Turbo-Power™ Laser Atherectomy Combined with Drug-coated Balloon Angioplasty is Associated with Improved One-Year Outcomes for the Treatment of Tosaka II and III Femoropopliteal In-stent Restenosis.

BACKGROUND: Femoropopliteal (FP) artery in-stent restenosis (ISR) is associated with high rates of re-intervention and occlusion. The combined use of laser atherectomy (LA) with balloon angioplasty (BA) is superior to conventional balloon angioplasty (BA). Drug-coated balloons (DCBs) when combined with LA have provided additional efficacy for the treatment of FP-ISR. The aim of this study was to investigate the combination of DCB + LA with the recently approved Turbo-Power™ (Spectranetics Inc., Colorado Springs, CO, USA) LA device. METHODS: This was a dual-center retrospective study enrolling 78 consecutive patients with Tosaka type II (n = 18) or III (n = 60) FP-ISR. The lesions were treated with either Turbo-Power™ LA followed by DCB (n = 27) or with other LA devices followed by plain BA (LA + BA; n = 51) from 2015 to 2017. A Cox regression analysis was performed to examine the association between the two groups in terms of target lesion revascularization (TLR) and occlusion rates over a follow up period of 12 months. Kaplan-Meier survival curves were estimated and compared with the log-rank test. RESULTS: The overall procedural success was 90%. Eight periprocedural complications occurred without any difference between the two groups (Turbo-Power™â€¯+ DCB: 7.4% vs LA + BA: 11.8%, p = .7). The 12-month KM estimates for freedom from TLR were 90.9% in the Turbo-Power™â€¯+ DCB group vs 55.7% in the LA + BA group (p = .005). Among Toasaka III lesions, the 12 m-KM survival estimates for freedom from TLR were 88.9% in the Turbo-Power™â€¯+ DCB group vs 54.2% in the LA + BA group (p = .009). The 12 m-KM estimates for freedom from re-occlusion were 89.0% in the Turbo-Power™â€¯+ DCB group vs 58.9% in the LA + BA group (p = .070). CONCLUSIONS: Turbo-Power™ laser atherectomy combined with DCB exerted synergistic mechanism of actions and improved 12-month TLR rates for the treatment of complex FP-ISR lesions.

Acute and Midterm Outcomes of Antegrade vs Retrograde Crossing Strategies for Endovascular Treatment of Iliac Artery Chronic Total Occlusions.

PURPOSE: To examine whether an antegrade or retrograde crossing strategy for treatment of iliac artery chronic total occlusions (CTOs) is associated with differences in procedural or midterm outcomes. MATERIALS AND METHODS: A dual-center retrospective cohort study was conducted in 168 patients (mean age 66.4±10.6 years; 116 men) treated for CTOs in 110 common iliac arteries (CIA), 52 external iliac arteries (EIA), and 26 combined CIA/EIAs. Logistic regression models were developed to determine the association between crossing strategy and procedural complications, 1- and 3-year target lesion revascularization (TLR), and major adverse limb events (MALE). Results are presented as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: An initial antegrade strategy was more common for EIA CTOs (p<0.005), and an initial retrograde strategy was more often used in CIA (p<0.005) and combined CIA/EIA (p<0.005) CTOs. Crossover to an alternate approach was required in 27.6% of initial antegrade attempts and 9.6% of initial retrograde attempts. EIA CTOs were the most likely lesions to be treated successfully with the initial attempt (either strategy). In all, 123 (65.4%) lesions were successfully crossed with a final retrograde approach and 65 with a final antegrade approach. Overall target lesion success was high for both groups (95.1% vs 93.2%, p=0.456). Lesions treated with a final retrograde approach were shorter (75.3±34.9 vs 87.6±31.3 mm, p=0.005) and were more likely to be treated with a reentry device (34.2% vs 9.2%, p<0.001) and with balloon-expandable stents (39.2% vs 17.7%, p=0.005). The final antegrade approach was associated with a lower risk of target lesion complications (OR 0.07, 95% CI 0.01 to 0.81, p=0.034). The two crossing approaches were associated with similar estimates of 1- and 3-year TLR and MALE. CONCLUSION: A final antegrade approach was associated with lower rates for complications but the 2 approaches were similar in terms of lesion success, TLR, and MALE. The EIA CTOs were more likely to be treated with an antegrade approach and more likely to be crossed successfully with the initial approach irrespective of the crossing direction.

