PENDAHULUAN High-density Lipoprotein (HDL) berperan penting dalam proses selular kolesterol efflu !

dan berefek tambahan didalam aterotrombosis" Hubungan antara tingginya kadar HDL dengan ke#adian Penyakit $antung %oroner telah teru#i dalam penelitian obser&asional dengan menggunakan u#i post ho' dan meta analisis terhadap terapi statin untuk pasien dengan fa'tor risiko tinggi penyakit #antung! penyakit #antung kronis atau sindrom koroner akut" (eskipun begitu! masih belum #elas apakah naiknya kadar HDL akibat terapi farmakologi dapat menurunkan resiko ter#adinya penyakit #antung" Akan tetapi perubahan kadar HDL tidak dapat merubah fungsi fisiologis HDL" %olesterol Ester )ransfer Protein (*E)P) dapat mentransfer kolesterol ester dari kadar HDL men#adi partikel aterogenik lipoprotein yang berisi apolipoprotein +! seperti Lo, Density Lipoprotein (LDL)" )etapi tidak semua analisis penelitian genetik polimorfis memiliki hasil *E)P berhubungan dengan tingginya kadar HDL kolesterol! rendahnya kadar LDL kolesterol! dan rendahnya resiko ke#adian penyakit #antung" Penelitian ini bertu#uan untuk mengetahui apakah inhibitor *E)P dapat menurunkan resiko penyakit #antung

1. A. Was the assignment of patients to treatments randomised? )his paper- Yes *omment.e randomly assigned /0!12/ patients ,ho had had a re'ent a'ute 'oronary syndrome to re'ei&e the *E)P inhibitor dal'etrapib! at a dose of 344 mg daily! or pla'ebo! in addition to the best a&ailable e&iden'e-based 'are" )he primary effi'a'y end point ,as a 'omposite of death from 'oronary heart disease! nonfatal myo'ardial infar'tion! is'hemi' stroke! unstable angina! or 'ardia' arrest ,ith resus'itation" +" Were the groups similar at the start of the trial? )his paper- Yes *omment)he baseline 'hara'teristi's of the t,o study groups (assessed at the time of randomi5ation) ,ere ,ell mat'hed" (ost patients in the t,o groups ,ere treated ,ith aspirin! statins! thienopyridines! betablo'kers! and angiotensin-'on&erting6en5yme (A*E) inhibitors or angiotensin-re'eptor blo'kers (A7+s) and under,ent a 'oronary re&as'ulari5ation pro'edure bet,een the time of the 8ualifying e&ent and random assignment" )he mean baseline LDL 'holesterol le&el ,as 23 mg per de'iliter (9"4 mmol per liter) (,ith a le&el of /44 mg per de'iliter or lo,er in 13: of the patients)! the mean HDL 'holesterol le&el ,as ;9 mg per de'iliter (/"/ mmol per liter)! the mean apolipoprotein A/ le&el ,as /<2 mg per de'iliter! and the mean apolipoprotein + le&el ,as 1/ mg per de'iliter" No Un'lear No Un'lear

2. A" Aside from the allocated treatment, were groups treated equally?

)his paper- Yes *omment-

No

Un'lear

After ; to /9 ,eeks of run-in! and no later than /9 ,eeks after the inde e&ent! 8ualifying patients ,ere randomly assigned! /-/ ratio! to re'ei&e dal'etrapib at a dose of 344 mg daily or mat'hing pla'ebo" +" Were all patients who entered the trial accounted for? and were they
analysed in the groups to which they were randomised?

