ASPIRIN FOR PREVENTING THE

RECURRENCE OF VENOUS
T H RO M B O E M B O L I S M

DIAN PRASTIWI
30101206775
SGD 12
 PICO

 P : patients with unprovoked venous thromboembolism

 I : aspirin

 C: placebo

 O : reduced the risk of recurrence in patient unprovoked venous

thromboembolism
 Question : Is aspirin can reduce the risk of reccurent in patient
unprovoked venous thromboembolism compared with placebo?

  TREATMENT
CRITICAL APPRAISAL
 MENILAI INTERNAL
VALIDITY

1. Apakah Kelompok perlakuan dan kontrol terwakili

(representative) dan sebanding?
 A . A PA K A H P E M I L I H A N S U B J E K
DILAKUKAN SECARA RANDOM?

 YA  METHODS  STUDY DESIGN

WARFASA was a multicenter, investigator-initiated,

randomized, double-blind clinical trial. Eligible patients were
randomly assigned to aspirin, 100 mg once daily, or placebo for 2
years, with the option of extending the study treatment.
Randomization occurred within 2 weeks after vitamin K antagonists
had been withdrawn.
 FA K T O R I N K L U S I DA N E K S K L U S I

Inclusion
 Patients older than 18 years of age were eligible for the study if they had been treated for 6 to 18
months with vitamin K antagonists (with a target international normalized ratio [INR] of 2.0 to 3.0)
 for first-ever,
 objectively confirmed,
 symptomat-ic,
 unprovoked proximal deep-vein thrombosis, pulmonary embolism, or both.

Exclusion
 The main exclusion cri-teria can be found in the Supplementary Appendix, available with the full
text of this article at NEJM.org
 S A M P L E B E S A R DA N D I L A K U K A N R A N D O M I S A S I
S U B J E K U N T U K D I BAG I K E DA L A M K E L O M P O K

 Result  Patient and study treatment

 From May 2004 through August 2010, a total of 403 patients were
randomly assigned to a study group; 205 patients received aspirin, 197 received
placebo, and 1 patient, who was assigned to the placebo group, did not receive
the study drug.
B . A PA K A H K E D UA K E L O M P O K T E R S E B U T S A M A
D A N S E B A N D I N G S E J A K AWA L P E N E L I T I A N ? Y A
 C . A PA K A H K E D UA K E L O M P O K M E N DA PA T
P E R L A K UA N YA N G S A M A ( D I L UA R P E R L A K UA N
E K S P E R I M E N YA N G A K A N D I B A N D I N G K A N ? ) Y A

 METHOD  Surveillance and follow-up

 Patients were reexamined every 3 months during the first year after
randomization and every 6 months thereafter. Patients were
instructed to report to the study center immediately if they had
symptoms suggestive of recurrent venous throm- boembolism or
bleeding complications. In cases of suspected recurrence, objective
testing was re-quired
 D. A PA K A H K E S E L U R U H A N S U B J E K YA N G I K U T D A L A M
P E N E L I T I A N D I H I T U N G H I N G G A A K H I R P E N E L I T I A N DA N
D I L A P O R K A N K E B E R A DA A N N YA ? Y A .
 2. APAKAH
PENGUKURANNYA
AKURAT?
 A . A PA K A H M E N G G U N A K A N S I N G L E B L I N D A T AU
D O U B L E B L I N D ( BA I K S U B J E K DA N I N V E S T I G AT O R
T I DA K M E N G E T A H U I T R E A T M E N T YA N G D I B E R I K A N
K E PA DA T I A P S U B J E K ) ? Y A

 Methods Study Design and Intervention

WARFASA was a multicenter, investigator-initiat-ed, randomized,
double-blind clinical trial.