Imaging Evaluation and Interpretation for Vascular Access for Transcatheter Aortic Valve Replacement.

Transcatheter aortic valve replacement (TAVR) has emerged as an effective therapy for aortic stenosis in patients who are at intermediate and high surgical risk. Vascular access remains critical to the success of the TAVR procedure. This article reviews the use of imaging in planning and executing TAVR access.

Long-term outcomes after re-entry device use for recanalization of common iliac artery chronic total occlusions.

OBJECTIVE: To examine the impact of re-entry device (RED) use on 1- and 5-year outcomes after endovascular treatment of common iliac artery (CIA) chronic total Occlusions (CTOs). BACKGROUND: There are not enough data regarding the long-term safety and efficacy of RED. METHODS: We performed a two-center retrospective study of 115 patients (140 lesions) undergoing CIA CTO endovascular intervention between 2006 and 2016. Baseline characteristics and long-term outcomes were described. A Cox proportional hazard model was developed to determine if REDs were associated with target lesion revascularization (TLR) or major adverse limb events (MALE) after 1 and 5 years. RESULTS: Among 140 lesions, 43 (31%) required use of a RED. The mean age was 63.9 years and the majority (n = 80) of patients were male. An antegrade crossing approach and treatment of restenotic lesions were less common in the RED group (10% vs. 29%, P < .05 and 0% vs. 21%, P < .05, respectively). There were no significant differences in Rutherford class, pre-procedure ABI, or patient presentation. The procedural complication rates were similar between the two groups. The 1- and 5-year TLR rates for lesions treated with re-entry device vs. standard approaches were 11% vs. 9%; P = 0.8 and 29% vs. 29%; P = 0.9 respectively. The 1 and 5-year MALE rates for lesions treated with re-entry device were 5% vs. 6%; P = 0.8 and 11% vs. 11%; P = 0.9 respectively. CONCLUSIONS: This retrospective analysis found that recanalization of CIA occlusions using a RED is safe and is associated with long-term clinical outcomes similar to that of standard crossing techniques.

Percutaneous closure of patent foramen ovale vs. medical treatment for patients with history of cryptogenic stroke: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients with history of cryptogenic stroke are more likely to have a patent foramen ovale (PFO) and should be managed with antithrombotic agents, while the alternative option is percutaneous closure of PFOs. Our aim was to perform a meta-analysis of randomized controlled trials (RCTs) comparing percutaneous closure vs. medical treatment for patients with PFO and prior cryptogenic stroke. METHODS: Medline, Scopus and Cochrane databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. New ischemic stroke was defined as the primary endpoint. A sensitivity analysis was performed for Amplatzer device. Subgroup analyses were performed for different patient and PFO characteristics for the composite endpoints as defined by the included RCTs. RESULTS: In total of 3440 patients were included in this meta-analysis. Closure devices were superior to medical therapy for prevention of recurrent ischemic strokes (HR = 0.29; CI: 0.02-0.56), but were associated with increased risk of new onset of atrial fibrillation (AF) and atrial flutter (RR = 4.67; CI: 2.22-9.81). However, in the sensitivity analysis for Amplatzer device, there was no difference between the two groups in new onset of atrial arrhythmias. Closure devices were superior across all different subgroups when compared to medical treatment with the exception of patients with a small shunt. CONCLUSION: This meta-analysis shows that closure devices for patients with PFO and history of cryptogenic stroke can significantly decrease the risk of a new ischemic stroke. The use of Amplatzer device was not associated with increased risk of newly diagnosed atrial arrhythmias.

Midterm Outcomes After Endovascular Intervention for Occluded vs Stenosed External Iliac Arteries.

