Medical management of peripheral arterial disease
Cardiol Rev 2001;9(4):238-45.
Peripheral arterial disease affects approximately 8-10 million people in
the United States.
Approximately one-third to one-half of these individuals are symptomatic.
The risk factors that
contribute to peripheral arterial disease are similar to those associated
with other forms of
atherosclerosis, including diabetes mellitus, cigarette smoking, hypercholesterolemia,
high blood
pressure, and hyperhomocysteinemia. Of these, diabetes and cigarette smoking
pose the greatest
risk for developing peripheral arterial disease. The prognosis of patients
with these risk factors is
limited because of their greater risks for myocardial infarction, stroke,
and cardiovascular death.
Cardiovascular mortality correlates inversely with the ankle/brachial index,
and the risk of death is
greatest in those with the most severe peripheral arterial disease. Treatment
regimens to reduce
cardiovascular morbidity and mortality in patients with peripheral arterial
disease should include
risk factor modification and antiplatelet therapy. The cardinal symptoms
of peripheral arterial
disease include intermittent claudication and rest pain, with the latter
being indicative of critical
limb ischemia. Therapeutic strategies that focus on improving the patient's
quality of life, reducing
the severity of claudication, and improving limb viability include supervised
exercise training,
pharmacotherapy, and revascularization. Two drugs-pentoxifylline and cilostazol-currently
are
approved by the Food and Drug Administration for the treatment of patients
with claudication.
Meta-analyses have suggested that, compared with placebo, pentoxifylline
improves maximal
walking distance by approximately 20-25%. Cilostazol is a phosphodiesterase
type 3 inhibitor. In
clinical trials, cilostazol has consistently improved maximal walking distance
as compared with
placebo, with the range of improvement being approximately 40-60%. Drugs
that are currently
under investigation include propionyl-L-carnitine, vasodilator prostaglandins,
L-arginine, and the
angiogenic factors, vascular endothelial growth factor and basic fibroblast
growth factors.
Effect of cilostazol on restenosis after coronary
angioplasty and stenting in
comparison to conventional coronary artery stenting with ticlopidine.
Int J Cardiol 2001;78(3):285-91.
Background: The role of antiplatelet therapy with ticlopidine plus aspirin
in the prevention of
subacute thrombosis after coronary artery stenting has been established.
However, restenosis
remains a major limitation in coronary artery stenting. Methods: To compare
the effect of
cilostazol on restenosis after coronary angioplasty and stenting with that
of ticlopidine after
coronary artery stenting, 213 patients with 230 lesions who underwent successful
coronary
interventions were evaluated. Optimal results (residual stenosis less than
30%) were obtained by
balloon angioplasty in 112 lesions, 64 lesions were treated with aspirin
81 mg/day
(balloon-aspirin group) and 48 lesions with cilostazol 200 mg/day and aspirin
81 mg/day
(balloon-cilostazol group). Stent implantation was performed in the remaining
118 lesions; 55
lesions were treated with ticlopidine 200 mg/day and aspirin 243 mg/day
(stent-ticlopidine group)
and 63 lesions with cilostazol 200 mg/day and aspirin 81 mg/day (stent-cilostazol
group).
Concomitant medications were continued for 4 to 6 months of follow-up.
Results: No adverse
events including acute occlusion and subacute thrombosis occurred in any
groups. Although
immediate gain and minimal lumen diameter immediately after angioplasty
were significantly larger
in stent groups than those in balloon groups, net gain at follow-up was
significantly larger in
cilostazol groups (1.54+/-0.83 mm in balloon-cilostazol group and 1.65+/-0.78
mm in
stent-cilostazol group) than other groups (1.02+/-0.81 mm in balloon-aspirin
group and
1.21+/-0.70 in stent-ticlopidine group) as a result of significantly lower
late loss and loss index in
cilostazol groups. The restenosis rate was significantly lower in cilostazol
groups (12.5% in
balloon-cilostazol group and 14.3% in stent-cilostazol group) than other
groups (43.8% in
balloon-aspirin group and 32.7% in stent-ticlopidine group). The rate of
recurrent angina was
significantly lower in cilostazol groups (4.3% in balloon-cilostazol group
and 1.9% in
stent-cilostazol group) than in other groups (17.5% in balloon-aspirin
group and 14.0% in
stent-ticlopidine groups). Conclusions: Both optimal balloon angioplasty
with cilostazol and
coronary artery stenting with cilostazol have a potential to reduce restenosis
compared with
optimal balloon angioplasty with aspirin or conventional coronary artery
stenting with ticlopidine
plus aspirin.
