Alexandre Abizaid

Lack of Neointimal Proliferation After Implantation of Sirolimus-Coated Stents in Human Coronary Arteries

Background—Restenosis remains an important limitation of interventional cardiology. Therefore, we aimed to determine the safety and efficacy of sirolimus (a cell-cycle inhibitor)-coated BX Velocity...

The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation

OBJECTIVES We compared the clinical outcomes following coronary stent implantation in insulin-treated diabetes mellitus (IDDM), non-IDDM patients, and nondiabetic patients. BACKGROUND Diabetic patients have increased restenosis and late morbidity following balloon angioplasty. The impact of diabetes mellitus (DM), especially IDDM, on in-stent restenosis is not known. METHODS We studied 954 consecutive patients with native coronary artery lesions treated with elective Palmaz-Schatz stents implantation using conventional coronary angiographic and intravascular ultrasound methodology. Procedural success, major in-hospital complications, and 1-year clinical outcome were compared according to the diabetic status. RESULTS. In-hospital mortality was 2% in IDDM, significantly higher (p <0.02) compared with non-IDDM (0%) and nondiabetics (0.3%). Stent thrombosis did not differ among groups (0.9% in IDDM vs. 0% in non-IDDM and 0% in nondiabetics, p >0.1). During follow-up, target lesion revascularization (TLR) was 28% in IDDM, significantly higher (p <0.05) compared with non-IDDM (17.6%) and nondiabetics (16.3%). Late cardiac event-free survival (including death, myocardial infarction [MI], and any coronary revascularization procedure) was significantly lower (p=0.0004) in IDDM (60%) compared with non-IDDM (70%) and nondiabetic patients (76%). By multivariate analysis, IDDM was an independent predictor for any late cardiac event (OR=2.05, p=0.0002) in general and TLR (odds ratio=2.51, p=0.0001) in particular. CONCLUSIONS. In a large consecutive series of patients treated by elective stent implantation, IDDM patients were at higher risk for in-hospital mortality and subsequent TLR and, as a result, had a significantly lower cardiac event-free survival rate. On the other hand, acute and long-term procedural outcome was found to be similar for non-IDDM compared with nondiabetic patients.

Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents The OPTIMIZE Randomized Trial

IMPORTANCE The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy with specific types of drug-eluting stents remains unknown. OBJECTIVE To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents. DESIGN, SETTING, AND PATIENTS The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction [MI], stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 [95% CI, -1.52 to 1.86]; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 [95% CI, 0.87-1.45]). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 [2.6%] vs 38 [2.6%] for the short- and long-term groups, respectively; HR, 1.03 [95% CI, 0.66-1.60]), MACE (78 [5.3%] vs 64 [4.3%]; HR, 1.22 [95% CI, 0.88-1.70]), or stent thrombosis (4 [0.3%] vs 1 [0.1%]; HR, 3.97 [95% CI, 0.44-35.49]). CONCLUSIONS AND RELEVANCE In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01113372.

Intravascular Ultrasound Findings in the Multicenter, Randomized, Double-Blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) Trial

Background—The goal of this intravascular ultrasound investigation was to provide a more detailed morphological analysis of the local biological effects of the implantation of a sirolimus-eluting stent compared with an uncoated stent. Methods and Results—In the RAVEL trial, 238 patients with single de novo lesions were randomized to receive either an 18-mm sirolimus-eluting stent (Bx VELOCITY stent, Cordis) or an uncoated stent (Bx VELOCITY stent). In a subset of 95 patients (sirolimus-eluting stent=48, uncoated stent=47), motorized intravascular ultrasound pullback (0.5 mm/s) was performed at a 6-month follow-up. Stent volumes, total vessel volumes, and plaque-behind-stent volumes were comparable. However, the difference in neointimal hyperplasia (2±5 versus 37±28 mm3) and percent of volume obstruction (1±3% versus 29±20%) at 6 months between the 2 groups was highly significant (P <0.001), emphasizing the nearly complete abolition of the proliferative process inside the drug-eluting stent. Analysis of the proximal and distal edge volumes showed no significant difference between the 2 groups in external elastic membrane or lumen and plaque volume at the proximal and distal edges. There was also no evidence of intrastent thrombosis or persisting dissection at the stent edges. Although there was a higher incidence of incomplete stent apposition in the sirolimus group compared with the uncoated stent group (P <0.05), it was not associated with any adverse clinical events at 1 year. Conclusions—Sirolimus-eluting stents are effective in preventing neointimal hyperplasia without creating edge effect and without affecting the plaque burden behind the struts.

