The IMPact of untReated nOn-Valvular atrial fibrillation on short-tErm clinical and economic outcomes in the US Medicare population: the IMPROVE-AF model

Figures & data

Figure 1. Population and intervention mix in base case and hypothetical scenario analyses.

Table 1. Model input parameters and values.

Parameter	Value for Model	Reference
Population Inputs
Starting population	51,300,000	CMS 2018
Prevalence of NVAF by age stratification	65–69: 4.04%	Turakhia 2018
	70–74: 6.26%
	75–79: 9.48%
	80–84: 12.37%
	85+: 14.28%
Proportion eligible for anticoagulation	96.4%	Marzec 2017
Proportion of patients treated with OACs (assumed the same for both high and moderate risk):
Base case scenario	49%	Munir 2021
Hypothetical scenario	54% (49% + absolute 5% increase)	Assumption
Among patients treated with OACs, proportion treated with (assumed same for base case and primary hypothetical scenario):
DOACs	High risk: 65%	Mazurek 2017
	Moderate risk: 76%
Warfarin	High risk: 35%	Mazurek 2017
	Moderate risk: 24%
Proportion of patients by CHA2DS2-VASc score	CHA2DS2-VASc score >2 (high risk): 91.1%	Hsu 2016
	CHA2DS2-VASc score = 1 (moderate risk): 8.9%
Clinical Inputs
Annual risk of ischemic stroke by risk categorization, age 65–84	CHA2DS2-VASc score > 2 (high risk): 4.6%	Friberg 2012, Lip 2010, Singer 2013
	CHA2DS2-VASc score = 1 (moderate risk): 0.6%
Annual risk of ischemic stroke by OAC exposure,   age 85+	6.3% (no OAC)	Patti 2017
	4.3% (warfarin)
Mortality rates by event	5.6% (ischemic stroke)	Sussman 2013
	23.1% (hemorrhagic stroke)
Treatment rates by class and stroke risk group	High risk: 28% warfarin, 53% DOAC, 19% neither	Mazurek 2017
	Moderate risk: 15% warfarin, 48% DOAC, 37% neither
Ischemic stroke, DOACs vs. warfarin	1.00 (relative risk)	Ruff 2014
Hemorrhagic stroke, DOACs vs. warfarin	0.49 (relative risk)	Ruff 2014
GI bleed, DOACs vs. warfarin	1.25 (relative risk)	Ruff 2014
Ischemic stroke, warfarin vs. baseline (untreated/aspirin)	0.59 (crude rate ratio)	Go 2003
Annual risk of hemorrhagic stroke, warfarin population	0.4%	Lip 2018
Annual risk of GI bleed, warfarin population	0.57% (based on 0.64% annualized risk of all extra-cranial hemorrhages, 89% of which were GI bleeds)	Fang 2006
Annual risk of GI bleed, untreated population	0.67% (based on 0.75% annualized risk of all extra-cranial hemorrhages, 89% of which were GI bleeds)	Fang 2006
Economic Inputs
Cost of warfarin treatment (1 year)	$492	Wang 2020
Cost of DOAC treatment (1 year)	$5,338	CMS 2018, Lip 2018
Cost of ischemic stroke	$18,465 (fatal stroke; 1-time cost of ischemic stroke)	Patel 2014
	$98,339 (non-fatal stroke; (1-time cost of moderate to severe ischemic stroke + 11 * 1-month cost of moderate to severe ischemic stroke)
Cost of hemorrhagic stroke	$52,021 (fatal stroke; 1-time cost of hemorrhagic stroke)	Patel 2014
	$136,419 (non-fatal stroke; 1-time cost of hemorrhagic stroke + 11 * 1-month cost of hemorrhagic stroke)
Cost of GI bleeding event	$8,366 (median 2010 payment for DRG 378 [GI bleed with complication])	Patel 2014
Daily work hours	1.05 (age 65–74)	BLS
	0.49 (age 75+)
Average hourly wage	$29.47	BLS
Hospital days per stroke	15	Thygesen 2009
Hospital days per GI bleed	6	Fanikos 2005, Charlton 2018
Caregiver costs per stroke survivor	$6,186	Joo 2014

Abbreviations. BLS, Bureau of Labor Statistics; DOAC, direct oral anticoagulant; GI, gastrointestinal; OAC, oral anticoagulant; NVAF, non-valvular atrial fibrillation.

