DyslipidemiaFrom Guidelines To Practice
ALAA WAFA. MDAssociate Professor of Internal Medicine
PGDIP DM CARDIFF University UKDiabetes and Endocrine unit
Mansoura university 2014
HTN treatment vs. lipid lowering• HTN TREATMENT LIPID LOWERING
Multiple mechanisms
Many drug classes More frequent ADE Disputes about
measurement Benefits reduced by
wt gain and high salt
Patients tend to need more drugs with ageing
Fewer mechanisms Fewer drugs Less frequent ADE Simple standard
measurement Benefits less
affected by life style The effective dose
remains effective
0
20
40
60
80
100
Atorvastatin(n=78)
Simvastatin(n=76)
Lovastatin(n=78)
Fluvastatin(n=76)
Overall(n=308)
Initial doseFirst dose adjustment
% P
atie
nts
not r
each
ing
goal
Many Pts Do Not Reach Goal even after First Dose Adjustment
Adapted from Brown AS J Am Coll Cardiol 1998;32:665–672.
68
47
78
61
90
69
9990
83
66
Long-term adherence with CV regimensBasal prescription & discontinuation (gray bar) at 1 yr
Kulkarni sp et al. Am Heart J 2006;151: 185-91
Dr.Sarma@works7
Atherosclerosis – Time line
The Continuum
Risk factorsHypertensionDyslipidemiaDiabetes
Death Death DeathAdapted from: Dzau V, et al. Am Heart J 1991;121:1244--1263.
CAD
Myocardialinfarction
HF
End--stage heart disease
Arteriosclerosis
Nizzar Qabbani .... Died with MI in 1998
Mohamed A. WahabEL AHLY Club playerDied in a match
No One is immune
12
CVD=cardiovascular disease; MRFIT=Multiple Risk Factor Intervention Trial.1. Stamler J et al. Diabetes Care. 1993;16:434–444.
CVD
Mor
talit
y pe
r10
,000
Per
son-
Year
s
DiabetesNo diabetes
Serum Cholesterol at Baseline, mg/dL
0
20
40
60
80
100120140
<180 180–199 200–219 220–239 240–259 260–279 ≥280
160
Higher CVD Mortality Risk in Patients With Diabetesand Low Cholesterol Than in Patients Without Diabetes and High Cholesterol1
• Cohort study in 347,978 men aged 35 to 57 years, screened in 20 centers for MRFIT• Vital status ascertained over an average of 12 years• Outcome measure was CVD mortality
n = 1105n = 972 n = 1038 n = 823
n = 529
n = 343n = 353
n = 62,448 n = 64,363 n = 75,112 n = 60,386 n = 40,090n = 22,802
n = 17,604
Mechanisms Contributing to Arterial Disease in Type 2 Diabetes
Adapted from Libby et al. Circulation. 2002;106:2760-2763.
361,662 men (age 35-57) screened during the MRFIT STUDYJAMA 1986, 258-282
Lipid research council study NEJM 1990; 322:1700
Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk
Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670 2001. http://hin.nhlbi.nih.gov/ncep_slds/menu.htm
1% decreasein LDL-C reduces
CHD risk by1%
1% increasein HDL-C reduces
CHD risk by3%
39-50 % of pts with high LDL-C achieve goal on current therapyNon-complianceFear of high dose titration
More effective cholesterol-lowering is needed to attain LDL-C goals1,2
1Kotseva, K, Wood D, de Backer, G et al. 20012Pearson T et al. 2000
Why Do We Need a powerful Statin?
Rosuva
Atorva
Simva
Prava
10 20 40 80
Fluva
Statin Dose Required to Achieve45–50% LDL-C Reduction
mg
Not achieved with max. authorised dose
Not achieved with max. authorised dose
Adapted from Jones P.H. et al. Am J Cardiol 2003;92:152–160
Rosuvastatin is the most effective statin to lower LDL-C
Expert Opin. Pharmacother. (2008), 9(12) :2145-2160
*P<0.002 RSV 20 mg vs ATV 20, 40 & 80 mg; RSV 40 mg vs ATV 40 & 80 mg
Jones P.H. et al. Am J Cardiol 2003;92:152–160
0
2
4
6
8
10
12
Mea
n ch
ange
in H
DL-C
from
bas
elin
e (%
)
7.7%
9.6%*
Rosuvastatin*
10 20 40 80Dose, mg (log scale)
3.2%
5.6%Pravastatin 6.8%
Simvastatin
5.3%
2.1% Atorvastatin
5.7%
Rosuvastatin achieves significantly greater increase in HDL-C than other statins (STELLAR)
JUPITERPrimary Trial Endpoint : MI, Stroke, UA/Revascularization, CV Death
Placebo 251 / 8901
Rosuvastatin 142 / 8901
HR 0.56, 95% CI 0.46-0.69P < 0.00001
Number Needed to Treat (NNT5) = 25
- 44 %
0 1 2 3 4
0.00
0.02
0.04
0.06
0.08
Cum
ulat
ive
Inci
denc
e
Number at Risk Follow-up (years)RosuvastatinPlacebo
8,901 8,631 8,412 6,540 3,893 1,958 1,353 983 544 1578,901 8,621 8,353 6,508 3,872 1,963 1,333 955 534 174
Ridker et al NEJM 2008
Cost-effectiveness issues
More effectLess effect
More cost
Less cost
Update on guideline content:History of ATP dyslipidemia guideline development
ATP IV Nov 122013
It is advised that intensity of therapy be sufficient to achieve at least a 45% to 50% reduction in LDL-C levels.
High Risk/Very High Risk
CHD or CHD risk equivalents
(10-yr risk >20%)
LDL-
C le
vel
100 -
160 -
130 -
190 -
Lower Risk
< 2 risk factors
Moderately High Risk≥ 2 risk factors
(10-yr risk 10-20%)
goal
160mg/dl
goal
130mg/dl
70 -
goal
100mg/dl
or optional
70mg/dl
Moderate Risk
≥ 2 risk factors
(10-yr risk <10%)
goal
130mg/dl
or optional
100mg/dl
Grundy SM et al. Circulation 2004;110:227-239
2002 LDL-C goals
revised 2004 LDL-C goals
NCEP ATP III
30
Who receives a statin without Risk calculation?
1. LDL above 1902. Type 1 or 2 DM over 40y3. Existing ASCVD
New risk calculator Age Gender Ethnicity Total cholesterol HDL cholesterol Systolic BP HYPERTENSION MEDS DIABETES SMOKING
36
Important risk factors not in the score
• CKD• COLLAGEN DISEASE• CANCER• MORBID OBESITY• DRUGS
• NSAID • CANCER CHEMO/RADIO• IMMUNOSUPPRESSIVE
38
IBRAHIM
Age Diabetes Smoking Cholesterol LDL HDL Systolic Hypertension
57 Y Non Diabetic Smoker 250 mg/dl 180 mg/dl 35 mg/dl 140 ibrahim.xls
Samira
Age Diabetes Smoking Cholesterol LDL HDL Systolic Hypertension
51 Y Non Diabetic non Smoker 300 mg/dl 200 mg/dl 45 mg/dl 180
Adel
Age Diabetes Smoking Cholesterol LDL HDL Systolic Hypertension
47 Y Diabetic Non Smoker 280 mg/dl 160 mg/dl 30 mg/dl 140 adel .xls
Living Under the Umbrella of Good
Cardiovascular Health
FBG<100
LDL-C<100 SBP
<140
45