Real world data from a multi-centre study on the effects of cilostazol on pain symptoms and walking distance in patients with peripheral arterial disease.

OBJECTIVE: to assess the effects of cilostazol on pain-free walking distance in PAD patients with IC at 3 and 6 months in a real world, prospective, observational study. We included 1015 PAD patients presenting with IC (71.3% men, 93.5% white, mean age 69.2 ± 8.7 years). Patients were followed up for 6 months by their physicians. RESULTS: Cilostazol significantly increased pain-free walking distance by a median of 285 and 387 m at 3 and 6 months, respectively (p < 0.01 for all comparisons). This effect was significant for patients 50-74 years (but not for those aged ≥ 75 years) and independent of smoking status, changes in physical activity, comorbidities and concomitant medication for PAD (i.e., acetylsalicylic acid and clopidogrel). Furthermore, significant reductions were observed in systolic (from 139 ± 16 to 133 ± 14 mmHg; p < 0.001) and diastolic blood pressure (from 84 ± 9 mmHg to 80 ± 10 mmHg; p < 0.001). Smoking cessation and increased physical activity were reported by the majority of participants. In conclusion, cilostazol was shown to safely decrease pain symptoms and improve pain-free walking in PAD patients with IC in a real world setting. Benefits also occurred in terms of BP and lifestyle changes.

Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials.

Beta-Adrenergic blockers have been considered relatively contraindicated in peripheral arterial disease because of the perceived risk that these drugs could worsen intermittent claudication. Therefore, we conducted a meta-analysis of available randomized controlled trials from the English-language literature to determine whether or not beta-blockers exacerbate intermittent claudication. The primary focus of this analysis was the effect of beta-blockers on exercise duration, measured as walking capacity or endurance time. Outcomes were pooled where appropriate. Of 11 eligible reports, six included 11 individual controlled treatment comparisons that provided data for an analysis of pain-free exercise capacity; no effect size was statistically significant. The pooled effect size for pain-free walking distance was -0.24 (95% confidence interval, -0.62 to 0.14), indicating no significant impairment of walking capacity compared with placebo. Only one study reported that certain beta-blockers were associated with worsening of intermittent claudication. These results strongly suggest that beta-blockers do not adversely affect walking capacity or symptoms of intermittent claudication in patients with mild to moderate peripheral arterial disease. In the absence of other contraindications, beta-blockers can probably be used safely in such patients.

Methysergide in the treatment of narcolepsy.

Five patients with narcolepsy (four with the allied symptom of cataplexy) were treated with the serotonin antagonist methysergide. All patients had as good control of their sleep attacks while on methysergide therapy as on a control period of dextroamphetamine therapy. The cataplexy was less well controlled by methysergide than by dextroamphetamine, but improved when compared to a period without medication. Two patients developed severe calf claudication while on methysergide.

Bilateral focal cortical atrophy and chronic ergotamine abuse.

A 67-year-old patient took 5 mg of ergotamine daily for 18 months. His headaches and dysphoria were greatly improved by stopping this drug. Brain imaging by CT and magnetic resonance techniques showed numerous atrophic lesions that may represent infarcts due to occlusion of superficial cortical vessels.

Lower extremity arterial insufficiency after long-term methysergide maleate therapy. Its evaluation with Doppler ultrasonic velocity detector.

Iatrogenic ergotism is the primary source of ergot intoxication. The patient whose case is reviewed had migraine headaches and received methysergide maleate for 13 years. She had, in July 1977, severe claudication of the lower extremities. Measurements of the peripheral arterial circulation were made using the Doppler ultrasonic velocity detector. The extent of disease and subsequent reversal were documented using arteriographic examination. Initial measurements showed the patient was able to walk for one minute and 34 seconds on a treadmill (2 mph, 10% grade) before stopping because of claudication. Symptoms cleared after drug withdrawal and repeated testing produced no claudication. The calculated index (posterior tibial/arm pressure) increased from a mean of 0.22 to 0.74 during the eight-month period following discontinuance of methysergide therapy with no recurrence of migraine headaches. A review of the literature is also presented.

