Search

Amputation remains a frequent and feared outcome in patients with peripheral artery disease (PAD). Although typically characterized as major or minor on the extent of tissue loss, the etiologies and outcomes after amputation by extent are not well-understood. In addition, emerging data suggest that the drivers and outcomes of amputation in patients with PAD may differ in those with and without diabetes mellitus (DM).The EUCLID trial randomized 13,885 patients with symptomatic PAD, including 5345 with concomitant diabetes, to ticagrelor or clopidogrel and followed them for long-term outcomes. Amputations were prospectively reported by trial investigators. Their primary and contributing drivers were adjudicated using safety data, including infection, ischemia, or multifactorial etiologies. Outcomes following major and minor amputations were analyzed, including recurrent amputation, major adverse limb events, adverse cardiovascular events, and mortality. Multivariable logistic regression models were used to identify independent predictors of minor amputations. Analyses were performed overall and stratified by the presence or absence of DM at baseline.Of the patients randomized, 398 (2.9%) underwent at least one lower extremity nontraumatic amputation, for a total of 511 amputations (255 major and 256 minor) over a median of 30 months. A history of minor amputation was the strongest independent predictor for a subsequent minor amputation (odds ratio, 7.29; 95% confidence interval, 5.17-10.30; P .001) followed by comorbid DM (odds ratio, 4.60; 95% confidence interval, 3.16-6.69; P .001). Compared with patients who had a major amputation, those with a minor amputation had similar rates of subsequent major amputation (12.2% vs 13.6%), major adverse limb events (15.1% vs 14.9%), and major adverse cardiovascular events (17.6% vs 16.3%). Ischemia alone was the primary driver of amputation (51%), followed by infection alone (27%), and multifactorial etiologies (22%); however, infection was the most frequent driver in those with DM (58%) but not in those without DM (15%).Outcomes after amputation remain poor regardless of whether they are categorized as major or minor. The pattern of amputation drivers in PAD differs by history of DM, with infection being the dominant etiology in those with DM and ischemia in those without DM. Greater focus is needed on the prognostic importance of minor amputation and of the multifactorial etiologies of amputation in PAD. Nomenclature with anatomical description of amputations and eliminating terms "major" or "minor" would seem appropriate.

Physical function is limited in patients with peripheral arterial disease who are symptomatic with intermittent claudication (PAD-IC). When patients with PAD-IC experience claudication, previous reports have described gait abnormalities, including alterations in step length and cadence. This study tested the hypothesis that patients with PAD-IC would have a decrease in usual and maximal walking speed and that this alteration in gait parameters would contribute to their decreased physical function scores, even in the absence of claudication. The aims were to evaluate usual and maximal walking speed and gait parameters (step length, cadence and toe out angle) in subjects with PAD-IC and control subjects with similar baseline activity levels.A cross-sectional study of 25 subjects with PAD-IC compared with 26 age-matched controls was conducted in a research laboratory in an academic medical center. Study subjects were similar in age, gender, and physical activity status. Subjects with PAD-IC had an ankle-brachial index0.90 in at least one leg and reported symptoms of intermittent claudication that limited walking ability. Subjects in either group were excluded if they used assistive devices to walk or were limited in walking ability by orthopedic, neurologic, cardiac, or pulmonary symptoms. Gait parameters were assessed at the onset of walking (before the development of claudication pain in the PAD-IC group) at self-selected and maximal walking speeds during which step and stride characteristics were collected. Subjects completed a physical activity recall, a Short Form questionnaire (SF-36), and a 6-minute walk that was limited by claudication in the PAD-IC group.During gait testing, no patient with PAD-IC developed claudication. There were no significant differences between the PAD-IC and control groups in usual or maximal walking speed or other gait variables (step length, cadence, stride width, toe out angle). In contrast, the SF-36 physical function score was reduced 15.2 percentage points (P.02) and the summary physical component score was reduced 6.7 percentage points in the PAD-IC group compared with controls (P = .002). In addition, the 6-minute walk distance was significantly less in the PAD-IC group than in the control group by 308.8 feet (P.001). A series of bivariate analyses demonstrated that PAD-IC was the best predictor of reduced physical function, whereas no gait parameter was associated with reduced physical function.Patients with PAD-IC have significantly reduced 6-minute walk distance and reduced physical function by questionnaire scores that was not explained by any effects of PAD-IC on walking speed and selected gait parameters assessed before the onset of claudication pain.

