dyslipidemia 'from guidelines to practice' prof.alaa wafaa

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