Presentation on Dyslipidemia on 20.11.13

Statin Evolution— Evidence, Efficacy, and Experience

SENIOR GP CONSULTANT

S1

DYSLIPIDEMIA

THE SILENT KILLER

DR. MOHAMMAD NASIM

SENIOR GP CONSULTANT

BADRUDDIN MEDICAL GROUP

WHAT IS DYSLIPIDEMIA?

DYSLIPIDEMIA IS A RANGE OF DISORDERS THAT INCLUDE ABNORMALLY HIGH AND LOW LEVELS OF LIPOPROTEINS AS WELL AS DISORDERS IN THE COMPOSITION OF THESE PARTICLES.

CAUSES

PRIMARY---

1.POLYGENIC HYPERCHOLESTROLEMIA

2.FAMILIAL HYPERCHOLESTEROLEMIA

3.FAMILIAL HYPERTRIGLYCERIDEMIA

4.CHYLOMICRONEMIA

5.FAMILIAL COMBINED DYSLIPIDEMIA

SECONDARY

1. TYPE 2 DYSLIPIDEMIA

2.EXCESSIVE ALCOHOL CONSUMPTION

3.CHOLESTATIC LIVER DISEASES

4.NEPHROTIC SYNDROME

5.CHRONIC RENAL FAILURE

6.HYPOTHYROIDISM

7.CIGARETTE SMOKING

8.OBESITY

9.DRUGS—RETINOIDS,ESTEROGENS/CONTRACEPTIVE PILLS,CORTICOSTEROIDS,CICLOSPORINS,DIURETICS,NON SELECTIVE BETA BLOCKER

10.SEDENTARY LIFESTYLE & EXCESSIVE INTAKE OF FATTY FOODS

SIGNS AND SYMPTOMS-

DERMATOLOGIC SIGNS

The most common dermatologic manifestation of dyslipidemia is xanthomas and xanthelasma.Xanthomas are firm and nontender cutaneous deposits of cholesteryl ester-enriched foam cells are most commonly observed with high levels of LDL. Xanthomas deposit in ligaments and tendons, although they may also be detected in periosteum and fascia. They are classified as tendinous, tuberous, tuberoeruptive, and planar. The most common location for tendinous xanthomas is the Achilles tendon[9] followed by the hands, feet, elbows, and knees

OPHTHALMOLOGIC SIGNS

Corneal Arcus

Corneal arcus is a grayish white opacification at the periphery of the cornea (Figure 1).[1] It is a particularly sensitive sign of familial hypercholesterolemia (FH), especially when detected in persons less than age 50 years, in which case it is also referred to as arcus juvenalis

Corneal Opacification

Patients with very low high-density lipoprotein (HDL) cholesterol because of mutations in regulatory genes may also exhibit ocular findings like corneal opacification.

Retinal Findings

In addition to the eruptive xanthomas that may accompany marked chylomicronemia, another important clinical sign is lipemia retinalis or a "milky-white" appearance of the retina.

MANAGEMENT-The management of lipid disorder greatly depends on the age, signs/symptoms of the affected persons. The following are remedies / treatment may apply to lower the level of LIPIDS in the body including:

Eat well-balanced diet – Almost fifteen (15) percent of cholesterol may decrease when strictly controlled. Eating foods that are naturally low in fat (whole grains, fruits, vegetables, etc.) a good sources of soluble fiber to prevent other health complications.

Weight Management

Exercise Regularly – (walking, yoga, dancing, etc.) – Exercise for at least thirty (30) minutes everyday. Maintain this habit and you will see the desired result.

Quit smoking – An important treatment to reduce the risk of heart disease and stroke.

Healthy Lifestyle – It is recommended that patients should eat fish, vegetables, in order to lower their cholesterol level.