Purpose Eicosanoids with vasodilating and angiogenic properties have been postulated to be effective therapies for critical leg ischemia (CLI) secondary to atherosclerotic peripheral arterial disease. The ability to deliver active drug to the site of action at adequate doses for sufficient duration has been a major limitation in the clinical development of such therapies. Lipo-ecraprost is a lipid-encapsulated prostaglandin E 1 prodrug with the potential to deliver active prostaglandin to the site of critical arterial ischemia. The current trial was designed to test the hypothesis that lipo-ecraprost would improve amputation-free survival in patients with CLI who had no revascularization options. Methods The study was randomized, multicenter, double blind, and placebo controlled. Patients who met clinical and hemodynamic criteria were randomized to receive placebo or lipo-ecraprost (60 μg) administered intravenously on each of 5 days per week, for a total of 8 weeks. The study's primary endpoint was the rate of a composite end point of death or amputation above the level of the ankle at 180 days (6 months). Results The study was terminated on a recommendation from the Data and Safety Monitoring Board after the completion of a protocol-specified interim analysis for futility. At the time of termination, 383 of the planned 560 patients had been randomized, of which 379 received at least one dose of study medication and thus were included in the intention-to-treat population. Twenty-three patients were lost to follow-up and were not available for 6-month assessments. At 6 months of follow-up, there were 23 amputations in the 177 patients who received placebo, and 29 amputations in the 179 patients randomized to lipo-ecraprost. At 6 months, 10 deaths had occurred in the placebo group and 18 deaths had occurred in the lipo-ecraprost arm. Changes in lower-extremity hemodynamics over the 6-month study period did not differ between the placebo and lipo-ecraprost treatment arms. Conclusion Intensive treatment with lipo-ecraprost failed to modify the 6-month amputation rate in patients with CLI who were not candidates for revascularization.

Background Intermittent claudication resulting from peripheral arterial disease (PAD) can substantially impair walking function. The Walking Impairment Questionnaire (WIQ) assesses patient self-reported difficulty in walking. Currently this questionnaire is validated for interviewer administration only. Since this can be burdensome in a large clinical trial, we examined the effects of alternative methods of administration on patient responses on the WIQ. Methods The WIQ, which consists of four subscales (pain severity, distance, speed, stairs), was modified to be self-administered or interviewer-administered by telephone. Patients with PAD were recruited from two sites and randomized into two groups: in group 1 the WIQ was self-administered, then telephone-administered; in group 2 the WIQ was telephone-administered, then self-administered. The two administrations occurred 4 to 7 days apart. Additional measures (SF-36, EQ-5D, and PAD symptom scale) and clinical data were included to further assess the validity of the WIQ and symptoms in patients with claudication. Telephone interviews were conducted by trained interviewers using standardized scripts. Two-week test-retest reliability was assessed for both the self-administered WIQ (group 1) and the telephone-administered WIQ (group 2). Results Sixty patients were recruited at two sites (n = 30 per group). Seventy-eight percent were men; mean patient age was 67.1 years; and 83% of patients were white. Mean duration of PAD symptoms was 6.8 years. No significant differences were observed in WIQ subscale scores between self administration and telephone administration. No interaction effects between order and method of administration were detected. Cronbach α for distance, speed, and stair-climbing subscales ranged from 0.82 to 0.94. Correlations among WIQ subscales and the symptom scale were good ( r = −0.34 to −0.57). Correlations of WIQ subscales with physical health subscales of the SF-36 ( r = 0.24-0.59) were higher than for mental health–related subscales ( r = 0.08-0.26). Conclusions The modified WIQ demonstrated good reliability and validity with both methods of administration. These results suggest that the self-administered and telephone-administered versions of the WIQ can be used reliably and efficiently in clinical trials.

