Volume 2, Number 6: June 1999

Guidelines - A missed opportunity
Reference: Atherosclerosis 1999;143(S1):S7-S12.

Summary:

Progress is slow in the integration of coronary heart disease prevention into daily clinical practice by cardiologists and other physicians working in cardiology, internal medicine and primary healthcare. This is not due to a lack of professional recommendations on coronary prevention. As new knowledge has become available, new generations of recommendations have been published. In surveys of secondary prevention practice, risk factor recording and management falls short of these recommendations and there is considerable potential to further reduce the risk of another major ischemic event in patients with established coronary disease. The most recent recommendations from the Joint Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension reinforce the importance of secondary prevention and how they can be extended to primary prevention by targeting high-risk individuals in the general population. It is hoped that development of guidelines at a national level will ensure a common approach to coronary heart disease prevention throughout Europe

Recommendations of the Second Joint Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension

Since the first joint recommendations on CHD prevention in clinical practice were published in 1994, new scientific evidence has emerged in both secondary and primary prevention, particularly in relation to lipid lowering. A second Task Force was therefore convened to revise the recommendations.

The first priority for prevention remains with patients with established CHD or other atherosclerotic disease. All patients with coronary artery disease require lifestyle advice — in relation to smoking, diet and physical activity — and appropriate management of blood pressure, lipids and other risk factors in order to achieve the goals defined in thenew recommendations. When goals are not achieved with lifestyle changes then drugtreatment should be used. Because of the high coronary risk of diabetic patients, their lipidsshould be managed according to the guidelines for secondary prevention [total cholesterol<5.0 mmol/l (190 mg/dl), LDL-cholesterol <3.0 mmol/l (115 mg/dl)], even in the absence of overt coronary artery disease. When these goals cannot be achieved with lifestyle interventions then lipid-lowering therapy should be used. The HMG-CoA reductase inhibitors (statins) have become the therapeutic group of choice in the management of these patients with elevated total and LDL-cholesterol levels.

The second focus for prevention is healthy individuals in the general population who are at high risk. In the recommendations high risk is defined as an absolute risk of greater than 20% of developing CHD (angina, non-fatal myocardial infarction and coronary death) over a 10-year period . For instance, the absolute risk of a 50-year-old man who is a smoker, has a systolic blood pressure of 142 mmHg and whose total blood cholesterol level is 5.8 mmol/l, of developing CHD over the next 10 years is 20% to 40%. In contrast, the absolute risk of a man of the same age who is a non-smoker and who has a systolic blood pressure of 138 mmHg and a total cholesterol level of 7.8 mmol/l is 10% to 20% over the next 10 years.

In addition if the risk in younger individuals when projected to age 60 exceeds 20%, they should also be regarded as high risk. For instance, a 30-year-old man who is a smoker, has a systolic blood pressure of 140 mmHg and whose total blood cholesterol level is 5.0 mmol/l, has an absolute CHD risk of 5–10% over the next 10 years . However, the same man at aged 60 has an absolute CHD risk of 20–40% over 10 years. Furthermore, the presence of other risk factors such as a low high-density lipoprotein (HDL) cholesterol level, high triglycerides or a family history of premature CHD will also increase the computed risk. A range of tools is available to physicians for calculating absolute risk from computer programs to charts . Where guidelines differ is the level of absolute risk at which treatment should be started. This is a matter of policy and not an argument about evidence.

The third focus for prevention is close relatives of patients with premature CHD or other atherosclerotic disease. These individuals may be at increased risk of CHD due to adverse lifestyles or hereditary factors such as familial dyslipidemias.

Since the 1994 recommendations were published, evidence has accumulated on the benefits of lifestyle and risk factor interventions for the patient with CHD. It is felt that the weight of this scientific evidence now justifies the recommendation of defined lifestyle and risk factor goals rather than suggested threshold levels for both lifestyle and risk factor interventions.

Lifestyle modification offers real potential to reduce cardiovascular risk factors. Patients should be strongly encouraged to adopt a healthy lifestyle, particularly if they have additional risk factors for premature cardiovascular disease, such as hypertension, dyslipidemia or diabetes mellitus. Even when lifestyle modifications alone are not adequate in controlling these other risk factors, they may reduce the number and dosage of drugs needed to reach the defined treatment goals.

Lifestyle changes for patients with CHD or other atherosclerotic disease include: smoking cessation, making healthy food choices and increasing physical activity. Cigarette smoking is a powerful risk factor for cardiovascular disease and avoidance of tobacco in any form is essential.

