26/09/2015

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Faculty and Fa c u l t y of o f Helth Heal t h a ndMedical M e dic alSciences S c ien ce s

Overskrift

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Initiation of statin therapy for primary prevention: Overprescribing in postmenopausal women with ‘hypercholesterolemia’?

Navn p å op læg sh old er

Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Helle Wallach Kildemoes Associate professor Section for Social and Clinical Pharmacy, Department of Pharmacy, University of Copenhagen, Denmark

Overskrift

Background

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Tekst st art er u d en p u n kt op st illin g For at få p u n kt -

op st illin g p å t ekst en , b ru g forøg in d rykn in g

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Tekst st art er u d en p u n kt op st illin g For at få p u n kt op st illin g p å t ekst en , b ru g forøg in d rykn in g

• • • • •

Back ground Aim s Data and Methods R e sults C onclusion and perspectivation

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Agenda

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For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

Navn p å KUen h ed

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

Overskrift

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Overskrift

Helle Wallach Kild emoes Dias 2

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Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

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1994 Statins, the first cholesterol-lowering medicine to reduce the high mortality after myocardial infarction (MI) op st illin g p å To day One of the most prescribed medicine Recommended in guidelines for  A range of ischemic cardiovascular diseases (CVD)  Diabetes  People without CVD or diabetes, but at high CVD risk  The high risk strategy for primary CVD prevention  Risk scoring charts (e.g. SCORE): Lipid & blood pressure  Lowering limits for ‘high’ - US vs Europe

Tekst st art er u d en p u n kt op st illin g For at få p u n kt t ekst en , b ru g forøg in d rykn in g

Statins for primary prevention, evidence based? 1) Trials on statins for primary prevention Participants with CVD (largely) excluded – not diabetes Unclear beneficial effect esp. in women; Stratifying by gender? Under reporting of ‘subjective’ side effect i.e. muscle problems

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

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Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

2) Treatment goal (expert): Total cholesterol < 5mmol/l3) Menopause: Increase in cholesterol levels 4) Cholesterol as risk factor: Sex differences

Overprescribing of statin for primary prevention – especially for women? Helle Wallach Kild emoes Dias 4

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26/09/2015

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Overskrift

Aims

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Overskrift

Tekst st art er u d en p u n kt op st illin g For at få p u n kt op st illin g p å t ekst en , b ru g forøg in d rykn in g

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at få p u n kt op st illin g p å t ekst en , b ru g forøg in d rykn in g

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

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Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Overskrift

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Tekst st art er u d en p u n kt op st illin g For at få p u n kt -

op st illin g p å t ekst en , b ru g forøg in d rykn in g

Register based indication hierarchy Actual CVD status for each cohort member • Information from Patient and Prescription Registry Applied as disease and diagnosis markers

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Overskrift

• Most serious CVD diagnosis or diabetes • Left with two groups 1) primary hypertension, 2) ‘no diagnosis’ (hypercholesterolemia) Target group for the high risk strategy / ‘Asymptomatic persons’ Wallach-Kildemoes H, Hendriksen C, Andersen M (2012 ) Drug utilization according to reason for prescribing: A pharmacoepidemiological register-based method. Pharmacoepidemiology and Drug Safety

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Study population: All Danish inhabitants aged 20+ (N=4,424,818, full follow-up since 1996 ) were followed in the individual-level registries during 1996-2009.

Register data • Demographic data: Linkage encrypted code; sex; birth, death, emigration • Patient registry: Discharge diagnoses, hospital procedures • Prescription registry: Dispensing date, ATC code, volume No information on prescribing indication

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date

 Register based indication hierarchy Helle Wallach Kild emoes Dias 6

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Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Two outcome measures

Tekst st art er u d en p u n kt op st illin g For at få p u n kt -

op st illin g p å t ekst en , b ru g forøg in d rykn in g

For at få ven st re-

Diagnosis markers as proxy for statin prescribing indication

Data and methods

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Tekst st art er u d en p u n kt op st illin g

1) Explore incident statin-prescribing for primary prevention according to gender and age during 2005-2009 2) Estimate the fraction of statin initiation prescribed for primary prevention.