Medicines / Drug Treatment – Available drugs for lowering cholesterol includes statins, bile acid, nicotinic acid, cholesterol absorption inhibitors. Helps in preventing the fastening of fatty deposits to arterial walls

MMNMM

MEDICAL MANAGEMENT—

1.STATIN– SIMVASTATIN,ATORVASTATIN,ROSUVASTATIN

2.FIBRATES

3.BILE ACID RESINS

4.NIACIN

5.NICOTINIC ACID

6.EZITIMIBE

7.FISH OIL

INCII

INCIDENCE IS MORE THAN HYPERTENSION AND DIABETES

RULE OF HALF APPLIES TO DYSLIPIODEMIA ALSO---HALF OF THE DYSLIPIDEMIA CASES ARE DIAGNOSED,HALF OF DIAGNOSED CASES BEING TREATED,HALF OF THE TREATED CASES ARE UNCONTROLLED

MANAGEMENT

The new guideline,ISSUED AT 12 NOV.,2013 BY ACC AND AHA, recommends moderate- or high-intensity statin therapy for these four groups:

Patients who have cardiovascular disease;

Patients with an LDL, or “bad” cholesterol level of 190 mg/dL or higher;

Patients with Type 2 diabetes who are between 40 and 75 years of age; and

Patients with an estimated 10-year risk of cardiovascular disease of 7.5 percent or higher who are between 40 and 75 years of age (the report provides formulas for calculating 10-year risk).

Atherosclerosis Timeline

Phase I: InitiationLDL-C plays a major role in initiating the development of atherosclerotic plaque.

Libby P. In: Heart Disease: A Textbook of Cardiovascular Medicine. 6th ed. Philadelphia, Pa: WB Saunders Co; 2001:995-1009; Libby P. J Intern Med. 2000;247:349-358.

Media

Intima

Phase II: ProgressionDisease progression results in the remodeling of the vascular wall so that the size of the lumen does not change significantly.

LDL-C

Phase III: ComplicationExtensive lipid accumulation and a greater inflammatory component can pose the threat of plaque rupture.

Lumen Unstable

Stable

S2

Lipid-lowering Goals

Joint European Societies1 LDL-C Goal

Established CHD, other atherosclerotic <115 mg/dL (3.0 mmol/L)

disease, or high absolute risk

US NCEP ATP III2

0-1 CHD risk factors <160 mg/dL (4.1 mmol/L)

>2 CHD risk factors <130 mg/dL (3.4 mmol/L)

CHD or CHD risk equivalent <100 mg/dL (2.6 mmol/L)

1 Wood D, et al. Atherosclerosis. 1998;140:1434-1503; 2 NCEP Expert Panel. JAMA. 2001;285:2486-2497. S3

Statin Evolution

• Evidence

• Efficacy

• Experience

S4

Statin Evidence: Landmark Statin Trials

*Extrapolated to 5 years

Adapted from Kastelein JP. Atherosclerosis. 1999;143(suppl 1):S17-S21.

S = statin treated P = placebo treated

Secondary prevention ( )Primary prevention ( )

Pravastatin

Lovastatin

Simvastatin

Atorvastatin

5.4 (210)2.3 (90) 2.8 (110) 3.4 (130) 3.9 (150) 4.4 (170) 4.9 (190)

0

5

10

15

20

25

AFCAPS-S

WOSCOPS-S

WOSCOPS-PCARE-S

LIPID-P

4S-P

LIPID-S

CARE-P

4S-S

AFCAPS-P

% w

ith

CH

D e

ven

t

LDL-C, mmol/L (mg/dL)

ASCOT-S*

ASCOT-P*

S5

Statin Evidence: Expanding Benefits

Acute coronary event

4S

CARE/LIPID

4 mo

No history of CAD Unstable CAD

3 mo

t = 0

6 mo

Stable CAD

Secondary preventionPrimary prevention

AFCAPS / TexCAPS/WOSCOPS

MIRACL

Hypertension

ASCOT-LLA

HPS

S6

Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.

Hypertensionn = 8457 (41%)

with CHD1458 (7%)

no CHD1822 (9%)

with CHD4042 (20%)

no CHD2701 (13%)

with CHD1978 (10%)

no CHD3982 (19%)

no CHDno CHD2860 (2860 (14%)%)

with CHD5595 (27%)

with MI8510 (41%)

no MI4876 (24%)

20,536patients

PATIENT POPULATION

Statin Evidence: Heart Protection Study

CHDn = 13,379 (65%)

Diabetesn = 5963 (29%)

PVDn = 6748 (33%)

CVDn = 3280 (16%)

S7

Dr. J. Genest

Vascular event

Major coronary eventNonfatal MICoronary death

Stroke

Revascularization

ANY MAJOR VASCULAR EVENT

27% risk reductionP <.0001

25% risk reductionP <.000124% risk reductionP <.000124% risk reductionP <.0001

Simvastatin Placebo

better better

0.4 0.6 0.8 1.0 1.2 1.4

Risk ratio and 95% CI

Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.