Differences in average levels of blood cholesterol between communities or populations are largely determined by differences in diet . Countries with high dietary saturated fat intake and a low ratio of polyunsaturated to saturated fatty acids have high average cholesterol levels. In relation to healthy food choices, the current recommendations are for a low-saturated fat diet which is rich in fruits, vegetables and cereals. In patients with established CHD, there is now evidence from three prospective, randomized, controlled trials of dietary supplementation, principally with polyunsaturated fats from vegetable and marine sources, in secondary prevention. All three trials show a reduction in coronary mortality, and two of the trials show a reduction in total mortalility. As a result of this evidence the recommendations are for partial substitution of saturated fat with poly-unsaturated fats from both vegetable and marine sources.

Patients should be encouraged to improve physical fitness through exercise. Regular aerobic activity can enhance weight loss and general well-being and reduce the risk for cardiovascular disease and all-cause mortality.

Pharmacological therapy

When the goals for secondary CHD prevention are not achieved by lifestyle intervention then pharmacological therapies may be warranted, such as blood pressure and lipid-lowering therapies. In addition to drugs needed to supplement lifestyle management of blood pressure, lipids and glucose, there are a number of classes of drug which have been shown either in single trials or in meta-analyses to reduce total mortality. These prophylactic drug therapies include aspirin and other platelet-modifying drugs, beta-blockers post-myocardial infarction, angiotensin-converting enzyme inhibitors in patients with heart failure at the time of infarction or with chronic left ventricular systolic dysfunction and anticoagulants in patients at high risk of systemic embolisation.

Primary prevention

The new recommendations recognize that the biological distinction between primary and secondary prevention is artificial. For instance, it is entirely possible for a patient with a non-Q-wave myocardial infarction to be at lower absolute risk of recurrent disease compared with an apparently healthy individual in the population who is a heavy smoker with hypertension and diabetes. It is therefore appropriate in defining goals for lifestyle and for the management of risk factors to treat patients with established CHD or atherosclerotic disease and high-risk individuals in the general population in the same way.

Conclusion

Significant reductions in the incidence of CHD can be achieved through appropriate lifestyle and therapeutic interventions.  Professional recommendations have been formulated to raise awareness of the problem and to guide physicians in patient management. However, the EUROASPIRE study, conducted in nine countries, revealed a remarkable similarity across
Europe amongst patients with coronary artery disease, many of whom have not received adequate lifestyle and therapeutic interventions.

The Second Joint Task Force recommendations state that the top priority for prevention should remain patients with established CHD or other atherosclerotic disease. Survivors of acute myocardial infarction, unstable angina and exertional angina are at increased risk for subsequent adverse cardiac events. These patients require intensive lifestyle and pharmacological interventions which can substantially reduce the risk of future morbidity and mortality. Other high-risk groups include individuals in the general population who are at high absolute multifactorial risk and close relatives of patients with premature CHD.

The real task facing cardiovascular medicine is implementation of these recommendations in clinical practice. However, the practical implementation of preventive strategies is strongly influenced by cultural, social and economic factors and not least by how medical practice is organized. Therefore, as the European Societies have produced and disseminated succinct and scientifically valid recommendations the responsibility for their implementation in both hospital and primary care lies at a national level.

Reference: American Family Physician 1999;59:2475-82.

Summary:

Clinical trials conducted during the past five years have yielded important results that have allowed us to refine our approach to stroke prevention. Treatment of isolated systolic hypertension prevents stroke and is generally well tolerated. New antiplatelet agents (clopidogrel and the combination of aspirin plus high-dose dipyridamole) have been shown to be effective in reducing vascular events in survivors of ischemic stroke, although aspirin remains the mainstay of antiplatelet therapy for stroke prevention. Several clinical trials support the benefit of lipid-lowering agents ("statins") in reducing stroke. Warfarin reduces stroke for high-risk patients with atrial fibrillation. Carotid endarterectomy is highly beneficial in reducing stroke for symptomatic patients with severe carotid stenosis (greater than 70 percent), but the benefit is less for symptomatic patients with a moderate degree of stenosis (50 to 69 percent) and for patients with asymptomatic carotid disease of any severity.