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

st illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

1. Incidence of statin therapy according to indication: Number incident users per person year at risk (PYR) 2. Incidence MI (fatal or non-fatal) in ‘asymptomatic’ individuals: Number MI events per PYR

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

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26/09/2015

Dep art men t of Ph armacy

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

2. Poisson regression analysis Incidence rate ratios (IRR) 95% confidence intervals (CI) Outcome: First statin prescription in naïve statin users Explanatory variables: Gender and age - Analyses stratified into ages below and above 65 Helle Wallach Kild emoes Dias 9

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For at få p u n kt -

350

op st illin g p å t ekst en , b ru g forøg in d rykn in g

300

Tekst st art er u d en p u n kt op st illin g

25

Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

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Overskrift

Female

Tekst st art er u d en p u n kt op st illin g

Male

Graphs by Sex 0 M 1 F

Helle Wallach Kild emoes

IHD

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Stroke

PAD

PAC

Diabetes

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Hypertension

No diagnosis

Dias 1 0

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Dep art men t of Ph armacy

Poisson regression analyses

Male

1.00

-

1.00

-

For at få ven st re-

Female

0.73 (0.72-0.74) 1.03 (1.01-1.05) Female 1.11

st illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

40-44

1.00

65-69

1.00

45-49

1.64 (1.58-1.71) 1.83 (1.77-1.90) 70-74

0.89

(0.87-0.91) 0.86

(0.83-0.89)

50-54

2.32 (2.24-2.40) 2.92 (2.82-3.01) 75-79

0.66

(0.64-0.68) 0.66

(0.63-0.69)

55-59

2.81 (2.72-2.91) 3.86 (3.74-3.99) 80-84

0.39

(0.38-0.41) 0.40

(0.37-0.43)

60-64

3.35 (3.24-3.46) 5.24 (5.07-5.40) 85+

0.14

(0.13-0.15) 0.13

(0.11-0.15)

20%

AMI

85

No diagnosis

20% 0,4

40-54

75

IRR

40%

MI

65

IRR

0,8 40% 0,6

Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

55

Hypertension

st illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

40-54 55-64 65-74 75-84 85+ (42,771) (76,744) (83,437) (43,286) (7,744)

45

95% CI

60%

0%

35

Myocardial Infarction

IRR

1 60%

40-54 55-64 65-74 75-84 85+ (28,921) (67,167) (81,014) (52,221) (13,540)

25

95% CI

For at få ven st re-

0

85

IRR

80%

0,20%

75

Hypertension No diagnosis

80% 1,2

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

65

Wallach-Kildemoes H, Diderichsen F, Krasnik A, Lange T, Andersen M (2012). Is the high-risk strategy to prevent cardiovascular disease equitable? A pharmacoepidemiological cohort study. BMC Public Health. 12(1): 610.

Tekst st art er u d en p u n kt op st illin g

op st illin g p å t ekst en , b ru g forøg in d rykn in g

Chart Title

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Statin treatment

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For at få p u n kt -

op st illin g p å t ekst en , b ru g forøg in d rykn in g

100%

45

U N I V E R S I T Y O F C O PE N H A G E N

100%

For at få p u n kt -

35

Age

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”:

Fraction of incident statin-users by indication Overskrift

Female

250

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Male

200

op st illin g p å t ekst en , b ru g forøg in d rykn in g

Incidence of statin use compared MI incidence in asymptomatic naïve statin users

150

For at få p u n kt -

Results

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0

Tekst st art er u d en p u n kt op st illin g

Overskrift

1. Graphical comparison across gender and age a. Asymptomatic individuals without prior statin use - Incidence of statin therapy compared to - Incidence of fatal myocardial b. Fraction of incident statin users (2005-2009) prescribed statins for primary prevention

100

Analysis

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Incidence (events/10.000 PYR)

Overskrift

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

50

U N I V E R S I T Y O F C O PE N H A G E N

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Helle Wallach Kild emoes Dias 1 2

-

1.00

-

Male

1.00

95% CI

-

1.00

(1.09-1.14) 1.36 -

1.00

95% CI

(1.32-1.40) -

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Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

Overskrift

Conclusion and perspectivation

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Tekst st art er u d en p u n kt op st illin g

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

•

Higher incidence in postmenopausal women than same aged men despite unclear beneficial effect esp. in women

•

Consequence of increasing cholesterol levels in postmenopausal women & recommendations on cholesterol goals?

