SGK cũ Đau bụng ở trẻ em.pdf rất hay luôn nha các bạn
Cập nhật statin ESC 2017
1. Statin trong điều trị rối loạn lipid máu
Có gì mới từ ESC 2017?
Đại học Y Dược Tp. Hồ Chì Minh
Khoa Tim Mạch Can Thiệp BV Chợ Rẫy
2.
3. Yếu tố nguy cơ xơ vữa huyết khối
Yusuf S, et al. Lancet. 2004;364:937--52.
Nghiên cứu INTERHEART: 52 nước, gồm Châu Phi, Châu Á, Úc, Châu
Âu, Trung Đông, và Nam và Bắc Mỹ
9 yếu tố nguy cơ:
1. Hút thuốc
2. THA
3. Rối loạn lipid máu
4. ĐTĐ
5. Béo phì
6. Chế độ ăn
7. Hoạt động thể lực
8. Rượu
9. Tâm lý
Chiếm 90% nguy cơ NMCT cấp
Yếu tố có thể điều chỉnh
Tương tự trong hầu hết chủng
tộc, giới trên thế giới
4. Tỉ lệ RLMM cao ở người Việt Nam,
đặc biệt ở người cao tuổi
Woman
Man
Hypertension Diabetes Overweight Dyslipidemia Smoking Drinking Low exercise Stress
Metabolism Risk Factors Behavorial Risk Factors
Nguyen NQ et al, 2012, Int J Hyperten 2012 doi:10.1155/2012/560397
5.
6.
7. Đạt LDL-C mục tiêu trong bệnh nhân
bệnh động mạch vành
Jones PH et al. J Am Heart Assoc. 2012;1:e001800
8.
9. Khả năng ức chế men khử HMG-CoA của
statins
*P<0.05 vs Rosuvastatin;
***P<0.001 vs Rosuvastatin
IC50 (nM) with 95% confidence limits
Rosuva
5.4
100
10
Ceriva *
10.0
Atorva
8.2
Fluva ***
27.6
Simva *
11.2
Prava
***
44.1
IC50
(nM)
(log scale)
10. Sự thay đổi LDL-C khi tăng liều statin
Nicholls SJ et al. Am J Cardiol 2010; 105: 69–76
*p<0.001 rosuvastatin 10 mg vs atorvastatin 10 mg and 20 mg; simvastatin 10 mg, 20 mg and 40 mg
†p<0.001 rosuvastatin 20 mg vs atorvastatin 20 mg and 40 mg; simvastatin 20 mg ,40 mg and 80mg
‡p<0.001 rosuvastatin 40 mg vs atorvastatin 40 mg and 80 mg; simvastatin 40 mg and 80 mg
#
p<0.05 atorvastatin 20 mg vs rosuvastatin 5 mg
##
p<0.05 atorvastatin 80mg vs rosuvastatin 5mg and 10mg
ChangeinLDL-Cfr
baseline(%)
Dose (log scale)
5 mg 10 mg 20 mg 40 mg 80 mg
-27
(n=365)
-33
(n=2929)
-39
(n=548)
-45
(n=479)
-50##
(n=2072)
-55‡
(n=2983)
-50†
(n=3554)
-44*
(n=11690)
-39
(n=670)
-36
(n= 7837)
-41#
(n=3908)
-46
(n=1324)
VOYAGER: 37 RCT với 32.258 bệnh nhân
11. Tăng mức độ tiếp xúc của statin ở người Châu Á
0 0,5 1 1,5 2
0 0,5 1 1,5 2
RSV
ATV
SIM
AUC(0-t)
1.55
(1.21‒
1.99)
Japanese:Caucasian ratio
1.69
(1.32‒
2.17)1.12
(0.87‒
1.44)
Geometric mean (90% CI)
RSV
ATV
SIM
Cmax
1.81
(1.38‒
2.37)
1.71
(1.31‒
2.23)1.24
(0.94‒
1.62)
RSV
ATV
SIM
AUC(0-t)
1.86
(1.45‒
2.39)
Chinese:Caucasian ratio
1.53
(1.20‒
1.96)1.23
(0.96‒
1.58)
RSV
ATV
SIM
Cmax
2.16
(1.65‒
2.82)
1.60
(1.22‒
2.08)1.29
(0.98‒
1.69)
Geometric mean (90%
CI)
Birmingham BK et al. Clin Pharmacol Ther 2008; 83: S15
Bệnh nhân Châu Á
Lưu ý đến việc tăng mức độ tiếp xúc với thuốc ở bệnh nhân Châu Á khi không
kiểm soát đủ với liều trên 20 mg/ngày.