A useful concept to assess the importance of a therapy is the "number-needed-to-treat." This approach combines the relative risk reduction provided by a therapy with the absolute rate of occurrence of the event(s) of interest, to yield the actual number of patients that would need to be treated to prevent one event. Considering relative risk reduction without also considering the absolute rate can distort the importance of a therapy. For example, carotid endarterectomy for patients with severe carotid artery stenosis reduces the incidence of stroke by about 60 percent both for patients with ipsilateral strokes or transient ischemic attacks (TIAs) and for asymptomatic patients. However, because patients with ipsilateral symptoms have a far greater risk of stroke, the number-needed-to-treat with carotid endarterectomy to prevent one stroke is 10 times greater for asymptomatic patients than for those with recent ipsilateral symptoms.

To calculate the number-needed-to-treat, the absolute risk reduction by a therapy is divided into100. For example, if the rate of stroke following a TIA averages 8 percent a year and aspirin therapy reduces this rate by 25 percent, the absolute rate reduction by aspirin is 2 percent per year (8 percent – 6 percent). The number of TIA patients that would need to be treated with aspirin for one year to prevent one stroke is 100 divided by 2, equaling 50.

Antiplatelet Therapies for Cerebrovascular Disease

Aspirin and ticlopidine (Ticlid) are widely recognized as being effective for prevention of recurrent stroke in patients with TIA or ischemic stroke. Two additional antiplatelet therapies for stroke prevention have recently emerged: clopidogrel (Plavix) and high-dose dipyridamole (Persantine). Other new antiplatelet agents, such as the oral glycoprotein-IIb/IIIa inhibitors triflusal and indobufen, have not yet been adequately tested in patients with threatened stroke because of cerebrovascular disease.

Aspirin reduces the incidence of stroke by about 25 percent (the number of typical TIA or minor ischemic stroke survivors that need to be treated with aspirin for one year to prevent one stroke is about  50. Aspirin dosages between 50 and 1,300 mg per day have been shown to be effective for stroke prevention. The optimal dosage of aspirin to prevent stroke remains controversial, and both extremes of this range have been advocated. In the absence of convincing evidence favoring a specific dosage, most clinicians prescribe 325 mg per day. No patient subgroups have been defined for whom aspirin offers more or less protection (i.e., by gender or age).

The preliminary report of a recently completed randomized trial comparing different dosages of aspirin in patients following carotid surgery indicated a statistically significant difference favoring the lower dosages (81 to 325 mg per day) when the event constellation of stroke, myocardial infarction and death was considered. Although the relevance of these findings to other situations is open to question, it lends support for the use of 325 mg per day pending additional trials. The U.S. Food and Drug Administration recently recommended that aspirin dosages between 50 and 325 mg per day be used for stroke prevention. The monthly cost of aspirin in a dosage of 325 mg per day is about $1.

Ticlopidine is significantly more effective than aspirin for prevention of stroke in patients with TIA or minor ischemic stroke.10 However, the magnitude of difference between ticlopidine and aspirin therapy appears to be relatively small: the number-needed-to-treat with ticlopidine instead of aspirin for one year to prevent one stroke is about 80.

Monitoring of the white blood cell count is required every two weeks during the first three months of therapy with ticlopidine to detect leukopenia, which occurs in 1 to 2 percent of recipients; skin rash and diarrhea preclude continued use of ticlopidine in about 15 percent of patients.10 Because of these potential side effects, most clinicians reserve ticlopidine for use in patients who experience cerebral ischemia while they are taking aspirin or for aspirin-intolerant patients. The monthly cost of ticlopidine at the usual dosage of 250 mg twice daily is about $115.

Clopidogrel, a congener of ticlopidine, was compared to aspirin in an international mega-trial involving more than 19,000 participants with varying clinical manifestations of vascular disease. Of the subset of 6,431 patients with recent ischemic stroke, the small reduction in subsequent stroke attained by use of clopidogrel compared to aspirin was not statistically significant. When all participants in the trial were considered, a small but statistically significant decrease in the event constellation of stroke, myocardial infarction and vascular death was achieved by use of clopidogrel relative to aspirin (P=0.04). The toxicity of clopidogrel in a dosage of 75 mg per day was comparable to that of aspirin in a dosage of 325 mg per day, with no increase in leukopenia. It is not clear whether clopidogrel offers important benefits over aspirin for most patients with recent cerebral ischemia who are able to take aspirin. The monthly cost of clopidogrel in a dosage of 75 mg per day is currently about $87.