S8


24% risk reductionP < .0001

Simvastatin Placebo

better betterBaseline level

LDL-C (mg/dL)<100 (2.6 mmol/L)>100 < 130>130 (3.4 mmol/L)

ALL PATIENTS

0.4 0.6 0.8 1.0 1.2 1.4

Risk Ratio and 95% CI

Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22. S9

Statin Evidence: ASCOT-LLA

ASCOT is a multicenter, international trial that involves 2 treatment comparisons in a factorial design:

• A Prospective, Randomized, Open, Blinded End point (PROBE) design comparing 2 antihypertensive regimens

• A double-blind, placebo-controlled trial of atorvastatin 10 mg in a large prospective cohort of those hypertensive patients studied (lipid-lowering arm [ASCOT-LLA])

ASCOT is composed of almost 20,000 hypertensive patients with multiple risk factors for CHD

S10


R

9000 beta-blocker ± diuretic

9000 CCB ± ACEI

5000 TC <250 mg/dL(<6.5 mmol/L)

4000 TC >250 mg/dL (>6.5 mmol/L)

4000 TC >250 mg/dL (>6.5 mmol/L)

5000 TC <250 mg/dL(<6.5 mmol/L)

R

500 open lipid lowering

4500

2250 statin

2250 placebo

2250 placebo

2250 statin

R

4500500

open lipid lowering

+

8000 open lipid lowering

18,000 patientsR=Randomized

These are the target numbers of patients.

CCB=calcium channel blocker, ACEI=angiotensin converting enzyme inhibitor S11


Eligibility criteria for ASCOT-LLA

• SBP >160 mm Hg and/or DBP >100 mm Hg (untreated) or SBP >140 mm Hg and/or DBP >90 mm Hg (treated)

• TC <250 mg/dL (<6.5 mmol/L) and triglycerides <400 mg/dL (<4.5 mmol/L)

• 40-79 years of age

• 3+ CVD risk factors

• No history of CHD

Sever PS, et al. Lancet. 2003;361:1149-1158. S12

Objective of ASCOT-LLA

To evaluate the cardiovascular benefits of cholesterol lowering with atorvastatin 10 mg in hypertensive patients with total cholesterol levels of <250 mg/dL (<6.5 mmol/L).

Study end points

Primary: Combined nonfatal MI (including silent MI)

and fatal CHD

Secondary: Fatal and nonfatal stroke

Total cardiovascular events and procedures

Total coronary events



September 2002

• The DSMB reported that in ASCOT-LLA there was a highly significant reduction in the primary end point as well as a significant reduction in stroke

• The DSMB recommended that the double-blind, cholesterol-lowering study treatment arm be terminated since the results were outside of the stopping rules of the trial

• The Steering Committee endorsed the recommendation of the DSMB, and the lipid arm was closed after a median follow-up period of 3.3 years; the blood pressure-lowering arm of the study is expected to complete in 2005



19,342 patients randomized to antihypertensive treatment

10,305 randomized in lipid-lowering arm

5168 atorvastatin

4928 alive with complete information

185 dead with complete information

Incomplete information: 39 alive after Oct 1, 2002 4 alive before Oct 1, 2002 5 withdrew consent 7 lost to follow-up

212 dead with complete information

5137 placebo

4861 alive with complete information

Incomplete information: 42 alive after Oct 1, 2002 3 alive before Oct 1, 2002 9 withdrew consent 10 lost to follow-up

Complete information obtained on 98.8% of patients

Patient Inclusion and Follow-Up Status


S15

Atorvastatin 10 mgPlacebo

Baseline 164/95 mm HgTreated 138/80 mm Hg

130

140

150

160

170

0 1 2 3

SB

P (

mm

Hg

)

LLA Close-out

DB

P (

mm

Hg

)

75

80

85

90

95

100

0 1 2 3Years

LLA Close-out

Sever PS, et al. Lancet. 2003;361:1149-1158.

Blood Pressure Changes


S16

Statin Evidence: ASCOT-LLAT

ota

l ch

ole

ster

ol

(mm

ol/L

)L

DL

ch

ole

ster

ol

(mm

ol/L

)6

0 1 2 3

200

150

100

(mg

/dL

)50 mg/dL (1.3 mmol/L)

38.7 mg/dL (1.0 mmol/L)

2

4

Atorvastatin 10 mg

Placebo

150

75

125

100 (mg

/dL

)

YearsLLA Close-out

1

2

3

4

0 1 2 3

Sever PS, et al. Lancet. 2003;361:1149-1158.

