Use Of Cilostazol Research Articles

Abstract 12823: Efficacy, Optimal Duration and Safety of Adjunctive Cilostazol in Acute ST-elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention With Drug-Eluting Stents; a Multicenter, Randomized, Open Label, Phase 4 Trial

Background: Previous studies showed that the triple antiplatelet therapy (TAT) which is an addition of cilostazol on the top of conventional dual antiplatelet therapy (DAT, aspirin + clopidogrel) was associated with better clinical outcomes in ST-elevation MI (STEMI) patients as compared with DAPT but the optimal duration of TAT was not determined yet. Method: A total 985 patients underwent primary percutaneous coronary intervention (PCI) with drug-eluting stents (DES) were prospectively enrolled in 14 medical centers in Korea. We randomly assigned patients into 3 groups of DAT (aspiring and clopidogrel) for 12 months, TAT (aspirin, clopidogrel and cilostazol) for 1month or 6months. The primary end point was 1-year major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction (MI), stroke or repeat revascularization. The secondary endpoints were the incidence of cardiac death, stent thrombosis, bleeding events and each component of primary end point. Results: The primary end point was not different among the 3 groups (8.4% in the DAT, 11.0% in the TAT for 1month, 11.3% in the TAT for 6 months, p=0.427). However, incidence of cardiac death was significantly higher in TAT groups (0.3% vs 2.5% vs 1.3%, respectively, p=0.047). Regarding in-hospital outcomes, higher bleeding events occurred in TAT groups than DAT group (0.3% vs 3.2% vs 1.9%, p=0.027) without significant difference in major bleeding. Conclusion: TAT strategy with cilostazol on the top of DAT did not associated with reduced incidence of 1-year MACE as compared with DAT but may be associated with increased cardiovascular death and bleeding risk. Whether routine additional use of cilostazol for STEMI patients would be beneficial need further studies with larger study population.

ADVISABILITY OF USING CILOSTAZOL IN PATIENTS WITH CHRONIC LIMB-THREATENING ISCHEMIA

The article presents the results of surgical and conservative treatment of patients with chronic limb-threatening ischemia (CLTI) of the lower extremities due to steno-occlusive atherosclerotic arterial lesions. The definite role of cilostazol in creating favorable conditions for the healing of trophic wounds is shown.
 Aim: to improve the results of surgical treatment of patients with CLTI, with use of surgical and conservative methods of treatment, in particular the use of the Cilostazol (Plestazol).
 Materials and methods. The research included 60 people aged 53 to 82 years with CLTI. All patients had trophic skin changes on the lower extremities (IV grade according to Fontaine classification; 5, 6 category according to Rutherford classification). The operations were performed by the open method (aorto-bifemoral bypass grafting / prosthetics, femoral-popliteal / distal bypass grafting) and X-ray endovascular method (percutaneous balloon angioplasty of the arteries of the lower extremities and stenting of the arteries). The examined patients were divided into 2 groups statistically and clinically comparable (in the main group, open operations were performed in 12 patients, endovascular interventions in 18 patients). In the comparison group - 17 patients were operated openly, endovascular – 13 patients).
 The research evaluated the microflora sown from wounds on the foot, the size of the skin defect, the rate of healing of which was assessed in the dynamics (reduction of wound area), the rate of body and changes in white blood, antibacterial drugs were prescribed according to sensitivity. During microbiological examination and culture of wounds of the lower extremities, it was found that the most common flora were gram-positive staphylococci (S. aureus, S. epidermidis). E. coli, Pr. mirabilis, Ps were also sown as accompanying flora. The area of necrosis was determined using a transparent film with a grid of squares of 1 mm². Wounds were treated topically with antiseptic and antimicrobial drugs according to the stages of the wound process without the use of hardware treatments.
 The drug was prescribed as an additional antiplatelet therapy and as a vasodilator to assess the effectiveness of cilostazol in the main group. In the comparison group, patients received antiplatelet therapy.
 Research results. A homogeneous category of patients with chronic limb-threatening ischemia, who underwent revascularization, demonstrate different rates of healing of the initial trophic ulcers and the appearance of fresh granulation tissue. The fresh granulation tissue after treatment of wounds on the foot, including after performed necrectomy in patients in the main group appeared in 6-11 days (9.7 ± 2.83, confidence interval 8.69-10.71), while the time of appearance of the newly formed granulation tissue in the comparison group was 9-16 days. The total time of wound healing in the main group averaged 70 (73.1 ± 2.05) days, in the comparison group this figure was 90 (89 ± 2.63) days.
 All patients who received the drug Cilostazol had a faster rate of healing of necrosis, which is explained, among other things, by the pro-angioproliferative properties of the drug.
 Conclusions. The use of surgical and conservative methods of treatment in particular use of cilostazol (plestazol) in patients with chronic limb-threatening ischemia, can shorten the healing time of wounds.