Blood pressure and other cardiovascular risk factors of long-term exposure to lead.

The coronary risk profile was studied for 96 heavily exposed lead smelter workers employed between 9 and 45 years and for a reference group not exposed to lead but comparable with respect to age, sex, height, weight, social grouping, occupational status, and alcohol and tobacco consumption. The lead smelter workers had a little higher diastolic blood pressure and significantly more ischemic electrocardiographic changes, and their high-density lipoprotein levels were lower than the corresponding values of the reference group. The lead workers with electrocardiographic changes had higher blood pressures than the referents with corresponding changes. These findings indicate a higher coronary risk profile for the examined lead smelter workers. The study supports the hypothesis of a positive association between lead exposure and arteriosclerosis and high blood pressure.

Severe vascular spasm due to erythromycin-ergotamine interaction.

We report a case of ergotism due to the interaction of erythromycin with a small dose of ergotamine tartrate (2 mg). Besides severe peripheral vasospasm with dysaesthesiae there was transient renal ischaemia. Recovery occurred after several weeks without sodium nitroprusside therapy. Cases previously reported in the literature are reviewed.

The effect of withdrawal of beta-adrenergic blockade on intermittent claudication.

Twenty-eight patients with intermittent claudication were studied before and one month after withdrawal of treatment with beta-adrenergic blocking drugs for hypertension, coronary heart disease or both. Heart rate, blood pressure, ankle/arm systolic blood pressure ratio and ankle pulse volume recording (PVR) at rest and after treadmill exercise were recorded, as well as walking distance, time of recovery from subjective symptoms, restitution time of pressure ratio and PVR. A control group of 14 patients, whose beta-adrenergic blocking drugs were not withdrawn, was also included. The result can be summarized as showing that withdrawal of beta-blockade was not demonstrably advantageous in patients with intermittent claudication. Significant improvement was observed only during the first month of the trial, a change which was independent of withdrawal of beta-blockade. The relief of subjective symptoms after exercise occurred significantly faster after withdrawal of nonselective beta-blockade. Otherwise, there was no difference between nonselective and cardioselective beta-adrenergic blocking drugs.

Ergotamine-induced intermittent claudication.

We report about a female patient with intermittent claudication caused by ergotamine. She used ergotamine as a treatment for migraine headaches for more than 4 years. The claudication began 7 month before admission. Colour Doppler sonography and angiography showed severe stenosis of the left external iliac and superficial femoral artery. The patient was treated with phenprocoumon for one year after withdrawal of ergotamine. After that the superficial femoral stenosis disappeared completely, but the external iliac stenosis was still present and was consequently successfully treated by atherectomy. The histology showed a fibrosis of the intima and a hypertrophy of the media.

The influence of chronic treatment with betablockade and angiotensin converting enzyme inhibition on the peripheral blood flow in hypertensive patients with and without concomitant intermittent claudication. A comparative cross-over trial.

In a comparative cross-over trial we examined the influence of the betablocker bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2 groups of hypertensive patients with and without concomitant intermittent claudication. In 11 patients with hypertension without peripheral arterial obstructive disease and 11 patients with hypertension and claudication we assessed the blood pressure, leg blood flow, vascular resistance, walking distance, transcutaneous oxygen consumption and Laser-Doppler flow after treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once daily. The walking distance of patients with claudication improved in all patients while participating in an exercise program. For both treatment groups this improvement was significant (p < 0.05) compared to baseline, from 264 m at baseline to 313 m with bisoprolol and to 400 m with lisinopril. The difference was not significant between the both drugs. In patients without peripheral vascular obstructive disease we found a significant (p < 0.05) reduction in blood flow for both drugs. The peripheral blood flow parameters of 38 legs showed no statistical significant effect of bisoprolol nor lisinopril on the local vascular resistance at rest, after occlusion or after exercise.