A new adjunctive Tx option for venous stasis ulcers

PURLs® Priority Updates from the Research Literature
from the Family Physicians Inquiries Network

Benjamin H. Crenshaw, A new adjunctive Tx option
MD; Kortnee Y. for venous stasis ulcers
Roberson, MD; James J.
Stevermer, MD, MSPH Adding simvastatin to standard wound care improves
Department of Family and ulcer healing rates and times as well as the patient’s
Community Medicine, quality of life.
University of Missouri-
Columbia (Drs. Crenshaw PRACTICE CHANGER ciated with systemic sclerosis and Raynaud’s
and Stevermer); University phenomenon.6 Evangelista et al1 investigated
of Chicago, Department Consider adding simvastatin 40 mg/d to stan- whether adding a statin to standard wound
of Family Medicine dard wound care and compression for pa- care and compression could improve venous
(Dr. Roberson) tients with venous stasis ulcers.1 stasis ulcer healing.

d e p u t y Ed i t o r STRENGTH OF RECOMMENDATION STUDY SUMMARY

Anne Mounsey, MD B: Based on a high-quality randomized con- Ulcers are more likely to close
University of North trolled trial (RCT). when a statin is added to standard care
Carolina at Chapel Hill This randomized, double-blind, placebo-
Evangelista MT, Casintahan MF, Villafuerte LL. Simvastatin as a novel controlled trial was performed at a large med-
instant therapeutic agent for venous ulcers: a randomized, double-blind, pla- ical center in the Philippines. It was designed
poll cebo-controlled trial. Br J Dermatol. 2014;170:1151-1157. to assess the efficacy and safety of simvastatin
40 mg/d for venous ulcer healing when com-
Do you ever ILLUSTRATIVE CASE bined with standard treatment (compression
prescribe a statin therapy, limb elevation, and standard wound
for the treatment A 74-year-old woman with chronic lower ex- care).1
of a venous stasis tremity edema seeks treatment for a nonheal-
ulcer? ing venous stasis ulcer. For the past 9 months, Researchers randomized 66 patients ages
n Yes she’s been wearing compression stockings and 41 to 71 who’d had one or more venous ulcers
n No receiving intermittent home-based wound for at least 3 months to receive either simvas-
care, but nothing seems to help. She asks if tatin 40 mg/d (N=32) or an identical appear-
jfponline.com there’s anything else she can try. ing placebo (N=34). Patients were excluded
if they were pregnant, had an ulcer that was
V enous stasis ulcers affect 1% of US infected or >10 cm in diameter, or were tak-
adults and lead to substantial mor- ing any medication that could interact with
bidity and more than $2 billion in a statin. Patients were stratified according
annual health care expenditures.1,2 Edema to ulcer diameter (≤5 cm and >5 cm). There
management—generally limb elevation and was no statistically significant difference be-
compression therapy—has been the main- tween the 2 groups in the duration of venous
stay of therapy. Treatment can be lengthy, ulceration (3.80 years in the placebo group vs
and ulcer recurrences are common.2,3 3.93 years in the simvastatin group) or inci-
dence of diabetes (5% in the placebo group vs
Statins have been found to help wound 3% in the simvastatin group).
healing through their diverse physiologic
(pleiotropic) effects. Evidence shows they
can be beneficial for treating diabetic foot ul-
cers,4 pressure ulcers,5 and ulcerations asso-