Usefulness of cilostazol in symptomatic bradycardia caused by cervical cord injury

Usefulness of cilostazol in symptomatic bradycardia caused by cervical cord injury

The Role of Cilostazol and Inflammation in Cognitive Impairment After Ischemic Stroke.

The aim of this study is to examine the potential effect of cilostazol and inflammation on cognitive impairment after stroke in an Asian population. Forty-five patients with cognitive impairment after ischemic stroke using cilostazol were enrolled as the study group and 45 patients using aspirin or clopidogrel were enrolled as the control group. Neuropsychiatric assessments were administered at the start of the study and after 6 months. Multiple logistic regression analysis was used to estimate the association between the cognitive change and cilostazol use. Macrophage polarization were assessed using flow cytometry in 7 patients. There were a significantly higher number of patients with peripheral arterial occlusive disease in the cilostazol group. No significant differences were observed in the cognitive change between the cilostazol and control groups. M1 macrophage subset increment were observed in the patient having a declined cognitive change. Cilostazol did not make a significant difference in cognitive change after ischemic stroke. M1 macrophage subset increment may indicate post stroke cognitive decline. Due to limited number of subjects, these findings should be examined further in large-scale randomized clinical trials.

Therapeutic Effects of Medication Use on Intermittent Claudication: A Network Meta-analysis.

To systematically evaluate the therapeutic effects of commonly used drugs for the treatment of intermittent claudication in patients with peripheral arterial diseases. We systematically searched bibliographic databases for randomized clinical trials published between 2000 and 2020, through the China National Knowledge Infrastructure, WanFang Data, PubMed, MEDLINE, Embase, and Cochrane library. Included studies focused on therapeutic effects of beraprost, clopidogrel, aspirin, sarpogrelate and cilostazol on treating intermittent claudication. The outcome measures were maximum walking distance, pain-free walking distance, ankle-brachial index, and severe adverse events. The quality of included trials was evaluated by using the bias risk assessment tool recommended by the Cochrane, after extracting data from the literatures. Stata was used to conduct the network meta-analysis. There were 27 randomized control trials included in the study, covering in total 9491 patients. The network meta-analysis results showed that for maximum walking distance, better therapeutic effect was noted in using beraprost, sarpogrelate, and cilostazol. Beraprost, beraprost combined with aspirin, and sarpogrelate were better in improving pain-free walking distance than other drugs. For the ankle-brachial index, cilostazol combined with clopidogrel, sarpogrelate, and beraprost had better therapeutic effects than others. The use of sarpogrelate, beraprost, and aspirin was associated with a lower ratio of severe adverse events than the use of cilostazol and placebo. Among the commonly used drugs for the treatment of intermittent claudication, beraprost and sarpogrelate may have better efficacy in improving the walking distance and ankle-brachial index, with a beneficial effect on cardiovascular and cerebrovascular comorbidities.