Dipyridamole combined with aspirin was widely used in the early 1980s for stroke prevention, until critical analysis cast doubt on its efficacy. A recent large European randomized trial found high-dose dipyridamole (200 mg twice daily, in a sustained-release preparation) plus aspirin (25 mg twice daily) to be superior to aspirin alone, with a 21 percent risk reduction relative to aspirin (P=0.006). The number-needed-to-treat with dipyridamole plus aspirin compared to aspirin alone for one year to prevent one stroke is about 80. Side effects of high-dose dipyridamole included headache and required discontinuation of the drug in 6 percent of participants. At present, the role of high-dose dipyridamole with aspirin for prevention of stroke in patients with cerebrovascular disease remains controversial. The sustained-release preparation is not currently available in the United States. The monthly cost of dipyridamide in a dosage of 200 mg twice daily ranges from about $27 for generic to $156 for a
 brand-name product.

Based on different mechanisms of platelet inhibition, the combination of aspirin with other antiplatelet agents could  theoretically enhance stroke prevention. Except for the combination of aspirin with dipyridamole, the efficacy and safety of combinations have not been established by clinical trials for patients with cerebrovascular disease. Thus, their routine use cannot be recommended at present.

With four antiplatelet agents proved to prevent stroke in patients with cerebrovascular disease, optimal antiplatelet therapy has become a subject of controversy. Each of the four agents has been advocated for use as first-line antiplatelet therapy to prevent stroke. Experts disagree about the strength of existing evidence and the clinical importance of therapy-related differences in outcome. The relative efficacies of these four agents, based on indirect comparisons, are estimated in  At present, we prescribe aspirin as first-line antiplatelet therapy, reserving clopidogrel for "aspirin failures" or aspirin-intolerant patients. More data are needed about the value of high-dose dipyridamole plus aspirin and other combinations

Understanding Intermittent Claudication
Reference: http://www.powerpak.com/CE/CLAUDICATION/lesson.htm

Drug Therapy for Claudication

                Numerous drugs have been proposed for the treatment of claudication. However, from the time that
                pentoxifylline was approved for treating claudication, no other drug has been approved until
                recently. Thus, claudication has proved an elusive target for treatment and many efforts are being
                made to find an efficacious and safe treatment. The following discussion is not meant to be
                exhaustive but provides an overview of the various classes of drug which have been and are being
                evaluated for treating claudication. Data on results of functional status/quality of life evaluation by
                questionnaire are provided when obtained.

                Vasodilators—Arteriolar vasodilators were the first class of agents used to treat claudication.
                Examples include drugs that inhibit the sympathetic nervous system (alpha-blockers), direct acting
                vasodilators (papaverine), beta2-agonists (nylidrin), calcium channel blockers (nifedipine), and
                angiotensin converting enzyme inhibitors. Randomized, controlled trials of these drugs did not
                demonstrate clinical efficacy. Lack of efficacy with these drugs may be due to several
                reasons. One potential explanation is that in PAD patients, the primary determinant of arterial blood
                flow and oxygen delivery to skeletal muscle is the degree of large vessel arterial occlusive disease.
                This means that drugs which dilate arterioles distal to the large vessel occlusions will not lead to
                increased blood flow because there is a fixed blockage. Thus, as a class of drugs, vasodilators are
                not likely to improve walking ability.

                Anticoagulant/antiplatelet drugs—Aspirin and other antiplatelet agents are very important for the
                purpose of treating the cardiovascular risks associated with systemic atherosclerosis (as previously
                discussed). However, an improvement in walking ability due to these agents has not been
                established. To date, no benefit on walking ability has been shown by studies that have evaluated
                the effects of aspirin or coumarin in patients with intermittent claudication. In contrast, data from
                some studies suggest that ticlopidine, a potent inhibitor of platelet aggregation which also has
                hemorheologic effects, may have some benefit for walking ability in persons with claudication.
                In five trials in Europe and Russia, the effect of ticlopidine on walking time has been evaluated.
                Balsano et al, in a randomized, controlled study of 151 people with claudication given ticlopidine or
                placebo, found that walking time (absolute and pain-free) improved significantly in the patients given
                ticlopidine. Benefits were sustained over a 21 month period. Arcan and others performed a
                randomized double-blind trial of ticlopidine vs placebo in 169 claudicants. As with the Balsano
                study, both absolute and pain-free walking time improved more with ticlopidine than with placebo.
                A study from the Swedish ticlopidine multicenter study group in 101 patients did not show
                improvement in walking time for ticlopidine, although this was not a primary endpoint of this
                study. A Russian study performed in claudicants which was not randomized or controlled
                showed that 73% of patients increased pain-free walking distance after 4 to 6 months of
                ticlopidine. An additional trial compared the effects of ticlopidine to nicotinate and found that
                ticlopidine improved walking ability more than nicotinate over a longer period. These studies
                collectively suggest that ticlopidine may benefit walking distance in patients with claudication.
                However, these studies have had some methodological problems; therefore, to evaluate the
                potential benefits of this type of drug to improve walking ability in patients with claudication, more
                well-designed studies will be needed.

