The role of lipid treatment in the cardiovascular ... · Lipids and Prevention of Cardiovascular Events in T2DM LDL Lp(a) Focus #1 All Guidelines ADA 2016: LDL-C is identified as

The role of lipid treatment in the cardiovascular prevention

of diabetic patients

Alberto Zambon Università di Padova

What dyslipidemia are we facing (not only LDL-C…)?

How relevant is to treat dyslipidemia in diabetic patients

Do we know where to start from (i.e. CV risk level)?

How can we treat diabetic dyslipidemia -no brainer

How Does AD impact on CV risk (at low/optimal LDL-C) ?

How can we further treat AD (select and hit smart!)

• Time for a better lipid target in patients with diabetic dyslipidemia?

Lipid Treatment in Diabetes

(n = 11.157)

1200

1000

800

600

400

200

0 64

LDL Cholesterol (mg/dL)

288 80 96 112 128 144 160 176 192 208 224 240 256 272

Median = 129 (3.3 mmol/L)

Pat

ien

ts (

abso

lute

nu

mb

er)

LDL-C >129 mg/dl (3.3 mmol/L)

Cardiovascular risk factors and metabolic control in type 2 diabetic subjects

attending outpatient clinics in Italy

The SFIDA (survey of risk factors in Italian diabetic subjects by AMD) study

Nutr Met Cardiovasc Dis 2005, 15;204-2011

TG-rich Lp(TRLs)

(fasting and PP)

Large VLDL particles

HDL-C Small, dense HDL

± LDL-C

Small, dense LDL

Austin et al. Circulation 1990

Diabetic Dyslipidemia

PP=postprandial

Visceral obesity

Type 2 diabetes

FCHL

Chronic kidney disease

LDL-C: - Normal/moderate increase in LDL-C levels - Increase in sd LDL

HDL-C: - Decrease in HDL-C levels - Increase in sd HDL

TG: - Increase in total Triglycerides - Increase in VLDL Triglycerides

Make sure you know what you try to treat!

How relevant is treating dyslipidemia to prevent CVD

in diabetic patients?


Variable

LDL-Cholesterol

HDL-Cholesterol

Glycated Hemoglobin (HbA1c)

Systolic blood pressure

Cigarette smoking

P Value

<0.0001

0.0001

0.0022

0.0065

0.056

UKPDS – Coronary Events (n=280)

Ranking in the model

First

Second

Third

Fourth

Fifth

0

10

20

30

40

50

60

70

80

Lipids HbA1c Blood Pressure

Att

rib

uta

ble

CV

ris

k

red

ucti

on

(%

)

Gaede P, and Pedersen O, Diabetes 2004;53:S39-S47

STENO 2

UKPDS -Lancet 1998;352:837–853

UKPDS –STENO 2: Cardiovascular Risk Reduction as it is Accounted for by Changes in Risk Factors on Therapy

(Patients with Type 2 Diabetes)


Because it is highly relevant to prevent CVD in diabetes

Do we know where to start from (i.e. CV risk level)?


Woman, 58 years old, high-school teacher, Menopause at 54 years (no HRT)

2005 hypertension (fair BP control at home - 125-130/80-85 mmHg)

Diabetes since 2011 (positive family history for T2DM, mother’s family)

Family history of CVD : father MI at 61 yrs., grandfather died of MI at 58 yrs., brother

PTCA at age 59.

Never smoked, regular follow-up visits at the local diabetes center

Patient Case

Weight: 86 kg, Height: 178 cm

BMI: 27,1, Waist circumference 92 cm

BP 115/75 mmHg

Physical exam: nothing remarkable

ECG: sinus rhythm 72 bpm, LV hypertrophy (normal LV EF)

Carotid Ultrasound: Calcified atherosclerotic plaque at the origin of the left internal

(ICA) carotid artery with a 40-45% stenosis. Nothing relevant on right CCA and ICA.

1st Visit

HbA1c (%) 6.9

Fasting glucose 118 (6.5)

Cholesterol 205 (5.3)

LDL-C 129 (3.3)

HDL-C 34 (0,9)

TG 208 (2.4)

Non-HDL-C 171 (4.4)

Hs-CRP 2.0

ApoB 109

ACR (spot urine

alb/Cr ratio) 18 mg/g

AST Normal

ALT Normal

TSH Normal

Lab Tests

• CV risk: High?