38.7 mg/dL (1.0 mmol/L)

46.5 mg/dL (1.2 mmol/L)

S17

Atorvastatin 10 mg Number of events 89

Placebo Number of events 121

0

1

2

3

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve I

nci

den

ce (

%)

HR = 0.73 (0.56-0.96)P = .0236

27% reduction


Primary Endpoint:

Nonfatal MI and Fatal CHD

Secondary Endpoint:

Fatal and Nonfatal Stroke

0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve

Inc

ide

nc

e (

%)



36% reduction

HR = 0.64 (0.50-0.83)P = .0005



Secondary Endpoint:

All CV Events and Procedures

Secondary Endpoint:

All Coronary Events

0

2

4

6

8

10

12

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve

In

cid

en

ce

(%

) 21% reduction

HR = 0.79 (0.69-0.90)P = .0005





0

1

2

3

4

5

6

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Years

Cu

mu

lati

ve

In

cid

en

ce

(%

) 29% reduction

HR = 0.71 (0.59-0.86)P = .0005


Safety

• No significant difference between atorvastatin and placebo in:

• Incidence of fatal cancers• Incidence of serious adverse events• Incidence of liver enzyme abnormalities



• Large given the short follow-up time (median 3.3 years) and emerged earlier than in many other statin trials

• Not significantly different among prespecified subgroups

• Unrelated to baseline cholesterol levels

• Occurred in the absence of any significant increase in adverse events.


The benefits of atorvastatin therapy in well-managed hypertensive patients at modest risk of cardiovascular events and with normal to mildly elevated cholesterol levels were:

S21

Schwartz GG, et al. JAMA. 2001;285:1711-1718.

Statin Evidence: MIRACL Study

Placebo plus usual care

Initial

hospitalization

Randomization(1-4 days)

3086 patients

Double-blind period

Atorvastatin 80 mg/day

16-week treatment phase

S22


Relative risk = 0.84P = .04895% CI 0.701-0.999

Atorvastatin

Placebo

0

5

10

15

0 4 8 12 16

Time Since Randomization (weeks)

Cu

mu

lati

ve In

cid

ence

(%

)

Time to first occurrence of:• Death (any cause)• Nonfatal MI• Resuscitated cardiac arrest• Worsening angina with new

objective evidence and urgent rehospitalization

17.4%

14.8%

Primary Efficacy Measure

Schwartz GG, et al. JAMA. 2001;285:1711-1718. S23


0

0.5

1

1.5

2

0 4 8 12 16

Time Since Randomization (weeks)

Cu

mu

lati

ve In

cid

ence

(%

)

Relative risk = 0.49P = .0495% CI 0.24-0.98

Atorvastatin

Placebo

Fatal and Nonfatal Stroke

Waters DD, et al. Circulation. 2002;106:1690-1695. S24

Αthyros VG, et al. Curr Med Res Opin. 2002;18:220-228.

Statin Evidence: GREACE Study

Begin recruitment January 1998

End recruitment November 1999

End of study December 2001

Mean follow-up, 3 years

Structured care (n = 800)Atorvastatin 10 to 80 mg/dGoal: LDL-C < 100 mg/dL

Usual care (n = 800)

1600 hypercholesterolemic patients with CHD

(LDL-C > 100 mg/dL[ > 2.59 mmol/L] after 6-week

trial of lipid-lowering diet)

S25

-4

-36

-5

-46

-3

-31

27

-3

-32

-6

-44

-60

-50

-40

-30

-20

-10

0

10

Total-C LDL-C TG HDL-C VLDL-C Non-HDL-C


Athyros VG, et al. Curr Med Res Opin. 2002;18:220-228.

**

**

** **

**

††

Mea

n %

Ch

ang

e F

rom

Bas

elin

e

Usual Care

Structured Care

*P < .0001; †P = .0028. Mean atorvastatin dose, 24 mg/day.

S26

5

2.9

4.8

2.5

6.4

2.6 2.6

1.2

5.6

2.7 2.7

1.3

2.1

1.1

0

2

4

6

8

TotalMortality

CoronaryMortality

Nonfatal MI UnstableAngina

PTCA/CABG CHF Stroke


P = .0021 P = .0017

P = .0011

P = .034

Athyros VG, et al. Curr Med Res Opin. 2002;18:220-228.

