Economic and healthcare resource utilization assessments of PET imaging in Coronary Artery Disease diagnosis: a systematic review and discussion of opportunities for future economic evaluations

Figures & data

Table 1. Description of eligibility criteria.

Study Parameter	Description of Eligibility Criteria
Population	Patients with suspected or confirmed CAD
Intervention	PET-MPI used for the detection of CAD with CA or FFR as the reference/gold standard
Comparator	SPECT-MPI used for the detection of CAD with CA or FFR as the reference/gold standard
Outcomes	Economic (e.g. cost-effectiveness, utilization), healthcare resource use (e.g. repeated testing, coronary angiography, revascularization [CABG or PCI], hospitalization visits), cardiac events (e.g. MI, CD)
Study Design	All individual clinical studies (single arm, comparative, observational) and economic evaluations
Region	Studies conducted in United States, Canada, United Kingdom, France, Finland, Germany, Switzerland, Spain, Italy, Denmark, and Japan.
Date	2012 to Present

Abbreviations: CA, coronary angiography; CABG, coronary artery bypass graft; CAD, coronary artery disease; CD, cardiac death; ECHO, echocardiography; FFR, fractional flow reserve; MPI, myocardial perfusion imaging; PCI, percutaneous coronary intervention; PET, positron emission tomography; SPECT, single-photon emission computed tomography.

Figure 1. Study identification, screening, and inclusion PRISMA diagram.

Table 2. Common characteristics and variability of included economic studies.

Author, Year	Study Type Duration PET Radiotracer	Population	Outcome Parameters			Cost parameters	Limitations	Economic Results
			HCRU (CA, revasc.)	Cardiac Events (MI, CD)	Diagnostic performance Linkage to HCRU and cardiac events
Comparative Studies (PET-MPI vs. SPECT-MPI)
Mimouni, 2023^58	CEA 1-year ^82Rubidium	Suspected CAD Female: 46.1% Diabetes: 77% Grouped by pCAD: PTP > 15%	CA^a	Not included	TP, FP, TN, FN No link to HCRU and cardiac events	Human resources Supplies, drugs Intervention room ICA admission Re-admissions Radiology technician Senior physician	Limited follow-up time to document clinical events No subgroup analysis	Costs were lower with PET-MPI (€973) vs. SPECT-MPI (€1,192) ICER (PET-MPI vs. SPECT-MPI): −€2,730 per accurate diagnosis Driven by shorter protocol time and more scans per week with PET-MPI
Lorenzoni, 2019^55	CEA 90-days NR	Suspected CAD Female: 33–58% Diabetes: 14–28% pCAD: 34–49%	Not included^b	Not included	TP, FP, TN, FN No link to HCRU and cardiac events	Modality ICA admission Cost of a FN assumed twice the cost of ICA and FP cost of unnecessary ICA	Very limited follow-up No subgroup analysis Limited economic inputs	Costs (100 patients) were higher with PET-MPI (€117,722) vs. SPECT-MPI (€90,125) ICER (PET-MPI vs. SPECT-MPI): NR Driven by increased procedure cost of PET-MPI
Hlatky, 2014^53	Registry with HCRU and costs 2-years NR	Suspected CAD Female: 48–59% Diabetes: 16–41% pCAD: 47–52%	CA, revasc.^a	MI	No diagnostic outcomes	Modality CA, revasc. MI, death	No subgroup analysis	Costs were higher with PET-MPI ($6,647) vs. SPECT-MPI ($3,965) Driven by higher rates of subsequent revascularization procedures with PET-MPI
Merhige, 2007^54	Utilization, costs and outcomes study 1-year ^82Rubidium	Known CAD: 44-49% 46% female pCAD in known CAD: 46–47% pCAD in suspected CAD: 29–33%	CA, revasc.	MI, CD	FP No link to HCRU and cardiac events	Modality CA, revasc.	Limited follow-up time to document clinical events No subgroup analysis	Costs were lower with PET-MPI ($4,110) vs. SPECT-MPI ($5,937) Driven by reduced CABG rates (>50% lower) with PET-MPI
Patterson, 1995^57	CEA 10-years NR	Men and women, various pCAD Women subgroup analysis provided	CA, revasc.	Rate of complications and mortality	Sensitivity, specificity No link to HCRU and cardiac events	Modality CA, revasc Mortality Bayes’ theorem was used to calculate the rate of complication as non-fatal MI in 20% of FN patients	Medically unnecessary CA was not considered for FP patients	Costs were lower with PET-MPI vs. SPECT-MPI for all pCAD^c (10%: $2,710 vs. $2,940; 50%: $5,020 vs. $5,400; 100%: $7,850 vs. $8,450) Cost/QALY^c (PET-MPI): $10,000 (pCAD 10%); $3,550 (pCAD 50%); $2,790 (pCAD 100%) Cost/QALY^c (SPECT-MPI): $12,700 (pCAD 10%); $4,600 (pCAD 50%); $3,460 (pCAD 100%) Driven by higher sensitivity and specificity with PET-MPI
Garber, 1999^56	CEA 30-years ^82Rubidium	Base: men, 55 years, pCAD: 50% Sensitivity: men 45 and 65 years, women 45, 55, and 65 years, pCAD: 25–75% Women subgroup analysis provided	CA, revasc.	MI	FP, FN, TP, TN TP: cost of CA TN: appropriate avoidance of CA FN: conservative management, no revasc. FP: unnecessary CA	Modality CA, revasc MI	Downstream cardiac events were not considered for FN patients	Costs were higher with PET-MPI vs. SPECT-MPI in men ($35,093 vs. $34,047) and women ($41,551 vs. $40,510) ICER (PET-MPI vs. SPECT-MPI): $523,000/QALY (men); $520,500/QALY (women) Driven by higher modality cost and increased angiography with PET-MPI
Single Arm PET-MPI Studies
Ma, 2021^59	Retrospective observational study 1-year NR	Suspected CAD Female: 58–59% Diabetes: 32–33%	CA, revasc.	Not included	No diagnostic outcomes	Modality CA, revasc Hospitalization costs (e.g. all-cause, cardiac, outpatient, emergency)	Limited follow-up time to document clinical events No subgroup analysis PET-MPI had more high-risk patients (could explain the higher utilization rates and costs)	Costs were higher with PET-MPI ($2,358.20) vs. conventional imaging ($1,774.30) Driven by higher utilization (hospitalizations, PCI) with PET-MPI
Siegrist, 2008^60	CEA 4-weeks ^13N-ammonia	Known CAD: 79% Female: 28%	CA, revasc.	Not included	No diagnostic outcomes	Modality CA, revasc Medical management	Limited follow-up time to document clinical events No subgroup analysis	Costs (total) were lower with PET-MPI (€152,450) vs. standard of care (€170,360) ICER: NR Driven by reduced diagnostic angiography with PET-MPI

