Plantar flexion as an alternative to treadmill exercise for evaluating patients with intermittent claudication.

OBJECTIVE: The aim of this study was to examine whether the plantar flexion test could adequately replace treadmill testing in patients who were unable to exercise. DESIGN: Prospective observational study. PATIENTS: Twenty-seven patients with intermittent claudication secondary to peripheral arterial disease (PAD). METHODS: Patients performed two treadmill tests and two plantar flexion tests. Ankle pressure, near infrared spectroscopy (NIRS) data, heart rate and blood pressures were monitored along with pain-free and maximum walking distances for treadmill, pain-free and maximum exercise time for plantar flexion. RESULTS: Maximum exercise time and walking distance were well correlated (R=0.74). Eleven patients (41%) developed non-claudicating symptoms during the treadmill test but not during the flexion test. Rate pressure product was significantly higher after the treadmill but not after the plantar flexion. CONCLUSIONS: Plantar flexion test showed good reliability and correlation. Plantar flexion may serve as an alternative to treadmill testing in evaluating muscle pain in patients with intermittent claudication.     

Reproducibility of constant-load treadmill testing with various treadmill protocols and predictability of treadmill test results in patients with intermittent claudication

BACKGROUND: Most trials on the reliability of constant-load treadmill testing use one pair of treadmill settings (speed, grade) only. The question of whether the results can be applied to tests with different settings is left open. Also, claudication distances measured with differing settings are not comparable, rendering the comparison of the results from different trials difficult. This study evaluates the reliability of constant-load testing with various workloads and compares them with claudication distances achieved with walking at normal speed on level ground but also evaluates whether metabolic equivalent (MET) normalization can be used to translate the results of different treadmill tests into each other. METHODS: Fifteen patients with claudication underwent repeated treadmill testing with different treadmill settings, including speeds of 2.0, 3.2, and 4.0 km/h (1.25, 2.0, and 2.5 mph, respectively) and grades of 0% and 12%. The walking capacity was also tested on level ground with a speed chosen by the individual patient. Results of virtual treadmill tests with all possible combinations of the speeds and the grades used were predicted from real tests, with MET normalization. The relationship between real and predicted claudication distances was tested with regression modeling. RESULTS: Reliability coefficients (RCs) for the absolute claudication distance (ACD) were superior to RCs for the initial claudication distance. RCs for ACD ranged between 0.61 and 0.95, with increasing values found with increasing workloads. The best coefficients for the regression of measured on predicted claudication distances were achieved with a model on the basis of a power function (r = 0.963). The model was only appropriate for the prediction of group mean results from clinical trials but cannot be applied to single patient data. For proof of concept, the model was tested with six published studies in which the claudication distances of a patient sample were double treadmill tested with different workloads. The result of the second test was predicted from the first test, and estimated and measured claudication distances were compared. The mean difference (all trials) was 7.9%, whereas the maximum difference amounted to 16.5%. CONCLUSION: For an optimal treadmill test reliability, higher workloads should be used and ACD should be preferred over initial claudication distance. MET normalization provides the basis for the comparability of treadmill test results achieved with different test conditions.     

Cardiovascular and musculoskeletal response to supervised exercise in patients with intermittent claudication

ObjectiveIntermittent claudication occurs in 20% of the population older than 70 years, and treatment includes a supervised exercise program (SEP). Whereas there is evidence demonstrating walking improvements after an SEP, there are conflicting data on the physiologic changes behind this. This study aimed to explore and to identify the potential cardiovascular and musculoskeletal changes with exercise.MethodsThis was a single-center study at a vascular unit in England. Following written informed consent, 109 patients were recruited for an SEP, three times per week for 12 weeks. Outcome measures included walking distances, quality of life, cardiorespiratory fitness, flow-mediated dilation, and muscle strength and endurance. For normal data, paired sample t-tests were performed to compare baseline data to all time points for significance. For nonparametric data, Wilcoxon signed rank tests were performed. Significance was set at P < .05. The association between functional improvement (ie, walking distance at 3 months after the SEP) and metabolic response and patients' characteristics was determined by multivariable regressions.ResultsMaximum walking distance significantly improved from baseline by 117% at 1 week, 143% at 4 weeks, and 143% at 12 weeks after exercise. Claudication distance also significantly improved from baseline by 222% at week 1, 393% at week 4, and 452% at week 12. Quality of life significantly improved at all time points in seven of nine domains of the 36-Item Short Form Health Survey and two of five domains of the Vascular Quality of Life questionnaire. Markers of cardiorespiratory fitness significantly improved at all time points. Flow-mediated dilation demonstrated a 50% improvement, but this was not statistically significant. Muscle strength and muscle endurance significantly improved at all time points. Multivariate regression demonstrated that the ventilatory anaerobic threshold and the physical component summary score for quality of life predicted improvements in 12-week walking distance.ConclusionsThis study identified that the ventilatory anaerobic threshold and physical component summary scores from quality of life were the best predictors of improvement in an SEP. Future studies should prioritize these outcomes and assess whether different SEPs have similar effects. Cardiorespiratory fitness was also a predictor of outcome and should be prioritized in future studies alongside traditional measures.     

