分别为38.1%，29.7%，
19.9%和21.1%，尤其高危和极高危患者达标率反而是最不理想的。
Zhou YJ, et al. 2012 ACC presented on March 26,2012，at Chicago
CV-1209-CR-0173
有效期至2013年9月
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
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谢谢