12. Nồng độ Rosuvastatin 40mg trong huyếtNồng độ Rosuvastatin 40mg trong huyết
tương cao hơn 2 lần ở người châu Átương cao hơn 2 lần ở người châu Á
-200-200
00
200200
400400
600600
800800
10001000
12001200
14001400
MalayMalayIndianIndianChineseChineseCaucasianCaucasian
n=35n=35n=35n=35n=36n=36n=36n=36
RosuvastatinAUC(0-t)ng.h/mL
AUCAUC 11 2.32.3 1.61.6 1.91.9
Liều đơn 40 mg (u)
Edmind Lee et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the
same environmentClin Pharmacol Ther 2005;78:330
13. Quy tắc của 6
37
19
35
27
28
18
12
12
6
12
0 10 20 30 40 50 60
Atorvastatin 10/80
Fluvastatin 20/80
Simvastatin 20/80
Pravastatin 20/40
Lovastatin 20/80
46 6
32 11
Rosuvastatin 10/20
Pitavastatin 1/4
Illingworth DR. Med Clin North Am 2000;84-23-
Mỗi lần gấp đôi liều statin sẽ dẫn đến việc giảm khoảng 6% nồng độ LDL-
C
Chất ức chế enzyme HMG-CoA Reductase
Tác động phụ thuộc liều
14.
15. Thoái triển mảng xơ vữa tùy thuộc vào
loại statin
Tsujita K, et al. J Am Coll Cardiol 2015;66:495–507
LDL-C: 75 mg/dl
16. Tác động của LDL-C trên tiến triển mảng
xơ vữa
Nicholls S et al. JAMA 2007;297:499-508
17. IBIS-4: Thoái triển xơ vữa trong NMCT
cấp với statin liều cao kéo dài
Raber L, et al. European Heart Journal 2014; 1-11. doi:10.1093/eurheartj/ehu373
Lumen
Area
Plaque Area
Baseline
Plaque Area
Lumen
Area
Follow up (13 tháng)
Rosuva 40mg
Thể tích
mảng XV toàn bộ
đoạn khảo sát
Thể tích mảng
XV đoạn 10
mm nặng nhất
n= 84 BN, 146 sang thương IVUS/RF
Integrated Biomarkers and Imaging Study-4
p<0.001
-2
-1
0
p value: follow-up vs. baseline
-2.94
P=0.007
-0.9
%Thayđổitrungbình
-3
18. COSMOS: Thoái triển xơ vữa trên BN châu Á
đạt được với liều thấp hơn
Takayama T, et al. Circ J 2009; 73(11): 2110-2117
Lumen
Area
Plaque Area
Baseline
Plaque Area
Lumen
Area
Follow up (19 tháng)
Rosuva 16,9mg
(%) Thể tích
mảng XV
Thể tích
lòng mạch
Thể tích
mạch máu
p<0.0001
p=0.4673
-10
-5
0
5
10
p value: follow-up vs. baseline
+7.25
p<0.0001
-5.07
+0.76
%Thayđổitrungbình
N=126
19. Đáp ứng kém với statins gây tiến triển
mảng xơ vữa
Kataoka Y, et al. Arterioscler Thromb Vasc Biol. 2015;35:990-995
Phân tích tổng hợp từ 7 n/c ngẫu nhiên tiến cứu sử dụng IVUS đánh
giá sự tiến triển/thoái triển mảng xơ vữa (n=647)
REVERSAL, CAMELOT, ACTIVATE, ASTEROID, ILLUSTRATE, PERISCOPE, và STRADIVARIUS.
Thời gian từ 18-24 tháng.