)his paper- Yes *omment-

No

Un'lear

.e randomly assigned /0!12/ patients ,ho had a re'ent a'ute 'oronary syndrome to re'ei&e the *E)P inhibitor dal'etrapib! at a dose of 344 mg daily! or pla'ebo! in addition to the best a&ailable e&iden'e-based 'are" =rom April 9441 through $uly 94/4! a total of /0!12/ patients ,ere enrolled at ><0 sites in 92 'ountries and ,ere in'luded in the intention-totreat population Patients ;0 years of age or older ,ho pro&ided ,ritten informed 'onsent ,ere eligible to parti'ipate if they had been hospitali5ed for an a'ute 'oronary syndrome 'hara'teri5ed by ele&ated 'ardia' biomarkers! ,ith symptoms of a'ute myo'ardial is'hemia! is'hemi' ele'tro'ardiographi' abnormalities that ,ere ne, or presumed to be ne,! or loss of &iable myo'ardium on imaging" Patients ,ithout ele&ated 'ardia' biomarkers ,ere eligible to parti'ipate if symptoms of a'ute myo'ardial is'hemia ,ere a''ompanied by ele'tro'ardiographi' 'hanges that ,ere ne, or presumed to be ne, and by additional e&iden'e of obstru'ti&e 'oronary disease" Patients ,ho had a myo'ardial infar'tion asso'iated ,ith per'utaneous 'oronary inter&ention ,ere also eligible" )here ,ere no e 'lusions on the basis of the HDL 'holesterol le&el? ho,e&er! patients ,ith serum trigly'eride le&els of ;44 mg per de'iliter (;"0 mmol per liter) or higher ,ere e 'luded" @ther e 'lusion 'riteria are listed in the Aupplementary Appendi ! a&ailable at NE$("org"
3. Were measures objective or were the patients and clinicians which treatment was being received? ept !blind" to

)his paper- Yes

No

Un'lear

*omment.e entered patients ,ho met the in'lusion 'riteria into a single-blind! pla'ebo run-in period to assess adheren'e! ensure that no e 'lusion 'riteria ,ere met! and allo, time for metaboli' steady state to be a'hie&ed after the inde a'ute 'oronary e&ent" After ; to /9 ,eeks of run-in! and no later than /9 ,eeks after the inde e&ent! 8ualifying patients ,ere randomly assigned! in a /-/ ratio! to re'ei&e dal'etrapib at a dose of 344 mg daily or mat'hing pla'ebo! ,ith randomi5ation stratified a''ording to 'ountry and status ,ith respe't to 'ardia' biomarker le&els (ele&ated or not ele&ated) at the time of the inde e&ent" The Result
#. $ow large was the treatment effect?

77 (7elati&e 7isk) B 4"491C4"49> B 4">3 77 D /! the treatment de'reases the risk of death" A77 (Absolute 7isk 7edu'tion) B 4!49>- 4!491 B 4!44/ )he absolute benefit of treatment is a 4!/: redu'tion in the death rate" 777 (7elati&e 7isk 7edu'tion) B 4"44/C4"49> B 4"4<; or <!;: )he treatment redu'ed the risk of death by <!;: relati&e to that o''urring in the 'ontrol group"

NN) (Number Needed to )reat) B in&erse of the A77 and is 'al'ulated as / C A77" /C 4!44/ B /444 .e ,ould need to treat /444 people for < years in order to pre&ent / death"

%. $ow precise was the estimate of the treatment effect?

Dal'etrapib had no signifi'ant effe't on the primary end point! ,hi'h o''urred in 1"<: of the patients in the dal'etrapib group and in 1"4: of the patients in the pla'ebo group (ha5ard ratio ,ith dal'etrapib! /"4;? >0: 'onfiden'e inter&al! 4">< to /"/3? P B 4"09) (=ig" 9)" Dal'etrapib also had no signifi'ant effe't on the rate of any 'omponent of the primary end point! on the rate of unanti'ipated 'oronary re&as'ulari5ation! or on the rate of death from any 'ause"
Will the results help me in caring for my patient? &'(ternal)alidity*Applicability+

Es my patient so different to those in the study that the results 'annot applyF

Ges! it is

Es the treatment feasible in my settingF Ges! it is .ill the potential benefits of treatment out,eigh the potential harms of treatment for my patientF Ges! it ,ill