Dataset Information

Literature review and meta-analysis of the efficacy of cilostazol on limb salvage rates after infrainguinal endovascular and open revascularization.

ABSTRACT:

Background

Current clinical guidelines recommend the use of cilostazol in the treatment of patients with infrainguinal peripheral artery disease (PAD) who experience intermittent claudication. However, the role of cilostazol therapy in patients with advanced PAD and critical limb ischemia (CLI) remains unclear. To conduct a meta-analysis of randomized controlled trials and cohort studies that evaluated the effect of cilostazol vs standard antiplatelet therapy on limb-related and arterial patency-related outcomes. We also reviewed literature pertinent to the effect of cilostazol on wound healing in patients with advanced PAD.

Methods

We performed a MEDLINE, EMBASE, COCHRANE (CENTRAL), SCOPUS, and US Clinical Trials database search for all trials and studies since 1999 that compared cilostazol with standard antiplatelet therapy in the setting of infrainguinal PAD revascularization procedures (endovascular or open). Aggregate data was collected from four randomized control trials and six retrospective cohort studies. The end point incidence ratios and treatment effects were generated from each study and reported as hazard ratios (HR) using a random-effect model. We also reviewed 10 studies that evaluated the effect of cilostazol on wound healing in patients with advanced PAD.

Results

From more than 25,000 total patients, 3136 patients met our inclusion criteria. All patients had at least lifestyle-impacting intermittent claudication, and more than 50% met the definition of CLI (Rutherford class ≥4). Patient age range was 53 to 83 years, and the majority were male (66%). The mean follow-up time averaged 2 years across all studies. Meta-analysis revealed that cilostazol treatment favored amputation-free survival (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69-0.91), limb salvage rate (HR, 0.42; 95% CI, 0.27-0.66), decreased repeat revascularization (risk ratio [RR], 0.44; 95% CI, 0.37-0.52), and decreased restenosis (RR, 0.68; 95% CI, 0.61-0.76). Cilostazol treatment also increased freedom from target lesion revascularization (RR, 1.35; 95% CI, 1.21-1.53) with no difference in all-cause mortality. Effective wound healing was found to be an inconsistent outcome measure in patients receiving cilostazol therapy.

Conclusions

We observed that cilostazol therapy has a beneficial impact on all limb-related and arterial patency-related outcomes, but no effect on all-cause mortality in patients with advanced PAD and CLI undergoing revascularization procedures. Additional studies are needed to evaluate the effect of cilostazol therapy on wound healing in patients with advanced PAD.

SUBMITTER: Desai K

PROVIDER: S-EPMC7944577 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectivesPeripheral artery disease is estimated to affect 237 million individuals worldwide. Critical limb ischaemia, also known as chronic limb threatening ischaemia is a consequence of the progression of peripheral artery disease which occurs in ∼21% of patients over a five-year period. The aim of this systematic review is to assess the use of additional below-the-ankle angioplasty in comparison to the use of above-the-ankle angioplasty alone, and the subsequent rates of amputation, wound healing, restenosis, rest pain, reintervention and complications.MethodsThis systematic review was undertaken in accordance with PRISMA guidelines following a registered protocol (CRD42019154893). Online databases were searched using a search strategy of 20 keywords. Included articles reported the outcome for inframalleolar (pedal artery, pedal arch, plantar arteries) angioplasty with additional proximal angioplasty in comparison to proximal angioplasty alone. GRADE assessment was applied to assess the quality of the evidence.ResultsAfter screening 1089 articles, 10 articles met the inclusion criteria. Comparative performance assessment of below-the-ankle with above-the-ankle versus above-the-ankle angioplasty alone was undertaken in 3 articles, with the remaining 7 articles reporting outcomes of below-the-ankle with above-the-ankle angioplasty with no distinct comparator group. Significant decrease in major lower limb amputation at the last follow-up in the below-the-ankle group when compared with the above-the-ankle angioplasty alone group was observed in a single study (3.45% vs. 14.9%, p < 0.05). Improved wound healing rate at follow-up in the below-the-ankle group versus above-the-ankle angioplasty alone group was also reported in a single study (59.3% vs. 38.1%, p < 0.05). Subsequent rate of amputation after below-the-ankle angioplasty has been estimated as 23.5%.ConclusionTo date, there is a lack of studies assessing inframalleolar interventions and their use in improving limb salvage, wound healing and symptomatology. Prospective RCTs should be undertaken with adequate participant numbers to be sufficiently powered and report clinically important end-points.

