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The abstract shown on the left applies to the next 3 items

Title:
Rivaroxaban in Patients with a Recent Acute Coronary Syndrome
Hypothesis:
Does inhibition of factor Xa with low-dose rivaroxaban improve
c ardiovascular outcomes in patients with a recent acute coronary
syndrome?
Methods:
Design: Randomized clinical trial (Phase 3)
Blinding: Double-blind, placebo-controlled trial
Follow-up: Mean duration of treatment with a study drug was 13.1
months.
Setting: Multicenter (766 sites in 44 countries)
Patients: The study included patients (~ 18 years of age) who had
presented w ith symptom s suggestive of an acute coronary syndrome
and in w hom an ST segment elevation m yocardial infarction (STEM!),
a non-ST -segment elevation m yocardial infarction (NSTEMI), or
unstable angina had been diagnosed .
Intervention: Patients w ere random ly assigned in a 1: 1: 1 fashion to
twice-daily administration of either 2.5 m g or 5.0 mg of rivaroxaban or
placebo.
Item 1 of 3
A 62-year-old African American man with a history of
dys lipidemia and type 2 diabetes mellitus comes to the
emergency department with severe substernal chest pain and
diaphoresis that began two hours ago. His electrocardiogram
(EGG) shows ST segment elevation in leads V1 to V4. He was
taken to the cardiac catheterization lab and a complete
occlusion of the mid left anterior descending artery (LAD) was
diagnosed. A drug-eluting stent was placed in the LAD with
complete restoration of flow, and the patient was started on
aspirin and clopidogrel. On the third day of hospitalization, the
option of adding rivaroxaban was discussed with the patient.
He asks about the benefits and risks of the added therapy.
Based on the research abstract, which of the following would
be the best measure of the net clinical benefit of rivoraxaban?
r A. All-cause m ortality and intracranial bleeding
r B. Com bined prim ary efficacy end-point
r C. Death from cardiovascular causes
r D. Death from m yocardial infarction
r E. Intracranial and fatal bleeding

Outcome measures: The primary efficacy end point w as a

composite of death from cardiovascular causes, m yocardial
infarction, or stroke. The primary safety end point was TIMI
(Thrombolysis In Myocardial Infarction) bleeding not related to
coronary-artery bypass grafting (CABG).

~~R_e_s_u_IG
__: ____________________________________ ___ J ~
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A total of 15,526 pat1ents underwent random1zat1on. Pat1ents w ere