 Methods  Outcome Measure

All suspected study outcome events were assessed by a central,
independent adjudication committee whose members were unaware of the group
assignments and who reviewed the imaging results.
 B . A PA K A H O U T C O M E P E N E L I T I A N D I U K U R
D E N G A N C A R A YA N G S A M A PA D A S E L U R U H
KELOMPOK? YA

 Methods Outcome Measures

The primary efficacy outcome was symptomatic, objectively confirmed
recurrence of venous thromboembolism, defined as the composite of deepvein
thrombosis or nonfatal or fatal pulmonary embolism.
Pulmonary embolism was considered(objectively confirmed on computed
tomography or lung scanning) or deep-vein thrombosis (objectively con-firmed on
compression ultrasonography) and whenever the cause could not be attributed to an
alternative diagnosis. Deaths were classified as being due to pulmonary embolism,
bleeding, or other causes.
 Secondary efficacy outcomes included nonfatal myocardial
infarction, unstable angi-na, stroke, transient ischemic attack, acute
ischemia of the lower limbs, and death from any cause
 The principal safety outcome was major bleeding. An overt bleeding event was
defined as major if it was fatal, occurred in a critical location (intracranial,
intraspinal, intraocular, retroperito-neal, intraarticular, pericardial, or intramuscular
[leading to a compartment syndrome]), or was associated with a decrease in the
hemoglobin level of at least 2.0 g per deciliter or required a transfusion of 2 or
more units of whole blood or red cells. Clinically relevant, nonmajor bleeding,
defined as any overt bleeding that required a medical intervention and did not
meet any of the criteria for major bleeding, was a secondary safety outcome.
 C . A PA K A H K E L O M P O K K O N T R O L
M E M P E ROL E H P L AC E B O? YA

METHODS  STUDY DESIGN

Eligible patients were randomly assigned to aspirin, 100 mg

once daily, or placebo for 2 years, with the option of extending the
study treatment. Randomization occurred within 2 weeks after
vitamin K antagonists had been withdrawn.
B. APAKAH HASILNYA
KARENA FAKTOR
PELUANG?
1 . A PA K A H P E N G U K U R A N YA N G D I P E R G U N A K A A N
D A N B A G A I M A N A P E N G A R U H D A R I P E R L A K UA N ?

Effek
Ya Tidak jumlah
Aspirin 177 28 205
Placebo 154 43 197
 RR = A/A+B : C/C+D = 0,58

RR<1 maka, terapi menggunakan aspirin menurunkan terjadinya

resiko kekambuhan vena tromboemboli/ kemungkinan subjek pada
kelompok terapi aspirin akan terjadi pengurangan kekambuhan vena
tromboemboli 0,58 kali dibanding placebo
 ARR = A/A+B – C/C+D = 177/205 - 154/197

= 0,86-0,78 = 0,08

Apabila aspirin digunakan sebagai terapi maka selisih jumlah

penurunan kekambuhan vena tromoboemboli antara aspirin dan
placebo sbesar 8 %
 RRR = ARR/(c/c+d) = 0,08/0,78 = 0,1

Apabila aspirin digunakan sebagai terapi maka jumlah kekambuhan

vena tromboemboli dapat diturunkan sebesar 10 kali dari insiden
sebelumnya
 NNT : 1/ARR = 1/0,08 = 13

Kita perlu melakukan terapi aspirin terhadap 13 pasien untuk

mengurangi terjadinya 1 kasus vena tromboemboli

 NNT kecil  penting

 B. A PA K A H A DA T E R J A D I N YA E F E K D I S E B A B K A N
K A R E N A FA K T O R P E L UA N G ATAU K A R E N A FA K T O R
P E R L A K UA N ?

 Nilai p untuk total episode kekambuhan VTE sebesar 0,02 berarti ada
perbedaan jumlah subjek kekambuhan pada VTE antar kelompok perlakuan
(aspirin) dengan kelompok kontrol (placebo)
 KESIMPULAN

 Validitas Internal penelitian baik

 Hasil : Aspirin Efektif sebagai upaya untuk menurunkan

kekambuhan VTE
 PENILAIAN APPLICABLE

 Penilaian Applicablen (Kemamputerapan pada pasien) Pertimbangkan

pertanyaan:
1. Apakah pasien kita terdapat perbedaan dengan subjek pada penelitian
2. Apakah terapi tersebut mungkin untuk diterapkan pada pasien kita (dengan setting
kita)?
3. Apakah pasien kita mempunyai potensi yang menguntungkan atau merugikan jika
terapi tersebut diterapkan?
4. Bagaimanakah pengharapan pasien kita bila hasil penelitian tersebut kita tawarkan
untuk mengobati (bersedia untuk diobati dengan terapi tersebut atau tidak?
5. Apakah terapi baru tersebut tersedia?
6. Dst.