Project description:OBJECTIVE:The optimal initial revascularization strategy remains uncertain for patients with peripheral arterial disease. The purpose of this study was to evaluate current nationwide selection and perioperative outcomes of patients undergoing bypass or endovascular intervention for infrainguinal disease in those with no prior ipsilateral revascularization. METHODS:Patients undergoing nonemergent first-time infrainguinal revascularization were identified in the Targeted Vascular module of the National Surgical Quality Improvement Program (NSQIP) for 2011 to 2014 and stratified by symptom status (chronic limb-threatening ischemia [CLTI] or claudication). Patients treated with endovascular intervention were compared with those who underwent bypass. Multivariable logistic regression was used to evaluate current selection of patients and to establish independent associations between first-time procedures and postoperative outcomes. RESULTS:Of 5998 first-time infrainguinal revascularizations performed, 3193 were bypass procedures (63% for CLTI) and 2805 were endovascular interventions (64% for CLTI). Current patient characteristics associated with an endovascular-first approach as opposed to bypass-first in CLTI patients were age ?80 years, tissue loss, nonsmoking, functional dependence, diabetes, dialysis, and tibial lesions, whereas age ?80 years, nonwhite race, nonsmoking, diabetes, and tibial lesions were associated with an endovascular approach for claudication. In comparing first-time endovascular intervention with bypass, there was no difference in 30-day mortality in CLTI patients (univariate: 2.1% vs 2.2%; adjusted: odds ratio [OR], 0.7; 95% confidence interval [CI], 0.4-1.1) or claudication patients (0.3% vs 0.6%). Among CLTI patients, endovascular-first intervention was associated with lower rates of major adverse cardiovascular event (3.6% vs 4.7%; OR, 0.6; 95% CI, 0.4-0.9), surgical site infection (0.9% vs 7.7%; OR, 0.1; 95% CI, 0.1-0.2), bleeding (8.5% vs 17%; OR, 0.4; 95% CI, 0.3-0.5), unplanned reoperation (13% vs 17%; OR, 0.7; 95% CI, 0.5-0.8), and unplanned readmission (17% vs 18%; OR, 0.8; 95% CI, 0.7-0.9). Patients with claudication undergoing endovascular-first intervention also had lower rates of major adverse cardiovascular event (0.8% vs 1.6%; OR, 0.4; 95% CI, 0.2-0.95), surgical site infection (0.7% vs 6.6%; OR, 0.1; 95% CI, 0.04-0.2), bleeding (2.3% vs 6.0%; OR, 0.3; 95% CI, 0.2-0.5), unplanned reoperation (4.3% vs 6.6%; OR, 0.6; 95% CI, 0.4-0.9), and unplanned readmission (5.9% vs 9.0%; OR, 0.6; 95% CI, 0.4-0.8). Conversely, endovascular-first intervention was associated with a higher rate of secondary revascularizations within 30 days for CLTI (4.3% vs 3.1%; OR, 1.6; 95% CI, 1.04-2.3) but not for claudication (2.6% vs 1.9%; OR, 1.7; 95% CI, 0.9-3.4). CONCLUSIONS:An endovascular-first approach as a revascularization strategy for infrainguinal disease was associated with substantially lower early morbidity but not mortality, at the cost of higher rates of postoperative secondary revascularizations. As a national representation of first-time revascularizations, this study highlights the early endovascular perioperative benefit, although more robust long-term data are needed to adopt either one strategy or the other in select patients with peripheral arterial disease.