Very High?

• LDL-C goal?

Lipids and CVD in Diabetes- Guidelines

ESC/EASD Guidelines European Heart Journal August 2013

Lipids and Prevention of

Cardiovascular Events in T2DM

LDL

Lp(a) Focus #1

All Guidelines

ADA 2016: LDL-C is identified as the primary target of lipid-lowering therapy. For patients of

all ages with diabetes statin (moderate or high-intensity statin therapy) should be added to lifestyle therapy1

ESC/EAS 2011: LDL-C primary target. All major statin trials have consistently demonstrated

significant benefits of statin therapy on CVD events in people with type 2 diabetes2

EASD/ESC 2013: Statin therapy is recommended in patients with T2DM at high

(recommended LDL-C<100 mg/dl) and very high-risk (LDL-C<70 mg/dl)3

1 Diabetes Care published online January, 2016, Suppl. 1

2 Eur Heart J (2011) 32, 1769–1818; 3 Eur Heart J. 2013 Oct;34(39):3035-87



Starting point: CV risk evaluation and identification of LDL-C

as #1 target to reduce CV risk

How can we treat diabetic dyslipidemia -no brainer


Lipids and Prevention of

Cardiovascular Events in T2DM

LDL

Lp(a) Focus #1

All Guidelines

ADA 2016: LDL-C is identified as the primary target of lipid-lowering therapy. For patients of all

ages with diabetes statin (moderate or high-intensity statin therapy) should be added to lifestyle therapy1

ESC/EAS 2011: LDL-C primary target. All major statin trials have consistently demonstrated

significant benefits of statin therapy on CVD events in people with type 2 diabetes2

EASD/ESC 2013: Statin therapy is recommended in patients with T2DM at high

(recommended LDL-C<100 mg/dl) and very high-risk (LDL-C<70 mg/dl)3

1 Diabetes Care published online January, 2016, Suppl. 1

2 Eur Heart J (2011) 32, 1769–1818; 3 Eur Heart J. 2013 Oct;34(39):3035-87

Statins

Istvan ES, Science, 2001;292:1160-64

Acetyl-CoA+Acetoacetyl-CoA

HMG-CoA

Mevalonate

Geranyl-PP

Farnesyl-PP

STATINS X

Liver

Cholesterol Synthesis Cholesterol lowering effect

Prenilation

Geranyl-Geranyl-PP

Rho

Modulation of Transcription Factors

Macrophages Endothelium

Antinflammatory Effects

Smooth muscle

cells

European Heart Journal (2011) 32, 1769–1818

Therapeutic equivalence of statins and simvastatin/ezetimibe

Weng TC, et al. J Clin Pharm Ther. 2010;35;139-151

Mukhtar RY, et al. Int J Clin Pract. 2005;59(2):239-252

A10 A20 A40 A80 F20 F40 F80 L20 L40 L80 L10 P10 P20 P40 S10 S20 S40 R5 R10 R20 R40 10/20

ATOR FLUVA LOVA PRAVA SIMVA ROSU SIMVA/EZE

70

60

50

40

30

20

10

0

LDL

%

10/40

Reduction in incidence of major coronary and mean absolute LDL-C reduction

(Meta-analysis of 14 trials, n=90.056 whole population, n=18686 diabetics, 1994-2004)

-10

0

40

50

30

Reduct

ion in E

vent

Rate

(%

)

Reduction in LDL-C (mmol/L)

10

20

0.5 1.0 1.5 2.0

Major Coronary Events

-23% every

1 mmol/L LDL-C

-21% every

1 mmol/L LDL-C LDL-C 1 mmol/L= 39 mg/dl

1990s-2004 Major statin trials: statin therapy vs placebo

CTT Collaborators Lancet 2005;366:1267–1278 CTT Collaborators Lancet 2008;371:117–125

Reduction in LDL-C (mmol/L)

Reduct

ion in E

vent

rate

(%

)

Major Coronary Events in Diabetics

-10

0

40

50

30

10

20

0,5 1,0 1,5 2,0

Dyslipidemia Simvastatin 40 mg qd

Hypertension Lisinopril 20 mg qd

Type 2 Diabetes

Sitagliptin 50 mg bid Metformin 1000 mg bid

Aspirin 100 mg qd

Echocardiogram: modest LV hypertrophy, normal EF and

kinetics Fundus Oculi: non-proliferative retinopathy (very mild)