The validity of ankle-brachial index for the differential diagnosis of peripheral arterial disease and lumbar spinal stenosis in patients with atypical claudication

Purpose

Claudication is a typical symptom of peripheral arterial disease (PAD) and lumbar spinal stenosis (LSS). Differential diagnosis of PAD and LSS is often difficult due to the subjective natures of symptoms and atypical signs. The authors aimed to determine the usefulness of ankle-brachial index (ABI) measurement for the differential diagnosis of PAD and LSS when the etiology of claudication is uncertain.

Methods

Forty-two consecutive patients who had been referred by spine surgeons to a lower extremity vascular surgeon for atypical claudication were retrospectively analyzed. Atypical claudication was defined as claudication not caused by PAD, as determined by clinical manifestations, or by LSS, as determined by MR imaging. A final diagnosis of PAD was established by CT angiography (CTA) and of LSS by excluding PAD. Diagnostic validity of ABI for PAD in atypical presentation was assessed.

Results

Sixty-two legs of 42 atypical claudication patients were analyzed. Mean patient age was 65.8 ± 8.2 years (38–85) and 29 (69.0%) had diabetes mellitus. Mean ABI was 0.73 ± 0.14 (0.53–0.94) in the PAD group and 0.92 ± 0.18 (0.52–1.10) in the LSS group (P < 0.001). Of the 33 legs with a low ABI (ABI < 0.9), 29 legs were diagnosed as true positives for PAD by CTA and 4 were false positives, and of the 29 legs with a high ABI, 5 were false negatives and 24 were true negatives. The sensitivity and specificity of ABI for the diagnosis of PAD in patients with atypical claudication were 85.3 and 85.7%, respectively, and its positive and negative predictive values were 87.9 and 82.8%.

Conclusions

ABI is a recommended screening test for the differential diagnosis of lower leg claudication when clinical symptoms are atypical.     

平板运动试验后心率恢复异常多囊卵巢综合征患者临床特征研究

目的探讨平板运动试验后心率恢复异常的多囊卵巢综合征(PCOS)女性的临床特征,提出此类心血管疾病易感人群干预的重点和方向。方法选择平板试验运动阴性PCOS患者50例为病例组,根据患者运动试验停止后心率恢复(HRR)结果分为HRR异常组和HRR正常组,另选同期我院健康体检年龄匹配的健康女性20例为对照组。检测所有受试者睾酮(T),检测空腹血糖(FBG)空腹胰岛素(FINS)水平并计算胰岛素抵抗指数HOMA-IR。比较各组平板运动试验结果并使用我科研发的糖尿病/肥胖综合评估与康复处方系统调查分析受试者运动行为。结果 HRR异常组PCOS患者表现出显著的中心性肥胖(0.94±0.07vs.0.81±0.07,P0.05),高雄激素血症(4.34±1.13vs.1.93±0.98,P0.05),其安静心率显著高于HRR正常组以及对照组而两项乘积(RPP)显著低于另两组(P0.05)。运动行为方面HRR异常组表现出明显增高的职业活动的比例(0.36±0.16vs.0.20±0.17,P0.05),而在日常活动以及运动方面三组没有显著差异。结论中心性肥胖、安静心率增高、最大收缩压下降以及职业压力大均是PCOS女性心血管疾病易感人群的显著特征。     

Cardiopulmonary exercise testing provides a predictive tool for early and late outcomes in abdominal aortic aneurysm patients

INTRODUCTION

The aim of this study was to determine if cardiopulmonary exercise testing (CPET) predicts 30-day and midterm outcomes when assessing suitability for abdominal aortic aneurysm (AAA) repair.

METHODS

Since July 2006 consecutive patients from a single centre identified with a large (≥5.5cm) AAA were sent for CPET. Follow-up was completed on 1 August 2009. Univariate logistical regression was used to compare CPET parameters with the Detsky score, the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Vascular Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (VPOSSUM) in predicting predefined early and late outcome measures.