Project description:Purpose: To investigate the outcomes of orbital atherectomy (OA) for the treatment of patients with peripheral artery disease (PAD) manifesting as claudication or chronic limb-threatening ischemia (CLTI). Materials and Methods: The database from the LIBERTY study (ClinicalTrials.gov identifier NCT01855412) was interrogated to identify 503 PAD patients treated with any commercially available endovascular devices and adjunctive OA for 617 femoropopliteal and/or infrapopliteal lesions. Cox regression analyses were employed to examine the association between baseline Rutherford category (RC) stratified as RC 2-3 (n=214), RC 4-5 (n=233), or RC 6 (n=56) and all-cause mortality, target vessel revascularization (TVR), major amputation, major adverse event (MAE), and major amputation/death at up to 3 years of follow-up. The mean lesion lengths were 78.7±73.7, 131.4±119.0, and 95.2±83.9 mm, respectively, for the 3 groups. Results: After OA, balloon angioplasty was used in >98% of cases, with bailout stenting necessary in 2.0%, 2.8%, and 0% of the RC groups, respectively. A small proportion (10.8%) of patients developed angiographic complications, without differences based on presentation. During the 3-year follow-up, claudicants were at lower risk for MAE, death, and major amputation/death than patients with CLTI. The 3-year Kaplan-Meier survival estimates were 84.6% for the RC 2-3 group, 76.2% for the RC 4-5 group, and 63.7% for the RC 6 group. The 3-year freedom from major amputation was estimated as 100%, 95.3%, and 88.6%, respectively. Among CLTI patients only, the RC at baseline was correlated with the combined outcome of major amputation/death, whereas RC classification did not affect TVR, MAE, major amputation, or death rates. Conclusion: Peripheral artery angioplasty with adjunctive OA in patients with CLTI or claudication is safe and associated with low major amputation rates after 3 years of follow-up. These results demonstrate the utility of OA for patients across the spectrum of PAD.

Project description:To determine whether diabetes mellitus has an independent impact on major limb outcomes at 1 year after endovascular treatment of lower extremity peripheral artery disease (PAD).The study involved 1906 consecutive patients (mean age 66 years; 1469 men) enrolled in the observational Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) between January 2005 and October 2015 after undergoing index endovascular procedures in 2426 limbs for arterial occlusive disease. Patient outcomes included 12-month target limb amputation (above ankle) and target limb revascularization as well as all-cause death. Kaplan-Meier analysis and adjusted Cox proportional hazard models were used for time-to-event analysis of outcomes for the entire study sample as well as for the critical limb ischemia (CLI) and claudication subgroups. Results of the Cox regression models are reported as the hazard ratio (HR) and 95% confidence interval (CI).Diabetics undergoing endovascular procedures had higher rates of comorbid conditions (p<0.001), CLI (p<0.001), heavily calcified lesions (p=0.002), multivessel disease (p=0.030), and fewer infrapopliteal runoff vessels (p<0.001). Regression analysis after adjusting for confounders revealed significantly higher target limb major amputation in diabetics compared with nondiabetics (HR 5.02, 95% CI 1.44 to 17.56, p=0.011). However, repeat revascularization rates were similar. When considering CLI and claudication subgroups, diabetes was associated with a nonsignificant increased risk of 12-month major amputation only for patients presenting with CLI (HR 3.48, 95% CI 0.97 to 12.51, p=0.056). Diabetes was also associated with an increased risk of 12-month all-cause mortality in the overall study sample (HR 4.64, 95% CI 2.01 to 10.70, p<0.001) and in the CLI subgroup (HR 14.15, 95% CI 3.16 to 63.32, p<0.001) but not in the claudication subgroup (HR 1.42, 95% CI 0.45 to 4.54, p=0.552).Diabetes increases the risk of major amputation and all-cause death at 12 months following endovascular revascularization in patients with symptomatic PAD. These risks are especially heightened in patients presenting with CLI.