Efficacy and safety of cilostazol-nimodipine combined therapy on delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage: a prospective, randomised, double-blinded, placebo-controlled trial protocol

IntroductionDelayed cerebral ischaemia (DCI) due to cerebral vasospasm (cVS) remains the foremost contributor to morbidity and mortality following aneurysmal subarachnoid haemorrhage (aSAH). Past efforts in preventing and treating DCI have...

Lumen Loss at 1 Year After Bare Nitinol Stent Implantation in the Superficial Femoral Artery

Purpose To investigate lumen loss (LL) at 1 year after bare nitinol stent (BNS) implantation for de novo superficial femoral artery (SFA) lesions. Materials and Methods The subjects were 701 consecutive patients (mean age 74±9 years; 492 men) with 817 de novo SFA lesions treated with BNS implantation between January 2004 and September 2015. The mean lesion length was 141±88 mm and the mean vessel diameter was 5.4±0.9 mm. The endpoint was LL at 1 year after BNS implantation. Secondary outcomes were restenosis and target lesion revascularization (TLR) estimated using the Kaplan-Meier method; estimates are reported with the 95% confidence interval (CI). LL was defined as the minimum lumen diameter immediately after BNS implantation minus that at 1 year measured by angiographic quantitative vessel analysis. The distribution of LL in the overall population was estimated using an accelerated failure time model. Results Mean LL at 1 year was estimated to be 1.74±1.28 mm (95% CI 1.63 to 1.84). Current smoking was positively associated with LL (p=0.015), whereas lack of cilostazol use was correlated with an increase in LL (p=0.001). Reference vessel diameter and lesion length did not have any significant association with LL at 1 year. The 1-year cumulative estimate of restenosis was 25% (95% CI 22% to 28%); the corresponding value for TLR was 18% (95% CI 15% to 21%). Conclusion Mean LL progressed by at least 1.6 mm up to 1 year after BNS implantation. The risk factors for increased LL were current smoker and lack of cilostazol use.

Cilostazol Improves Limb Salvage Rates After Infrainguinal Endovascular and Open Intervention: An Updated Meta-Analysis and Systematic Review

Current clinical guidelines recommend the use of cilostazol in the treatment of patients with infrainguinal peripheral arterial disease (PAD) who experience claudication. However, the role of cilostazol therapy in patients with advanced PAD and critical limb ischemia (CLI) remains unclear. Our objective was to conduct a meta-analysis of randomized controlled trials and cohort studies that evaluated the effect of cilostazol versus standard antiplatelet therapy on limb-related and arterial patency-related outcomes.

P1234SNF472 IMPROVES LIMB BLOOD PERFUSION AND WALKING ABILITY IN A PERIPHERAL ARTERY DISEASE VASCULAR CALCIFICATION RAT MODEL

