NSAID ULCERS & ACUTE UPPER GI BLEEDING

Question 1

NSAID Induced Ulcers
Development of ulcers
– 15 to 40% of chronic users1 & 5 to 80% in short term studies2

Answer 1

Mechanism: Inhibition of mucosal prostaglandin synthesis & direct irritation of gastric epithelium
• Clinically important GI events (serious)
– Incidence: 1-2% per year with NSAIDs as a class
– ~16,500 deaths & 107,000 hospitalizations/yr in the USA
• Definition of “NSAID” includes:
– Traditional NSAIDS: Ibuprofen, naproxen, diclofenac, etc.
– Salicylates: ASA, salsalate
– COX-2 Inhibitors: Celecoxib

Question 2

Clinical Characteristics

Peptic Ulcer Disease
h pylori vs NSAID induced

Answer 2

Condition: Chronic Chronic

Site: DU > GU GU > DU
Intragastric: pH More dependent Less dependent
Symptoms: Usually epigastric pain Often asymptomatic
Ulcer Depth: Superficial Deep
GI bleeding: Less severe, single vessel More severe, single vessel

Question 3

Primary Prevention of NSAID ulcers

Can we Prevent LL from getting Ulcers in the first place?

Answer 3

Risk based approach: Routine prophylaxis for all is not warranted
low risk: no risk factors
moderate risk (1-2 factors): Older age (>65 years) (70 yo)
§ NSAID use: high dose (7x)/ multiple* (9x)
§ History of uncomplicated ulcer
§ Concurrent ASA, Corticosteroids (2.2x), anticoagulants (6.4x), or SSRI (4.8x)
§ History of CV disease (1.8x)

High Risk: Hx of complicated PUD, esp. recent (13.5x)
§Multiple (>2) risk factors

Question 4

Low CV Risk

Answer 4

low risk: NSAID alone (least ulcerogenic at lowest dose)
mod risk: NSAID + PPI/Misoprostol
high risk: Alternative therapy or COXIB + PPI/misoprostol

Question 5

High CV risk

Answer 5

low risk: Naproxen + PPI/misoprostol
mod risk: Naproxen + PPI/misoprostol
high risk: Avoid NSAIDs or COXIBs.
Use Alternate Therapy

Moderate or high risk –> prophylatic therapy

Previous NSAID related bleed/peptic ulcer disease
CV risk complications by coxib meds
Trad NSAIDS also have risk

Naproxen has lowest CV risk

Question 6

NSAID GI Toxicity & COX-2 Selectivity

Answer 6

the greater the COX-2 selectivity, the greater the GI toxicity

Question 7

Primary Prevention of NSAID ulcers

Answer 7

• COX-2 inhibitors1
– Outcome: upper GI complication (perforation, obstruction, or bleed)
– All NSAIDS increase upper GI CCx, but COX-2 decrease events vs. naproxen & ibuprofen
– GI sparing effects are compromised when used with low dose ASA

• H. pylori testing & eradication prior to new long-term NSAID or LD ASA2
– Consider testing for H. pylori in pts taking ASA 81 mg OD
– Pts initiating chronic NSAID should be tested for H. pylori.
– The benefit of testing in pts already on NSAID is unclear (GRADE: Conditional, Low)

Question 8

Myths About NSAID Induced Ulcers

Answer 8

Low dose ASA does not cause GI ulcers
ASA 75 to 300 mg daily does # risk (~2 fold) of GI bleeding.

Buffered/coated ASA is better for preventing ulcers:
decrease endoscopic findings of injury may decrease dyspepsia, no decrease GI bleeds

Question 9

Acute Upper GI Bleeding (AGB)
• Accounts for >300,000 US hospital admissions/year
• Most are minor but, mortality rate ~7%

Answer 9

• Signs & Symptoms
– Hematemesis, melena, hematochezia
– Erratic mental status, weakness, dizziness, syncope
– Hemodynamic instability (shock, orthostatic hypotension)
• Etiology: Upper vs. Lower GI bleed
– Upper GI bleeding categorized as variceal or nonvariceal (liver disease)
– PUD accounts for ~50% of upper GI bleeds
• Goals:
– Stabilize the patient, Relieve ulcer pain, Heal ulcer, Prevent ulcer recurrence, Prevent complications

Question 10

Treatment of Peptic Ulcer Bleeding

diff types of ulcers

see slide 45

Answer 10

• Clean Ulcer Base
• Flat Spot
• Adherent Clot
  Low Re-bleed Risk, IV PPI not indicated
• Non-bleeding Visible Vessel
• Active Bleeding
  High Re-bleed Risk, HD PPI CIVI x 72 hr “ PO

Risk of rebleeding
Increases with non-bleeding visible vessel and active bleeding
PPI continuous IV to get max suppression to stop bleeding

Question 11

Treatment of Peptic Ulcer Bleeding

Answer 11

HD PPI CIVI: Pantoprazole 80mg IV bolus then 8mg/hr x72 hrs decrease re-bleed but no effect on mortality.
• Intermittent bolus PPI: Pantoprazole 80mg IV then 40mg IV q12h at least as effective vs. PPI CIVI.
• H2RA: Not an option. Can’t achieve & maintain optimal pH.
• Endoscopic therapy: Epinephrine, EtOH, thermal, laser, clipping.

Question 12

If you can STOP the NSAID

Answer 12

– Discontinue NSAID

– Treat the ulcer with PPI, H2RA (PPI superior; H2RA take longer)

Question 13

If CONTINUED NSAID is absolutely necessary

Answer 13

Secondary prevention with PPI or misoprostol co-therapy or COX-2 inhibitor1
• Test & treat for H. pylori

Question 14

Tx & Secondary Prevention of NSAID Ulcers

Answer 14

PPI superior to H2RA
Misoprostol similar to Omeprazole for ulcer healing, but increase A/E;
Omeprazole better for maintenance of remission

switching to celecoxib beneficial
If this was an ASA related bleed, what about switching to clopidogrel for CV protection? no reduction in rebleeding comp to ASA +PPI

Question 15

PPI Deprescribing

Answer 15

PPI use for 8 wks induces acid–related symptoms in healthy volunteers after withdrawal3
• Evidence for “On demand” PPI
Conclusion: Caution is needed when implementing PPI deprescribing. On demand prescribing may lead to inc GI symptoms probably a dec in pill burden. There was a dec in participant satisfaction.

“Tapering seems more effective than abrupt stopping.”
Bottom Line: No universally effective method to stop PPI & various approaches
– decrease the dose by 1⁄2, then dose every other day, then only “on-demand”

Question 16

Summary

Answer 16

see last slide