RESULTS

Full data were available for 102 patients (93% male, median age: 75 years, interquartile range (IQR): 70–80 years, median follow up: 28 months, IQR: 18–33 months). Ventilatory equivalents for oxygen and APACHE II predicted postoperative inotrope requirement (p=0.018 and p=0.019 respectively). The Detsky score predicted the length of stay in the intensive care unit (p=0.008). Midterm (30-month) survival was predicted by the anaerobic threshold (p=0.02).

CONCLUSIONS

CPET provided the only means in this study of predicting both 30-day outcome and 30-month mortality. CPET could therefore become an increasingly important tool in determining the optimum management for AAA patients.     

跑台运动对阿霉素联合醋酸戈舍瑞林诱导骨质疏松大鼠骨密度和骨代谢的影响

目的研究阿霉素(doxorubicin,DOX)和醋酸戈舍瑞林(goserelin acetate,GA)联合作用对大鼠骨密度和骨代谢的影响,以及跑台运动对DOX联合GA诱导的大鼠骨质疏松的防治效果。方法 8周龄雌性SD大鼠64只,被随机分为8组,每组8只:安静对照组(SED)、DOX干预组(SED+DOX)、GA干预组(SED+GA)、DOX和GA联合干预组(SED+DOX+GA)、跑台运动对照组(EX)、跑台运动结合DOX干预组(EX+DOX)、跑台运动结合GA干预组(EX+GA)、跑台运动结合DOX和GA联合干预组(EX+DOX+GA)。药物和跑台运动干预周期均为8周,8周后测试所有大鼠左侧股骨骨密度和血清骨代谢指标。结果与其相对应的非药物干预各组相比较,药物干预各组大鼠骨密度显著降低、骨形成指标ALP和BGP显著降低而骨吸收指标Ca2+和TRACP5b显著升高;与DOX单独干预组及GA单独干预组相比较,DOX和GA联合干预组大鼠骨密度显著降低、骨形成指标ALP和BGP显著降低而骨吸收指标Ca2+和TRACP5b显著升高;与其相对应的安静组相比较,跑台运动各组大鼠骨密度显著升高、骨形成指标ALP和BGP显著升高而骨吸收指标Ca2+和TRACP5b显著降低。结论 DOX和GA单独或联合作用均可导致大鼠骨质疏松症的发生,且DOX和GA联合作用诱导大鼠骨质疏松的程度显著大于DOX或GA单独作用的结果;跑台运动可以有效降低DOX和GA单独或联合作用诱导的大鼠骨质疏松。     

Early peripheral vascular interventions for claudication are associated with higher rates of late interventions and progression to chronic limb threatening ischemia

ObjectiveDespite societal guidelines that peripheral vascular intervention (PVI) should not be the first-line therapy for intermittent claudication, a significant number of patients will undergo PVI for claudication within 6 months of diagnosis. The aim of the present study was to investigate the association of early PVI for claudication with subsequent interventions.MethodsWe evaluated 100% of Medicare fee-for-service claims to identify all beneficiaries with a new diagnosis of claudication from January 1, 2015 to December 31, 2017. The primary outcome was late intervention, defined as any femoropopliteal PVI performed >6 months after the claudication diagnosis (through June 30, 2021). Kaplan-Meier curves were used to compare the cumulative incidence of late PVI for claudication patients with early (≤6 months) PVI vs those without early PVI. A hierarchical Cox proportional hazards model was used to evaluate the patient- and physician-level characteristics associated with late PVIs.ResultsA total of 187,442 patients had a new diagnosis of claudication during the study period, of whom 6069 (3.2%) had undergone early PVI. After a median follow-up of 4.39 years (interquartile range, 3.62-5.17 years), 22.5% of the early PVI patients had undergone late PVI vs 3.6% of those without early PVI (P < .001). Patients treated by high use physicians of early PVI (≥2 standard deviations; physician outliers) were more likely to have received late PVI than were patients treated by standard use physician of early PVI (9.8% vs 3.9%; P < .001). Patients who had undergone early PVI (16.4% vs 7.8%) and patients treated by outlier physicians (9.7% vs 8.0%) were more likely to have developed CLTI (P < .001 for both). After adjustment, the patient factors associated with late PVI included receipt of early PVI (adjusted hazard ratio [aHR], 6.89; 95% confidence interval [CI], 6.42-7.40) and Black race (vs White; aHR, 1.19; 95% CI, 1.10-1.30). The only physician factor associated with late PVI was a majority of practice in an ambulatory surgery center or office-based laboratory, with an increasing proportion of ambulatory surgery center or office-based laboratory services associated with significantly increased rates of late PVI (quartile 4 vs quartile 1; aHR, 1.57; 95% CI, 1.41-1.75).ConclusionsEarly PVI after the diagnosis of claudication was associated with higher late PVI rates compared with early nonoperative management. High use physicians of early PVI for claudication performed more late PVIs than did their peers, especially those primarily delivering care in high reimbursement settings. The appropriateness of early PVI for claudication needs critical evaluation, as do the incentives surrounding the delivery of these interventions in ambulatory intervention suites.     