randomly assigned to receive 2.5 mg of rivaroxaban (5174 patients), The abs1ract show n on the left applies to the next 3 items
5.0 mg of rivaroxaban (5176), or placebo (5176). Haz ard ratios (HR)
and their associated 95% confidence intervals are listed below Item 1 of 3
Rivaroxaban Rivaroxaban
Rivaroxaban A 62-year-old African American man w ith a history of
2.5 mg Twice 5 mg Twice
Combined dyslipidemia and type 2 diabetes mellitus comes to the
Dailyvs. Dailyvs.
vs. Placebo emergency department w ith severe substernal chest pain and
Placebo Placebo
diaphoresis that began two hours ago. His electrocardiogram
Primary efficacy (ECG) show s ST segment elevation in leads V1 to V4. He w as
end point of taken to the cardiac catheterization lab and a complete
death from occlusion of the mid left anterior descending artery (LAD) w as
cardiovascular 0.84 0.85 0.84 diagnosed. A drug-eluting stent w as placed in the LAD w ith
causes, (0.72- 0.97) (0.73-0.98) (0.74 to 0.96) complete restoration of flow , and the patient w as started on
myocardial aspirin and clopidogrel. On the third day of hospitalization, the
infarction, or option of adding rivaroxaban w as discussed w ith the patient.
stroke He asks about the benefits and risks of the added therapy.
Based on the research abstract, w hich of the follow ing w ould
Death from
0.66 0.94 0.80 be the best measure of the net clinical benefit of rivoraxaban?
cardiovascular
(0.51-0.86) (0.75-1.20) (0.65-0.99)
causes
Death from
r A. All-cause mortality and intracranial bleeding
0.90 0.79 0.85
myocardial
(0.75-1.09) (0.65-0.97) (0.72-1 .00)
r B. Combined primary efficacy end-point
infarction r C. Death from cardiovascular causes
Death from 1.13 1.34 1.24 r D. Death from m yocardial infarction
Stroke (0.74-1 .73) (0.90-2.02) (0.86-1.78)
r E. Intracranial and fatal bleeding
Death from any
cause,
myocardial
0.83 0.84 0.84
infaction, or
(0.72 - 0.97) (0.73 - 0.98) (0.74- 0.95)
stroke-
seconda ry end
point
TIMI major
I
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II
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---------------------------------
I D ea th f rom any
cause, The abstract shown on the left applies to the next 3 items
myocardial
0.83 0.84 0.84
infaction, or Item 1 of 3
(0.72- 0.97) (0.73- 0.98) (074 - 0.95)
stroke-
secondary end A 62-year-old African American man with a history of
point dyslipidemia and type 2 diabetes mellitus comes to the
TlMI major emergency department with severe substernal chest pain and
bleeding not 3.46 4.47 diaphoresis that began two hours ago. His electrocardiogram
3.96
associat ed with (2.08-5.77) (2.71-7.36) (2.46--6.38) (ECG) shows ST segment elevation in leads V1 to V4. He was
CAB G taken to the cardiac catheterization lab and a complete
occlusion of the mid left anterior descending artery (LAD) was
TlM I minor 1.62 2.52 2.07 diagnosed. A drug-eluting stent was placed in the LAD with
bleed ing (0.92-2.82) (1 .50-4.24) (1 .27-3.37) complete restoration of flow, and the patient was started on
TlM I bleed ing aspirin and clopidogrel. On the third day of hospitalization, the
1.79 2.39 2.09 option of adding rivaroxaban was discussed with the patient.
requiri ng
(1 .55-2.07) (2.08-2.75) (1 .83-2.38) He asks about the benefits and risks of the added therapy.
med ical atte ntion
Based on the research abstract, which of the following would
Intracra nial 2.83 3.74 3.28 be the best measure of the net clinical benefit of rivoraxaban?
hemo rrhage (1.02-7.86) (1.39-10.07) (1.28- 8.42)

Fata l bleeding
0.67 1.72 1 .19~ r A. All-cause mortality and intracranial bleeding
(0.24- 1.89) (0.75-3.92) (0.54- 2.59)
r B. Combined primary efficacy end-point
Conclusion : r C. Death from cardiovascular causes
In patients with a recent acute coronary syndrome, rivaroxaban r D. Death from myocardial infarction
reduced the risk of the composite end point of death from
cardiovascular causes, myocardial infarction, or stroke. r E. Intracranial and fatal bleeding

Funding Source: Funded by Johnson & Johnson and Bayer

Healthcare; ATLAS ACS 2-TIMI 51 ClinicaiTrials.gov number,
NCT00809965)

Structured abstract is based on: N EngI J Med. 2011 Nov 13. Epub
ahead of print.
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Title: Item 2 of 3
Rivaroxaban in Patients w ith a Recent Acute Coronary Syndrome
In the research paper, it is described in the statistical methods
Hypothesis: that the analysis w as performed using an 'intention-to-treat'
Does inhibition of factor Xa w ith low -dose rivaroxaban improve approach. The purpose of such an approach is most likely
cardiovascular outcomes in patients w ith a recent acute coronary w hich of the follow ing?
syndrome?

