clinical implications of pharmaco- epidemiology research
TRANSCRIPT
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
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
Statins
ACEi/ARBs
Beta-blockers
5
Drug safety - NSAIDs and CV risk
DFSE - Pharmacoepidemiology Gunnar Gislason
6
COX-2 inhibitors - a new generation of NSAIDs
with less risk of gastric ulcer
DFSE - Pharmacoepidemiology Gunnar Gislason
7
The scope of the problem
- NSAID use in Denmark
Fosbøl et al, Pharm Drug Saf 2008
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
9
Schjerning Olsen A et al. Circulation 2011;123:2226-2235
DFSE - Pharmacoepidemiology Gunnar Gislason
10
Schjerning Olsen A et al. Circulation 2011;123:2226-2235
DFSE - Pharmacoepidemiology Gunnar Gislason
11
Olsen A S et al. Circulation. 2012;126:1955-63
DFSE - Pharmacoepidemiology Gunnar Gislason
12
Schjerning Olsen et al, JAMA. 2015;313(8):805-814.
DFSE - Pharmacoepidemiology Gunnar Gislason
13
Schjerning Olsen et al, JAMA. 2015;313(8):805-814.
DFSE - Pharmacoepidemiology Gunnar Gislason
14
Olsen A S et al. PLoS ONE 2013;8(1):e54309
NSAID use and specific causes of death after
Myocardial Infarction
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
17
Charlot et al, BMJ 2011
HR 1.61 (1.45-1.79)
P < 0.001
Aspirin and PPI interaction
DFSE - Pharmacoepidemiology Gunnar Gislason
18
Charlot et al, BMJ 2011
DFSE - Pharmacoepidemiology Gunnar Gislason
19
Antitrombotic Treatment in Patients with AF
Hansen ML et al, Arch Int Med 2010
DFSE - Pharmacoepidemiology Gunnar Gislason
20Lock Hansen M et al, Arch Int Med 2010
Bleeding rates after hospital discharge for
atrial fibrllation
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
22
Sørensen R et al, the Lancet 2009
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
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)
DFSE - Pharmacoepidemiology Gunnar Gislason
26
Incidence Rates of myocardial infarction/coronary death in AF
patients after MI or PCI.
Lamberts et al, Circulation 2014
DFSE - Pharmacoepidemiology Gunnar Gislason
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
DFSE - Pharmacoepidemiology Gunnar Gislason
28
Sindet-Pedersen, C. et al. J Am Coll Cardiol. 2018;72(15):1790–800
DFSE - Pharmacoepidemiology Gunnar Gislason
29DFSE - Pharmacoepidemiology Gunnar Gislason
30
Sindet-Pedersen, C. et al. J Am Coll Cardiol. 2018;72(15):1790–800
DFSE - Pharmacoepidemiology Gunnar Gislason
31
Olesen J et al, New Engl J Med 2012
DFSE - Pharmacoepidemiology Gunnar Gislason
32
Olesen J et al, New Engl J Med 2012
DFSE - Pharmacoepidemiology Gunnar Gislason
33
Bonde et al. JACC 2014;64:2471-2482
Net Clinical Benefit of Antithrombotic Therapy in Patients With AF and CKD
DFSE - Pharmacoepidemiology Gunnar Gislason
34
Bonde et al. JACC 2014;64:2471-2482
Net Clinical Benefit of Antithrombotic Therapy in Patients With AF and CKD
DFSE - Pharmacoepidemiology Gunnar Gislason
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!