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2011 ; 15
(40
): 1-210
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gab.com Text
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English Wikipedia
A systematic review and economic evaluation of cilostazol, naftidrofuryl oxalate,
pentoxifylline and inositol nicotinate for the treatment of intermittent
claudication in people with peripheral arterial disease
#MMPMID22142554
Squires H
; Simpson E
; Meng Y
; Harnan S
; Stevens J
; Wong R
; Thomas S
; Michaels J
; Stansby G
Health Technol Assess
2011[Dec]; 15
(40
): 1-210
PMID22142554
show ga
BACKGROUND: Peripheral arterial disease (PAD) is a condition in which there is
blockage or narrowing of the arteries that carry blood to the legs and arms. It
is estimated to affect around 4.5% of people aged between 55 and 74 years within
the UK. The most common symptom of PAD is intermittent claudication (IC),
characterised by pain in the legs on walking that is relieved with rest.
OBJECTIVE: To assess the effectiveness and cost-effectiveness of cilostazol,
naftidrofuryl oxalate, pentoxifylline and inositol nicotinate, compared with no
vasoactive drugs, for IC due to PAD in adults whose symptoms continue despite a
period of conventional management. DATA SOURCE: Electronic bibliographic
databases were searched during April to June 2010 (MEDLINE, MEDLINE In-Process &
Other Non-Indexed Citations, EMBASE, The Cochrane Library databases, Cumulative
Index to Nursing and Allied Health Literature, Web of Science, Conference
Proceedings Citation Index, BIOSIS Previews). REVIEW METHODS: Effectiveness
outcomes sought were maximal walking distance (MWD), pain-free walking distance
(PFWD), ankle-brachial pressure index, cardiovascular events, mortality, adverse
events (AEs) and health-related quality of life (HRQoL). A narrative synthesis
was provided for all outcomes and a network meta-analysis was undertaken for the
walking distance outcomes. A Markov model was developed to assess the relative
cost-effectiveness of the interventions from a NHS perspective over a lifetime.
The model has three states: vasoactive drug treatment, no vasoactive drug
treatment and death. Each 1-week cycle, patients may continue with the drug,
discontinue the drug or die. Regression analysis was undertaken to model the
relationship between MWD and utility so that a cost per quality-adjusted
life-year (QALY) outcome measure could be presented. Univariate and probabilistic
sensitivity analyses were undertaken. All costs and outcomes were discounted at
3.5%. RESULTS: Twenty-six randomised controlled trials were identified that met
the inclusion criteria for the clinical effectiveness review. There was evidence
that walking distance outcomes were significantly improved by both cilostazol and
naftidrofuryl oxalate; the 95% credible intervals for the difference from placebo
in the logarithm mean change MWD from baseline were 0.108 to 0.337 and 0.181 to
0.762, respectively. It was not possible to include inositol nicotinate within
the meta-analysis of MWD and PFWD owing to the lack of 24-month data; however,
the shorter-term data did not suggest a significant effect. AEs were minor for
all drugs and included headaches and gastrointestinal difficulties. The incidence
of serious adverse events (SAEs), including cardiovascular events and mortality,
was not increased by the vasoactive drugs compared with placebo; however, most
studies had a relatively short follow-up time to address this outcome. HRQoL data
were limited. Two studies of limited quality were identified within the review of
cost-effectiveness. The de novo model developed suggests that naftidrofuryl
oxalate dominates cilostazol and pentoxifylline and has a cost per QALY gained of
around £6070 compared with no vasoactive drug. This result is reasonably robust
to changes within the key model assumptions. Inositol nicotinate was not included
within the main analysis owing to lack of data. However, it is unlikely to be
considered to be cost-effective due to its high acquisition cost (£900 vs
£100-500 per year for the other drugs). CONCLUSIONS: Naftidrofuryl oxalate and
cilostazol both appear to be effective treatments for this patient population,
with minimal SAEs. However, naftidrofuryl oxalate is the only treatment that is
likely to be considered cost-effective. The long-term effectiveness is uncertain
and hence a trial comparing cilostazol, naftidrofuryl oxalate and placebo beyond
24 weeks would be beneficial. Outcomes associated with naftidrofuryl oxalate
could also be compared with those associated with supervised exercise programmes
and angioplasty.