The diagnostic value of a treadmill test in predicting lumbar spinal stenosis

Lumbar spinal stenosis is a frequent indication for spinal surgery. The predictive quality of treadmill testing and MRI for diagnostic verification is not yet clearly defined. Aim of the current study was to assess correlations between treadmill testing and MRI findings in the lumbar spine. Twenty-five patients with lumbar spinal stenosis were prospectively examined. Treadmill tests were performed and the area of the dural sac and neuroforamina was examined with MRI for the narrowest spinal segment. VAS and ODI were used for clinical assessment. The median age of the patients was 67 years. In the narrowest spinal segment the median area of the dural sac was 91 mm². The median ODI was 66 per cent. The median walking distance in the treadmill test was 70 m. The distance reached in the treadmill test correlated with the area of the dural sac (Spearman’s ρ = 0.53) and ODI (ρ = −0.51), but not with the area of the neuroforamina and VAS. The distance reached in the treadmill test predicts the grade of stenosis in MRI but has a limited diagnostic importance for the level of clinical symptoms in lumbar spinal stenosis.     

Reproducibility of incremental maximal cycle ergometer testing in patients with restrictive lung disease.

BACKGROUND--Exercise testing has become an important tool in the diagnosis and treatment of restrictive lung disease. The reproducibility of variables measured during exercise testing was examined in subjects with stable restrictive lung disease. METHODS--Six subjects, who had never previously undergone exercise testing, each underwent three maximal incremental exercise studies on a bicycle ergometer conducted during a 28 day period. RESULTS--Data collected at rest, before exercise, were not significantly different during the three study days. Comparison of results at the end of the exercise tests from the three studies also revealed no evidence of a significant learning effect. Reproducibility of exercise performance by subjects was assessed by the coefficient of variation. The mean within subject coefficient of variation at the end of the exercise tests was 5.6% for work rate, 7.9% for exercise duration, and 9.5% for dyspnoea. The mean within subject coefficient of variation obtained at the end of the exercise tests was 5.3% for oxygen uptake (VO2), 2.5% for oxygen saturation (SaO2), 4.0% for heart rate (HR), 5.5% for minute ventilation (VE), 5.8% for respiratory frequency (f), and 4.6% for tidal volume (VT). The mean within subject coefficient of variation at 40% and 70% of maximal work rates for VO2 was 5.7% and 5.6% respectively, for SaO2 1.3% and 1.5%, for HR 4.8% and 4.0%, for VE 6.3% and 6.6%, for f 10.1% and 7.8%, and for VT 6.0% and 4.5%. CONCLUSIONS--Variables measured during clinical exercise testing in subjects with restrictive lung disease are highly reproducible. No significant learning effect was found on repeated testing in subjects who had never previously undergone exercise testing.     

Loading is more effective than posture in lumbar spinal stenosis: a study with a treadmill equipment

The objective of this study was to assess the correlation between neurogenic intermittent claudication (NIC) in LSS and different positions as well as loading status, using the treadmill device. The study was a prospective clinical trial on lumbar spinal stenosis (LSS) using a treadmill equipment. The study population comprised of 80 LSS patients with a mean age of 61. The equipment included a treadmill, unloading station and loading vests. The patients were instructed to walk in five different positions. The initiation time of symptoms and total walking time were recorded. The examination was stopped after 20 min or at the onset of severe symptoms. In order to obtain pretest demographic data on subjects, visual analog scale, Roland–Morris questionnaire, pain disability index, and Beck depression index were used. The initiation time of symptoms (ITS) and total walking time (TWT) were measured during the test. Unloading provided a longer and loading a shorter ITS and TWT. Decline or incline positions did not affect ITS or TWT. The changes in posture had no correlation with the appearance of symptoms in LSS patients with NIC on a treadmill in this study, rather ITS and TWT were determined by axial loading and unloading.     