Abstract Background and Aims Peripheral Artery disease (PAD) is a common vascular disease associated with functional impairment and increased risk of cardiovascular events in End Stage Kidney Disease (ESKD) patients undergoing dialysis. Poor limb salvage outcomes and high post-amputation mortality in hemodialysis (HD) patients highlight the need for earlier medical therapies. Cilostazol and pentoxifylline are approved for PAD. Their use in HD patients stays limited and cilostazol use requires caution in this population. Clinical studies demonstrate associations between arterial calcification and adverse outcomes in PAD patients. SNF472, a selective calcification inhibitor that interferes in the formation and growth of hydroxyapatite, is in Phase 3 for calciphylaxis treatment. This study aims to evaluate the effects of SNF472 on limb functional recovery and blood perfusion in a Vitamin D3 (VitD)-induced arterial calcification rat model. Method Arterial calcification was induced in 32 Sprague Dawley rats by 3 consecutive daily s.c. doses of 120 kIU/kg VitD. Rats were divided into four groups and treated during 12 days by: placebo s.c, placebo p.o, SNF472 (20 mg/kg/day, s.c.) or cilostazol (20 mg/kg/day, p.o.). An additional group of 8 rats without VitD received vehicle only (sham). Efficacy was evaluated at day 12 and 17 (5 days after treatment stop). Posterior limb blood perfusion was measured using Laser Doppler Imaging and limb walking ability was evaluated by measuring Maximum Walking Distance (MWD) and Maximum Walking Time (MWT) using a treadmill. Rats were sacrificed at day 26 (14 days after treatment stop), and aortas were collected for calcium analysis. Results VitD-induced arterial calcification was associated with decreased blood perfusion and impairment of limb walking ability (MWT and MWD) compared to sham. SNF472 reduced aorta calcification by 41% compared to placebo. No effects of cilostazol on vascular calcification were observed. The inhibition of calcification in SNF472-treated animals was associated with significant higher limb blood perfusion compared to placebo or Cilostazol (1.28 and 1.37-fold higher, respectively at day 12: p< 0.001) and it was translated into a significant improvement in walking ability compared to placebo (515±114 meters vs 334±187 meters, respectively: p<0.05). Conclusion SNF472 shows improvements in vascular calcification, blood perfusion and a functional parameter like walking distance in a PAD vascular calcification rat model. These results suggest that SNF472 may represent a new therapeutic approach for the treatment of PAD associated with high vascular calcification such as in renal disease.

Cilostazol and peripheral artery disease-specific health status in ambulatory patients with symptomatic PAD

BackgroundImprovement of symptoms and functional status is one of the main peripheral artery disease (PAD) treatment goals but pharmacological options are limited. The objective of this study was to assess the use of cilostazol and its association with patient-reported health status quantified by the Peripheral Artery Questionnaire (PAQ). MethodsInitiation of cilostazol therapy was assessed in 567 patients in the US cohort of PORTRAIT between June 2011 and December 2015. Patients with heart failure history, on cilostazol prior to enrollment, with no baseline or follow-up PAQ scores were excluded. Health status over time was quantified using linear mixed models adjusting for baseline PAQ scores and patient characteristics. ResultsOf the 567 cilostazol-naïve patients, 65 (11%) were started on cilostazol. Mean age was 68.5 ± 9.6 years, 43% were female and 71.1% white. There was no significant difference in the mean PAQ score changes from baseline to 12 months between the cilostazol and non-cilostazol group, with difference of 3.8 [CI (−2.6, 10.1), p = .24] for summary scores, 1.6 [CI (−5.5, 8.6), p = .66] for quality of life, 3.6 [CI (−4.3, 11.6), p = .37] for symptoms, 6.2 [CI (−3.1, 15.5), p = .19] for physical limitation and 3.2 [CI (−3.9, 10.2), p = .38] for social limitation scores. ConclusionsWe found a low rate of cilostazol use and while there was no significant association between cilostazol initiation and subsequent health status, the ability to define small differences in health status was limited due to the small sample size.

Impact of IVUS-Derived Vessel Size on Midterm Outcomes After Stent Implantation in Femoropopliteal Lesions

