Measuring treatment effects of cilostazol on clinical trial endpoints in
patients with intermittent claudication.
Reference: Clin Cardiol 2002;25(3):91-4.
Intermittent claudication (IC) comprises the most common presenting symptoms
of peripheral
arterial disease (PAD), which itself is a manifestation of systemic atherosclerosis.
Typical
symptoms of IC are aching pain, numbness, and fatigue in the lower extremities.
Symptoms are
induced by walking or exercise and usually resolve with rest. The cornerstone
of treating IC is
risk-factor reduction and a supervised exercise regimen. Pharmacotherapy
specifically indicated
for the treatment of IC includes a new drug, cilostazol, and the traditional
drug, pentoxifylline.
Cilostazol also has antiplatelet, antithrombotic, and vasodilatory activity,
as well as a positive
effect on serum lipids. Eight multicenter clinical trials, seven in the
U.S. and one in the U.K., used
objective and subjective clinical endpoints to assess the treatment efficacy
of cilostazol. Objective
endpoints included maximal and pain-free walking distance (MWD and PFWD,
respectively),
the ankle-brachial index, peripheral hemodynamic measurements, and serum
lipid levels.
Subjective endpoints, assessed by patient questionnaires, included perceived
functional status and
health-related quality of life. Cilostazol treatment showed statistically
significant increases in
MWD and PFWD within 4 weeks, as well as improvements in physical functional
status at 24
weeks, compared with placebo and pentoxifylline. Increases in high-density
lipoprotein
cholesterol and decreases in plasma triglycerides were also noted. Subjective
assessments
appeared to match objective parameters.
Steroid sex hormones for lower limb atherosclerosis (Cochrane Review).
Reference: Cochrane Database Syst Rev 2002;(1):CD000188
BACKGROUND: There is accumulating evidence that steroid sex hormones have
a beneficial
effect on a number of risk factors for peripheral arterial disease. OBJECTIVES:
The objective of
this review was to determine whether exogenous steroid sex hormones are
an effective treatment
for patients with lower limb atherosclerosis. SEARCH STRATEGY: The Cochrane
Peripheral
Vascular Diseases Group trials register was searched, together with reference
lists from relevant
articles and reviews obtained through searches of Embase and Medline (up
to May 2001).
SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of
steroid sex
hormones in patients with lower limb atherosclerosis were selected. DATA
COLLECTION
AND ANALYSIS: Both reviewers extracted data and assessed trial quality
independently.
Whenever possible investigators were contacted to obtain information needed
for the review that
could not be found in published reports. MAIN RESULTS: Four trials appeared
to meet the
inclusion criteria, but one was excluded because of poor methodology. The
three remaining trials
compared testosterone treatment with placebo in a total of 109 subjects
with intermittent
claudication or critical leg ischaemia. The most recent trial to meet the
inclusion criteria dated
from 1971. No trials were available which investigated the potentially
beneficial effects of
oestrogenic hormones in women with lower limb atherosclerosis. Testosterone
therapy produced
no significant improvement in tests of walking distance or in a variety
of other objective tests for
peripheral arterial disease, including venous filling time, muscle blood
flow and plethysmography.
The relative risk for subjective improvement in symptoms using the combined
trial results was
also non-significant (relative risk 1.10, 95% confidence interval 0.81
to 1.48). REVIEWER'S
CONCLUSIONS: There is no evidence to date that short-term testosterone
treatment is
beneficial in subjects with lower limb atherosclerosis. However, this might
reflect limited data
rather than the lack of a real effect.
Management of intermittent claudication: the importance of secondary prevention
Reference: Eur Vas Endovasc Surg 2001;23(2):100-7.
Atherosclerotic peripheral arterial disease (PAD) is a common disorder
usually associated with
silent or symptomatic arterial disease elsewhere in the circulation and
a cluster of cardiovascular
risk factors inducing atheroma progression and/or thrombotic complications.
Because of these
strong clinical associations, especially with coronary heart disease, the
ankle-brachial pressure
index (ABPI) is of prognostic significance. The clinical management of
IC should include relief of
symptoms combined with prevention of secondary cardiovascular complications,
e.g. acute
thrombotic events causing limb- or life-threatening ischaemia, which are
often due to
atherosclerotic plaque rupture leading to thrombotic vessel occlusion.
Many patients with PAD
do not receive an optimum package of secondary prevention, tailored to
include maximum
cholesterol reduction, BP and glycaemic control, ACE inhibition and single
or combination
anti-platelet therapy. This review considers recent information from large
secondary prevention
trials, e.g. the PAD subgroups within the HOPE, CAPRIE and statin studies.
Slowing
progression of atherosclerosis, and inducing stabilisation and regression
of atheromatous plaques,
is now feasible using long-term combination drug therapy. The phrase angle
quotation mark,
leftangle quotation mark, leftconservative therapyangle quotation mark,
rightangle quotation mark,
right, popular among vascular surgeons, implies a passive minimal-intervention
strategy of
surveillance and lifestyle advice; such terminology is perhaps no longer
appropriate since
considerable improvements in survival are likely to accrue if all patients
with PAD, especially
those with low ABPI, receive vigorous, titrated medical therapies, tailored
to individual patients,
as part of an evidence-based secondary prevention regime.
Episodes of ST-segment depression is related to changes in ambulatory
blood pressure and heart rate in intermittent claudication.
Reference: J Intern Med 2001;250(5):398-405.
OBJECTIVE: To study the prevalence and circadian distribution of ischaemic
ST-segment
depression detected with ambulatory electrocardiographic monitoring (AECG)
in patients with
intermittent claudication (IC) as well as to study ambulatory blood pressure
(ABP) and the
relation of ischaemic episodes to variations in ABP and heart rate. DESIGN:
A total of 40
patients with a history of IC and an ankle/brachial-index (ABI) <0.9
performed: (i) 24-h AECG
recordings, (ii) simultaneous 24 h recordings of ABP every 15 min (Spacelabs
90207), (iii) an
exercise treadmill test (ETT). An ischaemic episode was defined as a transient
ischaemic
ST-segment deviation > or =1 mm lasting >1 min. Eleven patients were excluded
from ECG
analysis because of uninterpretable ECG caused by treatment with digoxin
or technical problems.
RESULTS: Out of 29 patients, eight experienced a total of 15 episodes of
ST-depression on
AECG. The mean duration was 21+/-31 min. The majority of episodes (11 of
15) occurred
between 6 and 12 a.m. In eight patients with ST-segment depression three
had a history of
ischaemic heart disease (IHD), four were hypertensives and four had signs
of myocardial
ischaemia on ETT. There were no significant differences between patients
with and without
ST-segment depression in ABP, walking performance or ABI. During ST-depression
episodes
systolic and diastolic blood pressure and heart rate were higher than day
mean values; 178+/-41
vs. 166+/-30 mmHg (P= 0.09); 96+/-9 vs. 90+/-4 mmHg (P = 0.01) and 103+/-9
vs. 87+/-5
beats min(-1) (P < 0.01). CONCLUSION: Silent myocardial ischemia occurred
in about a third
of patients with IC. Episodes of ischaemia were associated with an increased
ABP and heart
rate. Whether treatment of high blood pressure may reduce silent ischaemia
and if this favourably
influences outcome is a matter of further research.
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Volume
5, Number 4: April 2002