Methods:
r A. Decrease the placebo effect
Design. Randomized clinical trial (Phase 3) r B. Eliminate observer bias
Blinding: Double-blind, placebo-controlled trial r C. Enhance external validity
r D. Preserve randomization
Follow-up: Mean duration of treatment w ith a study drug w as 13. 1
months. r E. Reduce type II errors
Setting: Multicenter (766 sites in 44 countries)

Patients: The study included patients (~

18 years of age) w ho had
presented w ith symptoms suggestive of an acute coronary syndrome
and in w hom an ST segment elevation m yocardial infarction (STEMI),
a non- ST-segment elevation m yocardial infarction (NSTEMI), or
unstable angina had been diagnosed.

Intervention: Patients w ere randomly assigned in a 1: 1: 1 fashion to

twice-daily administration of either 2.5 mg or 5.0 mg of rivaroxaban or
placebo.

Outcome measures: The primary efficacy end point w as a

composite of death from cardiovascular causes, m yocardial
infarction, or stroke. The primary safety end point w as TIMI
(Thrombolysis In Myocardial Infarction) bleeding not related to
coronary-artery bypass grafting (CABG).

-'~R_e_s_u_l_ts_: ________________________________________~ ~
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Title: Item 3 of 3
Rivaroxaban in Patients w ith a Recent Acute Coronary Syndrome
After a pharmaceutical drug is approved by the Food and Drug
Hypothesis: Administration (FDA), phase IV or postmarketing surveillance is
Does inhibition of factor Xa w ith low -dose rivaroxaban improve conducted to detect fatal and serious side effects. The failure
cardiovascular outcomes in patients w ith a recent acute coronary to detect such events in earlier phases of clinical testing is
syndrome? most likely due to w hich of the follow ing?

Methods:
r A. Biased allocation of patients
Design. Randomized clinical trial (Phase 3)
r B. Hidden confounders
Blinding: Double-blind, placebo-controlled trial
r C. Inadequate pow er
Follow-up: Mean duration of treatment w ith a study drug w as 13. 1 r D. Measurement bias
months.
r E. Use of placebo
Setting: Multicenter (766 sites in 44 countries)

Patients: The study included patients (~

18 years of age) w ho had
presented w ith symptoms suggestive of an acute coronary syndrome
and in w hom an ST segment elevation m yocardial infarction (STEMI),
a non- ST-segment elevation m yocardial infarction (NSTEMI), or
unstable angina had been diagnosed.

Intervention: Patients w ere randomly assigned in a 1: 1: 1 fashion to

twice-daily administration of either 2.5 mg or 5.0 mg of rivaroxaban or
placebo.

Outcome measures: The primary efficacy end point w as a

composite of death from cardiovascular causes, m yocardial
infarction, or stroke. The primary safety end point w as TIMI
(Thrombolysis In Myocardial Infarction) bleeding not related to
coronary-artery bypass grafting (CABG).

-'~R_e_s_u_l_ts_:________________________________________~ ~
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A study examines the role of different biomarkers in the early diagnosis of acute coronary syndrome. The
follow ing receiver-operating characteristic (ROC) curves w ere obtained for different biomarkers upon
participants' initial symptom presentation in the emergency department (the X marks the 99th percentile cutoff
point for the corresponding biomarker).

Receiver operating characteristic (ROC) curve

1.oT------::::::;;;;;:::;~;;==~:::::~
,.
/
/
/
/
0.8 /
/
/
/
/
/
0.6
/
/
/
/
/
0.4 /
/
/
/
/ Biomarker 1
/ Biomarker 2
0.2 / Biomarker 3
/ Biomarker 4

/
/
. -- Reference line

/
_______________. /
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0.6

" "
" "
0.4
" "
" "
" " Biomarker 1
Biomarker 2
0.2
" " Biomarker 3

" " . --
Biomarker4
Reference line

"
""
0.0~--------r--------r------~--------r-------~

0.0 0.2 0.4 0.6 0.8 1.0

1 - Specificity
@USMLEWorld, UC

Based on the study results and assuming the differences are statistically significant, which of the following
99th percentile cutoff points can best exclude acute coronary syndrome during initial symptom presentation in
the emergency department?

r A. Biomarker 1

r B. Biomarker 2

r C. Biomarker 3

r D. Biomarker 4