PURPOSE: To evaluate the association between a chronic total occlusion (CTO) and long-term outcomes among patients undergoing endovascular intervention to the external iliac artery (EIA). METHODS: A 2-center retrospective study was conducted of 331 patients (mean age 64.7±12.7 years; 221 men) who underwent endovascular intervention for 481 EIA atherosclerotic lesions between 2006 and 2016. A quarter of the lesions (115, 23.9%) were CTOs. The majority of patients (184, 60.9%) were treated for claudication; 172 (38%) lesions were TransAtlantic Inter-Society Consensus type C or D. Target lesion revascularization (TLR) and major adverse limb event (MALE) rates were compared between lesions with or without an EIA CTO. A Cox proportional hazard model was subsequently developed to determine baseline variables associated with long-term outcomes after successful endovascular intervention of stented EIAs; outcomes are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The mean lesion length was longer (84 vs 50 mm, p<0.001) among patients treated for CTOs. While overall the target lesion failure rates were very low (2.8%), vessel perforation (2.7% vs 0.3%, p=0.02) and distal embolization (2.7% vs 0.9%, p=0.02) were more common in the CTO group. Among 377 successfully crossed and stented lesions (93 CTOs), the overall 1-year primary patency was 78% and secondary patency was 92%. One-year and 5-year TLR rates were 8.2% and 15.4%, respectively. CTO intervention was associated with higher 5-year TLR rates in the unadjusted analysis (HR 1.72, 95% CI 1.00 to 2.56, p=0.050), but the association did not remain significant after multivariable adjustment. CONCLUSION: Intervention to EIA CTOs is associated with increased intraprocedural complexity but with similar midterm outcomes, including high patency and low rates of TLR to 5 years.

Laser Atherectomy Combined With Drug-Coated Balloon Angioplasty Is Associated With Improved 1-Year Outcomes for Treatment of Femoropopliteal In-Stent Restenosis.

PURPOSE: To examine whether laser atherectomy combined with drug-coated balloons (laser + DCB) can improve the outcomes of femoropopliteal (FP) in-stent restenosis (ISR). METHODS: A dual-center retrospective study was conducted of 112 consecutive patients (mean age 70.3±10.6 years; 86 men) with Tosaka class II (n=29; diffuse stenosis) or III (n=83; occlusion) FP-ISR lesions. Sixty-two patients (mean age 68.5±10 years; 51 men) underwent laser + DCB while the other 50 patients (mean age 72.5±10.8 years; 35 men) had laser atherectomy plus balloon angioplasty (laser + BA). Critical limb ischemia was the indication in 33% of the interventions. The average lesion length was 247 mm. A Cox regression hazard model was developed to examine the association between laser + DCB vs laser + BA; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). One-year target lesion revascularization (TLR) and reocclusion were estimated using the Kaplan-Meier method. RESULTS: Overall procedure success was 98% and was similar between groups. Bailout stenting was less often required in the laser + DCB group (31.7% vs 58%, p=0.006). The combination of laser + DCB was associated with improved 12-month estimates for freedom from TLR (72.5% vs 50.5%, p=0.043) and freedom from reocclusion (86.7% vs 56.9%, p=0.003). Among patients with Tosaka III FP-ISR, combination therapy with laser + DCB was also associated with increased freedom from reocclusion (87.1% vs 57.1%, p=0. 028). On multivariable analysis, treatment with laser + DCB was associated with a significantly reduced risk of reocclusion (HR 0.08, 95% CI 0.17 to 0.38; p=0.002). CONCLUSION: When used for treatment of complex FP-ISR lesions, DCB angioplasty combined with laser atherectomy is associated with significantly reduced 1-year TLR and reocclusion rates.

Pregnancy associated plasma protein-A as a prognostic biomarker of all-cause mortality and cardiovascular events in patients presenting with chest pain: a systematic review.

AIM: Novel biomarkers have been proposed for identification of patients at greater risk of future adverse events among those presenting with chest pain. In this review, we aim to elucidate the ability of pregnancy associated plasma protein-A (PAPP-A) to predict mortality and other cardiovascular events in this patient population. METHODS: A literature search of the electronic databases Medline, Scopus, Cochrane Library and ClinicalTrials.gov was performed in order to identify studies investigating the utility of PAPP-A to predict mortality and adverse cardiovascular events in patients with chest pain. RESULTS: Eight studies met our inclusion criteria. Five of these studies pertained to patients with confirmed ischemic chest pain, while the rest included patients presenting with chest pain possibly due to acute coronary syndrome, irrespectively of the underlying cause. Although the results for long-term events were inconclusive in both groups of patients, higher PAPP-A concentrations were found to be a significant predictor of short-term adverse events in patients with confirmed ischemic chest pain. CONCLUSIONS: PAPP-A appears to be a potentially useful biomarker for short-term risk stratification of patients presenting with chest pain of ischemic origin. However, there is an eminent need for more standardized clinical studies investigating the prognostic value of this biomarker.