Purpose: To identify intravascular ultrasound (IVUS) findings that predict midterm stent patency in femoropopliteal (FP) lesions. Materials and Methods: A retrospective analysis was undertaken of 335 de novo FP lesions in 274 consecutive patients (mean age 72.4±8.2 years; 210 men) who had IVUS assessment before and after successful stent implantation. The mean lesion length was 13.2±9.8 cm. The primary outcome was primary patency at 24 months, defined as freedom from major adverse limb event (MALE) and in-stent restenosis (ISR). MALE was defined as major amputation or any target lesion revascularization (TLR). ISR was defined by a peak systolic velocity ratio >2.4 by duplex ultrasonography. Logistic regression analyses were performed to identify independent predictors of stent patency at 24 months; the results are presented as the odds ratio (OR) and 95% confidence interval (CI). Receiver operator characteristic (ROC) curve analysis was performed to determine the optimal threshold for prediction of stent patency at 24 months. Results: Over the 24-month follow-up, 18 (7%) patients died and 43 (15%) of 286 lesions were responsible for MALE (42 TLRs and 1 major amputation). Primary patency was estimated at 82.5% (95% CI 78.1% to 86.9%) at 12 months and 73.2% (95% CI 67.9% to 78.5%) at 24 months. Multivariable analysis revealed that longer lesion length (OR 0.89, 95% CI 0.82 to 0.97, p<0.01) was an independent predictor of declining patency, while cilostazol use (OR 3.45, 95% CI 1.10 to 10.78, p=0.03) and increasing distal reference external elastic membrane (EEM) area (OR 1.18, 95% CI 1.02 to 1.37, p=0.03) were associated with midterm stent patency. ROC curve analysis identified a distal reference EEM area of 29.0 mm2 as the optimal cut-point for prediction of 24-month stent patency (area under the ROC curve 0.764). Kaplan-Meier estimates of 24-month primary patency were 83.7% (95% CI 78.3% to 89.2%) in lesions with a distal EEM area >29.0 mm2 vs 53.1% (95% CI 42.9% to 63.3%) in those with a distal EEM area ≤29.0 mm2 (p<0.001). Conclusion: In FP lesions with a larger distal vessel area estimated with IVUS, stent implantation can be considered as a reasonable treatment option, with the likelihood of acceptable midterm results.

Prospects of clinical application of cilostazol for peripheral artery disease

This article presents a review of the literature on studying Cilostazol, a type 3 phosphodiesterase inhibitor, also providing the Russian and foreign statistics on the prevalence of peripheral artery disease. It is underlined that the majority of patients with peripheral artery disease have atherosclerotic lesions in the coronary and cerebral vascular basins. Cilostazol deservedly occupies the first lines in the sections of pharmacotherapy for intermittent claudication in international and Russian consensus documents on peripheral artery disease. The drug has an extensive evidence base for the following pharmacological effects: vasodilating, antiplatelet, endothelial protective, and vasculogenic. Clinical efficacy of Cilostazol was confirmed in 15 randomized clinical trials (3 718 patients with intermittent claudication) studying the use of Cilostazol taken twice daily at doses of 50 mg, 100 mg, and 150 mg as compared with placebo or versus pentoxifylline given in a dose of 400 mg three times daily, with a demonstrable increase in the pain-free walking distance and the maximal walking distance on the background of taking Cilostazol. The drug significantly improves the outcomes of endovascular interventions on arteries of lower extremities, decreasing the incidence of restenosis, prolonging limb survival, and reducing the frequency of major amputations. Many studies addressing the use of Cilostazol in patients with coronary and cerebral atherosclerosis have investigated the effect of the drug as a component of dual antiplatelet therapy (aspirin + Cilostazol) and triple antiplatelet therapy (aspirin + clopidogrel + Cilostazol) after endovascular interventions. The addition of Cilostazol to treatment resulted in a significant decrease in the occurrence of re-stenosis, with no increase in the incidence of haemorrhage. Cilostazol may be recommended for patients with multifocal atherosclerosis and resistance to aspirin and clopidogrel. Also presented in the article are the results of a Russian clinical trial studying comparative efficacy of Cilostazol and pentoxifylline in patients with intermittent claudication.

Heterogeneous and dynamic lumen remodeling of the entire infrainguinal vein bypass grafts in patients