P<0.001
P<0.001
P<0.001
P=0.45
Đáp ứng kém với statin:
giảm LDL-C < 15%
22. Tăng gấp đôi liều Statin đem lại hiệu quả
giảm thêm chỉ 6%
Bays HE et al. Expert Opin Pharmacother 2003;4:779-790
1-STEP
COADMINISTRATIONStatin at starting doseStatin at starting dose
15–18%
+ Ezetimize+ Ezetimize
10mg10mg
% Reduction in LDL-C
3-STEP
TITRATIONStatin at starting doseStatin at starting dose 1st1st 2nd2nd 3rd3rd
Doubling
5–6% 5–6% 5–6%
% giảm LDL-C
Phối hợp ức chế kép liều thấp giảm thêm 18%
1-STEP
COADMINISTRATION
High or moderate
intensity statin (± EZ)
59%
+ Ức chế+ Ức chế
PCSK9PCSK9
Phối hợp ức chế PCSK9 giảm thêm 59%
23. NC phòng ngừa
tiên phát
NC phòng ngừa
thứ phát
50 70 110 130 150 170 19090 210
%bệnhnhânmắccácbiếncốtimmạch
LDL cholesterol
CARE-Rx
4S-Rx
LIPID-PL
4S-PL
CARE-PL
LIPID-Rx
AFCAPS-Rx
WOSCOPS-Rx
WOSCOPS-PL
AFCAPS-PL
25
20
15
10
5
0
ASCOT-PL
ASCOT-Rx
HPS-Rx
HPS-PL
HPS
LRC-PL
LRC-Rx
POSCH-PL
POSCH-Rx
PL: non statin
trials
Rx: Statin trials
(mg/dL)
1.3 1.8 2.3 2.8 3.4 3.9 4.4 4.9 5.4
(mmol/L)
TNT-80A
TNT-10A
Rosenson RS. Exp Opin Emerg Drugs 2004; 9(2):269-279, LaRosa JC et al. N Engl J Med 2005; 352: 1425-1435
LDL- C càng thấp càng tốt: Giảm biến cố TMGiảm thấp LDL-C làm giảm biến cố tim
mạch:
Hạ thấp vẫn có lợi và an toàn ?
24. Nghiên cứu IMPROVE-IT: Statin + Ezetimibe
Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
Patients stabilized post ACS ≤ 10 days:
LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx)
Standard Medical & Interventional Therapy
Ezetimibe / Simvastatin
10 / 40 mg
Simvastatin
40 mg
Follow-up Visit Day 30, every 4 months
Duration: Minimum 2 ½-year follow-up (at least 5250 events)
Primary Endpoint: CV death, MI, hospital admission for UA,
coronary revascularization (≥ 30 days after randomization), or stroke
N=18,144
Uptitrated to
Simva 80 mg
if LDL-C > 79
(adapted per
FDA label 2011)
*3.2mM
**2.6mM
90% power to detect
~9% difference
25. Nghiên cứu IMPROVE-IT: thay đổi LDL-C
Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
27. Tăng gấp đôi liều Statin đem lại hiệu quả
giảm thêm chỉ 6%
Bays HE et al. Expert Opin Pharmacother 2003;4:779-790
1-STEP
COADMINISTRATIONStatin at starting doseStatin at starting dose
15–18%
+ Ezetimize+ Ezetimize
10mg10mg
% Reduction in LDL-C
3-STEP
TITRATIONStatin at starting doseStatin at starting dose 1st1st 2nd2nd 3rd3rd
Doubling
5–6% 5–6% 5–6%
% giảm LDL-C
Phối hợp ức chế kép liều thấp giảm thêm 18%
1-STEP
COADMINISTRATION
High or moderate
intensity statin (± EZ)
59%
+ Ức chế+ Ức chế
PCSK9PCSK9
Phối hợp ức chế PCSK9 giảm thêm 59%
28. Statin cường độ mạnh và sự an toàn
Escobar C et al. vascular Health and Management 2008;4:525-533
29.
30.
31.
