NSAID Gastropathy :

Epidemiology and pathophysiolog

Hirlan
The use of NSAIDs is common in the treatment of
pain
inflamation
fever

Low dose ASA is use routinely in primary and secondary

Prophylaxis of CV event

NSAID use increase among elderly

The use of NSAID from OTC is also increase

Prevalence of NSAID use

Study in USA, NSAID use increase among elderly

70% at least once weekly

34% at least daily

More than 111 million NSAID prescription per year

Indonesia ?
Patofisiologi gastropati OAINS
Arachidonic acid

COX-1 COX-2
(constitutive) (induced by inflammatory st

COX-2 selective NSAIDs

Non-selective NSAIDs

Prostaglandins Prostaglandins

Gastrointestinal cytoprotection Inflammation

Platelet activity Pain
Vane & Botting 1995
Fever
COX 2 hypothesis

COX 2 is the primary intended target

for anti-inflamatory but no or little effect
on inhibition to COX 1 by selectivly activity

Animal model :
Indicated that both COX 1 and COX 2
must be inhibited for UGIE to occur
Upper GI events ( UGIE ) caused by NSAID

o Dispeptic and sign of GERD

with or without erosion

o Peptic ulceration
o Bleeding of peptic ulcer

o Perforation
o Stricture
Incidence of UGIE

o 1 of every 20 NSAID user

o 1 of ev severery 7 NSAID user

Annual incidence UGIE associated UGIE

2.0 4.5 %

Risk of severe complication 0.2 1.9 %

GI safety of COXIB
Cochrane systematic review :

o COXIB produced significantly fewer UGI Ulcer

( RR 0,26. 95% CI 0.23-0.30 )
and ulcer complication ( RR 0.39. 95% CI 0.31-
0.30.

o Fewer withdrawals caused by GI symptoms,

compared with conventional NSAID .
Risk factors of UGIE associated with NSA
High risk
- History of a previously complicated ulcer
- Multiple risk factors >2

Moderate risk
- Age 65 years or more
- High dose NSAID therapy
- A previous history of Uncomplicated ulcer
- Concurrent use of aspirin or corticosteroid or
anticoagulant

Low risk
- no risk factors
Cardiovascular events associated with NSAID
Meta-analysis :

o All COXIB were associated with an increase

CV risk compared to placebo
(rate ratio 1.42. 95% CI 1.13-1.78)

o Dose dependent increase in CV events was

also abserved with celecoxib

o No significant difference in CV risk between

COXIB and NSAID conventional, Naproxen
was the only posible exceptional
Treatment and Prevention of NSAID related

Because the central mechanism of UGIE are

prostaglandin depletion and topical injury by
the acidic property of NSAID,

Treatment and prophylaxis :

Replacement with prostaglandin

synthesis or acid suppression
Prevention and treatment

Selection of patients for therapy

o Indication for NSAID used

o The risk factors for having UGIE and CV events
associated with NSAID used
o What is the NSAID of choice : non selective or
Coxib
o The dose of NSAID
Early Dispepsia and symptom of acid regurgitation
o poorly correlated with the result of endoscopic
study.
50% patients with dispepsia had normal mucosal
appearance on endoscopy
40% patient with erosive and ulcer were
asymptomatic
o Adaptation proses ?
o H2RA induced masking effect to UGIE
o NSAID can be continued
Active ulcer associated with NSAID

NSAID should be discontinued, if possible.

PPI are superior to H2RA and misoprostol in

healing NSAID associated ulcers

If NSAID should be continued, PPI are the first

Choice.
Ulcer healing in those NSAID was discontinu

95
%
NSAID continued
63 NSAID discontinued

Gastric ulcer associated NSAID

H2RA standart dose at 8 weeks
PPI are superior to standart dose of H2RA
Omeprazole 20mg /day vs omeprazole 40mg/day
vs Ranitidine 150mg bid

%
80 79 Ome 20 m/dayg
Ome 40 mg/day
63 Ran 150mg BFD

Ulcer healing at 8 weeks

NSAID was used continuesly
 PPI are superior to Mesoprostol in healing
NSAID associated ulcer

% 89 89 Ome 20 mg/day
77
Ome 40 mg/day
Meso 200mg Qid

Ulcer healing at 8 weeks

NSAID was used continuosly
Role of COXIB in Ulcer healing
o Animal study : Cox 2 up regulated
in gastric ulcer
o Administration of COX 2 inhibitors retards
the healing of gastric ulcer

No data to support recommendation

of substitution of NSAID with COXIB
in patients with active ulcer
Misoprostol for NSAID related UGIE preventi

o Misoprostol 400 800 mg/day reduced

risk of NSAID induced ulcer

o Meta-analysis :
Only misoprostol 800 mg/day reduced
ulcer complication by 40% compared with placebo
Side effect occurred in 30% responders

o Lower dose fails to prevent ulcer complication

Prevention of NSAID related its complications

GI Risk Low moderate High

CV risk

Low NSAID NSAID+ PPI Alternatif therapy

or misoprostolor COXIB +PPI
/nisoprostol

HIGH Naproxen + Naproxen + Avoid NSAID and

PPI/misoprostolPPI/misoprostolCOXIB
PPI are tha agent of choice for therapy
and prophylaxis of NSAID associated UGIE
Thank you