Purpose: The intermediate success and outcome of primary forefoot amputations in patients with diabetes mellitus who have sepsis limited to the forefoot and presumed adequate forefoot perfusion, as determined by means of noninvasive methods, was studied. Methods: Cases of a university hospital-based practice from January 1984 to April 1998 were retrospectively reviewed. Patients included had diabetes mellitus with forefoot sepsis requiring immediate hospitalization for digit amputations who had adequate arterial circulation for healing based on noninvasive and clinical assessment: palpable pedal pulses (29%), "compressible" ankle pressure of 70 mm Hg or higher (48%), pulsatile metatarsal waveforms (67%), and/or toe pressure higher than 55 mm Hg (36%). All patients underwent a primary single- or multiple-digit amputation (through the interphalangeal joint, metatarsal head, or metatarsal shaft). Additional forefoot procedures (debridement, digit amputation) were performed during the follow-up period as needed for persistent or recurrent infection. The main outcome variables were recurrent or persistent foot infection (defined as requiring rehospitalization for antibiotics, wound care, and/or reoperation), the number of repeat operations and hospitalizations for salvage of limbs with recurrent or persistent infections, and time to complete forefoot healing or foot amputation. Results: Ninety-two patients who had diabetes mellitus with 97 forefoot infections comprised the study group. Ninety-seven primary digit amputations (34 through interphalangeal joints, 28 through metatarsal heads, 35 through metatarsal shafts) were performed. The median length of hospital stay was 10 days. There were no operative deaths. The mean follow-up period was 21 months (range, 3 days to 105 months). The primary amputation healed (without persistent infection) in only 38 limbs (39%), at a mean time of 13 ± 10 weeks. Twenty-three limbs (24%) had not healed the primary amputation without evidence of persistent infection at last follow-up (mean, 12 weeks). Infection persisted in 35 limbs (36%), and infection recurred in 15 of 38 (40%) healed limbs. An average of 1.0 reoperations (range, 0 to 3) and 1.6 rehospitalizations (range, 1 to 4) were involved in salvage attempts in these recurrent/persistent infections. Five persistent and five recurrent infections ultimately healed (mean, 53 weeks). Complete healing was achieved in only 33 of 97 limbs (34%). Twenty-two foot amputations (20 transtibial, two Syme's) were performed (mean, 49 ± 74 weeks; 20 for persistent infection). Eighteen persistent/recurrent infections remained unhealed at the last follow-up examination (mean, 105 weeks). Conclusion: Patients with diabetes mellitus who have sepsis limited to the forefoot requiring acute hospitalization and undergoing primary digit amputations have a high incidence of intermediate-term, persistent, and recurrent infection, leading to a modest rate of limb loss, despite having apparently salvageable lesions and noninvasive evidence of presumed adequate forefoot perfusion. (J Vasc Surg 1999;30:509-18.)

Background Critical limb ischemia (CLI) represents the most severe clinical manifestation of peripheral arterial disease (PAD) and is the major cause of ischemic amputation in the United States. Risk factors and the associated incidence and prevalence of CLI have not been well described in the general population. This study describes the risk factors for PAD progression to CLI and estimates the annual incidence and prevalence of CLI in a representative United States patient cohort. Methods This was a retrospective cohort analysis of adults with commercial, Medicare supplemental, or Medicaid health insurance who had at least one PAD or CLI health care claim from January 1, 2003, through December 31, 2008, and 12 months of continuous coverage. Two subgroups of CLI presentation were identified: primary CLI (patients without any prior PAD or subsequent PAD diagnostic code >30 days after CLI diagnostic code) and secondary CLI (patients with prior PAD or subsequent PAD diagnostic codes ≤30 days of a CLI diagnostic code). Patterns of presentation, annual incidence, and prevalence of CLI were stratified by health care plan. Risk factors for progression to CLI were compared by presentation type. Results From 2003 to 2008, the mean annual incidence of PAD was 2.35% (95% confidence interval [CI], 2.34%-2.36%) and the incidence of CLI was 0.35% (95% CI, 0.34%-0.35%) of the eligible study population, with primary and secondary presentations occurring at similar rates. The mean annualized prevalence of PAD was 10.69% (95% CI, 10.67%10.70%) and the mean annualized prevalence of CLI was 1.33% (95% CI, 1.32%-1.34%) of the eligible study population, and two-thirds of the cases presented as secondary CLI. CLI developed in 11.08% (95% CI, 11.30%-11.13%) of patients with PAD. A multivariable model demonstrated that diabetes, heart failure, stroke, and renal failure were stronger predictors of primary rather than secondary CLI presentation. Conclusions These data establish new national estimates of the incidence and prevalence of CLI and define key risk factors that contribute to primary or secondary presentations of CLI within a very large contemporary insured population cohort in the United States.

