Curriculum Vitae

Nama : Prof. Dr. dr H. Djanggan Sargowo SpPD,SpJP(K), FIHA, FACC, FCAPC, FESC, FASCC Tempat/Tgl lahir Alamat Pendidikan :
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

: Sragen, 21 September 1947 : Wilis Indah E-10 Malang, Telp. 0341-552395

Lulus Dokter dari UGM, tahun 1974 Lulus Cardiologist dari Univ. Indonesia, tahun 1983 Lulus Internist dari Univ. Airlangga, tahun 1986 Lulus Doktor, Univ. Airlangga, tahun 1996 Advanced Cardiology Course, Univ. Hongkong, tahun 1984 Senior Visiting Program, Institut Jantung Negara, Kualalumpur, 1996 Fellow American College of Cardiology (FACC), September 2006. Fellow Collage Asia Pacific Society of Cardiology (FCAPC), Desember 2007 Fellow European Sociaty of Cardiology (FESC), 2008 Fellow Asean Collage of Cardiology (FASCC), 2008

Jabatan :
1. 2. 3. 4. Direktur Program Pascasarjana Universitas Brawijaya Ketua MKEK Ikatan Dokter Indonesia Cabang Malang Raya Ketua PERKI Cabang Malang Raya Anggota Kolegium Kardiovaskuler Indonesia

NEW APPROACH FOR CV RISK MANAGEMENT

Djanggan Sargowo

Hotel Tugu Malang, 21 Maret 2009

EPIDEMIOLOGY

PATHOPHYSIOLOGY

CLINICAL BENEFIT

CVD RISK FACTORS

HYPERTENSION* Cigarette smoking

Obesity* (BMI >30 kg/m2)

Physical inactivity Dyslipidemia*

Diabetes mellitus*
Microalbuminuria or estimated GFR <60 ml/min Age (older than 55 for men, 65 for women) Family history of premature CVD (men under age 55 or women under age 65)
*Components of the metabolic syndrome.

EVOLUTION IN UNDERSTANDING CVD

ATHEROTHROMBOSIS SIGNIFICANTLY SHORTENS LIFE

ATHEROTHROMBOSIS REDUCES LIFE EXPECTANCY BY APPROXIMATELY 812 YEARS IN PATIENTS AGED OVER 60 YEARS1

Average remaining life expectancy at age 60 (men)

20 18 16

YEARS

14 12 10 8 6 4 2 0

-7.4 years

-9.2 years -12 years

Healthy

History of cardiovascular disease

History of AMI

History of stroke

Analysis of data from the Framingham Heart Study

1. Peeters et al. Eur Heart J 2002; 23: 458 466

CURRENT GUIDELINES RECOGNIZE IMPORTANCE OF TOTAL CV RISK MANAGEMENT

Hypertension ESH/ESC (2003) WHO/ISH (2003) JNC 7 (2003) BHS IV (2005) CHEP (2006) CV Prevention European Joint
Task Force (2003)

JBS 2 (2005)

Hypertension guidelines support the recognition of risk factors beyond hypertension in developing an appropriate treatment strategy for patients with hypertension
De Backer G et al. Eur Heart J. 2003;24:1601-1610. World Health Organization. J Hypertens. 2003;21:1983-1992. Williams B et al. Hum Hypertens. 2004;18:139-185. 2003 European Society of Hypertension. J Hypertens. 2003;21:1011-1053. Grundy SM et al. Circulation. 2004;110: 227-239. Chobanian AV et al. Hypertens. 2003;42:1206-1252. CHEP Recommendations for the management of Hypertension 2005. Available at www.hypertension.ca/recommendations_2005/ultrashortexecsummary2005.pdf. Accessed April 10, 2006. Joint British Societies guidelines on prevention of cardiovascular disease in clinical practice. Available at: heart.bmjjournals.com. Accessed 14 March 2006.

ESH-ESC HYPERTENSION GUIDELINES

No

Yes

MULTIPLE CV RISK MANAGEMENT RESULTS IN DRAMATIC REDUCTIONS IN CVD

10% Reduction in BP

10% Reduction in TC

45% Reduction in CVD

Attention should be moved from knowing ones BP and cholesterol concentrations to knowing ones absolute CV risk and its determinants.
J. Emberson et al and Jackson et al
Emberson J et al. Eur Heart J. 2004;25:484-491. Jackson R et al. Lancet. 2005;365:434-441.

