Nama: dr.

Damai Trilisnawati
NIM : 04082711822003
Bagian: Dermatologi dan Venereologi

1.1.Tabel PICO
Patient Problem Intervention Comparison Outcome
56 years old man Anti-hipertensive Natural remedy Lowering blood
with obesity, DM drug pressure
type 2, and
hypertension

1.2.Clinical Question: In patient with obesity, DM type 2, and hypertension, is anti-

hipertensive medication is more effective than natural remedy in lowering blood
pressure

1.3.Search term: Hypertension and drug and lowering blood pressure

1.4.Search

1.5.Abstract article

Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs.

discontinuations because of adverse drug events - meta-analyses of randomized trials

BACKGROUND:

Previous meta-analyses of randomized controlled trials (RCTs) of blood pressure (BP)-

lowering treatment provided overwhelming evidence that treatment markedly reduces
risk of cardiovascular outcomes in hypertensive patients. However, adverse events
associated with BP-lowering treatment have never been surveyed systematically.

OBJECTIVES:

Identifying among BP-lowering RCTs those reporting a common and meaningful index
of treatment-attributed adverse events, and describing the burden of these adverse events
accompanying the benefits of mortality and morbidity reduction induced by treatment.

METHODS:

The database consisted of the BP-lowering RCTs (active vs. placebo or less active
treatment) we have described (70 RCTs, 255 970 participants, 1 091 964 patient-years). A
common index of relevant adverse events was identified as permanent treatment
discontinuation attributed to treatment adverse events. Risk ratios and 95% confidence
intervals, standardized to a SBP/DBP reduction of 10/5 mmHg, of seven fatal and
nonfatal outcomes and of treatment discontinuations for adverse events were calculated
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(random-effects model). The relationships of outcome reductions and discontinuation

excess to SBP and DBP reductions were investigated by meta-regressions.

RESULTS:

Forty-four RCTs provided data on treatment discontinuations for adverse events and six
more on serious adverse events because of treatment (179 949 patients, 719 796 patient-
years). In these 50 RCTs, a significant 24% reduction of major cardiovascular event risk
was associated with a significant 89% increase in the risk of discontinuations (33 major
cardiovascular effects prevented and 84 excess discontinuations/1000 patients for 5
years). Metaregression analysis indicated that both outcome reductions and treatment
discontinuation excess were significantly related to the extent of SBP and DBP reduction,
but absolute treatment discontinuation excess disproportionally increased with larger BP
reductions than increase in outcome risk reduction. Furthermore, a standard SBP
reduction was found associated with a constant relative reduction, but a smaller absolute
reduction of cardiovascular events, and a greater relative excess of treatment
discontinuations when the achieved SBP was below 130 mmHg rather than in higher
ranges.

CONCLUSION:

The burden of adverse events associated with BP-lowering treatment should be

considered not to deny patients the overwhelming benefits of BP lowering, but whenever
the extent of the BP lowering or the BP target to be achieved are discussed.

1.6. Critical Appraisal

Are the results of this systematic review valid?

Is this a systematic review of randomised Yes

trials?

Does it include a methods section that Yes

describes:
a) finding and including all relevant trials?
b) assessing their individual validity?
Were the results consistent from study to Yes
study?

Were the individual patient data used in the Yes

analysis (or aggregate data)?
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Are the valid results of this systematic review important?

Translating odds ratios to NNTs:

The numbers in the body of the tables are the NNTs for the corresponding odds ratio at
that particular patient’s expected event rate (PEER).

1. When the odds ratio (OR) < 1

This table applies when a bad outcome is prevented by therapy.
OR < 1
0.9 0.8 0.7 0.6 0.5
2.09 a 104 69 52 41b
0.05
Patient’s 0.10 110 54 36 27 21
expected 0.20 61 30 20 14 11
event rate 0.30 46 22 14 10 8
(PEER) 0.40 40 19 12 9 7
0.50 38 18 11 8 6
0.70 44 20 13 9 6
101 c 46 27 18 12d
0.90

a The relative risk reduction (RRR) here is 10%

b The RRR here is 49%
c For any OR, NNT is lowest when PEER = 0.50
d The RRR here is 9%

2. When the odds ratio (OR) > 1

This table applies both when a good outcome is increased by therapy and when a
side-effect is caused by therapy.
OR > 1
1.1 1.2 1.3 1.4 1.5
0.05 212 106 71 54 43
Patient’s 0.10 112 57 38 29 23
expected 0.20 64 33 22 17 14
event rate 0.30 49 25 17 13 11
(PEER) 0.40 43 23 16 12 10
0.50 42 22 15 12 10
0.70 51 27 19 15 13
0.90 121 66 47 38 32
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Can you apply this valid, important evidence from a systematic review in caring for
your patient?

