Cost effectiveness analysis of a next generation risk assessment score for cardiovascular disease

Figures & data

Figure 1. Reclassification of intermediate risk group by strategy.

Figure 2. Markov model flow diagram. Flow diagram demonstrating the three treatment strategies outlined for a patient at intermediate risk of coronary heart disease (CHD): Current Guidelines; Current Practice at MESA; or MIRISK VP in MESA.

Table 1. Data included in the Markov model^a.

Parameters: Probabilities and risk characteristics of reclassification groups	Base-case value: Male (n = 129)^b	Base-case value: Female (n = 108)^b	Distribution	Data source	Reference
Intermediate risk group
n [Sample]	129	108	–	Validation cohort	Cross et al.19
n [Cohort]	998	943	–	Validation cohort (1)	Cross et al.19
Observed 5-year CHD risk [Cohort]	0.95	0.98	–	Validation cohort
Individuals not reclassified
n (%) [Sample]	44 (35)	35 (30)	–	Validation cohort	Cross et al.19
n (%) [Cohort]	348 (35)	284 (30)	–	Validation cohort (1)(2)	Cross et al.19
Observed 5-year CHD risk [Cohort]	0.96	0.98	–
Individuals reclassified to low-risk group
n (%) [Sample]	40 (36)	45 (47)	–	Validation cohort	Cross et al.19
n (%) [Cohort]	361 (36)	441 (47)	–	Validation cohort (1)(2)	Cross et al.19
Observed 5-year risk [Cohort]	0.98	0.99	–
Individuals reclassified to high-risk group
n (%) [Sample]	45 (29)	28 (23)	–	Validation cohort	Cross et al.19
n (%) [Cohort]	289 (28)	218 (23)	–	Validation cohort (1)	Cross et al.19
Observed 5-year CHD risk [Cohort]	0.91	0.96	–
CHD-related mortality after a CHD event
First year CHD-related mortality after a CHD event	0.03	0.03	Beta	Cohort study	Adabag et al.35
CHD-related mortality rate, after 1st year	0.012	0.012	–	–	–
RR of recurrent CHD event	1.5 (1.13–1.9)	1.5	Triangular	Cohort study	van Kempen et al.25
Statin effectiveness: RR on incident CHD, statins vs placebo	1.5 (1.13–1.9)	1.5 (1.13–1.9)	Normal	Meta-analysis	van Kempen et al.25
Anti-hypertensives effectiveness: RR on incident CHD, anti-hypertensives vs. placebo	0.85 (0.81–0.89)	1.5 (1.13–1.9)	Normal	Meta-analysis	van Kempen et al.25
Utilities
Utility (age-dependent)			–	–	Nyman et al.36
Ages 35–44	0.86	0.86
Ages 45–64	0.83	0.83
Ages 65–74	0.82	0.82
Ages 75+	0.76	0.76
Disutility due to CHD event	−0.10 (−0.13 to −0.08)	−0.16 (−0.2 to −0.12)	Triangular	Survey	van Kempen et al.25
Costs
Cost of MIRISK ($)	90	90	–	Aviir price	–
Cost of MIRISK VP ($)	1450 (800–1450)	1450 (800–1450)	–	Aviir price	–
First year cost of CHD event ($)	21,233 (17,196–25,207)	21,233 (17,196–25,207)	–	Cost study	van Kempen et al.25
Annual follow up post-CHD cost ($)	1330	1330	–	Cost study	van Kempen et al.25
Cost of statin per year^c	570 (160–760)	570 (160–760)	Triangular	Cost study, review	Pletcher et al.37, Consumer reports38
Cost of anti-hypertensives per year	936 (252–1624)	936 (252–1624)	Triangular	Modeling of survey data	Hong et al.39
Adherence (%)	70 (40–100)	70 (40–100)	Uniform	Expert opinion	van Kempen et al.25

^aThese values have been obtained from the MESA case-cohort sample using the cohort weights for events and non-events accounting for subjects with missing values.

^bPercentages have been rounded to closest integer value. Small differences between the sample and cohort percentages are due to the use and rounding of the cohort weights.

^cLow value based on $0.44/pill used from Pletcher et al.37. High value from consumer reports document using atorvastatin $63/month for 80 mg.

Table 2. Baseline demographics of study sample and cohort with CHD risk between 3.5–7.5% (5-year intermediate risk population based on a calibrated Framingham CHD risk score).

	Males (n = 129)		Females (n = 108)
Variable	Sample	Cohort	Sample	Cohort
Age (years)	63.89	62.99	65.33	64.84
Body Mass Index	27.56	27.40	30.21	30.08
Systolic blood pressure, mm Hg	123.08	123.65	137.28	136.62
Diastolic blood pressure, mm Hg	73.02	74.15	71.15	71.49
Total cholesterol, mg/dL	183.40	182.47	208.04	206.83
HDL cholesterol, mg/dL	44.12	43.67	49.66	48.76
LDL cholesterol, mg/dL	113.26	113.02	127.10	127.38
Statin use	16.28	12.40	0.22	0.20
Anti-hypertensive medication use	23.26	21.32	30.56	28.83
Smoking	16.28	16.28	12.04	11.92
Diabetes mellitus	14.73	13.11	14.81	12.29

Table 3. Probabilistic and univariate sensitivity analysis parameters and ranges.