10

DEVELOPMENT AND PROGRESSION OF CVD

Risk factors Oxidative stress Endothelial function EPCs Genetic factors Functional alterations Age, gender, smoking, inactivity, obesity, cholesterol, BP, glucose

Structural alterations

Clinical sequelae
EPCs = endothelial progenitor cells Adapted from Pepine CJ. Am J Cardiol. 2001;88(suppl):5K-9K.

11

TARGETING ATHEROSCLEROSIS-AN EVIDANCE UPDATE SUPPORTING : GLOBAL RISK REDUCTION

Atorvastatin 80 mg-18 months Introduction REVERSAL Endovascular Sciense Clinical Caveats

12

PATHOPHYSIOLOGY : ADDITIVE EFFECT OF CHOLESTEROL AND BP ON CHD RISK

13

SOFT END POINT (Better surrogate outcome)

Hard end point (Better Clinical Outcome)

14

Clinical Evidences

NORVASK (AMLODIPINE BESYLATE) EXTENSIVELY STUDIED IN LARGE TRIALS

CAMELOT/ NORMALISE
CHD patients (n=1991) Amlodipine besylate, enalapril, placebo 2 years

ALLHAT

ASCOT-BPLA
Moderate-risk hypertensive (N=19,342)

VALUE
High-risk hypertensive (N=15,245) Amlodipine besylate, valsartan 6 years

Patients studied

High-risk hypertensive (N=33,357) Amlodipine besylate, lisinopril, chlorthalidone 6 years

Comparators Trial duration

Amlodipine besylate perindopril, atenolol thiazide

Trial stopped early

End points: CHD death and nonfatal MI

End point: cardiac morbidity and mortality

End point: CV events and plaque progression

ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997; Julius et al, for the VALUE trial group. Lancet. 2004;363:2022-2031; Sever et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147; Nissen et al, for the CAMELOT Investigators. JAMA. 2004;292:2217-2226.

16

LIPITOR (ATORVASTATIN CALCIUM) EXTENSIVELY STUDIED IN LARGE TRIALS

Lipitor effectively reduces LDL-C Across a Broad Range of Patients

10 mg
without CHD
in ASCOT-LLA 133 mg/dL 10,305 patients

80 mg*
with diabetes
in CARDS 116 mg/dL 2838 patients 10,001 patients

with CHD
in TNT <130 mg/dL

654 patients in REVERSAL 150 mg/dL

with CHD

4162 patients in PROVE IT 106 mg/dL

with CHD

LDL-C level at randomisation

Follow-up LDL-C level

Outcomes

90
mg/dL 36% RRR of nonfatal MI and fatal CHD 27% RRR of stroke

77
mg/dL 37% RRR of death and major CV events 48% RR of stroke

77
mg/dL 22% RR of major CV events 25% RR of stroke

79
mg/dL Significantly impacted atherosclerotic disease progression; pravastatin was associated with further disease progression

62
mg/dL 16% RR of major CV events versus pravastatin

*80 mg is not
a starting dose. RR=risk reduction. Nissen et al. JAMA. 2004;291:1071-1080; Cannon et al. N Engl J Med. 2004;350:1495-1504; LaRosa et al. N Engl J Med. 2005;352:1425-1435; Sever et al, for the ASCOT Investigators. Lancet. 2003;361:1149-1158; Colhoun et al. Lancet. 2004;364:685-696.

17

HYPERTENSION INCREASES ATHEROGENIC LIPOPROTEIN CONTENT OF ARTERIAL VESSEL WALLS

BP

Atherogenic VLDL, VLDL-R, IDL, LDL

Pressure-driven convection

Intimamedia

Enhanced LP penetration LP retention

Pressure-induced distension Stretching
Sposito AC. Eur Heart J Suppl. 2004;6(suppl G):G8-G12.

Intimamedia
LP = lipoprotein

18

PLEIOTROPIC EFFECTS OF STATINS

Coagulation
Platelet activation

Endothelial progenitor cells

Effects on collagen MMPs AT1 receptor VSMC proliferation Endothelin
Liao JK. Am J Cardiol. 2005;96(suppl 1):24F-33F.