182 The Journal of Family Prac tice | MARCH 2 0 1 5 | V o l 6 4 , N o 3

The primary outcome was the propor- very small NNT for benefit, and improved pa-
tion of patients whose ulcers completely tient quality of life compared to placebo.
healed at 10 weeks. Secondary outcomes
were measures of the total surface area CAVEATS Sixty-seven
healed and healing time, and Dermatology percent of ulcers
Life Quality Index (DLQI) scores. Baseline Results were found in a carefully selected >5 cm in the
ulcer diameter and surface area and DLQI group of patients simvastatin
scores were obtained prior to therapy. The Many wounds will heal with compression group had
same dermatologist, who was blinded to the therapy alone, as occurred in this study, closure, while
patients’ assigned group, evaluated all pa- where 50% of ulcers ≤5 cm treated with stan- none of those
tients every 2 weeks until wound closure or dard therapy healed, albeit at a somewhat in the control
for a maximum of 10 weeks. slower rate. Adding another medication to group did.
the regimen when these patients generally
Overall, 90% of the patients who re- have multiple comorbidities should always
ceived simvastatin had complete ulcer clo- prompt caution.
sure at 10 weeks, compared with 34% of
patients in the control group (relative risk The study by Evangelista et al1 was per-
[RR]=0.16; 95% confidence interval [CI], formed in a select population, and the ex-
0.05-0.47; number needed to treat [NNT]=2). clusion criteria included the use of some
commonly prescribed medications, such as
Among patients with ulcers ≤5 cm, angiotensin-converting enzyme inhibitors.
100% of the ulcers healed in the simvas- No data were collected on patient body mass
tatin group, compared to 50% in the control index, which is a risk factor for delayed heal-
group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). ing. The prevalence of obesity is lower in the
Perhaps more importantly, in patients with Philippines than in the United States, and it
ulcers >5 cm, 67% of the ulcers in the simvas- is uncertain what role this difference would
tatin group had closure with a mean healing have in the statin’s effectiveness. Further
time of 9 weeks, whereas none of the ulcers of studies, especially those conducted with a
this size closed in the control group (RR=0.33; less selective population, would better clarify
95% CI, 0.12-0.84; NNT=1.5), and the mean the generalizability of this intervention.
healed area was significantly larger in pa-
tients who received simvastatin (28.9 cm2 vs We found the results of this study im-
19.6 cm2; P=.03). pressive. The methods reported are rig-
orous and consistent with standard RCT
In addition, in the simvastatin group, methodologies. This is the only study of a
healing times were significantly reduced statin in human venous stasis disease, but
(7.53±1.34 weeks vs 8.55±1.13 weeks) and studies in animals—and studies of statins
quality of life (as evaluated by DLQI scoring) for other types of ulcers in humans—have
significantly improved compared to the con- consistently suggested benefit. It seems
trol group. hard to argue against adding this low-cost,
low-risk intervention.
Study dropouts (8%; 2 in the placebo
group and 3 in the intervention group) were CHALLENGES TO IMPLEMENTATION
minimal. Using intention-to-treat analysis
and worst-case scenarios for dropouts did There are no known barriers to implementing
not affect the primary outcome. There were
no withdrawals for adverse reactions.

this practice. JFP

WHAT’S NEW Acknowledgement
The PURLs Surveillance System was supported in part by Grant
Statins offer significant benefits Number UL1RR024999 from the National Center For Research
for treating venous stasis ulcers Resources, a Clinical Translational Science Award to the Uni-
This is the first human study to investigate the versity of Chicago. The content is solely the responsibility of
use of a statin in venous stasis ulcer healing. the authors and does not necessarily represent the official
This intervention demonstrated significant views of the National Center For Research Resources or the
improvements in healing rate and time, a National Institutes of Health.

Copyright © 2015. The Family Physicians Inquiries Network.
All rights reserved.

CON T INUE D

jfponline.com Vol 64, No 3 | MARCH 2015 | The Journal of Family Practice 183

PURLs®

References nhmrc.gov.au/_files_nhmrc/publications/attachments/ext003_
venous_leg_ulcers_aust_nz_0.pdf. Accessed February 13, 2015.
1. E vangelista MT, Casintahan MF, Villafuerte LL. Simvastatin
as a novel therapeutic agent for venous ulcers: a randomized, 4. Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer
double-blind, placebo-controlled trial. Br J Dermatol. 2014;170: burden may be modified by high-dose atorvastatin: A 6-month
1151-1157. randomized controlled pilot trial. J Diabetes. 2009;1:182-187.

2. C ollins L, Seraj S. Diagnosis and treatment of venous ulcers. Am 5. F arsaei S, Khalili H, Farboud ES, et al. Efficacy of topical atorvas-
Fam Physician. 2010;81:989-996. tatin for the treatment of pressure ulcers: a randomized clinical
trial. Pharmacotherapy. 2014;34:19-27.
3. T he Australian Wound Management Association Inc, New Zea-
land Wound Care Society Inc. Australian and New Zealand clini- 6. A bou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful
cal practice guideline for prevention and management of venous in therapy of systemic sclerosis-related Raynaud’s phenomenon
leg ulcers. 2011. Australian Government National Health and and digital ulcers. J Rheumatol. 2008;35:1801-1808.
Medical Research Council Web site. Available at: http://www.

184 The Journal of Family Prac tice | MARCH 2 0 1 5 | V o l 6 4 , N o 3