% o

f P

atie

nts

P = .0001

P = .0032P = .021

Usual Care

Structured Care

S27


Structured Care Group

• 95% of patients reached the NCEP LDL-C goal

• Mean dose of atorvastatin 24 mg/day

• 96% of patients reached the European LDL-C goal

• Mean dose of atorvastatin was 22 mg/day

Usual Care Group

• 3% of patients reached the NCEP LDL-C goal

• 5.5% of patients reached the European LDL-C goal

Athyros VG, et al. Curr Med Res Opin. 2002;18:220-228; Athyros VG, et al. Data on file. S28

Statin Evidence: Benefits

• The statin trials have demonstrated significant decreases in

CVD morbidity and mortality.

• Reduction in CVD events has been demonstrated in patients

with stable CHD as well as acute coronary syndrome patients.

• Additionally, lowering LDL-C to target levels has beneficial

effects in patients with normal or moderately elevated LDL-C.

S29

Statin Evolution

• Evidence

• Efficacy

• Experience

S30

Drug Class LDL-C HDL-C Triglycerides

Statins* 18% to 60%*** 5% to 15% 7% to 37%***

Bile Acid 15% to 30% 3% to 5% No change or

Sequestrants increase

Nicotinic Acid 5% to 25% 15% to 35% 20% to 50%

Fibric Acids 5% to 20%** 10% to 20% 20% to 50%

Statin Efficacy: Lipid Lowering

*Lovastatin (20 to 80 mg), pravastatin (20 to 40 mg), simvastatin (20 to 80 mg), fluvastatin (20 to 80 mg), atorvastatin (10 to 80 mg), and rosuvastatin (10 to 40 mg).

**May be increased in patients with high triglycerides.

***Up to 60% reduction in LDL-C, and 37% reduction in triglycerides, as indicated in the atorvastatin PI.

Adapted from NCEP Expert Panel. JAMA. 2001;285:2486-2497. S31

v

v

v

v

v

v

v

v

v

v

v

Statin Efficacy: LDL-C Reduction

*Simvastatin 80 mg not available at time of study. **Significantly greater than mg-equivalent doses of comparative agents (P <.01). †Significantly less than atorvastatin 10 mg (P <.02). ‡Significantly less than atorvastatin 20 mg (P <.01).

Jones P, et al, for the CURVES Investigators. Am J Cardiol. 1998;81:582-587.

Atorvastatin

Simvastatin*

Pravastatin

Lovastatin

Fluvastatin

0 -60-50-40-30-20-10

10 mg (n = 73)

20 mg (n = 51)

40 mg (n = 61)

10 mg (n = 70)

20 mg (n = 49)

40 mg (n = 61)

10 mg (n = 14)

20 mg (n = 41)40 mg (n = 25)

20 mg (n = 16)40 mg (n = 16)

40 mg (n = 12)

20 mg (n = 12)

-38%**-46%**

-51%**

-28%†

-35%‡

-41%‡

-19%†

-24%†

-34%‡

-29%†

-31%†‡

-17%†

-23%†‡

80 mg (n = 10) -54%

80 mg (n = 11) -48%

% LDL-C reduction

S32

Primary efficacy parameter:

Reduction in plasma LDL-C from baseline

Men and women

With or without CHD and/or PAD

Type IIa/IIb

TG < 400 mg/dL (4.5 mmol/L)

~ 70% with CHD and/or PAD

Atorvastatin 10 to 80 mg

Simvastatin 10 to 40 mg

Pravastatin 10 to 40 mg

Lovastatin 10 to 80 mg

Fluvastatin 20 to 80 mg

54 week open-label treatment

Statin Efficacy: ACCESS

Andrews TC, et al. Am J Med. 2001;111:185-191. S33

Andrews TC, et al. Am J Med. 2001;111:185-191.