Endothelial function NO bioactivity Reactive oxygen species Macrophages Inflammation Immunomodulation

Statins

MMPs = matrix metalloproteinases

19

PLEIOTROPIC EFFECTS OF BP-LOWERING AGENTS

ACEIs/ARBs
Fibrinolysis Mononuclear cell migration Collagen matrix formation Endothelial function Plaque stability Arterial compliance

CCBs
NO MMP activity

BPAHTN lowering agents agents

Cholesterol deposition in membrane

Both
Oxidative stress Platelet aggregation Inflammation VSMC proliferation
Lonn E et al. Eur Heart J Suppl. 2003;5(suppl A):A43-A8. Wassman S and Nickenig G. Eur Heart J Suppl. 2004;6(suppl H):H3-H9. Mason RP et al. Arterioscler Thromb Vasc Biol. 2003;23:2155-63.

MMP = matrix metalloproteinase

20

APPROACHES TO CVD PREVENTION

Lipid modification Optimal CV risk reduction Glucose lowering BP lowering Lifestyle intervention

21

GEMINI: MORE THAN 55% OF PATIENTS ACHIEVED BOTH BP AND LDL-C GOALS
Amlodipine/Atorvastatin Gemini Study N = 1220, 14 weeks with amlodipine/atorvastatin single-pill therapy
90 70

82.1

65.5
57.7

Patients (%) 50
30 10 0

LDL-C goal (NCEP ATP III)

BP goal (JNC VI)

Both LDL-C and BP goals

Expert Panel. NCEP ATP III. JAMA. 2001;285:2486-97. JNC VI. Arch Intern Med. 1997;157:2413-46. Blank R et al. J Clin Hypertens. 2005;7:264-73.

22

ASCOT STUDY DESIGN

ASCOTBPLA
19,257 hypertensive patients with 3 CV risk factors and no CHD amlodipine-based regimen n=9639 atenolol regimen n=9618

ASCOT-LLA

10,305 hypertensive patients (3 CV risk factors and no CHD) with total cholesterol 6.5 mmol/L (251 mg/dL)

atorvastatin 10 mg n=5168

placebo n=5137

ASCOT-LLA 2x2

amlodipine-based regimen n=2584

atenolol-based regimen n=2584

amlodipine-based regimen n=2554

atenolol-based regimen n=2583

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

23

PATIENT INCLUSION CRITERIA

Screening and baseline BP

160/100 mm Hg untreated
140/90 mm Hg following treatment with 1 or more drugs Age 40-79 years No previous MI or current clinical CHD 3 or more CV risk factors
24

25

ASCOT-LLA: PATIENT POPULATION ROUTINELY SEEN IN CLINICAL PRACTICE (HYPERTENSION PLUS 3 RISK FACTORS FOR CHD*)
Hypertension Age 55 years Male Microalbuminuria/proteinuria Smoker Family history of early coronary disease Type 2 diabetes Certain ECG abnormalities Left ventricular hypertrophy Plasma TC/HDL-C ratio 6 Previous cerebrovascular events Peripheral vascular disease 0 100 84 81 62

33
26 26 23 23 14 10 5 80 40 60 20 Patients with Risk Factor (%) 100

Two of the most common additional risk factors were male sex and age 55 yearsrepresentative of patients frequently seen in practice
*These risk factors were used as inclusion criteria for the study. The ASCOT Investigators. Available at: http://www.ascotstudy.org/get_doc.php?id=56. Accessed: April 6, 2006. Data on file. Pfizer Inc, New York, NY. Please see prescribing information at the end of this slide presentation.

26

ASCOT-BPLA : AMLODIPINE-BASED THERAPY WAS ASSOCIATED WITH BETTER BP CONTROL COMPARED WITH ATENOLOL-BASED THERAPY
Atenolol bendroflumethiazide
180 SBP (mm Hg) 160 140 120 Amlodipine perindopril Mean difference 2.7 P<.0001 137.7 136.1

0.5

1.5

2.5

3.5

4.5

Years
Dahlf B et al for the ASCOT Investigators. Lancet. 2005;366:895-906.