ObjectiveTo examine the regional variation and temporal change in lumen size along the entire autogenous vein bypass graft used for treating arterial occlusive disease in lower extremity and to explore the factors associated with graft expansive or constrictive remodeling. MethodsPatients were prospectively scanned using contrast-enhanced computed tomography at 1 week and 1, 6, and 12 months postoperatively to obtain lumen cross-sectional areas at 1-mm intervals along the entire grafts. Graft lumen remodeling characteristics and the associated demographic and clinical factors were examined. ResultsFifty-six patients with at least two consecutive computed tomography scans were analyzed. Patients with a composite or longer graft, or with diabetes, had a larger lumen cross-sectional area variation along the graft. The mean lumen cross-sectional areas of all the grafts demonstrated no significant changes through 12 months. However, individually, graft remodeling was time dependent and there was a more dramatic change in lumen cross-sectional area within the first postoperative month. At 12 months, a near equal distribution between expansive and constrictive grafts existed. A negative relation between the initial lumen diameters and the subsequent lumen diameter changes was observed. Eleven grafts failed within 12 months; failed and patent grafts had similar mean lumen cross-sectional areas at all four time points, but failed grafts had a larger maximal local cross-sectional area reduction from 1 week to 1 month (58.0 ± 6.7% vs 38.1 ± 3.1%, mean ± standard error of the mean, failed vs patent, P = .004). Black patients had a smaller mean lumen cross-sectional area than white patients at all four time points and also had a higher early percent mean area reduction (−20.5 ± 6.3% vs −1.0 ± 3.7%, black vs white, P = .018). Cilostazol use was associated with early expansive graft remodeling. ConclusionsVein grafts remodel heterogeneously and dynamically. Remodeling is associated with initial graft lumen size, race, and cilostazol use. It is found that remodeling that produces some critical minimum area or maximal percent reduction during the first postoperative month may predispose to vein graft failure. These findings offer insight into further investigation to examine the underlying mechanisms and opportunities to improve graft remodeling and durability.

P1929A randomized controlled trial evaluating outcome impact of cilostazol in patients with coronary artery disease and at a high risk of cardiovascular disease

Abstract Background We and others have previously found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, anti-atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood that if this compound can provide better clinical outcome. Purpose This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. Methods We conducted a randomized, double-blind, placebo controlled trial involving 266 patients to receive cilostazol 200 mg/day (n=134) or dummy placebo (n=132). The primary endpoint was a composite of CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for congestive heart failure or unplanned coronary revascularization. Pre-specified secondary endpoints include the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE) on long-term follow-up. The mean duration of follow-up was 2.9 years. Results Relative to placebo, cilostazol treatment had a borderline effect on risk reduction in the primary endpoint (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34–1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (P for interaction, 0.02 and 0.06, respectively). Use of cilostazol, but not placebo, significantly reduced the risk of the MCE (HR, 0.38; 95% CI, 0.17–0.86) and MACCE (HR, 0.47; 95% CI, 0.23–0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17–0.86) and unplanned revascularization (HR, 0.13; 95% CI, 0.02–1.09) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of the MCE and MACCE. Conclusions Cilostazol treatment significantly reduced the risk of CV events in patients with CAD or at a high risk of CV disease. Acknowledgement/Funding MOST 106-2314-B-006-044, MOHW106-TDU-B-211-113003, MOHW107-TDU-B-211-113003, and MOST107-2314-B-006-076-MY2

Zastosowanie cilostazolu w chorobie tętnic obwodowych – wskazania i kontrowersje

Zastosowanie cilostazolu w chorobie tętnic obwodowych – wskazania i kontrowersje

Cilostazol use is associated with FIM cognitive improvement during convalescent rehabilitation in patients with ischemic stroke: a retrospective study.

