Volume 3, Number 4: APRIL 2000
Lifestyle
changes in free-living patients with peripheral vascular disease (Fontaine
stage II) related to plasma and LDL lipid composition: a 15 month follow-up
study.
Management
of myocardial infarction: looking beyond efficacy
A
Primary Care Approach to the Patient with Claudication
Can
diabetic neuropathy be prevented by angiotensin-converting enzyme inhibitors?
Lifestyle
changes in free-living patients with peripheral vascular disease (Fontaine
stage II) related to plasma and LDL lipid composition: a 15 month follow-up
study.
Reference: Clin Nutr 1999;18(5):281-9.
Management of myocardial infarction:
looking beyond efficacy
Reference: J
Am Coll Cardio 2000;35(2):380-1.
Over the last
two decades, management of acute myocardial infarction (MI) has shifted
from a ''wait and watch'' strategy to an increasingly aggressive strategy
of restoring and maintaining (e.g., thrombolytics, antiplatelet agents)
early patency to the infarct-related vessel and to other approaches that
directly protect the myocardium (e.g., beta-blockers, angiotensin-converting
enzyme inhibitors). Improved outcomes in MI have been achieved largely
by using a combination of simple pharmacologic therapies and by the introduction
of specialized coronary care units. In recent years advances in catheter
based technologies have improved reperfusion success in MI patients with
ST elevation. Randomized clinical trials of primary balloon percutaneous
transluminal coronary angioplasty (PTCA) versus thrombolytic therapy have
demonstrated that primary PTCA results in higher rates of coronary patency
and lower rates of stroke, reinfarction and death..
However, the relative benefit of PTCA over thrombolytic therapy is still
unknown in a community setting in which access to catheterization laboratories
(cath labs) and operator expertise is less uniform than in the trial setting
. Whether immediate availability of invasive facilities, compared with
referral of sick or high-risk patients to offsite cath labs, will improve
outcomes is not known. This question has important medical, organizational,
cost and training implications.
Rogers et al. attempt to answer this question using data from a large registry of 1,506 U.S. hospitals that represent a spectrum of hospital types (noninvasive, cath-capable, PTCA-capable, coronary artery bypass graft-capable) and regions. They observed that the time to thrombolytic therapy was similar among the four types of hospitals and, as expected, that a greater proportion of patients initially presenting to hospitals capable of cardiac catheterization received invasive therapy but a greater proportion of those admitted to noninvasive centers was transferred. However, the primary mode of reperfusion was still thrombolytic therapy in each of the four categories of patients. One would expect that availability of immediate PTCA would allow additional patients not eligible for thrombolytic therapy to receive a catheter based intervention. However, the overall rates of reperfusion attempts were not significantly different among the four types of hospitals, and the risk profiles of the patients receiving reperfusion treatment (i.e., either thrombolytic or PTCA) treated in hospitals with and without PTCA facilities were similar. Consequently in the approximately 10% of patients for whom out-of-hospital data are available, 90-day survival after discharge was not significantly different whether or not invasive facilities were available. Although the follow-up data are limited and only short-term, they are consistent with the hypothesis that the initial management of MI does not differ whether or not invasive facilities are available on site. This is consistent with other studies that show that availability of catheterization facilities does not broaden the types or increase the risk profiles of patients to be treated . Paradoxically, lower risk patients are more often selected to undergo catheterization. This bias reduces the potential benefits of invasive therapies, first by subjecting lower risk patients to a therapy they may not necessarily need—thereby resulting in higher peri-procedural complications (major bleeds, strokes and mortality)—and second, by not delivering the most aggressive care to the highest risk patients, who stand to benefit the most.
Before embarking on newer and more costly treatment strategies, perhaps efforts should be directed at optimizing the use of proven therapies. Such an approach is more likely to lead to a greater benefit. For instance, the average time to thrombolytic therapy across all hospital groups in this study (42 min) is still longer than recommended.. Efforts should be directed at continuously monitoring this variable and providing these data to local physicians at each center in an effort to improve the performance of those providing first-line therapy. Emergency personnel should also be appropriately trained in the early recognition of those patients who are at high risk and require immediate transfer to a facility with invasive capability. This will improve the selection for those patients who require invasive management and therefore improve the impact of these therapies. Although there may be, at best, modest benefits of one thrombolytic agent versus another (e.g., tissue plasminogen activator vs. streptokinase), the most important determinant of outcome is not which agent to use but, rather, whether a thrombolytic agent is indicated and, if so, how soon it is administered. Newer data, with combinations of thrombolytic agents and platelet GPIIb/IIIa receptor inhibitors or bolus administration of new generation thrombolytics, suggest that 90-min patency rates may be enhanced and approach those achieved with primary PTCA . However, these therapies are limited by the higher rates of intracranial bleeds and their high costs (both direct and indirect). In contrast, previous data from several sources indicate underutilization of proven and less expensive therapies (e.g., aspirin, beta-blockers or lipid lowering).