High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

BACKGROUND: The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. METHODS AND RESULTS: We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P=0.14). Demographics including age (68±12 versus 67±10 years, P=0.25), smoking history (76% versus 80%, P=0.42), diabetes mellitus (54% versus 48%, P=0.17), and hypertension (88% versus 89%, P=0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P=0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P=0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P=0.02). CONCLUSIONS: In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy.

Midterm Outcomes After Infrapopliteal Interventions in Patients With Critical Limb Ischemia Based on the TASC II Classification of Below-the-Knee Arteries.

PURPOSE: To analyze the relationship between the new TransAtlantic Inter-Society Consensus (TASC II) infrapopliteal classification and limb outcomes among patients with critical limb ischemia (CLI). METHODS: A single-center retrospective study was performed on 166 consecutive CLI patients (mean age 71 years; 113 men) undergoing endovascular treatment of 244 infrapopliteal lesions from 2006 to 2013. Patient, procedural, angiographic, and limb outcomes were compared for the new TASC A/B vs C/D classification for infrapopliteal lesions. Binary restenosis was determined by a peak systolic velocity ratio >2.0 by duplex ultrasound on follow-up at 1, 3, 6, and 12 months. RESULTS: Seventy-two (43.4%) patients had TASC A/B lesions, while 94 (56.6%) had TASC C/D patterns of infrapopliteal disease. Baseline demographics and tissue loss (93% vs 94%, p=0.59) were similar between the groups. TASC A/B lesions were shorter (53±35 vs 170±83 mm, p<0.001), less severely stenosed (77%±24% vs 93%±14%, p<0.001), had a larger target vessel diameter (2.9±0.5 vs 2.6±0.5 mm, p<0.001), and were less frequently chronic total occlusions (24% vs 64%, p<0.001) compared with the TASC C/D group. Three-year freedom from both amputation (85% vs 67%, p=0.02) and major adverse limb events (79% vs 61%, p=0.02) were significantly higher in the TASC A/B group. Technical success rates (95% vs 80%, p<0.001) and 1-year primary patency (58% vs 51%, p=0.04) were higher in the A/B group. Overall 3-year survival was similar between the groups (96% A/B vs 88% C/D, p=0.2). CONCLUSION: TASC C/D infrapopliteal lesions are associated with higher amputation and major adverse limb events rates and lower primary patency compared with TASC A/B infrapopliteal lesions. Further studies are needed to assess the association between TASC C/D infrapopliteal lesions and clinical outcomes in patients with CLI.

Mid-term outcomes of orbital atherectomy combined with drug-coated balloon angioplasty for treatment of femoropopliteal disease.

PURPOSE: To assess the intraprocedural and mid-term outcomes of orbital atherectomy (OA) combined with drug-coated balloon (DCB) angioplasty for the treatment of calcified femoropopliteal disease. METHODS: In this single-center cohort, 89 patients (139 lesions) were treated with DCB angioplasty for claudication or critical limb ischemia (CLI). Angiographic characteristics and procedural outcomes were reviewed for patients treated with or without adjunctive OA. Lesion calcification was graded using two previously published scoring systems, the angiographic calcium score (ACS) and the peripheral artery calcification scoring system (PACSS). RESULTS: Among 139 lesions, 40 (29%) were treated with OA + DCB. Mean lesion length was 135 ± 100 mm for lesions treated with OA + DCB and 139 ± 100 mm for DCB alone (P = 0.9). Moderate to severe calcification was present in 83% of patients treated with OA, compared to 42% of patients treated with DCB alone (P < 0.001). Lesions treated with OA + DCB were less likely to require bailout stenting (18% vs. 39%, P =0.01). Rates of embolization (0% in OA + DCB vs. 2% in DCB only, P = 0.4), dissection (13% vs. 14%, P = 0.8), and perforation (0%) did not differ significantly between groups. The freedom from TLR at 1 year was 82% in both groups (P = 0.6) while primary patency was 81% in-patients treated with DCB alone and 77% in-patients treated with DCB with concomitant OA (P = 0.8). CONCLUSION: In this single-center analysis of patients undergoing DCB angioplasty for claudication or CLI, OA was most often used for the treatment of severely calcified lesions. These lesions were more likely to be treated with scoring balloons and less likely to require bailout stenting. At 1 year, target lesion revascularization and primary patency was similar in patients treated with and without adjunctive OA, despite the higher lesion complexity among those receiving the combination procedure. © 2017 Wiley Periodicals, Inc.