ABSTRACTCilostazol is a phosphodiesterase III-inhibiting antiplatelet agent that is often used to prevent stroke and peripheral artery disease, and its administration has shown significant improvements for cognitive impairment. We investigate the potential of cilostazol for reducing or restoring cognitive decline during convalescent rehabilitation in patients with non-cardioembolic ischemic stroke. The study sample included 371 consecutive patients with lacunar (n = 44) and atherothrombosis (n = 327) subtypes of non-cardioembolic ischemic stroke (224 men and 147 women; mean age, 72.9 ± 8.1 years) who were required for inpatient convalescent rehabilitation. Their medical records were retrospectively surveyed to identify those who had received cilostazol (n = 101). Patients were grouped based on cilostazol condition, and Functional Independence Measure (FIM) scores (total and motor or cognitive subtest scores) were assessed both at admission and discharge. The gain and efficiency in FIM cognitive scores from admission to discharge were significantly higher in patients who received cilostazol than those who did not (p = 0.047 and p = 0.035, respectively); we found no significant differences in other clinical factors or scores. Multiple linear regression analysis confirmed that cilostazol was a significant factor in FIM cognitive scores at discharge (β = 0.041, B = 0.682, p = 0.045); the two tested dosages were not significantly different (100 mg/day, n = 43; 200 mg/day, n = 58). Cilostazol can potentially improve cognitive function during convalescent rehabilitation of patients with non-cardioembolic ischemic stroke, although another research must be needed to confirm this potential.

Outcomes with cilostazol after endovascular therapy of peripheral artery disease.

The role of cilostazol after endovascular therapy (EVT) of peripheral artery disease (PAD) remains unclear. We conducted a meta-analysis for all studies reporting the outcomes of cilostazol after EVT of PAD from January 2000 through November 2018 with the outcomes of interest including primary patency, major adverse limb events (MALE), target lesion revascularization (TLR), and major amputation. We included eight studies (three randomized controlled trials (RCTs) and five observational studies) with a total of 3846 patients (4713 lesions). During a mean follow-up duration of 12.5 ± 5 months, the use of cilostazol was associated with higher primary patency (OR 2.28, 95% CI (1.77, 2.94), p < 0.001, I2 = 24%), lower risk of TLR (OR 0.37, 95% CI (0.26, 0.52), p < 0.001, I2 = 0%), and lower risk of major amputation (OR 0.15, 95% CI (0.04, 0.62), p = 0.008, I2 = 0%). The use of cilostazol in RCTs was associated with significantly higher odds of primary patency compared with observational studies (OR 3.37 vs 2.28, p-interaction = 0.03). After further subgroup analysis, cilostazol remained associated with higher primary patency regardless of the use of anticoagulants (warfarin) (p-interaction = 0.49). We conclude that the use of cilostazol after EVT of femoropopliteal and iliac lesions is associated with improved primary patency and lower risk of major amputation and TLR. The favorable impact of cilostazol is independent of the use of warfarin. PROSPERO identifier: CRD42018092715.

Risk of Heart Failure Hospitalization Associated With Cilostazol in Diabetes: A Nationwide Case-Crossover Study

Background and Objective: It has been suggested to avoid cilostazol, the first-line therapy for peripheral arterial disease, in patients with congestive heart failure (HF). The objective of this study was to evaluate the risk of hospitalization for heart failure (HHF) associated with cilostazol use in the patients of diabetes mellitus. Methods: This case-crossover study retrieved records on diabetic patients > 20 years of age who were hospitalized for heart failure during the period of 2009-2011 from the Taiwan National Health Insurance Database. The period was defined as 1-30 days prior to HHF whereas the 91-120 days prior to HHF served as the period. The exposure status just preceding the event is compared with exposure of the same person in one or more referent remote to the event. Adjusted odds ratios (OR) were used to estimate time-varying discordant exposure by the ratio of the number exposed to cilostazol only during the case period to the number exposed to cilostazol only during the control period. Results: A total of 47,506 diabetic patients were included in the analysis (average age: 72.7 ± 12.4, percentage of males: 48%). A total of 399 patients (0.84%) received cilostazol only in the current period, and 252 (0.53%) received cilostazol only in the reference period. After adjustment for other medications, a significant association was found between cilostazol and HHF (OR: 1.35, 95% CI: 1.14-1.59). After further adjustment for time-varying co-morbidities the ORs remained essentially the same. Sensitivity analyses using different definitions of control period (ranging from 31-60, 61-90, to 121-150 days before index date) yielded adjusted ORs of 1.43 (95% CI: 1.14-1.79), 1.31 (95% CI: 1.09-1.57) and 1.23 (95% CI: 1.06-1.44), respectively suggesting the robustness of our study findings. Conclusion: Use of cilostazol may be positively related to the risk of HHF. Further studies are warranted to explore the underlying mechanisms and to confirm the association.