Variable	Range assessed
Disutility, men	−0.13 to −0.08
Disutility, women	−0.20 to −0.12
MIRISK VP unit price	$800–$1450
Anti-hypertensive cost	$252–$1624
Probability of adherence to regimen	0.4–1.0
Cost of a CHD (First year)	$17,196–$25,207
Cost of statin per year	$160–$760

Table 4. Clinical effectiveness of strategies at the end of the simulation. Number of individuals in each category at the end of the simulation.

	Practice at MESA enrollment	Current guidelines	MIRISK VP in MESA
Reference Model	n [proportion]	n [proportion]	n [proportion]
(population size simulated = 50,000)
Non-CHD death	49,001 [0.98]	49,083 [0.982]	49,266 [0.99]
Death after 1st CHD	815 [0.02]	752 [0.02]	624 [0.01]
Death after subsequent CHD	123 [0.002]	104 [0.002]	55 [0.001]
Sensitivity analysis	n [SE]	n [SE]	n [SE]
(population size simulated = 20,000; sampling size = 500)	Proportion [SE]	Proportion [SE]	Proportion [SE]
Non-CHD death	19682.506 [2.485]	19700.754 [2.371]	19809.594 [1.472]
	0.984 [0.001]	0.985 [0.001]	0.99 [0.001]
Death after 1st CHD	270.374 [2.167]	255.48 [2.071]	172.988 [1.348]
	0.014 [0.001]	0.013 [0.001]	0.009 [0.001]
Death after subsequent CHD	47.112 [0.482]	43.756 [0.46]	17.408 [0.24]
	0.002 [0]	0.002 [0]	0.001 [0]

Table 5. Itemized total costs, life expectancy, QALYs, ICERs, and net monetary benefits within the base model (reference values) and under a sensitivity analysis^a.

							Incremental cost/QALY ($/QALY)
	Mean life expectancy (years)	Mean CHD cost ($)	Mean lifetime medication cost ($)	Total test cost at baseline ($)	Total lifetime costs ($)	Quality adjusted life expectancy (years)	Compared with practice at MESA enrollment	Compared with next best strategy	Net monetary benefits ($) (WTP = $50,000)
Results for reference values - Full cohort
Practice at MESA enrollment	18.73 (0.047)	3878.84 (45.68)	3018.66 (28.21)	–	6897.5 (54.95)	15.07 (0.04)	Reference		746,760.15 (1921.28)
Current Guidelines	18.74 (0.047)	3547.68 (43.80)	6620.48 (37.34)	–	10,168.16 (59.42)	15.12 (0.04)	71,455.97	71,455.97	745,778.08 (1920.61)
MIRISK VP in MESA	18.78 (0.048)	2513.62 (37.76)	6578.46 (37.03)	1540.00	10,632.08 (55.38)	15.24 (0.04)	22,895.04	3953.48	751,181.44 (1953.08)
Results under probabilistic sensitivity analysis - Full cohort
Practice at MESA enrollment	18.74 (0.004)	3792.78 (9.53)	2867.38 (43.05)	–	6660.16 (44.62)	15.09 (0)	Reference		747,768.26 (155.24)
Current Guidelines	18.75 (0.004)	3464.43 (9.70)	6174.71 (89.24)	–	9639.13 (87.42)	15.13 (0)	67,436.62	67,436.62	746,998 (165.88)
MIRISK VP in MESA	18.80 (0.003)	2438.97 (7.43)	6179.20 (90.13)	1220.03	9838.19 (88.58)	15.26 (0)	18,966.66	1613.32	752,968.17 (158.5)
Results for reference values - Age 65+ cohort
Practice at MESA enrollment	13.35 (0.034)	4318.87 (48.24)	3406.24 (27.81)	–	7725.11 (58.1)	10.54 (0.03)	Reference		519,070.99
Current Guidelines	13.35 (0.034)	4081.37 (47.00)	5944.61 (34.61)	–	10,025.98 (59.49)	10.56 (0.03)	115,690.52	115,690.52	517,764.53
MIRISK VP in MESA	13.40 (0.034)	2472.98 (37.14)	6823.11 (34.64)	1,540.00	10,836.09 (52.66)	10.68 (0.03)	21,212.33	6390.36	523,292.96
Results under probabilistic sensitivity analysis - Age 65+ cohort
Practice at MESA enrollment	13.37 (0.003)	4309.50 (11.45)	3263.97 (48.66)	–	7573.47 (50.81)	10.55 (0)	Reference		519,984.12 (117.88)
Current Guidelines	13.38 (0.003)	4071.16 (11.11)	5652.97 (82.70)	–	9724.12 (82.22)	10.57 (0)	100,695.96	100,695.96	518,901.36 (129.37)
MIRISK VP in MESA	13.41 (0.002)	2470.13 (7.91)	6482.37 (94.94)	1220.01	10,172.5 (93.35)	10.69 (0)	18,661.76	3802.61	524,348.61 (132.11)

^aAll calculations assume the time origin to be the time of test administration at subject enrolment.

n (SD).

Table 6. Univariate sensitivity analyses.

Variable	Range assessed	Optimal Decision
Disutility, men	−0.13 to −0.08	MIRISK VP most effective (not dominant)
Disutility, women	−0.20 to −0.12	MIRISK VP most effective (not dominant)
MIRISK VP unit price	$800–$1450	MIRISK VP most effective (not dominant)
Anti-hypertensive cost	$252–$1624	MIRISK VP most effective (not dominant)
Probability of adherence to regimen	0.4–1.0	MIRISK VP most effective (not dominant)
Cost of a CHD (First year)	$17,196–$25,207	MIRISK VP most effective (not dominant)
Cost of statin per year	$160–$760	MIRISK VP most effective (not dominant)

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