32. LDL rất thấp và nguy cơ tim mạch: Vai trò
của thuốc PCSK9
Sabatine MS | Opening Session 400-14. Sabatine MS et al. Am Heart J 2016;173:94-101;
http://www.ahjonline.com/article/S0002-8703(15)00686-9/references
FOURIER
Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk
Evolocumab SC
140 mg q2w or 420 mg qm
Placebo SC
q2w or qm
LDL-C ≥70 mg/dL or
non-HDL-C ≥100 mg/dL
LDL-C ≥70 mg/dL or
non-HDL-C ≥100 mg/dL
Screening, Lipid Stabilization, and Placebo Run-in
High or moderate intensity statin therapy (± ezetimibe)
Screening, Lipid Stabilization, and Placebo Run-in
High or moderate intensity statin therapy (± ezetimibe)
27,564 high-risk, stable patients with established CV disease (prior MI, prior
stroke, or symptomatic PAD)
27,564 high-risk, stable patients with established CV disease (prior MI, prior
stroke, or symptomatic PAD)
Randomized
Double blind
33. LDL rất thấp và nguy cơ tim mạch: Vai trò
của thuốc ức chế PCSK9
Sabatine MS | Opening Session 400-14. Sabatine MS et al. Am Heart J 2016;173:94-101;
http://www.ahjonline.com/article/S0002-8703(15)00686-9/references
FOURIER
Further cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk
59% mean reduction (95%CI:58-60),P=0.00001
Absolute reduction: 56 mg/dl (95%CI:55-57)
Weeks
LDLcholesterol(mg/dl)
Placebo
Evolocumab
(median 30 mg/dl, IQR 19-46 mg/dl)
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168
0
10
20
30
40
50
60
70
80
90
100
Months from randomization
CVdeath,MI,stroke,hospitalizationforUA,or
coronaryrevascularization
Placebo
Evolocumab
0%
0
16%
14.6%
12.6%
6 12 18 24 30
HR 0.85 (95% CI, 0.79; 0.92)
P<0.0001
14%
12%
10%
8%
6%
4%
2%
BN bệnh tim mạch: ức chế PCSK9 giảm biến có TM ở BN đang sử dụng statin.
Lợi ích đạt được với giảm LDL thấp hơn đích điều trị hiện tại.
34. EBBINGHAUS
Cognitive Study of Patients Enrolled in the FOURIER
Trial
Giugliano RP | LBCT 404-16
Giugliano RP et al, Clin Card 2017;40:59-65
Cognitive assessments by Nadir – Achieved LDL-C and treatment (full population)
Primary CANTAB endpoint*: average change from baseline
Composite Global Score: average change from baseline
Nadir LDL-Achieved (mg/dL)
Mean∆ofboxes
Mean∆-Zscore
4
2
0
-2
-4
0
0.5
1
-0.5
-1
<25 mg/dL 25-39 mg/dL ≥ 40 mg/dL
<25 mg/dL 25-39 mg/dL ≥ 40 mg/dL
P=NS across LDL values achieved and also between treatments
# pts 0 661 13 206 969 115
Placebo
Evolocumab
Negative score improvement
Lower scores are better
*Spatial working memory
strategy index of
executive function, raw
score
35. EBBINGHAUS
Cognitive Study of Patients Enrolled in the FOURIER
Trial
Giugliano RP | LBCT 404-16
Giugliano RP et al, Clin Card 2017;40:59-65
Patient self-report: 23 questions regarding everyday cognition
All patients
Placebo
N=781
mean (SD)
Evolocumab
N=800
mean (SD)
P-value
Memory 1.16 (0.39) 1.17 (0.39) 0.81
Executive functioning total score
Planning
Organization
Divided attention
1.11 (0.32)
1.08 (0.31)
1.09 (0.32)
1.15 (1.42)
1.12 (0.32)
1.10 (0.32)
1.10 (0.33)
1.16 (0.41)
0.28
0.20
0.57
0.54
Total score 1.13 (0.33) 1.14 (0.33) 0.42
Patient self-report at end of study as compared
to randomization, graded as
1. Better or no change
2. Questionable/ occasionally worse
3. Consistently a little worse
4. Consistently much worse
Lower scores represent better cognition P=0.42 P=0.59
16/99011/586 19/9838/618
Investigator reported
cognitive adverse events
36. Tăng gấp đôi liều Statin đem lại hiệu quả
giảm thêm chỉ 6%
Bays HE et al. Expert Opin Pharmacother 2003;4:779-790
1-STEP
COADMINISTRATIONStatin at starting doseStatin at starting dose
15–18%
+ Ezetimize+ Ezetimize
10mg10mg
% Reduction in LDL-C
3-STEP
TITRATIONStatin at starting doseStatin at starting dose 1st1st 2nd2nd 3rd3rd
Doubling
5–6% 5–6% 5–6%
% giảm LDL-C
Phối hợp ức chế kép liều thấp giảm thêm 18%
1-STEP
COADMINISTRATION
High or moderate
intensity statin (± EZ)