The study by Rogers et al.does not distinguish between the management of MI patients presenting with and without ST elevation on the initial electrocardiogram. Patients without ST elevation MI tend to be older, have higher rates of three-vessel disease, diabetes and previous MI and consequently have higher mortality and heart failure. Unlike MI with ST elevation, it may be more difficult to identify the culprit lesion, and thrombolytic therapy has been shown to worsen outcome. Supporters of an invasive strategy argue that there are several benefits to catheterization, including: 1) early identification of surgical disease, including left main lesions; 2) early identification of non-coronary disease, so that the risks of prolonged anti-thrombin or antiplatelet therapy can be reduced; 3) potential cost savings in terms of hospital length of stay; and 4) reduced angina. However, studies randomizing patients to routine early catheterization versus selective catheterization based on failure of medical management or spontaneous ischemia do not show a significant benefit in terms of death or MI in favor of the invasive arm. Indeed some studies indicated a worse outcome . In the two studies that suggested a long-term benefit of death and MI in the invasive strategy the intervention was either selective or was performed a few days or even weeks later, thus allowing the patient to be first stabilized medically.
Substantial improvements
in the management of MI patients will result from organizational and system
changes that lead to rapid and more widespread use of proven and relatively
simple therapies (i.e., improving patient recognition of chest pain, early
presentation to emergency room, improving door to needle time of thrombolytic
therapy and use of early aspirin, beta blockers and angiotensin-converting
enzyme inhibitors in appropriate patients). A small change in these factors
(e.g., a 10-min decrease in door to needle time across the U.S. or a 10%
increase in use of aspirin, beta blocker, or lipid lowering therapy) is
likely to have a large beneficial effect in improving outcomes of MI patients
A
Primary Care Approach to the Patient with Claudication
Reference: Am Fam Physician 2000;61:1027-32.
ABSTRACT:
Peripheral arterial
occlusive disease occurs in about 18 percent of persons over 70 years of
age. Usually, patients who have this disease present with intermittent
claudication with pain in the calf, thigh or buttock that is elicited by
exertion and relieved with a few minutes of rest. The disease may also
present in a subacute or acute fashion. Symptoms of ischemic rest pain,
ulceration or gangrene may be present at the most advanced stage of the
disease. In most cases, the underlying etiology is atherosclerotic disease
of the arteries. In caring for these patients, the primary care physician
should focus on evaluation, risk factor modification
and exercise.
The physician should consider referral to a vascular subspecialist when
symptoms progress or are severe. While the prognosis for the affected limb
is quite good, patients with peripheral arterial occlusive disease are
at increased risk of myocardial infarction and stroke. Therefore, treatment
measures should address overall vascular health.
Management
Patients with intermittent claudication should receive conservative treatment. Aggressive risk factor modification, smoking cessation, antiplatelet therapy and a walking program are essential. In addition, medical treatment of the symptoms of claudication may benefit some patients.
Risk Factor Modification
The goals of
risk factor modification in patients with PAOD are the same as those in
patients with coronary artery disease.
Unfortunately,
many patients with PAOD are undertreated.All classes of antihypertensive
agents are suitable in the treatment of PAOD; the type of therapy is influenced
by coexisting disease. Vasodilators provide no symptomatic relief and are
not indicated over other agents. Historically, beta-blockers have been
avoided; however, the literature does not support worsening of symptoms
with their use. Many patients may have underlying coronary artery disease
and could benefit from treatment with beta blockers.
Lipid abnormalities must be recognized and treated. High levels of low-density lipoprotein (LDL) cholesterol, low levels of high-density lipoprotein (HDL) cholesterol and high levels of triglycerides are associated with the development and progression of atherosclerosis. Patients should be treated in accordance with the guidelines of the National Cholesterol Education Program, which recommend a target LDL cholesterol level of less than 100 mg per dL (2.60 mmol per L) in patients with symptomatic vascular disease.
Tobacco is directly toxic to the vascular endothelium and is implicated in initiating and perpetuating atherosclerosis.16 All patients must be strongly encouraged to abstain from tobacco use.
Antiplatelet Agents
Three antiplatelet
agents are available for use in patients with vascular disease. Aspirin
should be considered for use in any patient with coronary artery disease,
cerebrovascular disease or PAOD. In the Physicians' Health Study,patients
who were randomized to receive aspirin therapy had a relative risk of 0.54
for peripheral arterial surgery when compared with patients who received
placebo.