Project description:ImportanceThe Bypass Versus Angioplasty for Severe Ischemia of the Leg randomized controlled trial showed comparable outcomes between endovascular revascularization (ER) and surgical revascularization (SR) for patients with critical limb ischemia (CLI). However, several observational studies showed mixed results. Most of these studies were conducted before advanced endovascular technologies were available.ObjectiveTo compare ER and SR treatment strategies for 6-month outcomes among patients with CLI.Design, setting, and participantsThis retrospective, population-based cohort study used the Nationwide Readmissions Database to identify 66 277 patients with CLI who underwent ER or SR from January 1, 2016, to December 31, 2018. Data analyses were conducted from January 1, 2022, to February 8, 2022. A propensity score with 1:1 matching was applied. Patients with CLI who underwent ER or SR were identified, and those with missing information on the length of stay and/or younger than 18 years were excluded.ExposuresEndovascular or surgical revascularization.Main outcomes and measuresThe primary outcome was a major amputation at 6 months. Significant secondary outcomes were in-hospital and 6-month mortality and an in-hospital safety composite of acute kidney injury, major bleeding, and vascular complication. Subgroup analysis was conducted for major amputation in high-volume centers.ResultsA total of 66 277 patients were identified between 2016 and 2018 who underwent ER or SR for CLI. The Nationwide Readmissions Database does not provide racial and ethnic categories. The mean (SD) age of the cohort was 69.3 (12) years, and 62.5% of patients were male. A total of 54 546 patients (82.3%) underwent ER and 11 731 (17.7%) underwent SR. After propensity score matching, 11 106 matched pairs were found. Endovascular revascularization was associated with an 18% higher risk of major amputation compared with SR (997 of 10 090 [9.9%] vs 869 of 10 318 [8.4%]; hazard ratio, 1.18; 95% CI, 1.08-1.29; P = .001). However, no difference was observed in major amputation risk when both procedures were performed in high-volume centers. Endovascular revascularization and SR had similar mortality rates (517 of 11 106 [4.7%] vs 490 of 11 106 [4.4%]; hazard ratio, 1.06; 95% CI, 0.93-1.20; P = .39). However, the ER group had a 17% lower risk of in-hospital safety outcomes compared with the SR group (2584 of 11 106 [23.3%] vs 2979 of 11 106 [26.8%]; odds ratio, 0.83; 95% CI, 0.78-0.88; P < .001).Conclusions and relevanceThe results of this study suggest that ER was safer, without any difference in mortality, but ER was associated with an increased risk of major amputation compared with SR. However, the risk of major amputation was similar when both procedures were performed at high-volume centers.

Project description:BackgroundAcute limb ischemia (ALI) is an important clinical event threatening both life and the affected limbs, but the optimal treatment for ALI remains undefined. The aim of this study was to compare the safety and effectiveness of thrombectomy approaches via either catheter-based thrombectomy (CBT) or catheter-directed thrombolysis (CDT).MethodsA total of 98 patients (mean age 69.7 years, 60 male) who underwent endovascular intervention for ALI from January 2015 to July 2019 were included. Of these, 57 were treated with primary CBT via a large-bore catheter, an AngioJet catheter or Rotarex catheter, and/or underwent low-dose CDT, and 41 were treated with primary CDT. The safety and effectiveness of CBT compared to conventional CDT and other various endovascular techniques were evaluated.ResultsMore Rutherford IIb patients were treated with primary CBT (68.4%) than CDT (26.8%; P < .001). Patients who underwent primary CDT achieved a higher technical success rate than those who underwent primary CBT in a shorter procedure time (P < .001), whereas 42.1% of patients who underwent CBT did not need adjunctive CDT. The duration and dosage of adjunctive CDT in the CBT group were significantly decreased compared with those in the primary CDT group (both P < .001), and the CBT group achieved a shorter in-hospital length of stay (P < .001). Subgroup analysis revealed that patients treated with AngioJet and Rotarex catheters achieved slightly lower dosages, shorter CDT durations and shorter in-hospital stay lengths than those treated with large-bore catheters (P > .05). Clinical success was estimated to be achieved in 98.2% of patients who underwent CBT, which is similar to the 97.6% estimated in those who underwent primary CDT (P = 1.000), and this finding was similar among the CBT subgroups. Patients who underwent CBT had a higher procedure-related distal embolization rate and economic cost than those who underwent primary CDT (P < .05), but it had slightly fewer complications than those who underwent primary CDT (P = .059), especially minor complications (P = .036). The freedom from amputation at 6 and 12 months for CBT and CDT was assessed (93.0% vs 90.2% respectively, P = .625; 89.5% vs 82.9%, respectively, P = .34,). Comparable limb salvage was found for different techniques of large bore catheters, AngioJet catheters and Rotarex catheters. The Kaplan-Meier table analysis also showed similar limb salvage rates between groups.ConclusionsEndovascular treatment of ALI with the use of catheter-based therapies is an effective modality that can reduce the requirement for thrombolysis, with expected reductions in hemorrhagic complications, but at the risk of remediable distal emboli and increased economic cost. It has a similar clinical outcome to conventional CDT alone. Different CBT techniques have comparable efficacy but different adverse event profiles.