59%
+ Ức chế+ Ức chế
PCSK9PCSK9
Phối hợp ức chế PCSK9 giảm thêm 59%
37. Khi nào cần chuyển thuốc ?
Beck DL, 2017. Medscape
Dữ liệu từ Nghiên cứu MarketScan của công
ty Truven Health Analytics:
105,269 bệnh nhân bị ASCVD (tuổi trung bình
65.1 và nam giới 57.2%) cho thấy 53.2% điều
trị statins (1,7% statin + eztimibe) và chỉ
25.2% đạt LDL-C dưới 70 mg%.
Nghiên cứu mô phỏng, điều trị tích cực trong
nhóm BN không điều trị statin: atorvastatin 20
mg, tăng dần 80 mg thêm ezetimibe
alirocumab nếu chưa đạt LDL mục tiêu.
Chỉ 0.7% thất bại đạt LDL < 70 mg%.
38.
39.
40.
41. Xu hướng mới trong điều trị hội chứng
mạch vành: ESC 2017
Borja Ibanez, et al. European Heart Journal. 2017;00:1–66
What is new in 2017 STEMI Guidelines. BMS =
bare metal stent; DES = drug eluting stent; IRA =
infarct related artery; i.v. = intravenous; LDL = low-
density lipoprotein; PCI = percutaneous coronary
intervention; SaO2 = arterial oxygen saturation;
STEMI = ST-elevation myocardial infarction; TNK-
tPA = Tenecteplase tissue plasminogen activator.
For explanation of trial names, see list of.
a Only for experienced radial operators. b Before
hospital discharge (either immediate or staged). c
Routine thrombus aspiration (bailout in certain
cases may be considered). d In 2012 early
discharge was considered after 72h, in 2017 early
discharge is 48–72h. e If symptoms or
haemodynamic instability IRA should be opened
regardless time from symptoms onset.
In left and mid panels, below each
recommendation, the most representative trial
(acronym and reference) driving the indication is
mentioned.
[[Propose that this slide would be updated when Long Beach 1 and 2 manuscripts are published]]
In an open-label, parallel-group, randomised, three-way crossover study, the pharmacokinetics of single doses of rosuvastatin 20 mg, atorvastatin 40 mg and simvastatin 40 mg in healthy Chinese and Japanese subjects were compared with Caucasian controls. The ratio of Asian:Caucasian data for Cmax and AUC0-t are shown on this slide.
Plasma exposure to rosuvastatin, atorvastatin and simvastatin was higher in the Chinese and Japanese groups compared with Caucasian controls.
The magnitude of the ethnic effect was not significantly different for atorvastatin and rosuvastatin in these Asian subjects. However, the difference between simvastatin and rosuvastatin was statistically significant.
Reference
1.Birmingham BK et al. Increased exposure levels of rosuvastatin, atorvastatin and simvastatin in Chinese and Japanese subjects: a class effect? Clin Pharmacol Ther 2008; 83: S15
[Data from table in abstract]
I now want to address the PK difference between Asian and non-Asian patients. Because we developed Crestor after the Cerivastatin problem AZ had to do much more clinical trial work than any of the other statins. One areas we looked at was ethnic differences in PK.
The data above is from a very impressive study done by Professor Edmund lee in Singapore. This was one of the best studies that has been done in this area and it confirmed observations we had seen in smaller numbers of Japanese patients – plasma levels in Asia patients seems to be about 2x that of non-Asians for the same dose.
Prof Lee looked extensively across the literature but there didn’t seem to be any similar studies for other statins. There were hints that other statins such as simvastatin do have this effect as well, but because they were developed so long ago they were never studied in this way.
The recommended starting dose for each statin results in a mean reduction in the LDL-C level between 19% to 37%. Thereafter, each doubling of the dose results in an approximate 6% further lowering of the LDL-C level. Titration to the maximum approved dose produces a mean reduction of approximately 31% to 51%.