Background Supervised walking programs offered at medical facilities for patients with peripheral artery disease (PAD) and intermittent claudication (IC), although effective, are often not used due to barriers, including lack of reimbursement and the need to travel to specialized locations for the training intervention. Walking programs for PAD patients that occur in community settings, such as those outside of supervised settings, may be a viable treatment option because they are convenient and potentially bypass the need for supervised walking. This review evaluated the various methods and outcomes of community walking programs for PAD. Methods A literature review using appropriate search terms was conducted within PubMed/MEDLINE and the Cochrane databases to identify studies in the English language that used community walking programs to treat PAD patients with IC. Search results were reviewed, and relevant articles were identified that form the basis of this review. The primary outcome was peak walking performance on the treadmill. Results Ten randomized controlled trials examining peak walking outcomes in 558 PAD patients demonstrated that supervised exercise programs were more effective than community walking studies that consisted of general recommendations for patients with IC to walk at home. Recent community trials that incorporated more advice and feedback for PAD patients in general resulted in similar outcomes, with no differences in peak walking time compared with supervised walking exercise groups. Conclusions Unstructured recommendations for patients with symptomatic PAD to exercise in the community are not efficacious. Community walking programs with more feedback and monitoring offer improvements in walking performance for patients with claudication and may bypass some obstacles associated with facility-based exercise programs.

Cardiovascular diseases are the most common cause of morbidity and mortality in the United States. Remarkable growth has occurred in the medical community regarding the recognition, understanding, and treatment of these diseases. This growth has been skewed, however, because most of the available resources have been directed toward the diagnosis and therapy of coronary artery disease. The impact that peripheral vascular diseases have on our national health is now receiving increased attention, but it is critical that strategies for the prevention, diagnosis, and treatment of these diseases be improved. Peripheral vascular diseases (noncardiac circulatory disorders) are highly prevalent in the United States. For example, peripheral arterial disease (PAD) affects 10% to 12% of the adult population. 1,2 Approximately one third of persons with PAD have clinically significant symptoms in their legs (e.g., claudication, rest pain, or nonhealing wounds) that severely impair daily walldng, ambulatory activities, and vocation. ~-s Thus PAD is a major cause of disability in the United States. Despite the association of peripheral atherosclerosis with a markedly increased risk of cardiovascular mortality, there is little awareness of the pathogencsis, natural history, and

BackgroundPatients with claudication secondary to peripheral artery disease have a substantial impairment in walking capacity. This study evaluated factors suspected to be correlated with treadmill walking performance in an effort to gain insights into the pathophysiology of the impairment.MethodsA multivariate model was developed to define the associations between clinical and laboratory biomarkers with treadmill peak walking time (PWT) in patients enrolled in three clinical trials. The model was initially developed in a cohort of 385 patients from one trial using 23 candidate-independent variables and then tested in the combined data from the other two trials (351 patients).ResultsThe final model was built from 14 variables that met the predefined univariate criteria of P < .15. Main effects remaining in the model were age, resting ankle-brachial index, smoking status, hypertension, statin use, country (United States vs non-United States countries), and high-sensitivity C-reactive protein. The model was highly statistically significant (P < .0001) but explained only a limited portion of the population heterogeneity (r2 = 0.173). The main effects plus interaction terms had an r2 = 0.2178. The main effects model was tested in an independent cohort of 351 patients from two other clinical trials in peripheral arterial disease that did not include high-sensitivity C-reactive protein. The model successfully fit the data set, based on prospectively defined root mean squared error and was statistically significant (P = .0005) but had lower overall explanatory power than in the index cohort (r2 = 0.0687).ConclusionsAs expected, age and ankle-brachial index contributed to exercise limitation among patients with PAD. The association of C-reactive protein, hypertension, and smoking with PWT is consistent with a role for inflammation or oxidative stress in determining treadmill walking performance. In contrast to previous reports from smaller and more homogenous populations, clinical attributes and biomarkers explain only a small portion of PWT heterogeneity.