Clinical and economic impact of diabetes mellitus on percutaneous and surgical treatment of multivessel coronary disease patients: insights from the Arterial Revascularization Therapy Study (ARTS) trial.

Background—Our aims were to compare coronary artery bypass grafting (CABG) and stenting for the treatment of diabetic patients with multivessel coronary disease enrolled in the Arterial Revascularization Therapy Study (ARTS) trial and to determine the costs of these 2 treatment strategies. Methods and Results—Patients (n=1205) were randomly assigned to stent implantation (n=600; diabetic, 112) or CABG (n=605; diabetic, 96). Costs per patient were calculated as the product of each patient’s use of resources and the corresponding unit costs. Baseline characteristics were similar between the groups. At 1 year, diabetic patients treated with stenting had the lowest event-free survival rate (63.4%) because of a higher incidence of repeat revascularization compared with both diabetic patients treated with CABG (84.4%, P <0.001) and nondiabetic patients treated with stents (76.2%, P =0.04). Conversely, diabetic and nondiabetic patients experienced similar 1-year event-free survival rates when treated with CABG (84.4% and 88.4%). The total 1-year costs for stenting and CABG in diabetic patients were

Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

12 855 and

Sirolimus-Eluting Stent for the Treatment of In-Stent Restenosis. A Quantitative Coronary Angiography and Three-Dimensional Intravascular Ultrasound Study

16 585 (P <0.001) and in the nondiabetic groups,

Long-Term Follow-Up After Percutaneous Transluminal Coronary Angioplasty Was Not Performed Based on Intravascular Ultrasound Findings Importance of Lumen Dimensions

10 164 for stenting and

Clinical and Economic Impact of Diabetes Mellitus on Percutaneous and Surgical Treatment of Multivessel Coronary Disease Patients

13 082 for surgery. Conclusions—Multivessel diabetic patients treated with stenting had a worse 1-year outcome than patients assigned to CABG or nondiabetics treated with stenting. The strategy of stenting was less costly than CABG, however, regardless of diabetic status.

Mortality in patients treated with extended duration dual antiplatelet therapy after drug-eluting stent implantation: a pairwise and Bayesian network meta-analysis of randomised trials

BACKGROUND Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual antiplatelet therapy. The primary safety end point, tested for both noninferiority and superiority, was a composite of cardiac death, myocardial infarction, or stent thrombosis. The primary efficacy end point was clinically driven target-lesion revascularization. RESULTS We enrolled 2466 patients. At 390 days, the primary safety end point had occurred in 112 patients (9.4%) in the drug-coated-stent group and in 154 patients (12.9%) in the bare-metal-stent group (risk difference, -3.6 percentage points; 95% confidence interval [CI], -6.1 to -1.0; hazard ratio, 0.71; 95% CI, 0.56 to 0.91; P<0.001 for noninferiority and P=0.005 for superiority). During the same time period, clinically driven target-lesion revascularization was needed in 59 patients (5.1%) in the drug-coated-stent group and in 113 patients (9.8%) in the bare-metal-stent group (risk difference, -4.8 percentage points; 95% CI, -6.9 to -2.6; hazard ratio, 0.50; 95% CI, 0.37 to 0.69; P<0.001). CONCLUSIONS Among patients at high risk for bleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet therapy. (Funded by Biosensors Europe; LEADERS FREE ClinicalTrials.gov number, NCT01623180.).