Do these results apply to our patient?

Is your patient so different from those in No
the study that its results cannot apply?
Is the treatment feasible in your setting? Yes
Are your patient’s values and preferences satisfied by the regimen and its
consequences?
Do you and you patient have a clear Yes
assessment of their values and preferences?
Are they met by this regimen and its Yes
consequences?

Should you believe apparent qualitative differences in the efficacy of therapy in some
subgroups of patients?—Only if you can say ‘yes’ to all of the following:

Do they really make biologic and clincal Yes

sense?
Is the qualitative difference both clinically Yes
(beneficial for some but useless or harmful
for others) and statistically significant?
Was this difference hypothesised before Yes
the study began (rather than the product of
dredging the data), and has it been
confirmed in other, independent studies?
Was this one of just a few subgroup Yes
analyses carried out in this study?
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2.
Meninggal Hidup
Eksperimen 20 180 200
Kontrol 30 170 200
50 350 400

2.1. EER = a/a+b = 20/200 = 10%

2.2. CER = c/c+d = 30/200 = 15%

2.3. ARR = CER-EER = 15-10 = 5%

2.4. RRR = CER-EER/CER = (15-10)/15 = 33%

2.5. RR = EER/CER = 10/15= 0.66

2.6. NNT = 1/ARR = 1/0.05 = 20

2.7. Cara lain menghitung RRR= 1-RR x 100% = 1-0.66 x 100% = 34%

2.8. Kesimpulan = Dari perhitungan diatas didapatkan RR 0.66 yang berarti kemungkinan orang yang
memakai obat eksperimen untuk meninggal lebih rendah 0.6 kali dari orang memakai obat control.
Penurunan resiko orang meninggal dalam pemakaian obat eksperimen sebesar 33% disbanding
memakai obat control. Nilai NNT didapatkan 20 yang berarti dibutuhkan 20 orang yang diobati pakai
obat eksperimen untuk mencegah kematian 1 orang.

3.

Remisi Tidak
Stent +CAD 40 160 200
ASA+atorvastatin 30 170 200
70 330 400

3.1. EER = a/a+b = 40/200 = 20%

3.2. CER = c/c+d = 30/200 = 15%

3.3. RBI = EER-CER/CER = (20-15)/15 = 0.33 = 33%

3.4. ABI = EER-CER = 20-15 = 5%

3.5. RR = EER/CER = 20/15= 1.33

3.6. NNT = 1/ABI = 1/0.05 = 20

3.7. Cara lain menghitung RBI= RR-1 x 100% = 1.33-1 x 100% = 33%
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3.8. Kesimpulan = Dari perhitungan diatas didapatkan RR 1.33 yang berarti kemungkinan orang yang
memakai stent+CAD untuk mengalami remisi lebih tinggi 1.33 kali dari orang memakai
ASA+atorvastatin. Peningkatan remisi MCI pemakaian stent+CAD sebesar 33% dibandingkan
pemakaian ASA+atorvastatin. Nilai NNT didapatkan 20 yang berarti dibutuhkan 20 orang yang
diobati pakai stent+CAD agar 1 orang memperoleh manfaat pengobatannya.

4. NTT pada trial effectiveness menghitung jumlah orang yang harus diobati sehingga ada 1 orang
yang mendapat manfaat dari pengobatan tersebut. NNT pada trial adverse effect menghitung
jumlah orang yang diberi obat sehingga ada 1 orang yang mendapat efek samping dari pengobatan.

5.