Background Treadmill walking is commonly used to evaluate walking impairment and efficacy of treatment for intermittent claudication (IC) in clinical and research settings. Although this is an important measure, it does not provide information about how patients perceive the effects of their treatments on more global measures of health-related quality of life (HRQOL). Methods PubMed/Medline was searched to find publications about the most commonly used questionnaires to assess functional status and/or general and disease-specific HRQOL in patients with peripheral artery disease (PAD) who experience IC. Inclusion criteria for questionnaires were based on existence of a body of literature in symptomatic PAD. Results Six general questionnaires and seven disease-specific questionnaires are included, with details about the number of domains covered and how each tool is scored. The Medical Outcomes Study Short Form 36-item questionnaire and Walking Impairment Questionnaire are currently the most used general and disease-specific questionnaires at baseline and after treatment for IC, respectively. Conclusions The use of tools that assess functional status and HRQOL has importance in both the clinical and research areas to assess treatment efficacy from the patient's perspective. Therefore, assessing HRQOL in addition to treadmill-measured walking ability provides insight as to the effects of treatments on patient outcomes and may help guide therapy.

Purpose In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E 1 prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. Methods The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-μg dose of lipo-ecraprost administered intravenously starting ≤72 hours of the index revascularization and then 5 days per week for 8 weeks. The study primary end point was the composite end point of death or amputation at or above the level of the ankle at 180 days. Results The study randomized 322 patients, and 284 received at least one dose of study medication and were included in the intention-to-treat population. A total of 213 patients underwent surgical bypass, and 71 underwent endovascular revascularization before receiving study medication. The distribution of index revascularization procedures and location of distal target arteries were similar for both placebo and lipo-ecraprost groups. At 180 days, 21 patients (7.4%) were lost to follow-up before reaching the primary end point. Seventy-one percent of the patients taking the placebo completed at least half the doses of the study medication compared with 48% of those taking lipo-ecraprost. Index leg revascularization-assisted primary patency was 82% in the placebo group and 84% in the lipo-ecraprost group ( P = .874). Changes in lower extremity hemodynamics as a result of the revascularization during the study period did not differ between the placebo and lipo-ecraprost treatment arms. For the primary event of amputation-free survival, there were no differences between groups: 19 major amputations occurred in the placebo group and 17 in the lipo-ecraprost group; 19 deaths occurred in the placebo group and 13 in the lipo-ecraprost group. Conclusion Eight weeks of parenteral therapy with lipo-ecraprost after distal revascularization in patients with CLI provided no additional benefit in the reduction of major amputation or death at 180 days.

Contemporary care of critical limb ischemia (CLI) consists of near universal attempts at aggressive limb salvage. In our opinion this approach is excessively lesion focused and inadequately patient focused. Subgroups of the CLI population currently undergoing extensive limb salvage efforts may be better served with primary amputation or nonoperative management. We describe limitations in the knowledge base underlying modern care of CLI. First, our understanding of the natural history of CLI is limited, with minimal ability to identify at-risk patients and prevent disease progression. Most patients with symptomatic CLI have a tremendous disease burden, with poor baseline function, including loss of ability to ambulate and ability to live independently in many and abbreviated survival for most. Second, surgical treatment is graft and limb focused, with only modest understanding of the effects of treatment on patient morbidity and function. While surgical revascularization may prevent limb loss, this outcome does not universally result in ambulation or functional independence. Third, the advantage of revascularization over primary amputation in patients who do not regain independent ambulation is unclear. Fourth, the influence of the extent of ischemic foot lesions on overall outcomes has not been clearly defined. Finally, even if limb ischemia can be relieved, a critical concern remains the high cardiovascular mortality risk in the CLI population. We do not know if cardiovascular risk factor modification can modify this natural history. We do not know whether a chronically ischemic limb may actually increase the systemic risk for myocardial infarction or stroke by inducing a proinflammatory state and generating reactive oxygen species. 1 What is clear is that further study of CLI is needed in the form of clinical trials with patient-oriented rather than limb-oriented outcomes. We will briefly examine the reasons for each of these statements. We will then propose an approach to addressing acquisition of the data relevant to each issue, including proposal for some relevant clinical trials.

