Clinical implications of pharmaco- epidemiology research

Clinical implications of pharmaco-

epidemiology research

- ”past experience”

Gunnar H. Gislason MD, PhD, FESC, FACC, FAHA

Professor of Cardiology and Cardiovascular Epidemiology,

University of Copenhagen

Director of Research, The Danish Heart Foundation

2

121250-1233

280254-0534

180677-3457

DFSE - Pharmacoepidemiology Gunnar Gislason

3

Evidence-based treatment and compliance

Acute Myocardial Infarction Heart Failure

Days from discharge until first dispensing

0 30 60 90 120 150 180 210 240 270 300 330 360

Pro

po

rtio

n o

f p

ati

en

ts (

%)

0

20

40

60

80

100

ACEi/ARBs

Beta-blockers

Spironolactone

Statins

Gislason et al, Eur H J 2006 Gislason et al, Circulation 2007


Statins

ACEi/ARBs

Beta-blockers

4

Compliance

Years from first dispensing

0 1 2 3 4 5

Pro

port

ion

of

patients

(%

)

0

20

40

60

80

100

Beta-blockers

ACEi/ARBs

Statins

Years from first dispensing

0 1 2 3 4 5

Pro

po

rtio

n o

f P

ati

en

ts (

%)

0

20

40

60

80

100

ACEi/ARBs

Beta-blockers

Spironolactone

Statins

Gislason et al, Eur H J 2006 Gislason et al, Circulation 2007

Acute Myocardial Infarction Heart Failure


Statins

ACEi/ARBs

Beta-blockers

5

Drug safety - NSAIDs and CV risk


6

COX-2 inhibitors - a new generation of NSAIDs

with less risk of gastric ulcer


7

The scope of the problem

- NSAID use in Denmark

Fosbøl et al, Pharm Drug Saf 2008


8

Risk of Death associated with NSAID treatment

in patients with Acute Myocardial Infarction

Hazard Ratio

(Horizontal bars symbolize 95% Confidence Intervals)

0,5 0,6 0,7 0,8 0,9 1,5 2 2,5 3 4 5 6 7 8 91 10

No use

Other NSAIDs any use

Diclofenac =>100 mg

Diclofenac < 100 mg

Diclofenac any use

Ibuprofen > 1200 mg

Ibuprofen <= 1200 mg

Ibuprofen any use

Celecoxib > 200 mg

Celecoxib <= 200 mg

Celecoxib any use

Rofecoxib > 25 mg

Rofecoxib <= 25 mg

Rofecoxib any use

Gislason et al, Circulation 2006;113:2906-13


9

Schjerning Olsen A et al. Circulation 2011;123:2226-2235


10

Schjerning Olsen A et al. Circulation 2011;123:2226-2235


11

Olsen A S et al. Circulation. 2012;126:1955-63


12

Schjerning Olsen et al, JAMA. 2015;313(8):805-814.


13

Schjerning Olsen et al, JAMA. 2015;313(8):805-814.


14

Olsen A S et al. PLoS ONE 2013;8(1):e54309

NSAID use and specific causes of death after

Myocardial Infarction


15

Charlot et al, Annals of Internal Medicine 2010;153:378-86

Clopidogrel / no PPI

Clopidogrel / + PPI

No Clopidogrel / No PPI

No Clopidogrel / + PPI

Clopidogrel and the PPI interaction (CYP2C19)

-CV death, MI or stroke


16

Risk of Cardiovascular death, recurrent MI or strokeassociated with use of PPI in patients after first MI

Hazard Ratio

0,9 1,5 21

PPI and clopidogrel (PS)

Only PPI (PS)

Hazard Rate Ratio

PPI and clopidogrel

Only PPI

No PPI (ref)

(p for interaction 0.72)

Pro

pen

sit

y s

co

re

matc

het

co

ho

rtW

ho

le c

oh

ort

C

ox r

eg

ressio

n

Charlot et al, Annals of Internal Medicine 2010;153:378-86


17

Charlot et al, BMJ 2011

HR 1.61 (1.45-1.79)

P < 0.001

Aspirin and PPI interaction


18

Charlot et al, BMJ 2011


19

Antitrombotic Treatment in Patients with AF

Hansen ML et al, Arch Int Med 2010


20Lock Hansen M et al, Arch Int Med 2010

Bleeding rates after hospital discharge for

atrial fibrllation


21

Hazard ratios for the risk of hospitalization or death because of bleeding

or anemia associated with the use of warfarin, aspirin, clopidogrel in

patients with AF

NNH 8 (6-11)

NNH 9 (7-13)

Hansen ML et al, Arch Int Med 2010


22

Sørensen R et al, the Lancet 2009


23

Crude incidence rates of fatal and nonfatal bleeding according to

antithrombotic regimen in patients with MI or PC and Atrial Fibrillation

Lamberts M et al. Circulation 2012;126:1185-1193


24

Thromboembolic and bleeding outcomes following MI or PCI in

AF patients according to antithrombotic treatment regimen.

Lamberts M et al. Circulation 2012;126:1185-1193


25

Lamberts et al, J Am Coll Cardiol. 2013;62(11):981-989.

Benefit and Safety With Triple Therapy Versus Dual Therapies in

patients with AF and recent MI or PCI

Triple

Therapy(ref)


26

Incidence Rates of myocardial infarction/coronary death in AF

patients after MI or PCI.

Lamberts et al, Circulation 2014


27

Antithrombotic treatment in AF patients with

stable coronary artery disease

Stroke / MI / CV Death Major Bleeding All-cause Mortality

Lamberts et al, Circulation 2014


28

Sindet-Pedersen, C. et al. J Am Coll Cardiol. 2018;72(15):1790–800


29DFSE - Pharmacoepidemiology Gunnar Gislason

30

Sindet-Pedersen, C. et al. J Am Coll Cardiol. 2018;72(15):1790–800


31

Olesen J et al, New Engl J Med 2012


32

Olesen J et al, New Engl J Med 2012


33

Bonde et al. JACC 2014;64:2471-2482

Net Clinical Benefit of Antithrombotic Therapy in Patients With AF and CKD


34

Bonde et al. JACC 2014;64:2471-2482

Net Clinical Benefit of Antithrombotic Therapy in Patients With AF and CKD


35

DAN-WAR-D

Danish Warfarin-Dialysis StudySafety and efficacy of warfarin in patients with atrial fibrillation on dialysis -

A nationwide parallel-group open randomized clinical trial

DFSE - Pharmacoepidemiology Gunnar Gislason35

36DFSE - Pharmacoepidemiology Gunnar Gislason

Thank you for your

attention!

Documents

Clinical implications of pharmaco- epidemiology research