Supine arm cycling during the post-flap recovery period for persons with spinal cord injuries: The multi-purpose arm cycle ergometer (M-PACE) safety and pilot testing

Objective:To describe how using a supine arm cycle ergometer can safely reduce deconditioning experienced by patients with spinal cord injury or disorder (SCI/D) during their four to six weeks of complete bed rest after surgery to close a stage 4 pressure injury.Design:This pilot project used a newly designed arm cycle ergometer (known as the M-PACE) that extends over the bed, allowing a patient to lie completely supine while exercising.Setting:The M-PACE was designed and built at the Minneapolis Veterans Affairs Health Care System (MVAHCS) and pilot tested at the MVAHCS SCI/D Center.Participants:Patients with SCI/D, recovering from flap surgery and deemed appropriate to use the arm cycle ergometer were enrolled in the pilot study (n = 47).Outcome Measures:A pre–post six-minute arm test (6MAT), a proxy for conditioning, was conducted on a subset (n = 15) of participants before and after the supine cycling exercise training program. Participants’ rating of perceived exertion (RPE) scores were collected at cessation of each 6MAT. Participants gave feedback on their perception of using the M-PACE.Results/Conclusions:The 6MAT RPE was significantly reduced after training with the M-PACE while on bed rest (P = 0.003). Also, significantly more rotations were performed after completing the training program (P = 0.02). Further, study participants who accessed the M-PACE found using it helped offset the tedium of laying supine during flap surgery recovery. The differences in the 6MAT pre- to post measures indicate the M-PACE should be further studied for offsetting the normal deconditioning that occurs with extended bedrest.     

Tamoxifen as an alternative to surgical resection for selected geriatric patients with primary breast cancer

Thirty elderly patients with primary operable breast cancer were treated initially, because of refusal of surgery or because of infirmity, only with the antiestrogen tamoxifen citrate. Nineteen patients had regression of the primary tumor (complete in five and partial in 14). Eight patients were stable with no change, and three had measurable increases in the size of their primary tumors. Nine of the 30 eventually required locoregional treatment with surgery or radiotherapy for progression or recrudescence of their tumors after initial regression. No patient developed uncontrollable locoregional disease. For selected geriatric patients, treatment with tamoxifen alone permits a delay of surgery, which for some exceeds life expectancy.     

Regional anesthesia as an alternative to general anesthesia for abdominal surgery in patients with severe pulmonary impairment

BACKGROUND: It is known that smokers and patients with chronic obstructive pulmonary disease (COPD) experience a higher rate of pulmonary-related complications following abdominal surgery. The impact of anesthetic technique (regional [RA] versus general [GA] versus combination of both) on the complication rate has not been established. This study examined the outcomes of abdominal surgery performed using RA (epidural or continuous spinal) as the sole anesthetic technique in patients with severe pulmonary impairment (SPI). METHODS: We reviewed a series of 8 general surgery cases performed using RA alone (T4-T6 sensory level) in patients with SPI, as evidenced by an forced expiratory volume in 1 second (FEV(1)) less than 50% predicted and/or home oxygen requirement. One patient also received postoperative epidural analgesia. FEV(1) ranged from 0.3 to 1.84 L; 3 patients required home oxygen therapy, and 5 of the 8 were American Society of Anesthesiology (ASA) class 4. Operations included segmental colectomy (n = 2), open cholecystectomy (n = 1), incisional herniorrhaphy (n = 1), and laparoscopic herniorrhaphy (n = 4). RESULTS: Intraoperative conditions were adequate with RA alone for successful completion of the procedure in all cases. All patients recovered uneventfully except for 1 who developed postoperative pneumonia that resolved with standard therapy. Length of stay was less than 24 hours for 5 of 8 patients. Mortality was 0%. CONCLUSIONS: Abdominal surgery can be safely performed using RA alone in selected high-risk patients, making this option an attractive alternative to GA for those with severe pulmonary impairment.     

The monocortical critical size bone defect as an alternative experimental model in testing bone substitute materials.