^a Refer to Table 3 for specific reported rates.

^b Coronary revascularization derived from ENVINCI data set as an alternate measure of effectiveness.

^c Data digitized from publication.

Abbreviations: CA, coronary angiography; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CD, cardiac death; CEA, cost-effectiveness analysis; FN, false negative; FP, false positive; HCRU, healthcare resource utilization; ICA, invasive coronary angiography; ICER, incremental cost-effectiveness ratio; MI, myocardial infarction; MPI, myocardial perfusion imaging; pCAD, pretest likelihood of coronary artery disease; PCI, percutaneous coronary intervention; PET, positron emission tomography; PTP, pretest probability; QALY, quality-adjusted life-year; revasc., revascularization; SPECT, single-photon emission computed tomography; TN, true negative; TP, true positive.

Figure 2. Variability in reported outcomes of interest in comparative PET- vs. SPECT-MPI studies.

Table 3. Characteristics of PET- vs. SPECT-MPI studies and outcomes.

Author, Year	Article type	Modality	N	Key Patient Characteristics	Suspected (or Known) CAD	FU Time (months)	Coronary Angiography (%)		Coronary Revascularization (%)		Repeat Testing (%)	MACE^a (%)	Acute MI^a (%)
							Early ≤90 d	Late^a	Early ≤90 d	Late^a
Mimouni, 2023^58	Retrospective cost‑effectiveness using prospectively collected data during the RUBIS trial	PET	308	Age: 61 Female: 46.1% DM: 76.9% Mean BMI: 31.8	100% (0 %)	12	–	15	–	–	–	–	–
		CZT-SPECT	308	Age: 61 Female: 46.1% DM: 76.9% Mean BMI: 31.8		12	–	10	–	–	–	–	–
Ananthasubramaniam, 2022^62	Retrospective, analysis of IBM MarketScan commercial and Medicare claims data	PET	224	Age: 59 Female: 58.5% DM: 50.7%	–	–	56.7	–	19.9	–	10.0	–	–
		SPECT	12,905	Age: 59 Female: 52.8% DM: 38%	–	–	70.7	–	27.3	–	14.1	–	–
Patel, 2019^61	Prospective single-center randomized comparison of clinical effectiveness	PET	161	Age: 66.5 Female: 37.3% DM: 26.7% Mean BMI: 28.8	0% (100%)	12	20.5	28.6	11.2	15.5	–	–	0.0
		CZT-SPECT	161	Age: 66.1 Female: 32.9% DM: 28.6% Mean BMI: 29.2		12	15.5	28	9.9	14.9	–	–	1.2
Knight, 2018^123	Retrospective analysis of prospectively collected data	PET	7,130	Age: 64.5 Female: 44.9% DM: 29.8% Mean BMI: 31.9	59.5% (40.5%)	12	13.9^b*	–	7.9^b*	–	–	5.7	–
		SPECT	6,686	Age: 63.8 Female: 47% DM: 29.2% Mean BMI: 31.2	63.3% (36.7%)	12	9.3^b*	–	4.3^b*	1.6	–	5.2	–
Hlatky, 2014^53	Retrospective economic evaluation using prospectively collected data during the SPARC trial	PET	548	Age: 63 Female: 59% DM: 41% Mean PTP: 47%	100% (0%)	24	11.0	15	2–5^d	2–6^d	–	–	1.1
		SPECT	565	Age: 60 Female: 51% DM: 30% Mean PTP: 51%		24	4.0	7	0.4–1^d	0.4–2^d	–	–	1.2