Project description:Unplanned hospital readmissions following surgical interventions are associated with adverse events and contribute to increasing health care costs. Despite numerous studies defining risk factors following lower extremity bypass surgery, evidence regarding readmission after endovascular interventions is limited. This study aimed to identify predictors of 30-day unplanned readmission following infrainguinal endovascular interventions.We identified all patients undergoing an infrainguinal endovascular intervention in the targeted vascular module of the American College of Surgeons National Surgical Quality Improvement Program between 2012 and 2014. Perioperative outcomes were stratified by symptom status (chronic limb-threatening ischemia [CLI] vs claudication). Patients who died during index admission and those who remained in the hospital after 30 days were excluded. Indications for unplanned readmission related to the index procedure were evaluated. Multivariable logistic regression was used to identify preoperative and in-hospital (during index admission) risk factors of 30-day unplanned readmission.There were 4449 patients who underwent infrainguinal endovascular intervention, of whom 2802 (63%) had CLI (66% tissue loss) and 1647 (37%) had claudication. The unplanned readmission rates for CLI and claudication patients were 16% (n = 447) and 6.5% (n = 107), respectively. Mortality after index admission was higher for readmitted patients compared with those not readmitted (CLI, 3.4% vs 0.7% [P < .001]; claudication, 2.8% vs 0.1% [P < .01]). Approximately 50% of all unplanned readmissions were related to the index procedure. Among CLI patients, the most common indication for readmission related to the index procedure was wound or infection related (42%), whereas patients with claudication were mainly readmitted for recurrent symptoms of peripheral vascular disease (28%). In patients with CLI, predictors of unplanned readmission included diabetes (odds ratio, 1.3; 95% confidence interval, 1.01-1.6), congestive heart failure (1.6; 1.1-2.5), renal insufficiency (1.7; 1.3-2.2), preoperative dialysis (1.4; 1.02-1.9), tibial angioplasty/stenting (1.3; 1.04-1.6), in-hospital bleeding (1.9; 1.04-3.5), in-hospital unplanned return to the operating room (1.9; 1.1-3.5), and discharge other than to home (1.5; 1.1-2.0). Risk factors for those with claudication were dependent functional status (3.5; 1.4-8.7), smoking (1.6; 1.02-2.5), diabetes (1.5; 1.01-2.3), preoperative dialysis (3.6; 1.6-8.3), procedure time exceeding 120 minutes (1.8; 1.1-2.7), in-hospital bleeding (2.9; 1.2-7.4), and in-hospital unplanned return to the operating room (3.4; 1.2-9.4).Unplanned readmission after endovascular treatment is relatively common, especially in patients with CLI, and is associated with substantially increased mortality. Awareness of these risk factors will help providers identify patients at high risk who may benefit from early surveillance, and prophylactic measures focused on decreasing postoperative complications may reduce the rate of readmission.