Totalkolesterol1
100

80
Sensitivity

60
Sensitivity: 60,0
Specificity: 38,6
Criterion : >168,205
40

20

0
0 20 40 60 80 100
100-Specificity

5.2.
Criterion Sensitivity Specificity +LR -LR +PV -PV
≥99,906 100,00 0,00 1,00 28,3
>121,337 100,00 15,35 1,18 0,00 31,8 100,0
>123,575 98,82 15,35 1,17 0,077 31,6 97,1
>127,064 98,82 19,07 1,22 0,062 32,6 97,6
>134,78 95,29 19,07 1,18 0,25 31,8 91,1
>143,571 95,29 23,26 1,24 0,20 32,9 92,6
>144,715 94,12 23,26 1,23 0,25 32,7 90,9
>149,288 94,12 28,84 1,32 0,20 34,3 92,5
>151,694 83,53 28,84 1,17 0,57 31,7 81,6
>155,346 83,53 33,02 1,25 0,50 33,0 83,5
>155,504 80,00 33,02 1,19 0,61 32,1 80,7
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>157,941 80,00 34,88 1,23 0,57 32,7 81,5

>158,498 75,29 34,88 1,16 0,71 31,4 78,1
>160,255 75,29 36,28 1,18 0,68 31,8 78,8
>164,366 67,06 36,28 1,05 0,91 29,4 73,6
>165,692 67,06 37,21 1,07 0,89 29,7 74,1
>167,936 60,00 37,21 0,96 1,08 27,4 70,2
>171,806 60,00 45,12 1,09 0,89 30,2 74,0
>174,571 58,82 45,12 1,07 0,91 29,8 73,5
>180,989 58,82 48,37 1,14 0,85 31,1 74,8
>181,007 55,29 48,37 1,07 0,92 29,7 73,2
>182,982 55,29 51,16 1,13 0,87 30,9 74,3
>183,114 48,24 51,16 0,99 1,01 28,1 71,4
>187,018 48,24 53,49 1,04 0,97 29,1 72,3
>189,943 40,00 53,49 0,86 1,12 25,4 69,3
>194,242 40,00 59,07 0,98 1,02 27,9 71,3
>194,439 32,94 59,07 0,80 1,14 24,1 69,0
>197,234 32,94 63,26 0,90 1,06 26,2 70,5
>200,242 27,06 63,26 0,74 1,15 22,5 68,7
>204,034 27,06 65,58 0,79 1,11 23,7 69,5
>207,478 25,88 65,58 0,75 1,13 22,9 69,1
>213,439 25,88 68,37 0,82 1,08 24,4 70,0
>214,4 22,35 68,37 0,71 1,14 21,8 69,0
>219,686 22,35 76,28 0,94 1,02 27,1 71,3
>224,248 18,82 76,28 0,79 1,06 23,9 70,4
>235,008 18,82 86,98 1,45 0,93 36,4 73,0
>236,515 17,65 86,98 1,36 0,95 34,9 72,8
>236,748 17,65 87,91 1,46 0,94 36,6 73,0
>240,69 16,47 87,91 1,36 0,95 35,0 72,7
>241,407 16,47 91,16 1,86 0,92 42,4 73,4
>245,422 14,12 91,16 1,60 0,94 38,7 72,9
>256,018 14,12 93,95 2,33 0,91 48,0 73,5
>256,713 11,76 93,95 1,95 0,94 43,5 72,9
>263,534 11,76 95,35 2,53 0,93 50,0 73,2
>265,139 4,71 95,35 1,01 1,00 28,6 71,7
>278,663 4,71 97,67 2,02 0,98 44,4 72,2
>288,976 1,18 97,67 0,51 1,01 16,7 71,4
>346,228 1,18 98,60 0,84 1,00 25,0 71,6
>398,626 0,00 98,60 0,00 1,01 0,0 71,4
>398,706 100,00 98,3 - 100,0 1,00

5.3. Kesimpulan

Pada nilai totalkolesterol1 yang rendah, nilai sensitifitas semakin tinggi dan spesifisitas semakin
rendah. Hal ini berarti pada totalkolesterol rendah, kemampuan untuk mengidentifikasi pasien
dengan PJK lebih tinggi, namun banyak positif palsu yang didapatkan. Pada nilai totalkolesterol yang
tinggi, nilai spesifitas tinggi, yang berarti kemampuan mengidentifikasi PJK diakibatkan
totalkolesterol semakin tinggi dibandingkan penyebab lainnya.