5.5 Last visit

27

REDUCTIONS OBSERVED IN MOST PRIMARY, SECONDARY, AND TERTIARY END POINTS IN ASCOT-BPLA
Primary Nonfatal MI (incl silent) + fatal CHD Secondary Nonfatal MI (exc. silent) + fatal CHD Total coronary end point Total CV events and procedures All-cause mortality CV mortality Fatal and nonfatal stroke Fatal and nonfatal heart failure Tertiary Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Life-threatening arrhythmias New-onset diabetes mellitus New-onset renal impairment Post hoc Primary end point + coronary revasc procs CV death + MI + stroke Unadjusted Hazard Ratio (95% CI) 0.90 (0.79-1.02) 0.87 (0.76-1.00) 0.87 (0.79-0.96) 0.84 (0.78-0.90) 0.89 (0.81-0.99) 0.76 (0.65-0.90) 0.77 (0.66-0.89) 0.84 (0.66-1.05)

1.27 (0.80-2.00) 0.68 (0.51-0.92) 0.98 (0.81-1.19) 0.65 (0.52-0.81) 1.07 (0.62-1.85) 0.70 (0.63-.078) 0.85 (0.75-0.97)

0.86 (0.77-0.96) 0.84 (0.76-0.92)

Dahlf B et al for the ASCOT Investigators. Lancet. 2005;366:895-906. Please see prescribing information at the end of this slide presentation.

Amlodipine perindopril better

0.50

0.70

1.00

Atenolol bendroflumethiazide better

1.45

2.00

28

ASCOT-LLA: SBP AND LDL-C CHANGES

170
SBP (mm Hg)

Atorvastatin

Placebo

160 150 140 130 0

150

Final mean BP: Atorvastatin 138/80 mm Hg Placebo 138/80 mm Hg

LDL-C (mg/dL)

125
100 75

1.2 mmol/L (46 mg/dL)

1.0 mmol/L (38.7 mg/dL)

Years

Last visit

Adapted from Sever PS et al for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Available at https://www.ascotstudy.org. Accessed April 12, 2006.

ASCOT-LLA: SUMMARY OF ALL END POINTS

Primary End Points Nonfatal MI (incl silent) + fatal CHD Secondary End Points Total CV events and procedures Total coronary events Nonfatal MI (excl silent) + fatal CHD All-cause mortality CV mortality Fatal and nonfatal stroke Fatal and nonfatal heart failure Tertiary End Points Silent MI Unstable angina Chronic stable angina Peripheral arterial disease Development of diabetes mellitus Development of renal impairment
Risk Ratio

Hazard Ratio 0.64 (0.50-0.83) 0.79 (0.69-0.90) 0.71 (0.59-0.86) 0.62 (0.47-0.81) 0.87 (0.71-1.06) 0.90 (0.66-1.23) 0.73 (0.56-0.96) 1.13 (0.73-1.78) 0.82 (0.40-1.66) 0.87 (0.49-1.57) 0.59 (0.38-0.90) 1.02 (0.66-1.57) 1.15 (0.91-1.44) 1.29 (0.76-2.19)

0.5 1.0 1.5 Atorvastatin better Placebo better

Sever PS et al for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Please see prescribing information at the end of this slide presentation.

ASCOT-BPLA AND -LLA COMBINED: INSIGHT INTO OPTIMAL CVD PREVENTION

Rates/1000 Patient-Years

End Point

Amlodipine Atenolol Relative Perindopril + Thiazide + Risk Statin Placebo Reduction

Fatal CHD and nonfatal MI

4.8

9.2

48%

Fatal and nonfatal stroke

4.6

8.2

44%

The ASCOT Study Investigators. Available at: http://www.ascotstudy.org/get_doc.php?id=86#52. Accessed: June 30, 2006.

ASCOT-LLA 2X2 ANALYSIS

LDL-C reduction BP reduction

LDL-C & BP reduction comparable between amlodipine base regimen vs atenolol base regimen

ASCOT-LLA 2X2 ANALYSIS: THE SPECIFIC COMBINATION OF AN AMLODIPINE-BASED REGIMEN AND ATORVASTATIN DELIVERED AN EVEN GREATER RELATIVE RISK REDUCTION
Cumulative incidence (%) Cumulative incidence (%)
4 3 2 1 0 0 0.5 1 1.5 2 2.5 3 3.5
Amlodipine-based regimen + placebo

4 3 2 1 0 0 0.5 1 1.5

NOT SIGNIFICANT
Atenolol-based regimen + placebo

53%

16%

Amlodipine-based regimen + atorvastatin

Atenolol-based regimen + atorvastatin

2.5

3.5

Time (years)