                The next generation of antiplatelet agents, the glycoprotein IIb/IIIa receptor antagonists, will be the
                next type of antiplatelet drugs to be evaluated for improving walking ability for persons with
                claudication.

                Hemorheologic Agents—Patients with PAD have been shown to have hemorheologic defects
                including non-deformable red cells, elevated fibrinogen levels, and increased platelet aggregation
                leading to increased blood viscosity. The effects of these phenomena on blood flow are
                unknown. However, it has been seen that pentoxifylline, an agent which improves red cell
                deformability, lowers fibrinogen levels, and decreases platelet aggregation, increases walking
                distance in patients with PAD. Pentoxifylline, in controlled trials, produced a 22% improvement
                over placebo in walking distance prior to the onset of claudication and a 12% improvement in the
                maximal walking distance. However, there are some methodological considerations with this
                study, and other studies have shown ambiguous results.

                Ketanserin is a selective serotonin (S2) antagonist which lowers blood viscosity and also has
                vasodilator and anti-platelet properties. However, in controlled trials this drug has not been effective
                in treating claudication.

                Cilostazol—Cilostazol is the first drug to gain FDA approval for the indication of treating
                intermittent claudication since pentoxifylline was approved. Cilostazol belongs to the class of drugs
                called phosphodiesterase inhibitors. This drug also has significant antiplatelet and vasodilatory
                capacity. In addition, cilostazol has antiproliferative properties. In several randomized, controlled
                clinical trials, cilostazol proved to be efficacious for increasing absolute walking distance. For
                example, in a phase III trial, 239 patients with claudication were randomized to placebo or
                cilostazol 100 mg BID. Administration of cilostazol resulted in a 47% increase (significant) in
                maximal walking distance compared to placebo at 16 weeks. In addition, taking active drug was
                also associated with improvements in functional status and quality of life according to some
                measures of the Walking Impairment Questionnaire and the SF-36. Thus, cilostazol appears to be a
                very effective agent for patients with claudication.

                Prostaglandins—The goal of using prostaglandin drugs to treat claudication is being explored.
                Beraprost sodium, a PGI2 analogue which is taken orally, was used in a single phase II
                dose-ranging study where 164 patients were randomized to placebo or one of three doses of
                drug. No significant improvement in absolute walking time was reported. All of the treated
                groups showed an improved pain-free walking time at weeks 10 and 12 with the greatest
                improvements seen in the groups taking the two lower doses of drug. In addition, at the highest
                dose, 62% of the patients reported side effects including headache, flushing, and gastrointestinal
                intolerance.

                Prostaglandin E1, available for intravenous use, has been administered in several studies. In a
                randomized, double-blind, placebo-controlled multicenter clinical trial, 213 persons limited by
                intermittent claudication received PGE1 or placebo for 4 weeks administered intravenously 5 days a
                week. Subsequently, infusions were given biweekly for 4 more weeks. Patients who received the
                active drug improved their maximum walking time significantly more (101%) than those treated with
                placebo (60%).

                Finally, a smaller study using PGE1 showed that the drug may benefit quality of life. In 104
                patients with intermittent claudication, PGE1 was administered daily for 4 weeks in a non-blinded,
                non-controlled study. Quality of life was assessed using a disease-specific questionnaire as well as
                by the MHIQ. The study showed that improvements resulted in all of the questionnaire domains
                assessed, in concordance with treadmill findings. Because this study was a pilot project, further
                studies which are randomized and controlled will be required to confirm the observed results.

                An additional drug in this class which is now being evaluated is AS-013, a prostaglandin E1
                prodrug. This drug, which is incorporated into lipid microspheres, was administered intravenously
                to patients with intermittent claudication. Eighty patients received either placebo or one of three
                dosage regimens. A statistically significant increase in maximum walking time was observed at 4 and
                8 weeks for the active control vs placebo.

