Download Cardiovascular disease screening in HIV- infected patients

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CARDIOVASCULAR DISEASE SCREENING IN HIV-INFECTED PATIENTS – A COST-EFFECTIVENESS
ANALYSIS
Julia EH Nolte, MBA # , †; Till Neumann, MD, PhD ††; Anja Neumann, MD, MBA, PhD †;
Jennifer Manne, MSc; Sarah Mostardt, MBA†; Suhny Abbara, MD §; Thomas Brady, MD §;
Udo Hoffmann, MD, MPH §; G. Scott Gazelle, MD, MPH, PhD § , # , ¶; Juergen Wasem, PhD †;
Alexander Goehler, MD, MPH, MSc, PhD # , † , ‡
Cardiovascular disease screening in HIVinfected patients
# Institute
for Technology Assessment and Department of Radiology, Massachusetts General Hospital, Harvard
Medical School, Boston, MA, USA
A cost-effectiveness analysis
†
Alfried Krupp von Bohlen und Halbach Foundation Chair for Health Services Research and Management,
University Duisburg-Essen, Essen, Germany
Clinic for Cardiology, University Hospital Essen, Essen, Germany
††
ISPOR 16th Annual International Meeting, May 24, 2011
‡
Julia EH Nolte, MBA; Till Neumann, MD, PhD; Anja Neumann, MD, MBA, PhD;
Jennifer Manne, MSc; Sarah Mostardt, MBA; Suhny Abbara, MD; Thomas Brady, MD;
Udo Hoffmann, MD, MPH; G. Scott Gazelle, MD, MPH, PhD; Juergen Wasem, PhD;
Alexander Goehler, MD, MPH, MSc, PhD
Department of Public Health, Information Systems and Health Technology Assessment, UMIT – University for
Health Sciences, Medical Informatics and Technology, Hall i.T., Austria
¶
Department of Health Policy and Management, Harvard School of Public Health, Boston, MA, USA
§
Department of Radiology, Massachusetts General Hospital, Boston, MA, USA
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HIV-HEART_ISPOR 2011_09May11_JN.ppt
Context – Relevance of cardiovascular disease in
HIV-infected patients
HIV-positive patients at increased risk
for cardiovascular disease (CVD) ...
• Lo and colleagues observed an increased
prevalence of subclinical atherosclerosis in
HIV-positive men1
• The D:A:D study group reported HIV-infected
patients to be at an elevated risk for myocardial
infarction2
• Reinsch et al found the prevalence of
asymptomatic left ventricular diastolic
dysfunction (ALVDD) to be 48% in the HIVHEART cohort as compared to 6% in a noninfected population of similar age3,4
Objective – Evaluation of CVD screening interventions
in HIV-positive men
... due to behavioral,
virus, and HAART factors5,6
•
• Increased prevalence of traditional CVD risk
factors in the HIV-infected population, e.g.,
> 50% current smokers in the HIV-HEART
cohort3
• Development of traditional CVD risk factors due
to HIV or HAART, e.g., lipid-altering effect of
protease inhibitors
•
• Effects of HIV or HAART on the pathogenetic
process leading to CVD through other
mechanisms, e.g., inflammation
Thus, the American Heart Association encourages the screening of
HIV-infected patients for cardiac diseases7
Methods – Overview of CVD screening strategies
M
"Outpatient"
M
"Cardiologist"
Base case: One-time screening of HIV-positive men at intermediate risk of CVD (10-year Framingham CAD
risk ≥ 7.5%)
−
Secondary analysis: Screening at different 10-year CAD risk thresholds
−
Secondary analysis: Screening at regular time intervals, i.e., every 5 or 3 years
−
Probabilistic sensitivity analysis applied to the base case
Estimation of main outcome measures
−
Diagnostic outcomes: Number of patients correctly diagnosed with CVD, screening costs per patient
−
Lifetime outcomes: Discounted quality-adjusted life years (QALYs), discounted direct costs, incremental
cost-effectiveness ratios (ICERs)a
a. Annual discounting rate of 3%, costs reported in 2007 Euros.
2
HIV-HEART_ISPOR 2011_09May11_JN.ppt
M
−
Input parameters derived from patient-level data of the HIV-HEART
cohort (558 men, age 44.3 ±10.0 years) and the published literature
Note: HAART = highly active antiretroviral therapy.