There is marked variability in the potency of the available statin medications. In general, fluvastatin is regarded as the least potent and rosuvastatin is regarded as the most potent.
METHODSThis trial was a prospective, randomized, controlled, multicenter study. Eligible patients who underwent PCI
were randomly assigned to atorvastatin alone or atorvastatin plus ezetimibe (10 mg) daily. Atorvastatin was uptitrated with
a treatment goal of low-density lipoprotein cholesterol (LDL-C)&lt;70 mg/dl. Serial volumetric intravascular ultrasound was
performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients.
RESULTSThe combination of atorvastatin/ezetimibe resulted in lower levels of LDL-C than atorvastatin monotherapy
(63.216.3 mg/dl vs. 73.320.3 mg/dl; p&lt;0.001). For the absolute change in percent atheroma volume (PAV),
the mean difference between the 2 groups (–1.538%; 95% confidence interval [CI]:–3.079% to 0.003%) did not
exceed the pre-defined noninferiority margin of 3%, but the absolute change in PAV did show superiority for the dual
lipid-lowering strategy (–1.4%; 95% CI:–3.4% to–0.1% vs.–0.3%; 95% CI:–1.9% to 0.9% with atorvastatin alone;
p¼0.001). For PAV, a significantly greater percentage of patients who received atorvastatin/ezetimibe showed coronary
plaque regression (78% vs. 58%; p¼0.004). Both strategies had acceptable side effect profiles, with a low incidence
of laboratory abnormalities and cardiovascular events.
CONCLUSIONSCompared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater
coronary plaque regression, which might be attributed to cholesterol absorption inhibition–induced aggressive lipid
lowering.
Rất nhiều nghiên cứu phòng ngừa tiên phát lẫn thứ phát đã được thực hiện và kết quả từ những nghiên cứu này đã củng cố thêm lý thuyết trên về vai trò của LDL-C đối với việc giảm biến cố tim mạch. Các nghiên cứu càng về sau càng cho thấy lợi ích của việc giảm biến cố tim mạch nhiều hơn khi hạ LDL-C thấp hơn, và đó cũng chính là những nghiên cứu được xem xét nhằm đề ra các mục tiêu điều trị trong các khuyến cáo về điều trị lipid máu. Và rõ ràng, LDL-C chính là mục tiêu nền tảng.
There is no proof that statins cause life-threatening liver damage.
Mild asymptomatic elevations in liver enzymes are found in about 3 patients per 1,000 person-years who participate in clinical trials. Elevations are reversible on stopping the statin and do not cause lasting harm.
Liver failure has been reported in 1 person out of 1 million person-years of statin use, as well as in 1 person in 1 million people not taking a statin.
Routine liver function monitoring during statin therapy is not needed. The Task Force recommends that statin manufacturers work with the FDA to remove the requirement for liver function monitoring from prescribing information.
Though all marketed statins have a small potential for inducing muscle side effects, 5 in 100,000 patients taking a statin have muscle complaints and are found to have an increase in muscle enzymes, suggesting muscle injury. This finding is not statistically significant.
1.5-3.0 percent of patients taking a statin complain of muscle pain, weakness, or cramps. The numbers are similar for patients receiving placebo.
Exercise, trauma, falls, accidents, seizures, infections, chills, and alcohol and drug abuse can cause muscle injury. Physicians should carefully identify and address the risk factors for muscle problems before prescribing a statin.
Rhabdomyolysis, the most serious potential problem associated with statin therapy, occurs in about 2 of 100,000 patients taking a statin. This is rarely life threatening and is reversible when the statin is stopped.
The panel found no evidence that statins, whentaken in approved doses, cause kidney injury.
Protein may be found in the urine of patients receiving a statin as frequently as it is found in the urine of patients who do not receive a statin.
If protein is found in the urine of patients who are taking a statin, it is not necessary to discontinue the statin.
If kidney function worsens in patients taking a statin, discontinuation is not necessary, although a dose adjustment may be indicated.