Patient Case #1 - Therapy

1st Visit 2nd Visit

HbA1c% 6.9 6.8

Fasting glucose 118 (6.5) 121 (6,7)

Cholesterol 205 (5.3) 159 (4,1)

LDL-C 129 (3.3) 84 (2,1)

HDL-C 34 (0,9) 38 (1,0)

TG 208 (2.4) 189 (2,1)

Non-HDL-C ? 171 (4.4) 121 (3,1)

Hs-CRP 2.0 NA

ApoB 109 94

AST/ALT/CPK Normal Normal

Follow-up visit Lab Tests (+ 6 months)

Simva 40

Individual Lipid Goals

LDL-C: <70 mg/dl <1.8 mmol/L

Non HDL-C: ?

Lipid Targets and Pharmacological Approaches

STATIN

Target LDL-C

Not at target for LDL-C

Statin High intensity

Statin + Ezetimibe

Statin + Colesevelam

Recommendations for Statin and Combination Treatment in Persons With Diabetes

ACS = acute coronary syndrome; ASCVD = atherosclerotic cardiovascular disease; LDL = low-density lipoprotein.

* In addition to lifestyle therapy. † LDL cholesterol level ≥2.6 mmol/L (≥100 mg/dL), high blood pressure, smoking, overweight or obesity, and family history of premature ASCVD.

ADA Standards of Care in Diabetes 2016, Diabetes Care January 2016 Volume 39, Suppl. 1

European Heart Journal (2011) 32, 1769–1818

Therapeutic equivalence of statins and simvastatin/ezetimibe

Weng TC, et al. J Clin Pharm Ther. 2010;35;139-151

Mukhtar RY, et al. Int J Clin Pract. 2005;59(2):239-252

A10 A20 A40 A80 F20 F40 F80 L20 L40 L80 L10 P10 P20 P40 S10 S20 S40 R5 R10 R20 R40 10/20

ATOR FLUVA LOVA PRAVA SIMVA ROSU SIMVA/EZE

70

60

50

40

30

20

10

0

LDL

%

10/40

Terapia Ipolipemizzante intensiva: atorvastatina ≥40 mg/die ± EZE; rosuvastatina ≥40 mg/die ± EZE

simvastatina+EZE (20) 40/10 mg/die


STATIN

Target LDL-C

Not at target for LDL-C

Statina High intensity

Statin + Ezetimibe


24

Ateroma

Liver

Blood

Cholesterol Pool (Micelle)

NPC1L1 Remnant receptors

LDL receptor

Expression

Cholesterol

HMG-CoA

CMR

CM

Statins

Ezetimibe

X

X

2

1 Reduction of liver cholesterol pool

2 Increased expression of LDL-receptors

3 Increased LDL-C clearance

Ezetimibe combined with statin

therapy results in:

LDL-C

NPC1L1 = Niemann-Pick C1-like 1; HMG-CoA = 3-hydroxy-3-methylglutaryl acetyl coenzyme A; CMR = chylomicron remnant. 1. Grigore L et al. Vas Health Risk Manag. 2008;4:267–278.

1 Pool Cholesterol

3

Complementary mode of action of statins

and ezetimibe1

IMPROVE-IT: Primary Endpoint Diabetes YES vs Diabetes NO

HR 0.98 (0.91-1.04)

No DM 7 yr event rate

Plac/Simva 30.8%

EZE/Simva 30.2%

Years After Randomization

Cardiovascular death, MI, documented unstable angina requiring

rehospitalization, coronary rivascularization (≥30 days), stroke

0 1 2 3 4 5 6 7

50%

40%

30%

20%

10%

0%

Presented at 2015 ESC London

HR 0.86 (0.78-0.94)

DM Present 7 yr event rate

Plac/Simva 45.5%

EZE/Simva 40.0% - 14%

- 2%

Baseline mg/dL 95 (2.5)

Simvastatin 40-80 mg/dL 70 (1.8) dashed lines

Simva 40/Ezetimibe 10 mg/dL 53 (1.4) solid lines

Dyslipidemia

Simvastatin 20 mg qd Rosuvastatin 20 mg qd

Hypertension

Lisinopril 20 mg qd

Type 2 Diabetes

Sitagliptin 50 mg bid Metformina 1000 mg bid

Aspirin 100 mg qd

Improved lifestyle counselling

Patient Case #1 – Updated Therapy (Visit 2)