BACKGROUND: Reproducibility and comparability are prerequisites in testing bone substitute materials in an animal study. Various animal test models are used. The standard in testing bone substitute materials is the so-called critical size defect (CSD) model described by Schmitz and Hollinger. In most studies a bicortical (full thickness defect) CSD is used. OBJECTIVE: In this study, monocortical defects (10 x 10 mm) in calvarias of adult pigs were created and compared to examine the spontaneous physiologic healing process and the required criteria for a CSD. STUDY DESIGN: Regeneration of defects, either filled using autogenous bone (group 1) or unfilled (group 2), was evaluated by means of microradiography and light microscopy after 2, 4, 12, 26, and 52 weeks. RESULTS: No complete osseous regeneration was found microradiographically and light microscopically in the control group at week 52 (nonmineralized area: 30% +/- 1.7%; mineralized area: 55% +/- 1.7%; bone marrow area: 15% +/- 1.7%). Defects treated with autogenous bone showed a 100% osseous defect filling after 26 weeks. CONCLUSION: The monocortical CSD fulfills the requirements for a CSD and represents a procedure which can be handled simply for investigations focusing on bone regeneration and testing of bone substitute materials.     

Sublingual tacrolimus as an alternative to intravenous route in patients with thoracic transplant: a retrospective study

Tacrolimus (TRL) is an immunosuppressive drug characterized by a narrow therapeutic index, low bioavailability, and pharmacokinetic variability. Intravenous (i.v.) TRL may be needed whenever the oral route is unavailable. The small amount of infusion formulation (5 mg/mL) results in a large dilution and need for careful technical management of the infusion. This study addressed the feasibility to provide sublingual (SL) as an alternative to i.v.. TRL for transplanted patients. In a substudy, we performed a retrospective analysis of 17 lung and heart transplant patients using SL TRL. It included therapeutic drug monitoring and 4 area under curve (AUC) measurements. Patients received SL TRL on a dose-to-dose basis from the oral formulation. The mean age of the subjects (14 male, 3 female) was 35.3 ± 15.6 years; 146 trough (C(0)) samples were collected during the SL period (15.8 ± 20.6 days) showing a conformity level of 90.4%. Mean dose, C(0), and AUC of SL tacrolimus were 0.116 ± 0.096 mg/kg, 12.9 ± 5 ng/mL, and 230 ± 74 ng·h/mL, respectively, with an average 1 hour time to peak concentration. Acute rejection episodes, renal toxicity, and drug interactions were not observed. This study supported the convenience of short-term SL TRL administration, even in unconscious patients. Further investigations are needed to validate the dose range of the SL route.     

Sedation as an alternative to general anaesthesia

Dental patients are generally in good health, the procedures are often short, and it is fear and anxiety about pain rather than the nature of the procedure that dictates the use of sedation or general anaesthesia. Indications and contra-indications for sedation, appropriate agents and techniques, and facilities and personnel needed for managing and monitoring patients are discussed. Safe and effective use of sedation in combination with local anaesthesia is a realistic alternative to general anaesthesia for many outpatient procedures.     

Variability in responsiveness to clopidogrel in patients with intermittent claudication.

OBJECTIVE: The concept of clopidogrel resistance is frequently evoked in the cardiac literature. The variability of antiplatelet response in patients with intermittent claudication has not been investigated. The aim of this study was to describe the effect of the addition of clopidogrel to aspirin using ex vivo measures of platelet activation in patients with life-style limiting intermittent claudication. DESIGN OF STUDY: Data from randomised controlled trial. MATERIALS: Data from 67 patients with intermittent claudication taking part in a randomised controlled trial and who received clopidogrel in addition to aspirin was analysed. METHODS: Platelet activation was measured using whole-blood flow cytometric measurement of ADP-stimulated fibrinogen binding at baseline and 12h after administration of a loading dose of 300 mg clopidogrel. Patients continued to receive 75 mg clopidogrel daily for 30 days and platelet activation was again measured at day 30. Compliance with treatment was assessed by counting returned tablets. RESULTS: Six patients were excluded from analysis because of incomplete compliance with treatment. Six of the sixty-one patients (9.8%) showed no reduction in platelet activation 12h after administration of the loading dose of clopidogrel. At 30 days these six patients still showed no response to clopidogrel. Amongst the remaining 55 patients, the mean reduction in fibrinogen binding after clopidogrel administration was 51.5% (95% CI: 43.8-59.2). Amongst responders there was a wide variability in reduction of fibrinogen binding in response to clopidogrel (range 8.11-97.7%). Four of these patients (6.6%) showed a reduction of more than 95% in fibrinogen binding. CONCLUSIONS: Patients with intermittent claudication show a wide variability in their response to clopidogrel. While a small proportion of these patients shows no response at all, another small group appears to respond excessively to clopidogrel. Clinical studies are required to identify whether hyper-responders are at increased risk of bleeding complications and whether hyporesponders are at a higher risk of thrombotic events.