Background Phosphodiesterase inhibitors have been shown to improve claudication-limited exercise performance in patients with peripheral artery disease. K-134, a novel phosphodiesterase inhibitor, was evaluated in a phase II trial incorporating an adaptive design to assess its safety, tolerability, and effect on treadmill walking time. Design Patients with peripheral artery disease were randomized to receive placebo (n = 87), K-134 at a dose of 25 mg (n = 42), 50 mg (n = 85), or 100 mg (n = 84), or cilostazol at a dose of 100 mg (n = 89), each twice daily for 26 weeks. Peak walking time (PWT) was assessed using a graded treadmill protocol at baseline and after 14 and 26 weeks of treatment. A Data and Safety Monitoring Board–implemented adaptive design was used that allowed early discontinuation of unsafe or minimally informative K-134 arms. Results As determined by the prospectively defined adaptive criteria, the 25-mg K-134 arm was discontinued after 42 individuals had been randomized to the arm. During the 26-week treatment period, PWT increased by 23%, 33%, 37%, and 46% in the placebo, 50-mg K-134, 100-mg K-134, and cilostazol arms, respectively (primary analysis placebo vs 100-mg K-134 arm not statistically significant, P = .089). Secondary analyses showed that cilostazol significantly increased PWT after 14 weeks of treatment and that the 100-mg K-134 dose and cilostazol both increased PWT vs placebo after 14 and 26 weeks in those individuals who completed the 26-week trial and were compliant with the study drug, or when the data were analyzed using a mixed-effects model incorporating all time points. K-134 had tolerability and adverse effect profiles similar to that of cilostazol. Both drugs were associated with an increase in withdrawals before study completion due to adverse events compared with placebo. Conclusions K-134 was generally well tolerated. K-134 at a dose of 100 mg twice daily did not affect PWT according to the primary analysis, but K-134 and cilostazol both increased PWT when analyzed using a mixed-effects model and in the per-protocol population.

Purpose: In patients with intermittent claudication (IC) a structured walking exercise program improves exercise performance. However, few studies have evaluated the effects of exercise training on functional status during daily activities. We hypothesized that a supervised exercise training program would improve functional status in patients with IC, with 24 weeks of training more beneficial than 12 weeks. A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status.Methods: Twenty-nine men with disabling IC were randomized to 12 weeks of either supervised treadmill training (3 hr/wk at a work intensity sufficient to produce claudication), strength training (3 hr/wk of resistive training of six muscle groups of each leg), or to a nonexercising control group. Functional status was assessed by questionnaires characterizing walking ability (Walking Impairment Questionnaire, WIQ), habitual physical activity level (Physical Activity Recall, PAR), and physical, social, and role functioning, well-being, and overall health (Medical Outcomes Study SF-20, MOS). Patients also had their activity levels monitored with an activity monitor (Vitalog).Results: After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk, the MOS physical functioning score by 24 percentage points, and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr (all p

ObjectiveThe pattern and distribution of arterial occlusions and stenoses in patients with critical limb ischemia presenting at two academic medical centers was described.MethodsFrom January 1998 to December 2006, 450 consecutive critical limb ischemia patients who underwent arteriography and infrainguinal revascularization at the University of Colorado Health Sciences Center or Southern Illinois University were retrospectively evaluated. Demographics, clinical morbidities, and Fontaine stage were recorded. The arterial tree was categorized into three groups: the aorta and iliac arteries (A-I); the common femoral, superficial femoral, and profunda femoral arteries (Fem); and the popliteal and tibial arteries (Pop-Tib). Arterial segments within groups were categorized as subcritical stenoses (patent or 50% stenoses), or occluded (segmental occlusions of any length). Patients with diabetes mellitus, end-stage renal disease, and Fontaine stage (III vs IV) were analyzed for differing disease patterns according to their chart history.ResultsOcclusive disease was present in 5% in all arterial segments (A-I + Fem + Pop-Tib), in 1% in the A-I + Fem group, in 2% in the A-I + Pop-Tib group, in 3% in A-I group, in 4% in the Fem group, in 30% in the Fem + Pop-Tib group, and in 55% in the Pop-Tib group. Descriptive comparisons among subgroups demonstrated a 61% to 69% prevalence of popliteal and tibial occlusive patterns in patients with diabetes mellitus, end-stage renal disease, and Fontaine stage IV. Furthermore, 65% of patients with Pop-Tib occlusions had associated critical stenoses in the proximal arterial groups.ConclusionMore than half of critical limb ischemia patients undergoing infrainguinal revascularization have arterial occlusions in the popliteal or tibial arterial segments, or both, with associated critical stenoses in the femoral arterial segments, which is even greater in the subgroups with diabetes mellitus, end-stage renal disease, and Fontaine stage IV. Knowledge of such occlusive patterns is important for the development of novel infrainguinal endovascular and angiogenesis therapies for critical limb ischemia.