1st Visit 2nd Visit 3rd Visit

HbA1c% 6.9 6.8 6.9

Fasting glucose 118 (6.5) 121 (6,7) 128 (7,1)

Cholesterol 205 (5.3) 159 (4,1) 145 (3,7)

LDL-C 129 (3.3) 84 (2,2) 72 (1,9)

HDL-C 34 (0,9) 38 (1,0) 35 (0,9)

TG 208 (2.4) 189 (2,1) 192 (2.2)

Non-HDL-C ? 171 (4.4) 121 (3,1) 110 (2,8)

Hs-CRP 2.0 NA NA

ApoB 109 94 94

AST/ALT/CPK Normal Normal Normal

2° Follow-up visit - Lab Tests (+ 12 months)

Simva 40 Rosuva 20

Patients With Diabetes Have Particularly High

Residual CVD Risk After Statin Treatment

Event Rate

(No Diabetes)

Event Rate

(Diabetes)

On Statin On Placebo On Statin On Placebo

HPS1* (CHD patients) 19.8% 25.7% 33.4% 37.8%

CARE2† 19.4% 24.6% 28.7% 36.8%

LIPID3‡ 11.7% 15.2% 19.2% 22.8%

PROSPER4§ 13.1% 16.0% 23.1% 18.4%

ASCOT-LLA5‡ 4.9% 8.7% 9.6% 11.4%

TNT6║ 7.8% 9.7% 13.8% 17.9%

*CHD death, nonfatal MI, stroke, revascularizations †CHD death, nonfatal MI, CABG, PTCA ‡CHD death and nonfatal MI §CHD death, nonfatal MI, stroke ║CHD death, nonfatal MI, resuscitated cardiac arrest, stroke

(80 mg versus 10mg atorvastatin)

1HPS Collaborative Group. Lancet. 2003;361:2005-2016. 2Sacks FM, et al. N Engl J Med. 1996;335:1001-1009. 3LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 4Shepherd J, et al. Lancet. 2002;360:1623-1630. 5Sever PS, et al. Lancet. 2003;361:1149-1158. 6Shepherd J, et al. Diabetes Care. 2006;29:1220-1226.

Statin Therapy in Patients with Diabetes: Open Issues

Statin Intolerance

Increased prevalence of new onset

diabetes (not really of an issue for patients who already

are diabetic)



Starting point: CV risk evaluation and identification of #1

target to reduce risk (LDL-C)

Statin therapy highly effective (and safe)

- High intensity statins often needed

- Risk (Residual) of CV event remains clinically relevant!

Do TG and HDL-C impact on CV risk (at low/optimal LDL-C) ?


ACCORD-Lipid Study Diabetes and Residual Risk on Statin* (placebo group)

ACCORD Study Group NEJM 2010;362:1563–1574

Previous CVD Lipid sub-groups Overall

Yes No TG 204

+

HDL 34

HDL

34

TG

204

All pts

–

[TG 204

+

HDL 34]

Eve

nts

, %

TG =2,3, HDL-c=0,84 in mmol/L

% events = non-fatal MI, non-fatal stroke, CV death (follow-up : 4.7 years)

* LDL-c ≈ 2.0 mmol/L (80 mg/dL) on simvastatin



Starting point: CV risk evaluation and identification of #1

target to reduce risk (LDL-C)

Statin therapy highly effective (and safe)

- High intensity statins often needed

- Risk (Residual) of CV event remains clinically relevant!

At low/optimal LDL-C high TG and low HDL-C impact on CV risk!


Combination statin + 2° lipid-lowering drug STATIN

Target LDL-C

At target LDL-C: NO

Target HDL-C and TG

Small dense

LDL Triglycerides

HDL-C

At target LDL-C: YES,

but…..