Contemporary evaluation and management of lower extremity peripheral artery disease.

Peripheral artery disease (PAD) includes atherosclerosis of the aorta and lower extremities. Affecting a large segment of the population, PAD is associated with impaired functional capacity and reduced quality of life as well as an increased risk of stroke, myocardial infarction and cardiovascular death. The evaluation of PAD begins with the physical examination, incorporating non-invasive testing such as ankle-brachial indices to confirm the diagnosis. Therapeutic interventions are aimed at alleviating symptoms while preserving limb integrity and reducing overall cardiovascular risk. With this in mind, risk factor modification with exercise and medical therapy are the mainstays of treatment for many patients with PAD. Persistent symptoms or non-healing wounds should prompt more aggressive therapies with endovascular or surgical revascularisation. The following manuscript provides a comprehensive review on the contemporary evaluation and management of PAD.

Medical Therapy in Peripheral Artery Disease and Critical Limb Ischemia.

OPINION STATEMENT: Peripheral artery disease (PAD) comprises atherosclerosis of the aorta and lower extremities. Many patients with PAD are asymptomatic, while others present with intermittent claudication (IC) or critical limb ischemia (CLI). Defined as rest pain or tissue loss that persists for >2 weeks, CLI represents the most severe clinical manifestation of PAD and is associated with an increased risk of limb loss and death. Patients with PAD, including those with CLI, are underdiagnosed and undertreated. In addition to smoking cessation, medical therapy with an antiplatelet agent and statin is recommended for all patients with PAD. Regular exercise has been shown to improve walking distance and quality of life in patients with symptomatic PAD and should be incorporated into each patient's treatment plan. In patients who have CLI and in those with persistent lifestyle-limiting claudication despite optimal medical therapy and an exercise program, revascularization is indicated for limb salvage and symptom relief, respectively. Consensus guidelines currently support an endovascular first approach to revascularization in the majority of cases. Surgical procedures provide an alternative to endovascular therapy in select cases.

Endovascular Therapy for Chronic Mesenteric Ischemia.

OPINION STATEMENT: Chronic mesenteric ischemia (CMI) most commonly occurs as a consequence of multivessel atherosclerotic disease of the mesenteric vasculature. Risk factors include smoking, hypertension, dyslipidemia, and advanced age, and women are more commonly affected than men. The clinical presentation of CMI is characterized by postprandial abdominal pain and weight loss. Left untreated, patients often develop severe malnutrition. Current consensus guidelines recommend secondary prevention medications such as statins and aspirin for all patients with known atherosclerosis to reduce the risk of stroke and MI, but data specific to medical therapy in CMI are lacking. To date, no medical therapy has been proven to be effective in preventing the progression of mesenteric atherosclerosis. Revascularization through surgical bypass is associated with significant perioperative morbidity and mortality. The evolution of endovascular techniques and equipment has made catheter-based therapy a first-line option for revascularization in CMI.

Antithrombotic therapy in peripheral artery disease.

Antiplatelet agents are recommended for the reduction of major adverse cardiovascular events among all patients with symptomatic peripheral artery disease. However, the optimal antiplatelet regimen and duration of therapy in peripheral artery disease (PAD) remains unclear, largely due to limited and conflicting data in this patient population. This article reviews current data on antithrombotic therapy in PAD and discusses the implications of this data for current practice and future research.

Five-year efficacy and safety analysis of the Adenoma Prevention with Celecoxib Trial.

The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.

Celecoxib for the prevention of sporadic colorectal adenomas.

BACKGROUND: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).