Publications & year

Question 1

Fralick

Publication
Year
General findings

Answer 1

AIM (Annals of Internal Medicine)
2020
Almost 100k patients Optum database -
Less stroke and less GIB with apixaban compared to rivaroxaban

Question 2

Hohnloser (First study)

Publication
Year
General findings

Answer 2

Eur Heart J - 2012 (Aristotle Pre-specified sub)
SCR>2.5 or CrCl <25
Stoke/SE rate was more than double if you had impaired renal function
No significant interaction between normal and impaired renal function
Impaired renal function retained same ARISTOTLE benefits as normal renal function

Question 3

AUGUSTUS

Publication, year, general findings

Answer 3

Apixaban vs Warfarin in patients also taking a P2Y inhibitor with or without ASA s/p PCI or recent ACS

Primary outcome = Time to first ISTH Major or CRNM bleeding events

Results:
• 31% reduction in primary outcome with apixaban compared to warfarin (superior) at 6 months
• 17% reduction in death+hospitalization with apixaban (primarily driven by reduction in all-cause hospitalization)
• Regarding ASA vs placebo, there were significantly more primary endpoint events in the ASA group, regardless of SCr
• Renal:
○ No differences between SCr <1.5 and SCr ≥1.5 in primary outcome

Conclusion:
Apixaban showed significantly less bleeding and fewer deaths or hospitalizations. There was a similar rate of death or ischemic events between apixaban and warfarin

Question 4

Alexander

Publication
Year
General findings

Answer 4

JAMA Cardiol 2016

What if you had ONLY ONE of the 3 ABC criteria?

	○ Apixaban was consistently associated with numerically lower risk of major bleeding across the spectrum of low weight, advanced age, and renal dysfunction
	○ Apixaban should be the preferred agent over warfarin in patients with only one dose-reduction criterion

Question 5

Hijazi second study

Publication, year

General findings

Answer 5

Renal function subanalysis of AUGUSTUS - Circulation 2021

Apixaban compared to warfarin - patients had lower rates of all 3 outcomes (ISTM major, CRNM bleeding, death/hospitalization/ischemic events ACROSS GFR categories

Question 6

Hijazi first study

Publication, year

General findings

Answer 6

JAMA Cardiol 2016

Subanalysis of ARISTOTLE

	○ Lower relative risk of stroke/SE, ischemic, or unspecified stroke, and major bleeding with apixaban compared to warfarin, but the confidence intervals cross 1.0 except for major bleeding in patients with GFR <50.  And the lower the GFR, the more pronounced this is with all endpoints.
	○ Treatment with apixaban compared to warfarin had no effect on renal function.

Question 7

Stanifer

Publication, year, general findings

Answer 7

American Society of Nephrology poster 2017
ARISTOTLE sub

Safety CrCl between 25-30

	○ For these patients, major bleeding occurred more often with warfarin compared to apixaban (HR 0.34)

Question 8

AVERROES

Publication, year, general findings

Answer 8

NEJM 2011

• Apixaban vs ASA in NVAF stroke prevention in patients who failed or have demonstrated or were expected to be unsuitable for VKAs

• N = 5,599 multinational
• Stopped early due to significant reduction in stroke and systemic embolism for apixaban compared to ASA without significant increase in major bleeding
	○ Treatment benefit >4 standard deviations in favor of apixaban
	○ Median follow up 1.1 years
	○ Fewer patient in apixaban group D/C study drug before end of study

Question 9

ARISTOTLE

Publication, year, general findings

Answer 9

NEJM 2011

21-31-11

21% reduction in stroke/SE with apix compared to warfarin
31% reduction in ISTH major bleeding/CRNM bleeding
11% reduction in all-cause mortality

Question 10

Amin

Answer 10

Current Medical Research and Opinion
2017

Medicare claims

• Results:
	○ Apixaban vs warfarin
		§ ALL endpoints statistically favor Apixaban tremendously
	○ Apixaban vs dabigatran
		§ All endpoints statistically favor Apixaban except:
			□ Hemorrhagic stroke, SE, ICH, other bleeding (BUT all point estimates favor apixaban except hemorrhagic stroke)
		§ All endpoints statistically favor Apixaban except:
			□ Ischemic stroke (but point estimate favors apixaban)
• Conclusions:
	○ Apixaban was associated with significantly lower all-cause health care costs as well as major-bleeding-related medical costs
	○ Costs: all-cause total health care costs -  per patient per month (apixaban statistically lower than all other 3) - 
		§ Apixaban = $3060-$3183
		§ Rivaroxaban = $3,878
		§ Warfarin = $3,577
		§ Dabigatran = $3,217