No screening
Assessment of effectiveness, costs, and cost-effectiveness of screening HIV-positive men without
known CVD for coronary artery disease (CAD) and cardiac dysfunction using a Markov
microsimulation model
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HIV-HEART_ISPOR 2011_09May11_JN.ppt
Methods – State transition diagram of the Markov model
CAD
No screening
• Disease progression under current HIV treatment guidelines, i.e., no CVD
screening
Cardiac function
HIV +
normal
function
HIV + no CAD
HIV +
mild/moderate
CADa
"Outpatient" screening
• Electrocardiogram (ECG) and brain natriuretic peptide (BNP)
measurement for all patients
• Additional echocardiography and stress-testing if indicated
Patients can
have
(1) neither
cardiac disease,
(2) CAD or cardiac
dysfunction,
or (3) both
HIV +
severe CADb
"Cardiologist" screening
• ECG, BNP measurement, echocardiography, and stress-testing for all
patients
HIV +
ALVDD
HIV +
ALVSD
HIV + CHF
Death
a. 1-49% coronary lumininal stenosis for left main or 1-69% for any other coronary artery. b. ≥50% coronary luminal stenosis for left main or ≥70% for any other coronary artery.
Note: ALVDD = asymptomatic left ventricular diastolic dysfunction, ALVSD = asymptomatic left ventricular systolic dysfunction, CHF = congestive heart failure.
HIV-HEART_ISPOR 2011_09May11_JN.ppt
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Results – One-time CVD screening of HIV-positive men
at intermediate risk for cardiac diseases
Results – Cost-effectiveness of CVD screening strategies
at different screening thresholds
ICER (€/QALY)
No screening
"Outpatient"
"Cardiologist"
129
129
129
# true positives per 1,000
0
17
93
€ / patient screened
0
126
618
# patients w/ CAD per 1,000
Diagnostic
outcomes
100,000
"Outpatient"
"Cardiologist"
79,114
73,315
65,552
54,815
53,878
52,085 55,277
50,000
Cost (€)
Lifetime
outcomes
∆ Cost (€)
QALYs
ICER
(€/QALY)
∆ QALYs
No Screening
195,389
-
10.522
-
-
"Outpatient"
196,024
635
10.534
0.012
54,815
"Cardiologist"
198,541
2,517
10.572
0.038
65,552
0
% Severe CAD
At a WTP of 100,000 US$/QALY (83,000 €/QALY), screening HIVinfected men using the "Cardiologist" approach is cost-effective
All
CAD risk
≥ 5%
CAD risk
≥ 7.5%
CAD risk
≥ 10%
CAD risk
≥ 15%
6.5
9.3
12.9
17.7
33.4
Screening
threshold
Screening most cost-effective in a high-risk population; screening all
HIV-positive men stays below the WTP threshold of 100,000 US$/QALY
Note: Deviations in numbers due to rounding. WTP = willingness-to-pay.
Note: CAD risk denotes Framingham 10-year CAD risk; only non-dominated CVD screening strategies are shown. WTP = willingness-to-pay.
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HIV-HEART_ISPOR 2011_09May11_JN.ppt
Results – Cost-effectiveness of CVD screening strategies
at different screening intervals
∆ Cost (€)
QALYs
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HIV-HEART_ISPOR 2011_09May11_JN.ppt
Results – Probabilistic sensitivity analysis
Cost-effectiveness acceptability curve
∆ QALYs
ICER
(€/QALY)
No Screening
195,389
-
10.522
-
-
"Outpatient" – one-time
196,024
635
10.534
0.012
54,815
"Outpatient" – every 5 years
196,546
522
10.543
0.009
Extended
dominated
"Outpatient" – every 3 years
196,834
288
10.548
0.005
58,874
"Cardiologist" – one-time
198,541
1,707
10.572
0.024
69,281
"Cardiologist" – every 5 years
199,051
510
10.574
0.002
Extended
dominated
"Cardiologist" – every 3 years
199,404
353
10.582
0.008
86,819
1.0
0.9
Probability cost-effective
Cost (€)
48,809
0.8
0.7
"No screening"
0.6
"Outpatient"
0.5
"Cardiologist"
0.4
0.3
0.2
0.1
0.0
0
20,000
40,000
60,000
80,000
100,000 120,000 140,000 160,000 180,000 200,000
Willingness-to-pay (€/QALY)
Screening at five year intervals extended dominated; "Cardiologist"
every 3 years marginally exceeds the threshold of 100,000 US$/QALY
At a WTP of 100,000 US$/QALY, screening HIV-infected men for CVD is
cost-effective with a probability of greater 80%
Note: Deviations in numbers due to rounding.
HIV-HEART_ISPOR 2011_09May11_JN.ppt
Note: WTP = willingness-to-pay.