Statin High intensity

Statin + Ezetimibe


Statin + Fenofibrate

Statin + Niacin

Statin + Omega 3 fatty acids


Fibrates: Mechanism of Action

Fibrates

Nuclear

Membrane

Nuclear

Receptor PPAR alpha

PPAR:Peroxisome proliferator-activated receptor

TARGET GENE

Nuclear

Receptor

TARGET GENE

Anti-inflammatory

properties

GENE Repression

Lipid metabolism

Glucose metabolism

GENE Activation

Effect of fibrates in subgroups without (A) and with (B) dyslipidemia

Sacks FM et al. N Engl J Med 2010

A total of 2428 fibrate-treated subjects (302 events) and 2298 placebo-treated subjects (408 events) with dyslipidemia were included in the analysis

B Subgroups with Dyslipidemia

Study Odds Ratio (95% CI)

FIELD

BIP

HHS

VA-HIT

Summary 0.65 (0.54-0.78)

0.16 0.25 0.40 0.63 1.00 1.58

A Complementary Subgroups

Study Odds Ratio (95% CI)

FIELD

BIP

HHS

VA-HIT

Summary 0.94 (0.84-1.05)

0.16 0.25 0.40 0.63 1.00 1.58

-6%

Bruckert E et al J Cardiovasc PharmacolT 57:267, 2011

35%

27%

39%

78%

28%

DYSLIPIDEMIA: TG 200 mg/dl, HDL-C 34-40 mg/dl

Fibrates reduce CVD among patients with

the lipid phenotype of the diabetic dyslipidemia

ACCORD Optimizing Outcomes in Patients with Type 2 Diabetes

ACCORD-LIPID: Atherogenic dyslipidaemia 70% risk of major CV events

ACCORD Study Group. N Engl J Med 2010; 362: 1563. FDA EMDAC Meeting 19 May 2011.

0

5

10

15

20 SMV SMV+Fenofibrate

4.95% ARR 17.32%

12.37%

10.11% 10.11%

7.6% ARR

16.3%

8.8%

NNT5=20

TG< 204

and/or

HDL-C >34

(82.4% of ACCORD pts)

TG≥204

and/or

HDL-C34


15.6%

8,0%

7.6% ARR

TG =2,3, HDL-c=0,84 in mmol/L

% events = non-fatal MI, non-fatal stroke, CV death (follow-up : 4.7 years)

* LDL-c ≈ 2.0 mmol/L (80 mg/dL) on simvastatin

Non-HDL Cholesterol: Emerging Target for

the Treatment of (Residual) CV Risk

Cholesterol

HDL LDL IDL VLDL (remnants)

Anti- atherogenic

lipoproteins Atherogenic lipoproteins

Non HDL-C= Total Cholesterol minus HDL-C

Accounts for all atherogenic lipoproteins and may provide an improved estimate of CV risk in patients with diabetes, metabolic syndrome or chronic kidney disease

Recommended as secondary target in the EAS/ESC guidelines

Target levels= LDL-C goal + 30 mg/dl (0.8 mmol/L)

Easy to calculate: Total cholesterol minus HDL-C

Triglycerides

1st Visit 2nd Visit 3rd Visit

HbA1c% 6.9 6.8 6.9

Fasting glucose 118 (6.5) 121 (6,7) 128

Cholesterol 205 (5.3) 159 (4,1) 145 (3,7)

LDL-C 129 (3.3) 84 (2,2) 72 (1,9)

HDL-C 34 (0,9) 38 (1,0) 35 (0,9)

TG 208 (2.4) 189 (2,1) 192 (2,2)

Non-HDL-C ? 171 (4.4) 121 (3,1) 110 (2,8)

Hs-CRP 2.0 NA NA

ApoB 109 94 94

AST/ALT/CPK Normal Normal Normali


Simva 40 Rosuva 20

Individual Lipid Goals

LDL-C: <70 mg/dl <1.8 mmol/L

Non HDL-C: <100mg/dl <2.6 mmol/L

Association of LDL-C, Non–HDL cholesterol, and Apo B with risk

of cardiovascular events among patients treated with statins

A meta-analysis 62 154 patients enrolled in 8 trials published between 1994 and 2008

Risk of major cardiovascular events by LDL and non-HDL cholesterol categories

Data markers indicate hazard ratios (HRs) and 95% CIs for risk of major cardiovascular events.

Results are shown for 4 categories of statin-treated patients based on whether or not they reached

the LDL-c target of 100 mg/dL (2.6 mmol/L) and the non–HDL-C target of 130 mg/dL (3.4 mmol/L).

HRs were adjusted for sex, age, smoking, diabetes, systolic blood pressure and trial

Boekholdt et al. JAMA 2012;307(12):1302–1309

+ 32%

Same LDL-C!