Risk of Heart Failure Hospitalization Associated With Cilostazol in Diabetes: A Nationwide Case-Crossover Study.

Background and Objective: It has been suggested to avoid cilostazol, the first-line therapy for peripheral arterial disease, in patients with congestive heart failure (HF). The objective of this study was to evaluate the risk of hospitalization for heart failure (HHF) associated with cilostazol use in the patients of diabetes mellitus.Methods: This case-crossover study retrieved records on diabetic patients > 20 years of age who were hospitalized for heart failure during the period of 2009–2011 from the Taiwan National Health Insurance Database. The “current” period was defined as 1–30 days prior to HHF whereas the 91–120 days prior to HHF served as the “reference” period. The exposure status just preceding the event is compared with exposure of the same person in one or more referent remote to the event. Adjusted odds ratios (OR) were used to estimate time-varying discordant exposure by the ratio of the number exposed to cilostazol only during the case period to the number exposed to cilostazol only during the control period.Results: A total of 47,506 diabetic patients were included in the analysis (average age: 72.7 ± 12.4, percentage of males: 48%). A total of 399 patients (0.84%) received cilostazol only in the current period, and 252 (0.53%) received cilostazol only in the reference period. After adjustment for other medications, a significant association was found between cilostazol and HHF (OR: 1.35, 95% CI: 1.14–1.59). After further adjustment for time-varying co-morbidities the ORs remained essentially the same. Sensitivity analyses using different definitions of control period (ranging from 31–60, 61–90, to 121–150 days before index date) yielded adjusted ORs of 1.43 (95% CI: 1.14–1.79), 1.31 (95% CI: 1.09–1.57) and 1.23 (95% CI: 1.06–1.44), respectively suggesting the robustness of our study findings.Conclusion: Use of cilostazol may be positively related to the risk of HHF. Further studies are warranted to explore the underlying mechanisms and to confirm the association.

Effectiveness of risk minimization measures for the use of cilostazol in United Kingdom, Spain, Sweden, and Germany.

PurposeThe purpose of the study is to evaluate the effectiveness of risk minimization measures—labeling changes and communication to health care professionals—recommended by the European Medicines Agency for use of cilostazol for the treatment of intermittent claudication in Europe.MethodsObservational study of cilostazol in The Health Improvement Network (United Kingdom), EpiChron Cohort (Spain), SIDIAP (Spain), Swedish National Databases, and GePaRD (Germany).Among new users of cilostazol, we compared the prevalence of conditions targeted by the risk minimization measures in the periods before (2002‐2012) and after (2014) implementation. Conditions evaluated were prevalence of smoking, cardiovascular conditions, concurrent use of ≥2 antiplatelet agents, concurrent use of potent CYP3A4/CYP2C19 inhibitors and high‐dose cilostazol, early monitoring of all users, and continuous monitoring of users at high cardiovascular risk.ResultsWe included 22 593 and 1821 new users of cilostazol before and after implementation of risk minimization measures, respectively. After implementation, the frequency of several conditions related to the labeling changes improved in all the study populations: prevalence of use decreased between 13% (EpiChron) and 57% (SIDIAP), frequency of cardiovascular contraindications decreased between 8% (GePaRD) and 84% (EpiChron), and concurrent use of high‐dose cilostazol and potent CYP3A4/CYP2C19 inhibitors decreased between 6% (Sweden) and 100% (EpiChron). The frequency of other conditions improved in most study populations, except smoking, which decreased only in EpiChron (48% reduction).ConclusionsThis study indicates that the risk minimization measures implemented by the EMA for the use of cilostazol have been effective in all European countries studied, except for smoking cessation before initiating cilostazol, which remains an area of improvement.