Note. All costs, with the exception of warfarin plus INR monitoring costs, were inflated to 2020 USD using the medical care component of the Consumer Price Index (CPI). The annual cost of warfarin plus INR monitoring was not inflated to 2020 USD, and remained in 2018 USD, given (1) the wide variation of these costs in the current literature and (2) the close approximation of our value in 2018 USD to the average of inflated values in the literature.

Table 2. Annual clinical and economic outcomes for the overall Medicare population and 85+ subgroup, presented for the base case and hypothetical scenario analyses.

	Overall Medicare Population			85+ Subgroup
	Base Case Scenario	Hypothetical Scenario	Difference (Hypothetical minus Base Case)	Base Case Scenario	Hypothetical Scenario	Difference (Hypothetical minus Base Case)
Total CMS Medicare Population	51,300,000			6,669,000
Counts of Patients Diagnosed with NVAF and Eligible for Anticoagulation	3,985,087			918,049
Counts of treated patients
Total	1,952,693	2,151,947	199,255	449,844	495,747	45,902
High risk	1,889,624	2,082,442	192,819	449,844	495,747	45,902
Moderate risk	63,069	69,505	6,436	0 (all patients age 75+ are considered high risk)
Clinical outcomes, per year
Number of stroke events	166,657	163,093	−3,564	50,961	50,076	−885
Number of ischemic stroke events	157,466	153,761	-3,705	48,840	47,922	−918
Number of hemorrhagic stroke events	9,191	9,332	141	2,121	2,153	33
Number of gastrointestinal bleeds	26,566	26,552	−14	6,118	6,114	−3
Number of deaths	10,941	10,766	−175	3,225	3,181	−44
Direct economic outcomes, per year
Cost of stroke events	$15,797,452,618	$15,467,655,544	-$329,797,074	$4,832,394,084	$4,750,052,249	−$82,341,834
Cost of ischemic stroke events	$14,722,833,827	$14,376,571,281	-$346,262,546	$4,584,451,683	$4,498,277,779	−$86,173,904
Cost of hemorrhagic stroke events	$1,074,618,791	$1,091,084,263	$16,465,472	$247,942,401	$251,774,470	$3,832,069
Cost of gastrointestinal bleeds	$222,241,518	$222,127,024	-$114,494	$51,178,986	$51,150,666	-$28,320
Cost of NVAF-related pharmacy care	$7,144,877,023	$7,873,946,107	$729,069,084	$1,638,229,584	$1,805,395,868	$167,166,284
Total direct costs	$23,164,571,159	$23,563,728,675	$399,157,516	$6,521,802,654	$6,606,598,783	$84,796,129
PMPM budget impact			$0.65			$0.14
Indirect economic outcomes, per year
Patient
Days lost due to stroke	2,499,854	2,446,395	−53,458	764,412	751,133	−13,279
Productivity costs due to stroke	$51,070,509	$49,978,384	-$1,092,124	$11,038,335	$10,846,580	-$191,755
Days lost due to gastrointestinal bleeds	159,396	159,314	−82	36,707	36,686	−20
Productivity costs due to gastrointestinal bleeds	$956,375	$955,882	−$493	$220,239	$220,117	-$122
All patient productivity costs	$52,026,883	$50,934,266	-$1,092,617	$11,258,574	$11,066,698	-$191,876
Caregiver
Caregiver costs due to nonfatal stroke	$963,182,744	$942,220,240	−$20,962,505	$295,271,241	$290,066,528	−$5,204,713
Total indirect costs	$1,015,209,627	$993,154,505	−$22,055,122	$306,529,815	$301,133,226	−$5,396,589
Combined Direct and Indirect Costs, per year	$24,179,780,786	$24,556,883,180	$377,102,394	$6,828,332,469	$6,907,732,009	$79,399,540

Abbreviations. NVAF, non-valvular atrial fibrillation; PMPM, per-member per-month.

Figure 2. Model structure diagram. Abbreviations. DOAC, direct oral anticoagulant; NVAF, non-valvular atrial fibrillation; US, United States.

Figure 3. Annual clinical outcomes for the overall Medicare population, presented for the base case and hypothetical scenario analyses.

Figure 4. Annual economic outcomes for the overall Medicare population from the societal perspective, presented for the base case and hypothetical scenario analyses.

Figure 5. Sensitivity analysis results for the overall Medicare population from the payer perspective, presented as PMPM. Abbreviations. BI, budget impact; DOAC, direct oral anticoagulant; NVAF, non-valvular atrial fibrillation; PMPM, per-member per-month; WAC, wholesale acquisition cost.