Perspectivation •

Overprescribing of statins in postmenopausal healthy women - More harm than good, e.g. muscle problems - Waste of health care resources

•

Preventing overdiagnosis/treatment of ‘hypercholesterolemia’:

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Questions

Initiation of statin for primary prevention

For at få p u n kt op st illin g p å t ekst en , b ru g forøg in d rykn in g

Not m e rely a question of arguing on the evidence? Helle Wallach Kild emoes Dias 1 3

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Helle Wallach Kild emoes Wash1in Dias 4 g t on 2 01 5 Sept emb er 1

Dep art men t of Ph armacy

U N I V E R S I T Y O F C O PE N H A G E N

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Overskrift 450

For at få p u n kt -

op st illin g p å t ekst en , b ru g forøg in d rykn in g

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Tekst st art er u d en p u n kt op st illin g

350 300 250

200

20 - 39 years

For at få p u n kt -

40 - 64 years

op st illin g p å t ekst en , b ru g forøg in d rykn in g

65 - 79 years

150

80+ years

100

2013

2012

2011

2010

2009

2008

2007

2006

2005

2004

2003

st illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

2002

For at få ven st re-

0

2001

50

st illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

2000

For at få ven st re-

400

Prevention of CVD in General Practice Risk scoring charts

Men

400

Tekst st art er u d en p u n kt op st illin g

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U N I V E R S I T Y O F C O PE N H A G E N

Prevalence of statin use in Denmark between 2000-2013 Overskrift

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U N I V E R S I T Y O F C O PE N H A G E N

Women

10 years risk of fatal CVD (cholesterol & blood pressure levels) • Preventive drug if fatal CVD risk is high, 10%? • Lowering the limit for ‘high’ in guidelines - US vs Europe  Increasing statin prescribing for primary prevention

350 300

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

250

20 - 39 years

200

40 - 64 years 65 - 79 years

150

80+ years 100 50

0 2000

Helle Wallach Kild emoes Dias 1 5

2003

2006

2009

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2012

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

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U N I V E R S I T Y O F C O PE N H A G E N

Overskrift

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Tekst st art er u d en p u n kt op st illin g For at få p u n kt op st illin g p å t ekst en , b ru g forøg in d rykn in g

For at få ven st rest illet t ekst u d en p u n kt op st illin g , b ru g formin d sk in d rykn in g

For at æn d re ”E n h ed en s n avn ” og ”St ed og d at o”: Klik i men u lin jen , vælg ”In d sæt ” > ”Sid eh oved / Sid efod ”. In d føj ”St ed og d at o” i felt et for d at o og ”E n h ed en s n avn ” i Sid efod

Diagnoses in the hierarchy 1. Myocardial Infarction (MI) 2. Ischemic Heart Disease (IHD)

Indication Hierarchy No markers of

Register-marker description2 Hospital diagnosis

1

Angina pectoris

3. Stroke

1-2

Ischemic stroke

4. Peripheral Arterial Disease (PAD)

1-3

5. Potential Atherosclerotic Conditions (PAC)

1-4

6. Diabetes

1-5

7. Primary hypertension 8. No diagnosis/ hypercholesterolemia

Hospital procedures

Dispensed prescriptions

MI (acute or previous)

1-6 1-7

Consecutive Coronary by-pass, nitrate PCI dispensing, ASA

Peripheral arterial Lower limb disease: lower limbs revascularization E.g. arrhythmia, heart Peripheral; e.g. loopfailure, aorta aneurism, central; intestinal diuretics, nephropathies Revascularization antiarrhythmic Antidiabetics: Diabetes, type I or Insulin or pertype II oral Primary hypertension, Antihypertensive i.e., no organ damage No register markers of arteriosclerotic cardiovascular disease or diabetes

Wallach-Kildemoes H, Hendriksen C, Andersen M (2012 ) Drug utilization according to reason for prescribing: A pharmacoepidemiological register-based method. Helle Wallach Kild emoes Wash in g t on 20 15 Sep tember 1 Pharmacoepidemiology and Drug Safety Dias 1 7

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