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Conclusions
•
Limitations and next steps
Screening HIV-positive men without known CVD for cardiac diseases increases quality-
Key limitations
adjusted life expectancy and is associated with additional health care expenditure
•
• Due to the lack of angiographic data, the
prevalence of CAD in the HIV-HEART cohort
was estimated using an Framingham risk
based algorithm
“Cardiologist” screening (65,552 €/QALY, 78,976 US$/QALY in 2007 US$) comes at an
ICER comparable to those of other interventions recommended in HIV-infected
individuals:
− Fusion inhibitor enfuvirtide (89,436 US$/QALY in 2007 US$*)8
• Due to insufficient data on incidence and
progression of CVD in HIV-infected patients,
we applied adjusted values derived from the
general population
− Genotypic resistance testing for HAART optimization (92,410 US$/QALY in 2007 US$*)9
•
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HIV-HEART_ISPOR 2011_09May11_JN.ppt
In the context of recommended screenings, it comes at an ICER comparable to that of:
− Breast cancer screening in women aged 50 to 74 years compared to no screening (69,750
US$/QALY in 2007 US$*)10
Next steps
• Given the high degree of uncertainty
associated with selected input parameters, we
intend to complement the cost-effectiveness
analysis by an expected value of information
analysis
• Based on the results of the expected value of
information analysis, we plan to give
recommendations for future research priorities
• Due to the lack of data on CVD prevalence in
HIV-infected women, we chose to evaluate
CVD screening strategies in HIV-positive men
only
Thus, the incorporation of routine CVD screening into HIV treatment
guidelines could improve health outcomes and be cost-effective
* ICERs reported in the original paper were inflated to the year 2007 using the medical care component of the consumer price index for the US.
Note: HAART = highly active antiretroviral therapy.
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References
Appendix – "Cardiologist plus" screening strategy
1. Lo, J., et al., Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed
tomography angiography in HIV-infected men. Aids, 2010. 24(2): p. 243-53.
2. Law, M.G., et al., The use of the Framingham equation to predict myocardial infarctions in HIV-infected
patients: comparison with observed events in the D:A:D Study. HIV Med, 2006. 7(4): p. 218-30.
3. Reinsch, N., et al., Prevalence of cardiac diastolic dysfunction in HIV-infected patients: results of the HIVHEART study. HIV Clin Trials, 2010. 11(3): p. 156-62.
4. Redfield, M.M., et al., Burden of systolic and diastolic ventricular dysfunction in the community: appreciating
the scope of the heart failure epidemic. Jama, 2003. 289(2): p. 194-202.
5. Currier, J.S., Update on cardiovascular complications in HIV infection. Top HIV Med, 2009. 17(3): p. 98-103.
6. Currier, J.S., et al., Epidemiological evidence for cardiovascular disease in HIV-infected patients and
relationship to highly active antiretroviral therapy. Circulation, 2008. 118(2): p. e29-35.
7. Hsue, P.Y., et al., Screening and assessment of coronary heart disease in HIV-infected patients. Circulation,
2008. 118(2): p. e41-7.
8. Sax, P.E., et al., Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced HIV
disease. J Acquir Immune Defic Syndr, 2005. 39(1): p. 69-77.
9. Yazdanpanah, Y., et al., The long-term benefits of genotypic resistance testing in patients with extensive prior
antiretroviral therapy: a model-based approach. HIV Med, 2007. 8(7): p. 439-50.
10. Stout, N.K., et al., Retrospective cost-effectiveness analysis of screening mammography. J Natl Cancer Inst,
2006. 98(11): p. 774-82.
Input
Diagnostic Pathway
Outcome
obstructive
CAD
abnormal
stress-ECG
normal
ECG
CCTA
mild/moderate
CAD
no CAD
BNP, Echo,
Stress-ECG
normal
stress-ECG
CCTA
BNP, Echo,
Stress-echo
mild/moderate
CAD
no CAD
normal
stress-echo
d/c
CAD: TP / FP / FNb
Dys.: TP / TN
d/c
CAD: TN / FN
Dys.: TP / TN
CAD: TN / FN
Dys.: TP / TN
obstructive
CAD
abnormal
ECG
CAD: TP / TN / FNa
Dys.: TP / TN
d/c
Patients with
CAD risk ≥ 7.5%
abnormal
stress-echo
ICA
d/c
ICA
CAD: TP / TN / FNa
Dys.: TP / TN
d/c
CAD: TP / FP / FNb
Dys.: TP / TN
d/c
CAD: TN / FN
Dys.: TP / TN
CAD: TN / FN
Dys.: TP / TN
a. FN referring to patients suffering from mild/moderate CAD with an ICA result of no CAD. b. FN referring to patients suffering from obstructive CAD with a CCTA result of mild/moderate CAD.
Note: Echo = echocardiography, ICA = invasive coronary angiography, CCTA = coronary computed tomography angiography, d/c = discharged/no further testing, Dys. = asymptomatic cardiac
dysfunction, TP = true positive, TN = true negative, FN = false negative, FP = false positive.
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Appendix – Lifetime outcomes including "Cardiologist
plus" screening
Cost (€)
∆ Cost (€)
QALYs
∆ QALYs
ICER
(€/QALY)
No Screening
195,389
-
10.522
-
-
"Outpatient"
196,024
635
10.534
0.012
54,815
"Cardiologist"
198,541
2,517
10.572
0.038
Extended
dominated
"Cardiologist plus"
198,377
- 165
10.574
0.001
59,308
"Cardiologist plus" identifies more patients in early disease states
leading to better health outcomes
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