Novel risk factors for systemic atherosclerosis:
a comparison of C-reactive
protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol
screening as predictors of peripheral arterial disease.
JAMA 2001;285(19):2481-5.
CONTEXT: Several novel risk factors for atherosclerosis have recently been
proposed, but few
comparative data exist to guide clinical use of these emerging biomarkers.
OBJECTIVE: To
compare the predictive value of 11 lipid and nonlipid biomarkers as risk
factors for development
of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND
PARTICIPANTS: Nested case-control study using plasma samples collected
at baseline from a
prospective cohort of 14 916 initially healthy US male physicians aged
40 to 84 years, of whom
140 subsequently developed symptomatic PAD (cases); 140 age- and smoking
status-matched
men who remained free of vascular disease during an average 9-year follow-up
period were
randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined
by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C),
low-density
lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides,
homocysteine,
C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins
(apo) A-I and B-100.
RESULTS: In univariate analyses, plasma levels of total cholesterol (PZ.001),
LDL-C (P =.001),
triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP
(P =.006), and the total
cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline
among men who
subsequently developed PAD compared with those who did not, while levels
of HDL-C (P
=.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations
of lipoprotein(a) (P
=.40) and homocysteine (P =.90) were observed. In multivariable analyses,
the total
cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative
risk [RR] for those in
the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6),
while CRP was the
strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8;
95% CI, 1.3-5.9). In
assessing joint effects, addition of CRP to standard lipid screening significantly
improved risk
prediction models based on lipid screening alone (P<.001). CONCLUSIONS:
Of 11
atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C
ratio and CRP
were the strongest independent predictors of development of peripheral
arterial disease.
C-reactive protein provided additive prognostic information over standard
lipid measures.
Antithrombotic drugs for older subjects. Guidelines formulated jointly
by
the Italian Societies of Haemostasis and Thrombosis (SISET) and of
Gerontology and Geriatrics (SIGG).
Nutr Metab Cardiovas Dis 2001;11(1):41-62.
Older individuals contribute heavily to the percentage of deaths due to
myocardial infarction (MI)
and stroke. The incidence of venous thromboembolism (VTE) is highest in
subjects > 65 years.
Prospective intervention trials involving groups of clinically comparable
subjects > or = 60 allow
the following statements to be made with regard to the use of antithrombotic
drugs in the elderly.
Antiplatelet agents. To prevent recurrence of ischaemic stroke and MI in
stable/unstable angina,
MI, TIA/stroke or peripheral arterial disease, aspirin is the drug of choice.
Clopidogrel is more
effective than aspirin in this respect. Heparin. For the treatment of acute
deep venous thrombosis
(DVT) and pulmonary embolism (PE), intravenous standard heparin or subcutaneous
standard
heparin are effective (aPTT 1.5-2.0 times baseline values). As the risk
of bleeding increases with
age, low-molecular-weight heparins (LMWH) are preferable in the elderly.
For the prophylaxis
of VTE in general surgery in subjects at low-moderate risk, low-dose heparin
or low doses of
LMWH are effective. In subjects at high risk, adjusted-dose heparin plus
physical devices or
high-dose LMWH are recommended. The combination of heparin and aspirin
is the standard
treatment for unstable angina and non-Q wave MI. LMWH are as active as
standard heparin in
this indication. Vitamin K antagonists. For the chronic treatment of VTE,
warfarin is also the
treatment of choice (INR 2.0-3.0) in the elderly, though lower doses are
needed due to their
hypersensitivity to oral anticoagulants. For the prevention of thromboembolic
stroke in patients >
75 with atrial fibrillation, warfarin is the drug of choice. Patients aged
65-75 may receive warfarin
or aspirin. Thrombolytic agents. Thrombolytic agents are not recommended
for treating DVT in
the elderly because of their limited risk/benefit ratio and should be confined
to massive PE. In the
absence of contraindications, thrombolysis for MI may be considered in
the elderly.
|
Volume
4, Number 7: July 2001