Time (years)
HR=0.84 (0.60-1.17) P<0.30

HR=0.47 (0.32-0.69) P<0.001 The most common adverse events seen in ASCOT were diarrhoea, dizziness, dyspepsia, dyspnoea, erectile dysfunction, fatigue, headache, muscle cramps, myalgia, nausea, pain in limb and peripheral oedema. Important Safety Information CADUET is indicated for prevention of cardiovascular events in hypertensive patients, with three concomitant cardiovascular risk factors, normal to mildly elevated cholesterol levels, without clinically evident coronary heart disease where combined use of amlodipine and a low dose of atorvastatin is considered appropriate, in accordance with current treatment guidelines. CADUET is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases; in women who are pregnant or may become pregnant and/or nursing; in patients with hypersensitivity to any component of this medication. Patient should promptly report muscle pain, tenderness, or weakness to their physician. In clinical trials, the most common adverse events were dizziness, headache, abdominal pain/nausea (amlodipine-specific adverse events: palpitations, flushing, oedema/peripheral oedema, and fatigue; atorvastatin-specific events: insomnia, hypothesia, paresthesia, dyspepsia, diarrhoea, constipation, flatulence, pruritus, rash, arthralgia, myalgia, back pain, chest pain, asthenia, hepatic enzyme elevations, ALT, AST, CPK increased levels). Additional specific safety information from the local label should be inserted. Sever PS, et al. Eur Heart J. 2006;27:2982-2988.

ASCOT CONCLUSIONS
Patient population common in clinical practice
ASCOT-BPLA: Amlodipine-based treatment compared with atenololbased treatment resulted in
Hypertensive patients with 3 additional CV risk factors Low-to-moderate risk Significant benefits in all-cause mortality

ASCOT-LLA: Atorvastatin added to a hypertensive regimen results in

significant reductions
Nonfatal MI and fatal CHD (36% RRR) Nonfatal MI (45% RRR) Stroke (27% RRR)

ASCOT-BPLA and ASCOT-LLA combined: Significant reductions with

amlodipine-based therapy + statin compared with atenolol-based therapy + placebo
Cummulative reduction in CV events (%53% RRR) Nonfatal MI and fatal CHD (48% RRR) Fatal and nonfatal stroke (44% RRR)

Lipid-lowering benefits seen in patients with normal to mildly elevated

cholesterol levels
Sever PS et al for the ASCOT Investigators. Lancet. 2003;361:1149-1158. Dahlf et al, for the ASCOT Investigators. Lancet. 2005;366:895-906. Sever PS et al, for the ASCOT Investigators. J Hypertens. 2001;19:1139-1147. Data on file. Pfizer Inc, New York, NY. The ASCOT Study Investigators. Available at: http://www.ascotstudy.org/get_doc.php?id=86#52. Accessed: June 30, 2006.

34

WHAT ARE THE IMPLICATIONS FOR CLINICAL PRACTICE ?

Assessment of overall CV risk critical to
maximizing CV event reduction

Hypertensive patients frequently seen in clinical

practice, emphasizing need for comprehensive risk assessment

Atorvastatin added to antihypertensive (especially

Amlodipine) therapy results in significant benefits in low to moderate and high-risk patient populations
35

ASCOT: CLINICAL IMPLICATIONS

ASCOT-BPLA demonstrated greater benefits of CCB ACEI vs -blocker diuretic in lowering BP and preventing CVD Improved BP control with amlodipine perindopril may explain some, but not all, of the benefit ASCOT-LLA extended benefit of lipid lowering to hypertensive patients Survival curves separated almost immediately, with significant difference at 90 days
ASCOT supports use of newer BP drugs and statins, especially in patients with complicated hypertension Treatment should depend on global assessment of risk, not on individual risk factors
Dahlf B et al. Lancet. 2005;366:895-906. Sever PS et al. Lancet. 2003;361:1149-58.