The Antiplatelet
Trialists' Collaboration Study demonstrated that patients with intermittent
claudication who were treated with antiplatelet therapy had a 17.8 percent
relative reduction in the incidence of myocardial infarction, stroke and
vascular death.
Exercise
Walking improves the symptoms of claudication in several ways. The muscle can better adapt to anaerobic metabolism with repeated exposure to an ischemic environment. Oxidative metabolism and the overall number of available mitochondria increase. A meta-analysis showed an increase of 179 percent in the initial claudication distance and 122 percent in the absolute claudication distance in patients who followed a walking program. Five components of a successful program were also identified. Walking is the preferred mode of exercise. Patients should walk at least three times per week for at least 30 minutes at each session. Near-maximal claudication pain (absolute claudication distance) should be the resting point, and the patients should follow the program for at least six months. A supervised program is superior to a home-based exercise program. A walking program can increase the objective distance that the patient with claudication can ambulate. This may result in subjective improvement and lead to an enhanced quality of life.
Medication
Pentoxifylline (Trental) is approved for the treatment of intermittent claudication. While the overall efficacy of pentoxifylline has been questioned, a recent meta-analysis of patients treated with pentoxifylline demonstrated small improvements in the initial claudication distance and absolute claudication distance. Sometimes, small gains obtained by patients on a treadmill protocol equal much larger gains in walking associated with daily activities. Because of this, a trial of pentoxifylline therapy can be considered. If no improvement occurs after three months, therapy may be discontinued.
The newest agent for treating intermittent claudication is cilostazol (Pletal). Cilostazol is a phosphodiesterase inhibitor that suppresses platelet aggregation and acts as a direct arterial vasodilator. In one study, the patients who received cilostazol had a 35 percent increase in the distance they could walk before claudication and a 41 percent increase in absolute claudication distance when compared with the subjects who received placebo. One half of the patients treated with cilostazol judged their walking to be "better" or "much better"; 84 percent of patients taking placebo felt that their symptoms were unchanged or worse. Other patients taking cilostazol documented improvement in the absolute claudication distance and ankle-brachial index, along with similar subjective improvements in quality of life and walking ability.
Final Comment
Identifying the
patient with intermittent claudication is highly important. Successful
management of the disease involves aggressive risk factor modification,
antiplatelet therapy and an exercise program. Overall, the prognosis for
the diseased extremity is favorable. However, the excessive five- and 10-year
mortality rate is heavily influenced by underlying cardiovascular disease.
Can
diabetic neuropathy be prevented by angiotensin-converting enzyme inhibitors?
Reference: Ann Med 2000;32(1):1-5.
The incidence
of diabetes and its complications is increasing to staggering proportions.
Presently the WHO estimates an overall prevalence of 130 million, but by
2025 there will be 300 million individuals with diabetes mellitus. The
incidence of diabetic neuropathy approaches 50% in most diabetic populations;
there is no treatment, and its consequences in the form of foot ulceration
and amputation are financially punishing for health care providers. Attempts
to develop treatments have faltered for want of an understanding of the
aetiology of diabetic neuropathy. As a consequence, 1999 saw the demise
of two further compounds: recombinant growth factor by Roche-Genentech
and the aldose reductase inhibitor zopolrestat, by Pfizer, both had reached
phase III clinical trials. They joined an impressive list of at least 30
other compounds which have reached phase III clinical trials
and failed to
establish efficacy. The need to establish a viable treatment for human
diabetic neuropathy is absolutely paramount. To provide a rational answer
as to whether angiotensin-converting enzyme (ACE) inhibitors can prevent
human diabetic neuropathy, two major issues need addressing:
1) Does vascular dysfunction cause human diabetic neuropathy?
2) Can ACE inhibitors ameliorate diabetic vascular dysfunction and hence neuropathy?
Epidemiological
studies support a strong association between neuropathy, retinopathy and
nephropathy. Microangiopathy is deemed as the root cause of both nephropathy,
and retinopathy and mounting evidence provides support for a vascular basis
of diabetic neuropathy. ACE inhibitors appear to correct many of the abnormalities
associated with the vascular dysfunction found in diabetes. Thus effective
ACE inhibition impacts very positively on cardiovascular outcomes in patients
with ischaemic heart disease, particularly in diabetic patients. ACE inhibition
also prevents the development and progression of incipient and established
diabetic nephropathy and delays progression of background retinopathy.
Quinapril improves measures of diabetic autonomic
neuropathy.
Our recent study has demonstrated a significant improvement in peripheral
neuropathy following 12 months of treatment with the ACE inhibitor trandolapril.
