Assessment of clinical and economic impact of rivaroxaban plus aspirin vs. aspirin alone as a secondary prophylaxis in patients with chronic and symptomatic peripheral arterial disease in the United States

Figures & data

Table 1. Model inputs.

Inputs for Model	Aggregated Cohort	Subgroup analysis: patients with ≥1 high-risk factors^a
Patients Observed in the Optum Clinformatics Database, n	710,088	339,459
COMPASS	672,567 (95%)	315,068 (93%)
VOYAGER	37,521 (5%)	24,391 (7%)
Enrollees with chronic/symptomatic PAD in a Plan of One Million Members, n^b	15,651	7,482
Incidence rates per 100 person-years^c
Any MACE (include CV-related death)/MALE
COMPASS	8.9	10.5
VOYAGER	16.3	19.0
Major Bleeding
COMPASS	3.5	4.0
VOYAGER	8.2	9.0
Hazard Ratio (95% Confidence Interval) RIVA + ASA vs. ASA^d
Any MACE (include CV-related death)/MALE
COMPASS	0.69 (0.56–0.85)^eCitation14
VOYAGER	0.85 (0.76–0.96)^fCitation12
Major Bleeding
COMPASS	1.61 (1.12–2.31)^14
VOYAGER	1.43 (0.97–2.10)^12
Drug cost, WAC for 30-day supply, $^17
Rivaroxaban	387.45^g
Aspirin	1.01
Incremental Annual Healthcare Cost per Event, $
Any MACE/MALE	39,904.58^h Citation9,Citation18
Bleeding event w/o MACE/MALE	20,218.45^i Citation15,Citation18

Abbreviations. ASA, aspirin; CV, cardiovascular; MACE, major adverse cardiovascular event; MALE, major adverse limb event; PAD, peripheral artery disease; RIVA + ASA, Rivaroxaban 2.5 mg BID + aspirin; WAC, wholesale acquisition cost.

^aHigh-risk factors include heart failure, diabetes, renal insufficiency, and history of vascular disease affecting 2 or more vascular beds¹⁶.

^bTotal number of unique members in the Optum Clinformatics were 45,369,951 between January 1, 2010 to June 30, 2021.

^cDerived from the analysis of claims data from the Optum Clinformatics between January 1, 2010 to June 30, 2021; details of the analysis are provided in the supplementary material.

^dThe efficacy and safety of rivaroxaban plus aspirin versus aspirin alone in subgroups was assumed to be equivalent to the overall trial population.

^eHazard ratio reported for the key composite outcome - Cardiovascular death, stroke, myocardial infarction or major adverse limb event including a major amputation – in PAD¹⁴.

^fHazard ratio reported for primary efficacy outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or CV death¹².

^gReflects a 25% rebate to the published WAC price of $861 for a pack of 100 rivaroxaban tablets (2.5 mg each).

^h2016 US dollar values were inflated to 2022 values using a factor of 1.166255¹⁸.

ⁱ2019 US dollar values were inflated to 2022 values using a factor of 1.084967¹⁸.

Table 2. Base-case results for aggregated cohort.

Parameter	Patients with chronic or symptomatic PAD
	Treatment without rivaroxaban	Treatment with rivaroxaban		Net benefit (treatment with vs without rivaroxaban)^a
	Aspirin (N = 15,651)	Aspirin (N = 14,869)	Rivaroxaban + aspirin (N = 782)
Number of events
Any MACE/MALE, COMPASS, N	1319	1253	46	−20
Any MACE/MALE, VOYAGER, N	135	128	6	−1
Major bleeding, N	522	496	42	16
Cost, $
Any MACE/MALE, COMPASS	50,372,926	47,854,280	1,761,701	−756,945
Any MACE/MALE, VOYAGER	4,963,661	4,715,478	213,485	−34,698
Major bleeding	10,549,286	10,021,822	852,736	325,272
Drug acquisition	192,934	183,287	3,701,110	3,691,463
Total costs	66,078,806	62,774,866	6,529,032	3,225,092
Incremental outcomes, $
Cost per MACE/MALE avoided				150,278
Cost PMPM				0.27

Abbreviations. MACE, major adverse cardiovascular event; MALE, major adverse limb event; PAD, peripheral artery disease; PMPM, per member per month.

^aNegative value indicates benefit/savings due to rivaroxaban.

Table 3. Subgroup analysis results.

Parameter	Patients with chronic or symptomatic PAD + presence of any 1 or more risk factors of heart failure, diabetes, renal insufficiency, history of vascular disease affecting 2 or more beds
	Treatment without rivaroxaban	Treatment with rivaroxaban		Net benefit (treatment with vs without rivaroxaban)^a
	Aspirin (N = 7482)	Aspirin (N = 7108)	Rivaroxaban + aspirin (N = 374)
Number of events
Any MACE/MALE, COMPASS, N	729	693	25	−11
Any MACE/MALE, VOYAGER, N	102	97	4	−1
Major bleeding, N	283	269	23	9
Cost, $
Any MACE/MALE, COMPASS	27,621,484	26,240,410	968,344	−412,730
Any MACE/MALE, VOYAGER	3,712,211	3,526,601	159,967	−25,644
Major bleeding	5,730,264	5,443,751	463,098	176,585
Drug acquisition	92,232	87,621	1,769,323	1,764,711
Total costs	37,156,192	35,298,383	3,360,731	1,502,922
Incremental outcomes, $
Cost per MACE/MALE avoided				124,536
Cost PMPM				0.13

Abbreviations. MACE, major adverse cardiovascular event; MALE, major adverse limb event; PAD, peripheral artery disease; PMPM, per member per month.

^aNegative value indicates benefit/savings due to rivaroxaban.

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Data availability statement

The source data for this study is available online with the exception of data obtained from the Optum^® Clinformatics^® Data Mart. Restrictions apply to the Optum data, which were licensed by Janssen for this study. The Optum database can be licensed for a fee (https://www.optum.com/business/life-sciences/real-world-data/claims-data.html).