                Metabolic Agents—Although PAD is clearly associated with a limitation in arterial blood flow,
                patients with PAD also develop metabolic abnormalities in their skeletal muscle. Changes in
                carnitine metabolism are one example of this in PAD. Carnitine, an important cofactor for skeletal
                muscle intermediary metabolism during exercise, is required for the mitochondrial oxidation of
                long-chain fatty acids, and also helps to maintain normal cellular metabolism under conditions of
                metabolic or hypoxic stress. Patients with PAD have been shown to accumulate acylcarnitines
                (intermediates of oxidative metabolism) in their skeletal muscle, which is directly correlated with
                impaired exercise performance. It has thus been hypothesized that supplementation of patients
                with carnitine would improve ischemic muscle metabolism since carnitine, and an acyl form of
                carnitine (propionyl-L-carnitine), have been shown to increase exercise performance in patients with
                PAD in some trials.

                A double-blind, dose titration study was conducted to evaluate the efficacy of
                propionyl-L-Carnitine (PLC) in 245 patients with claudication. Maximal walking time improved
                in persons taking the active drug vs placebo. Quality of life was measured using the MHIQ
                questionnaire. It was found that patients who received the drug had a higher global MHIQ score
                than those who received placebo. This was due to an improvement in emotional domains. The
                Physical Function score tended to improve although it did not reach significance, possibly because
                many of the items in this category relate to self-care activities not necessarily affected by
                claudication.

                Angiogenic Growth Factors—Vascular endothelial growth factor (VEGF) and basic fibroblast
                growth factor (bFGF) are mitogenic agents for the development of new collateral channels in
                models of peripheral ischemia. Vascular endothelial growth factor has been shown to augment
                collateral vessel development and increase capillary density in skeletal muscle in a rabbit model.128
                This effect has been observed when the VEGF protein is administered by intra-arterial infusion and
                when the DNA encoding for VEGF is given by intra-muscular injection. Trials are now
                underway in the United States and Europe to determine if this therapy has clinical application in
                patients with claudication and critical leg ischemia.

                Other Drugs to Treat Intermittent Claudication—Sulodexide is a glycosaminoglycan drug,
                administered orally, which has anticoagulant and antithrombotic properties as well as beneficial
                effects on lipids. This drug has been used to treat intermittent claudication primarily in Russia and in
                parts of Europe. In one study in 107 persons with intermittent claudication, sulodexide was given
                in a randomized study controlled with pentoxifylline. At the end of the study, absolute walking time
                was significantly greater in sulodexide-treated patients compared to the other group. These findings
                were corroborated in the results of an Italian meta-analysis. In addition to its effects on walking
                time, the drug was very well tolerated.

                Aminophylline inhibits adenosine receptors and thus may blunt the vasodilation response during
                exercise. This effect would theoretically limit the steal of blood away from ischemic skeletal muscle.
                Intravenous aminophylline was shown to improve treadmill exercise performance in patients with
                claudication in one study.

                A final comment should be made about drugs which are used without scientific basis for the purpose
                of improving claudication. Chelation therapy has been suggested (albeit without scientific supporting
                data) as a means to relieve symptoms of cardiovascular disease. One randomized, double-blind,
                multi-center trial has been conducted of EDTA in patients with PAD. The drug was not shown to
                be effective in treating the symptoms of claudication nor in improving the ABI. Other substances
                which have been suggested to treat claudication include garlic and ginkgo biloba. Scientific data are
                also lacking to support these claims.

Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial.

Reference: Drugs Exp Clin Res 1999;25(1):29-36.

The authors evaluated the efficacy of propionyl-l-carnitine, a drug able to reduce peripheral resistance and protect the cells against oxidative stress damage, in patients affected by peripheral arterial obliterative disease at class II of Fontaine. The study was performed on 22 patients according to a double-blind, randomized design in parallel with placebo. The drug was administered at a dosage of 1 g three times a day orally for 90 days. At recruitment and at the end of the study all patients underwent physical examination, treadmill test, doppler C.W. of the lower limbs, ankle/brachial index, dosage of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), hematocrit, hematic filtration, and viscosity. In the group treated with propionyl-l-carnitine a statistically significant increase of claudication distance, blood flow velocity, PAI-1 activity and red blood cell deformity was observed. These data suggest the usefulness of propionyl-l-carnitine in the treatment of patients affected by peripheral arterial obliterative disease.