7-10 2014

:
, ;
. MD,
Phds, FESC, FEAS
.

25%
Deaths<65y by in men

18%
Deaths<65y by in women

European CVD Statistics 2012 Edition

European Heart Union & ESC Sept.2012

36%
Deaths by cause in men

~ 192 billion in direct & indirect healthcare costs

43%
Deaths by cause in women

European CVD Statistics 2012 Edition

European Heart Union & ESC Sept.2012

LIPID LOWERING DRUGS

Action substance
Statins

Mechanism
Cholesterol biosynthesis,
LDL-R-Expression

Fibrates

Catabolism of Lipoproteins
rich of TG

Resins

Interruption of the
interohepatic circuit of the bile
acids

Nicotinic acid
Ezetimibe
3 FA

VLDL-Synthesis
absorption
VLDL-Synthesis

Effects
LDL
VLDL
VLDL

, LDL

LDL

VLDL
LDL

VLDL

LDL

Effects of Combination Lipid Therapy on Coronary Stenosis Progression

& Clinical Cardiovascular Events in CAD Pts with Mets: A Combined
Analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL
Atherosclerosis Treatment Study (HATS), & the Armed Forces
Regressio Study (AFREGS)

FATS (lovastatin+colestipol+niacin): 146 62 yrs (Jan. 1984-Feb.

1987), with apoB (125 mg/dl) & family history of CAD. All
subjects had evidence of coronary atherosclerosis on their baseline
angiograms with at least one 50% stenosis/ 3 lesions of 30%
stenosis
HATS (simvastatin+niacin): 160 <63 ys &<70 with clinical CAD
angiographically confirmed (at least one 50% stenosis/3 lesions
30% stenosis), with HDL-C35 mg/dl in & 40 mg/dl in
(Jan.1995-Jan. 1997)
AFREGS (gemfibrozil+niacin+cholestyramine): recruited 143 military
retirees <76 yrs with angiographically measurable stenosis 30%- 80%
& HDL-C <40 mg/dl in 1993
Am J Cardiol. 2009 December

 Combination lipid therapy significantly stenosis

progression 83% (0.5 vs. 2.9, p<0.001) in pts with MS, & a
small net regression in those without (0.3 vs. 2.0, p<0.001)
Combination therapythe event rate by 54% (13 vs. 28%,
p=0.03) in those with MS & by 82% (3 vs. 17%, p=0.002)
without
Each 10% in LDL-C/ 10% in HDL-C was significantly
associated with 0.3 %Sprox reduction
Each 10% LDL-C / 10% HDL-C was associated with
11% (p=0.02) or22% (p<0.001) event risk reduction
Greater stenosis progression rate is associated with a higher
event rate. LDL-C-lowering and HDL-C-raising therapies
independently and significantly decrease coronary

stenosis progression & reduce CV events

Am J Cardiol. 2009 December

Colesevelam + Ezetimibe
TOTAL-C

LDL-C

TG

HDL-C

% change from baseline1

20

10
5

0
-3

-10

(2)

-14

-20

(2,3)

-20

(2)

-21
(2,4)

-30

Ezetimibe 10mg per day + Placebo

Ezetimibe 10mg + Colesevelam 3.75g per day

-32

-40

10
1. LDLC-C, HDL-C and Total-C values are expressed as mean, whereas TG values are expressed as median.
2. p < 0.0001 vs. Baseline; 3. p < 0.05 vs. Ezetimibe + placebo; 4. p < 0.0001 vs. Ezetimibe + placebo

Bays et al. Cur Med Res Opin. 22, 2006.

Colesevelam + Atorvastatin

Atherosclerosis 2001;158:407-416
LDL-C (%)

Placebo

3%

Colesevelam (3.8g/d)

-12%

Atorvastatin (10mg/d)

-38%

Colesevelam
+
Atorvastatin (10 mg/d)

-48%

Atorvastatin (80mg/d)

-53%


FH +
Colesevelam (3.8g/d) vs placebo

LDL-C:

HDL-C:
Apo:

-18.5%

6w

-12.0%

12 w

+3.3%

12 w

-12.2%

12 w
Clin Ther 2010

Colesevelam (3.8g/d)
hs CRP 16%
Am J Cardiol 2006;98: 641-643

Colesevelam + Statin vs placebo+statin

hs CRP 23%
Am J Cardiol 2006;97: 1198-1205

Intensive lipid Lowering with S+E in Aortic Stenosis

(SEAS Study)

N Engl J Med 2008

N Engl J Med 2008

N Engl J Med 2008

SHARP: Randomisation structure

Randomised
(9438)
Simva/Eze
(4193)

Simvastatin
(1054)

Placebo
(4191)
Not re-randomised
(168)

Randomised
(886)
Placebo
(4620)

Simv/Eze
(4650)
Median follow-up 4.9 years
Lost to mortality follow-up 1.5%

The Lancet,, June 2011

SHARP: Major Atherosclerotic Events

Proportion suffering event (%)

25

20

Risk ratio 0.83 (0.74-0.94)

Logrank 2P=0.0021

Placebo

15

Simv/Eze
10

0
0

Years of follow-up
The Lancet,, June 2011

SHARP: Major Vascular Events

Event

Simv/Eze
(n=4650)

Placebo
(n=4620)

Major coronary event

Non-haemorrhagic stroke
Any revascularisation procedure

213
131
284

Major Atherosclerotic Event

526 (11.3%) 619 (13.4%)

Other cardiac death

Haemorrhagic stroke

162
45

(3.5%) 182
(1.0%) 37

(3.9%)
(0.8%)

Other Major Vascular Events

207

(4.5%) 218

(4.7%)

Major Vascular Event

701 (15.1%) 814 (17.6%)

(4.6%) 230
(2.8%) 174
(6.1%) 352

Risk ratio & 95% CI

(5.0%)
(3.8%)
(7.6%)
16.6% SE 5.4
reduction
(p=0.0021)

5.5% SE 9.4
reduction
(p=0.56)
15.4% SE 4.7
reduction
(p=0.0012)
0.6

0.8

1.0

Simv/Eze better

1.2

1.4

Placebo better

The Lancet,, June 2011

Effects of Combination Lipid Therapy in Type

2 Diabetes Mellitus (The ACCORD Study)

NEJM 2010

NEJM 2010

NEJM 2010

FIELD Study

Lancet 2005;366:1849-61

ACS, Israeli Surveys data

8982 pts from ACSIS 2000, 2002, 2004, 2006, 2008 and 2010
8545 received statin alone and 437 (5%) received fibrate/statin
MACE: death, recurrent MI, recurrent ischemia, stent thrombosis,
stroke, revascularization
MACE statin 6% vs. 3% fibrate/statin
30-day re-hospitalization rate statin 20% vs 16% fibrate/statin
Multivariable analysis identified the fibrate/statin is an
independent predictor of reduced risk of MACE with OR 0.54
(95% CI 0.32-0.94)
Tenenbaum, et al. APLoS One

Tenenbaum, et al. APLoS One

Rate (%) of 30-day Major Adverse Coronary Events (MACE) among the study
patients according to the age, gender, level of HDL cholesterol, triglycerides, smoking
status, presence of diabetes and hypertension
Tenenbaum, et al. APLoS One