Purpose We undertook this study to document the functional natural history of patients undergoing major amputation in an academic vascular surgery and rehabilitation medicine practice. Methods A retrospective review was conducted of consecutive patients undergoing major lower extremity amputation and rehabilitation in a university and Department of Veterans Affairs hospital. Main outcome variables included operative mortality, follow-up, survival, median time to incision healing, secondary operative procedures for wound management, and conversion from below-knee amputation (BKA) to above-knee amputation (AKA). For surviving patients, quality of life was determined by degree of ambulation, eg, outdoors, indoors only, or no ambulation; use of a prosthesis; and independence, eg, community housing or nursing facility. Results From August 1997 through March 2002, 154 patients (130 men; median age, 62 years) underwent 172 major amputations, 78 AKA and 94 BKA, because of either critical limb ischemia (87%) or diabetic neuropathy (13%). Thirty-day operative mortality was 10%. Mean follow-up was 14 months. Healing at 100 and 200 days, as determined with the Kaplan-Meier method, was 55% and 83%, respectively, for BKA, and 76% and 85%, respectively, for AKA. Twenty-three BKA and 16 AKA required additional operative revision, and 18 BKA ultimately were converted to AKA. Survival was 78% at 1 year and 55% at 3 years. Function in surviving patients at 10 and 17 months, respectively, was as follows: 21% and 29% of patients ambulated outdoors, 28% and 25% ambulated indoors only, and 51% and 46% of patients were nonambulatory; 32% and 42% of patients used prosthetic limbs; and 17% and 8% of patients who lived in the community before amputation required care in a nursing facility. Conclusions We were surprised to find that vascular patients in a contemporary setting who require major lower extremity amputation and rehabilitation often remain independent despite infrequent prosthesis use and outdoor ambulation. Although any hope for postoperative ambulation in this population requires salvaging the knee joint, because of the morbidity incurred in both wound healing and rehabilitation efforts, aggressive effort should be reserved for selected patients at good risk. Ability to predict ambulation after BKA in the vascular population is poor.

Background Cilostazol, a phosphodiesterase III inhibitor, is indicated to treat the symptoms of intermittent claudication and increase walking distance in patients with peripheral arterial disease (PAD). At the time of approval, the United States Food and Drug Administration required an additional long-term safety study to evaluate the effect cilostazol on mortality. Methods A total of 1899 subjects with a clinical diagnosis of PAD and symptoms of claudication were screened for participation in a randomized, double-blinded, placebo-controlled safety study of cilostazol. The intent-to-treat (ITT) population, which was the primary analysis (n = 1435), was defined as all randomized patients who received at least one dose of study medication and included patients who were followed up >30 days after discontinuation of study drug. A total of 717 patients received cilostazol and 718 received placebo. Cilostazol was administered at a primary dose of 100 mg twice daily. The dose could be reduced to 50 mg twice daily if patients experienced an adverse event that might have been drug related. Results Long-term adherence to study medication was poor, with >60% of participants discontinuing therapy by 36 months. The mortality analysis therefore focused on deaths during the period on-treatment, defined as the period during which the study drug was taken plus a 30-day follow-up period after dosing. Total patient-years of exposure were 1046 on-treatment for cilostazol and 1090 for placebo. On-treatment, there were 18 deaths on cilostazol and 19 deaths on placebo for a hazard ratio of 0.99 (95% confidence interval [CI], 0.52-1.88). Cardiovascular deaths on-treatment occurred in 14 patients on cilostazol and 14 on placebo. In the full ITT population at 36 months, there were 101 deaths, 49 on cilostazol and 52 on placebo, with hazard ratio of 0.94 (95% CI, 0.64-1.39). Thus, most deaths occurred >30 days after study drug discontinuation. Serious bleeding events affected 18 patients taking cilostazol in the on-treatment population and 22 taking placebo. The rates of bleeding events were similar in patients who used aspirin, aspirin plus clopidogrel, or anticoagulants at anytime during the course of the study Conclusions This long-term study demonstrated no safety signal for cilostazol on all-cause or cardiovascular mortality. The study, however, was underpowered to detect a small adverse impact of cilostazol on mortality (hazard ratio upper bound of the 95% CI was 1.88 in the on-treatment population). Serious bleeding events appeared not to be increased by cilostazol.