Pelletier-Galarneau, 2023^63	Real-world, retrospective study of de-identified claims and electronic health records	PET	83,100^e	Age: - (matched based on age) Female: 41–69% Obesity: 42–61% DM: 14–54%	45.1% (54.9%)	24	12.8	–	–	–	2.2	–	–
		SPECT	1,951,500^e		58.4% (41.6%)	24	12.4	–	–	–	3.4	–	–

^a Follow-up time as specified in previous column.

^b ≤60 days.

^c n = 6,777.

^d Includes CABG and PCI rates.

^e Calculated based on 2.5 million patients who underwent diagnostic imaging, 77% who underwent SPECT and 3.2% who underwent PET.

* p <.0001.

Abbreviations: -, not reported; ACM, all-cause mortality; BMI, body-mass index (kg/m²); CAD, coronary artery disease; CZT, cadmium zinc telluride; d, days; DM, diabetes mellitus; FU, follow-up; MACE, major adverse cardiovascular events; MI, myocardial infarction; PET, positron emission tomography; PTP, pre-test probability; SPECT, single-photon emission computed tomography.

Table 4. Meta-analysis of PET- vs. SPECT-MPI studies.

Outcome	HR	95% CI	p-value
Early Coronary Angiography (<3 months)	1.05	1.03–1.07	<.0001
Late Coronary Angiography	1.58	1.25–2.01	.0002
Early Revascularization (<3 months)	1.58	1.39–1.79	<.0001
Late Revascularization	1.78	1.17–2.70	.0067
Acute MI	0.76	0.28–2.05	.5896
Repeat Testing (e.g. repeat SPECT-MPI, ECHO, etc.)	0.64	0.61–.67	<.0001

Abbreviations: ECHO, echocardiography; HR, hazard ratio; MI, myocardial infarction; MPI, myocardial perfusion imaging; PET, positron emission tomography; SPECT, single-photon emission computed tomography.

Figure 3. Annualized rates of HCRU and CAD events adjusted for time in single-arm MPI studies (excluding outlier studies).

Table 5. Pooled annualized rates (%) of HCRU and CAD events across MPI studies adjusted for time (excluding outlier studies).

	Early ICA % (n)	Early Revasc. % (n)	Late ICA % (n)	Late Revasc. % (n)	MI % (n)	Cardiac Death % (n)
<25% suspected CAD	17.3 (3)	10.6 (2)	28.3 (2)	15.2 (2)	1.2 (2)	NA
25–75% suspected CAD	9.7 (7)	5.1 (10)	NA	1.9 (21)	0.8 (20)	1.2 (13)
>75% suspected CAD	7.7 (6)	2.4 (7)	7.3 (8)	1.6 (9)	0.5 (12)	0.5 (11)
General Population	9.8 (16)	3.7 (19)	9.6 (10)	2.0 (32)	0.6 (34)	0.8 (24)

Note: “n” indicates the number of studies included in pooled analysis, including all studies with available outcome and suspected CAD data. Bolded percentage indicates that the annualized rate of HCRU is lower than that of <25% suspected CAD subgroup (25–75% suspected CAD subgroup for cardiac mortality), and the results were statistically significant in meta-regression. Early is defined as <30 days.

Abbreviations: CAD, coronary artery disease; HCRU, health care resource utilization; ICA, invasive coronary angiography; MI, myocardial infarction; MPI, myocardial perfusion imaging; revasc., revascularization.

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