Authors Robert P. Giugliano, Francois Mach, Kenton Zavitz, Anthony Keech, Terje Pedersen, Marc Sabatine, Peter Sever, Christopher Kurtz, Narimon Honarpour, Brian R. Ott, Brigham and Women&apos;s Hospital, Boston, MA, USA, Brown University, Providence, RI, USA Abstract Background:Statins and PCSK9 inhibitors lower LDL-C by upregulating LDL receptor expression. Non-randomized data raised concern that statins may cause memory impairment. Similar questions were raised during the development of PCSK9 inhibitors. We performed a dedicated neurocognitive study of pts enrolled in the FOURIER trial, a randomized, double-blind placebo-controlled cardiovascular outcome trial of the PCSK9 inhibitor evolocumab.Methods: FOURIER enrolled pts with prior MI, prior stroke or symptomatic PAD, treated with maximally tolerated statin. Pts in FOURIER could elect to participate in this prospective assessment of cognitive function (EBBINGHAUS). Key exclusions for EBBINGHAUS were diagnoses of dementia, cognitive impairment, or other significant mental/neurological disorders. Neurocognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB); a validated tablet-based tool that assesses executive function and reaction time. The primary endpoint was the change in spatial working memory strategy index of executive function (SWMsi). The hypothesis was that evolocumab is non-inferior to placebo in the mean change from baseline over time in SWMsi. Pts were tested at baseline, week 24, week 48, every 48 weeks thereafter and at the end of the study. 1500 pts completing the assessments will provide approximately 97% power to demonstrate that the upper 95% confidence limit for the treatment difference in mean change from baseline in SWM strategy index over time is &lt;20% of the common standard deviation of the mean change. An exploratory analysis will compare neurocognitive function in pts with, versus without, at least 1 post-baseline LDL-C value &lt;25 mg/dL.Results: A total of 1974 pts (mean age 63 yrs, 28% women, 71% high-intensity statin, 75% prior MI) participated in the study. The median follow-up was ~19 months. Primary results will be ready for presentation at ACC 2017.Conclusions: EBBINGHAUS primary results will provide a first indication as to whether the addition of evolocumab to statin therapy affects cognitive function over time in pts with stable cardiovascular disease already receiving moderate to high intensity statin.
Authors Robert P. Giugliano, Francois Mach, Kenton Zavitz, Anthony Keech, Terje Pedersen, Marc Sabatine, Peter Sever, Christopher Kurtz, Narimon Honarpour, Brian R. Ott, Brigham and Women&apos;s Hospital, Boston, MA, USA, Brown University, Providence, RI, USA Abstract Background:Statins and PCSK9 inhibitors lower LDL-C by upregulating LDL receptor expression. Non-randomized data raised concern that statins may cause memory impairment. Similar questions were raised during the development of PCSK9 inhibitors. We performed a dedicated neurocognitive study of pts enrolled in the FOURIER trial, a randomized, double-blind placebo-controlled cardiovascular outcome trial of the PCSK9 inhibitor evolocumab.Methods: FOURIER enrolled pts with prior MI, prior stroke or symptomatic PAD, treated with maximally tolerated statin. Pts in FOURIER could elect to participate in this prospective assessment of cognitive function (EBBINGHAUS). Key exclusions for EBBINGHAUS were diagnoses of dementia, cognitive impairment, or other significant mental/neurological disorders. Neurocognitive testing was performed using the Cambridge Neuropsychological Test Automated Battery (CANTAB); a validated tablet-based tool that assesses executive function and reaction time. The primary endpoint was the change in spatial working memory strategy index of executive function (SWMsi). The hypothesis was that evolocumab is non-inferior to placebo in the mean change from baseline over time in SWMsi. Pts were tested at baseline, week 24, week 48, every 48 weeks thereafter and at the end of the study. 1500 pts completing the assessments will provide approximately 97% power to demonstrate that the upper 95% confidence limit for the treatment difference in mean change from baseline in SWM strategy index over time is &lt;20% of the common standard deviation of the mean change. An exploratory analysis will compare neurocognitive function in pts with, versus without, at least 1 post-baseline LDL-C value &lt;25 mg/dL.Results: A total of 1974 pts (mean age 63 yrs, 28% women, 71% high-intensity statin, 75% prior MI) participated in the study. The median follow-up was ~19 months. Primary results will be ready for presentation at ACC 2017.Conclusions: EBBINGHAUS primary results will provide a first indication as to whether the addition of evolocumab to statin therapy affects cognitive function over time in pts with stable cardiovascular disease already receiving moderate to high intensity statin.