*P < .01 vs all other treatments

Atorvastatin Effectively Lowered LDL-C

% C

han

ge

LDL-C TG HDL-C

**

**

-42%

-29%

-36%

-28%

-36%

-19%

-7%

-12%

-9%

-13%

5%6%

10

0

-10

-20

-30

-40

-50

5%6% 6%

Atorvastatin 10 to 80 (avg 24) mg (n = 1902)Fluvastatin 20 to 80 (avg 62) mg (n = 477)

Simvastatin 10 to 80 (avg 23) mg (n = 468)

Lovastatin 20 to 80 (avg 52) mg(n = 476) Pravastatin 10 to 40 (avg 31) mg (n = 462)


S34


*Significant difference vs atorvastatin (P < 0.05)

*

**

*

0

25

50

100

Atorvastatin10 to 80 mg

Per

cen

t o

f p

atie

nts

ach

ievi

ng

go

al

75

Simvastatin10 to 80 mg

Pravastatin10 to 40 mg

Lovastatin20 to 80 mg

Fluvastatin20 to 80 mg

NCEP ATP II LDL-C Goals< 2 CHD risk factors is < 160 mg/dL (4.1 mmol/L)

> 2 CHD risk factors is < 130 mg/dL (3.4 mmol/L)Andrews TC, et al. Am J Med. 2001;111:185-191.

NCEP Goal Attainment

S35

Statin Efficacy: NASDAC Study

NASDAC study—88% of dyslipidemic patients receiving a starting dose of 10 to 40 mg atorvastatin once daily reached their NCEP ATP III LDL-C goal.

88% Percentage of patients reaching LDL-C goal at 10, 20, or 40 mg

10 mg 20 mg 40 mg

79% 88% 98%(n = 76) (n = 68) (n = 64)

Patients without CHD and no CHD equivalents

Pfizer Inc. Data on file: NASDAC study. S36

Statin Efficacy: Atorvastatin

• Excellent efficacy across the dose range for all lipid parameters:

LDL-C -39% to -60%

Triglycerides -19% to -37%

HDL-C +5% to +9%

• In clinical trials, the vast majority of patients onatorvastatin reached LDL-C goal.

Pfizer Inc. Data on file. S37

Statin Evolution

• Evidence

• Efficacy

• Experience

S38

Atorvastatin Experience: Clinical Safety Data

• Safety of atorvastatin derived from analysis of 44 completed

clinical trials in 9416 patients:

• Involved many different patient types:

• eg, mixed dyslipidemia, diabetes, postmenopausal women, FH

Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials.

Atorvastatin (all doses) 9416

Other statins 5290

Placebo 1789

n

S39



Digestive 4 8 9Body as a whole 5 5 6Musculoskeletal 1 3 4Nervous 2 3 3Skin and appendages 1 2 2Metabolic/Nutritional 1 1 1Special senses < 1 1 < 1Urogenital 1 1 1Cardiovascular 2 1 1

Body system

Placebon = 1789

Atorvastatin(all doses)n = 9416

All other statins combined

n = 5290

(%)

Treatment-Associated AEs > 1% of Patients

(%) (%)

S40

Patient Withdrawal due to Treatment-Associated AEs

Atorvastatin(all doses)

n = 241/9416

2.6%

5

4

3

2

0All other

statins combined n = 188/5290

3.6%

1

Pat

ien

ts w

ith

dra

win

g d

ue

to t

reat

men

t-as

soci

ated

ad

vers

e ev

ents

(%

)

0.9%

Placebo n = 16/1789



S41


• ALT/AST elevations > 3x ULN:

• 0.5% of patients treated with atorvastatin 10 to 80 mg experienced ALT/AST elevations > 3x ULN.

• Myalgia

• Incidence of myalgia across all the atorvastatin doses was low (1.9%) and directly comparable to the incidence of myalgia observed in patients receiving other statins combined.

Source: Pfizer Inc. Data on file. Review of 44 completed clinical trials. S42

Atorvastatin Experience: Summary


• A recent analysis of 44 completed clinical trials demonstrated

that atorvastatin is well tolerated and has excellent safety

across the 10 mg to 80 mg atorvastatin dose range.

• The overall incidence of AEs with atorvastatin in clinical trials

does not increase across the dose range, and is similar to

that observed with placebo, and in patients treated with other

statins.

• Specific analysis of musculoskeletal and hepatic AEs showed

that these occurred infrequently and rarely resulted in

treatment discontinuation.

S43

Atorvastatin Clinical Trial Program (> 44,000 Patients)

Atorvastatin Evolution: Future

2003 2004

TNT

4D

SAGE

BONES

SPARKS

BELLES

CARDS

ASPEN

ASCOT

REVERSAL LEADe

S44

Atorvastatin Evolution

• Evidence

• Efficacy

• Experience

When choosing a statin consider:

S45

Presentation on Dyslipidemia on 20.11.13

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Transcript of Presentation on Dyslipidemia on 20.11.13