36

SUMMARY: OPTIMIZING OUTCOMES IN PATIENTS WITH MULTIPLE CVD RISKS

Traditional risk factors Emerging biomarkers Clinical trials

Multifactorial risk reduction

Improved clinical outcome

37

CV RISK MANAGEMENT PROBLEM

MOST HYPERTENSIVE PATIENTS NEED MULTIPLE MEDICATIONS FOR EFFECTIVE MANAGEMENT, YET ADHERENCE TO CONCOMITANT ANTIHYPERTENSIVE AND LIPID-LOWERING THERAPY DECREASES AS NUMBER OF MEDICATIONS INCREASES
No. of Additional Medications

0 1 2
42.0% 32.7% 28.3% 24.5% 0 10 20 30 40 50 48.6%

58.8%

8 9 10

60

70

Median PDC*
Incremental pill burden had greatest effect on adherence in patients taking the fewest medications
*Calculated for first year of concomitant therapy with antihypertensive and lipid-lowering drugs. Patients adherent if PDC 80% for both classes. PDC=proportion of days covered by antihypertensive and lipid-lowering drugs. Benner JS et al. ACC 2006. Abstract.

39

INCREASES IN OUT-OF-POCKET COSTS ARE ASSOCIATED WITH DECREASED ADHERENCE RATES

Doubling copayments is associated with significant reductions in medication use across several widely prescribed therapeutic classes
Antidepressants Antihypertensives Antihyperlipidaemics Antiulcerants Antiasthmatics Antidiabetics NSAIDs Antihistamines 0 10 20 30 40 50 Reduction In Days Supplied When Copayments Double (%)
NSAIDs=nonsteroidal anti-inflammatory drugs. Retrospective study of pharmacy claims data and health plan benefit data from 30 employers and 52 health plans, 1997-2000. N=528,969 members aged 18-64 years. Goldman DP et al. JAMA. 2004;291:2344-2350.

40

MEDICATION ADHERENCE DECLINES WHEN A SECOND DRUG IS PRESCRIBED

AHT LLT
80 Patients with MPR 80 (%) 70 60 P=0.05 vs both

Both

50
40

30
20 10

Month 1-2

Month 3-4

Month 5-6

Month 7-8

Month 9-10

Study description: retrospective claims analysis using data from managed care organizations (PharMetrics Integrated Outcomes Database). 5341 patients receiving AHT and LLT had their MPR (medication possession ratio) assessed at 2-month intervals to determine adherence. Schwartz JS, et al. J Am Coll Cardiol. 2003: 41: 526A.

41

MANY PATIENTS ARE NONADHERENT TO AHT AND LLT

100 90 80

36% of patients remained adherent to both AHT and LLT after 1 year

70
Patients (%) 60 50 40 30 20 10 0 3 6 9 12 15 18 21 24 27 30 33 36 Time since the index date (months)
Nonadherent (PDC <80%) Adherent to LLT (PDC 80%) and nonadherent to AHT (PDC <80%) Adherent to AHT (PDC 80%) and nonadherent to LLT (PDC <80%) Adherent to LLT and AHT (PDC 80%)

Study description: retrospective cohort study of 8406 patients from a managed care population. Synchronised start: LLT and AHT initiated within 90 days of each other. Adherence: PDC by a given drug class in each time interval. Index date: date when concomitant therapy (ie, second drug) was initiated. Chapman RH, et al. Arch Intern Med. 2005.

42

Norvask
(amlodipine besylate)

Lipitor
(atorvastatin calcium)

+
Potential Solution To Prevent CV Events

Not Just Lowering BP but also

REDUCE Cardiovascular Risk

43

Inflammation Repair

Unstable plaque

Stable plague

44

UNSTABLE CORONARY ARTERY DISEASE (II)

Thrombus forms and extends into the lumen

Thrombus

Lipid core

Adventitia

45

Inflammation

Repair

- STATINS
- ACEI / AIIRA - CCB

Unstable plaque

Stable plague
Weissberg, 1999

46

CARPE: CADUET (AMLODIPINE BESYLATE/ATORVASTATIN CALCIUM) THERAPY RESULTS IN MORE PATIENTS ACHIEVING ADHERENCE COMPARED TO CONCOMITANT CCB AND STATIN THERAPIES

Percentage of Patients with PDC 80%

Unadjusted Proportion of Patients Achieving Adherence

100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
CADUET Atorvastatin + Amlodipine Amlodipine + Other Statin Other CCB + Atorvastatin Other CCB + Other Statin

67.7% 49.9% 40.4% 46.9% 37.4%

All comparison cohorts significantly lower than CADUET, P <.0001

CARPE Research Investigators. Presented at 2006 American Society of Hypertension, May 19, 2006. New York, NY.

