Critical Appraisal EMB Harm

Isti Ilmiati Fujiati Dept. Ilmu Kedokteran Komunitas FK USU

Artikel tentang Harm

Title: CLOPIDOGREL Versus ASPIRIN and ESOMEPRAZOLE to PREVENT ULCER BLEEDING
The New England Journal of Medicine 2005

There has been no prospective trail to assess whether clopidogrel is an alternative to aspirin plus a proton-pump inhibitor for patients at risk for ulcer.

Hypothesis: Clopidogrel would not be inferior to aspirin plus esomeprazole in the prevention of recurrent ulcer bleeding among the high risk patients.

Research design:

Randomized clinical trial (RCT): prospective, randomized, double-blind trial

Ethics committee approval Informed consent Adjudication committee study end points

Random assign:
Clopidogrel daily + esomeprazole placebo twice daily Aspirin daily + esomeprazole twice daily

Follow up: 12 months Clinical outcome: recurrent ulcer bleeding Based on assumptions the sample size calculation would be: total sample 319, consecutive sampling

Are the results of this harm study valid?

1.

Were there clearly defined groups of patients, similar in all important ways other than exposure to the treatment or other cause?

Yes. Randomization would tend to make the two groups identical. It balances the groups for cofounders.
o Randomization random numbers

Eligible patients based on criteria:

o o

Inclusion: ulcer healing, H.pylori (-), anticipated regular used use of antiplatelet Exclusion

Are the results of this harm study valid?

2.

Were treatments/exposures and clinical outcomes measured in the same ways in both groups (Was the assessment of outcomes either objective or blinded to exposure)?

Yes, Treatments: seal envelopes; drugs identical Outcomes: Endoscopy was performed in a treatmentblinded fashion to determine the ulcer.

Are the results of this harm study valid?

3.

Was the follow-up of study patients sufficiently long (for the outcome to occur) and complete?

Yes,

long up to 15% of those taking aspirin who have a history of bleeding from ulcers had recurrent bleeding within one year. follow up 12 month
complete sample size calculation: 319 patients with assumption 10% loss to follow-up. Nearly 320 patients completed follow-up.

Are the results of this harm study valid?

4.

Do the results of the harm study fulfill some of the diagnostic test for causation?

Yes, Another study reported that 12% who took clopidogrel had ulcer bleeding within one year. clopidogrel impairs the healing of gastric ulcers by supressing the release of platelet-derived factors.

Are the valid results of this harm study important?

1.

What is the magnitude of the association between the exposure and outcome RR = ? NNH =?

Importance:
Recurrent Recurrent Bleeding (+) Bleeding (-)

total 161 159 320

clopidogrel 13 Aspirin and 1 esomeprazol total 14

148 158 306

RELATIVE RISK (RR) = A/(A+B) : C/(C+D) = 13/161 : 1/159 = 0.081/0.0063 =12.86

NNH = 1 / { A/(A+B)} {C/(C+D)} NNH = 1/ 0.081-0.0063 NNH= 1/0.0747 NNH= 13.4

We need 13 patients to be exposed to clopidogrel to produce one additional recurrent ulcer bleeding of gastrointestinal events.

Are the valid results of this harm study important?

2.

What is the precision of the estimate of the association between the exposure and the outcome

RR with Confidence interval 95%: 11,49-14,19

Can this valid and important evidence about harm be applied to our patient?
1.

Is our patient so different from those included in the study that its results cannot apply?
No, our patients mostly similar to the patients in the study

2.

What is our patients risk of benefit and harm from the agent?
avoiding the recurrent ulcer bleeding from clopidogrel

Can this valid and important evidence about harm be applied to our patient?
3.

What are our patients preferences, concerns and expectations from this treatment? no more symptoms of gastric bleeding as consequences of clopidogrel therapy. What alternative treatments are available? Yes, aspirin plus esomeprazole therapy or taking aspirin with enteric coated preparation. clopidogrel may given to patient with no history of gastric ulcers.

4.