LDL HDL IDL VLDL

Non-HDL Cholesterol

Non HDL-C ≥130 mg/dl or 3.4 mmol/L NOT AT TARGET

Atherogenic Lipoproteins

AT TARGET

<100 mg/dl

<2.6 mmol/L

Triglycerides

Anti

Atherogenic

Lipoproteins

(Remnants)

Non-HDL cholesterol: Emerging # 1 TARGET for

treatment of (Residual) Cardiovascular Risk

ACCORD Optimizing Outcomes in Patients with Type 2 Diabetes

ACCORD-LIPID: Atherogenic dyslipidaemia 70% risk of major CV events

ACCORD Study Group. N Engl J Med 2010; 362: 1563. FDA EMDAC Meeting 19 May 2011.

0

5

10

15

20 SMV SMV+Fenofibrate

4.95% ARR 17.32%

12.37%

10.11% 10.11%

7.6% ARR

16.3%

8.8%

NNT5=13 NNT5=20

TG< 204

and/or

HDL-C >34


Major CV event (1º endpoint): CV death, nonfatal MI or nonfatal stroke

TG≥204

and/or

HDL-C34


15.6%

8,0%

7.6% ARR

LDL-C<100

+

NON HDL-C >130

NNT5=13

LDL-C<70

+

NON HDL-C >100

What if we use a combination of LDL-C and non HDL-C to select

patients who may benefit from combination therapy?

Dyslipidemia Simvastatin 20 mg qd Rosuvastatin 20 mg qd Rosuvastatin 20 mg qd Rosuva 20 + Fenofibrate 145 qd

Hypertension Lisinopril 20 mg qd

Type 2 Diabetes

Sitagliptin 50 mg bid Metformin 1000 mg bid

Aspirin 100 mg qd

Patient Case #1 – Updated Therapy (Visit 3)

1st Visit 2nd Visit 3rd Visit 4th Visit

HbA1c% 6.9 6.8 6.9 6.7

Fasting glucose 118 (6.5) 121 (6,7) 128 (7,1) 117 (6,5)

Cholesterol 205 (5.3) 159 (4,1) 145 (3,7) 140 (3,6)

LDL-C 129 (3.3) 84 (2,2) 72 (1,9) 71 (1,8)

HDL-C 34 (0,9) 38 (1,0) 35 (0,9) 43 (1,1)

TG 208 (2.4) 189 (2,1) 192 (2,2) 139 (1,6)

Non-HDL-C ? 171 (4.4) 121 (3,1) 110 (2,8) 99 (2,6)

Hs-CRP 2.0 NA NA 1.8

ApoB 109 94 94 81

AST/ALT/CPK Normal Normal Normal Normal

Simva 20 Rosuva 20 Rosuva 20

Feno 145


Full Lipid Profile (Chol, LDL-C, HDL-C, TG, Non HDL-C)

NO NO

Check compliance to therapy – Life Style

+COMBINATION STATIN +2° lipid-lowering agent

Priority #2

Residual CVD Risk

Reduction

YES

OK STOP

YES

OK STOP

LDL-C AT GOAL FOR

INDIVIDUAL CV RISK Priority #1

CVD Risk Reduction

EAS Consensus, Eur.Heart J 29 aprile 2011 e-pub

*PAD

Aortic aneurysm

Carotid Artery disease

CHD risk >10 (SCORE)

NO

High CVD Risk

LDL-C target # 1 Approach

<100 mg/dl LifeStyle + STATIN

<2.6 mmol/L

CHD or other RF or

CVD Equivalent*

Very High CVD Risk

YES

LDL-C Target # 1 Approach

<70 mg/dl LifeStyle + STATIN*

<1.8 mmol/L or Statin-Ezetimibe

Phenotype-Tailored

Effective CVD

Risk Reduction

In Diabetes CONSIDER NON-HDL-C: AT GOAL?

NON HDL-C goals < 100 mg/dl (2.6 mmol/L) very high CV risk

< 130 mg/dl (3.4 mmol/L) high CV risk

know what you try to treat!

CV risk evaluation and identification of #1 target LDL-C

Statin (±ezetimibe) highly effective CV events reduction

Risk (Residual) of CV event remains clinically relevant!

Documents

The role of lipid treatment in the cardiovascular ... · Lipids and Prevention of Cardiovascular Events in T2DM LDL Lp(a) Focus #1 All Guidelines ADA 2016: LDL-C is identified as