47

Are you hungry or sleepy ????

Sciences
48

CARPE STUDY: SINGLE-PILL CADUET (AMLODIPINE BESYLATE/ATORVASTATIN CALCIUM) IMPROVES ADHERENCE COMPARED TO 2-PILL COMBINATION THERAPIES
Multivariate Odds Ratios of Achieving PDC 80% (95% Confidence Interval)
CADUET vs Amlo + Atorva 1.95 (1.80-2.13)**

CADUET vs Amlo + Other Statin

3.10 (2.85-3.38)**

CADUET vs Other CCB + Atorva

2.05 (1.89-2.24)**

CADUET vs Other CCB + Other Statin

2.84 (2.61-3.10)**

0
**P<.0001

0.5

1.5

2.5

3.5

CADUET is less likely to achieve adherence CADUET is more likely to achieve adherence

CARPE Research Investigators. Presented at 2006 American Society of Hypertension, May 19, 2006. New York, NY.

49

IMPLICATIONS OF CARPE
In this insured population, CADUET (amlodipine
besylate/atorvastatin calcium) may bring substantial improvements to adherence compared to existing single-agent combination therapies in multiple risk-factor treatment settings

CADUET may result in a greater likelihood of

achieving adherence than Norvask + Lipitor

CADUET is particularly valuable for treating

patients who need to follow simple drug regimens
CARPE Research Investigators. Presented at 2006 American Society of Hypertension, May 19, 2006. New York, NY.

Please see prescribing information at the end of this slide presentation.

50

IMPROVED OUTCOMES ACHIEVED IN CLINICAL TRIALS WITH HIGHER ADHERENCE

CV Death
0

Coronary Death or Nonfatal MI

Revascularisation Procedures

Percent Event Reduction

-10 -20 -30

-32% -31% -37% -37% -37% -46%

-40 -50

Entire cohort

75%-100% adherent

The West of Scotland Coronary Prevention Study Group. Eur Heart J. 1997;18:1718-1724.

51

IS POOR ADHERENCE AN ESSENTIAL CV RISK FACTOR?

Increasing pill burden decreases adherence In clinical trials, worse outcomes were attained when
adherence was lower

Patients need to adhere to their medications in order to

effectively treat their CV risk factors
Improved adherence when starting 2 medications concurrently Combination therapy reduces pill burden Reduced pill burden improves adherence

Nonadherence to medication increases CV risk

52

Adherence is the sixth vital sign, as important as respiration, heart rate, temperature, blood pressure, and pain.
Dr. Edward C. Rosenow III, Mayo Clinic of Medicine

Take control with CADUET.

Important Safety Information CADUET is indicated for prevention of cardiovascular events in hypertensive patients, with three concomitant cardiovascular risk factors, normal to mildly elevated cholesterol levels, without clinically evident coronary heart disease where combined use of amlodipine and a low dose of atorvastatin is considered appropriate, in accordance with current treatment guidelines. CADUET is contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases; in women who are pregnant or may become pregnant and/or nursing; in patients with hypersensitivity to any component of this medication. Patient should promptly report muscle pain, tenderness, or weakness to their physician. In clinical trials, the most common adverse events were dizziness, headache, abdominal pain/nausea (amlodipine-specific adverse events: palpitations, flushing, oedema/peripheral oedema, and fatigue; atorvastatin-specific events: insomnia, hypothesia, paresthesia, dyspepsia, diarrhoea, constipation, flatulence, pruritus, rash, arthralgia, myalgia, back pain, chest pain, asthenia, hepatic enzyme elevations, ALT, AST, CPK increased levels). Additional specific safety information from the local label should be inserted. Sever PS, et al. Eur Heart J. 2006;27:2982-2988.

53

CONCLUSION

Hypertension is highly prevalent

CVD: leading cause of death worldwide

Most patients with hypertension have additional CV risk factors: and are at increased risk of CVD and CV events

Caduet has better surrogate and clinical outcome

Single CV risk factor treatment has suboptimal therapeutic benefit

Optimal management of CV risk may involve the use of single-pill combination therapies to improve adherence and to simultaneously target multiple risk factors

55

Thank You

Take control with CADUET.

56