To date, limited information is available on the long-term discontinuation rates of antiplatelet therapy after drug-eluting stent implantation. The aim of the present study was to determine the ...prevalence and predictors of premature discontinuation of oral antiplatelet therapy after drug-eluting stent implantation and to evaluate its effects on long-term prognosis. We studied 1,358 consecutive patients successfully treated with drug-eluting stents and discharged with dual oral antiplatelet therapy. Aspirin was to be maintained lifelong, and clopidogrel was prescribed for 12 months. The patients were followed for 36 months. The prevalence and predictors of aspirin and clopidogrel discontinuation were assessed. Major adverse cardiac events, defined as death, myocardial infarction, destabilizing symptoms leading to hospitalization, and nonfatal stroke, were recorded. Definite, probable, and possible stent thrombosis (ST) and major and minor bleeding were also determined. Of the 1,358 patients, 8.8% had discontinued one or both antiplatelet agents within the first 12 months (“early” discontinuation) and 4.8% had discontinued aspirin after 1 year (“late” discontinuation). Early discontinuation was predicted by in-hospital major bleeding, the use of oral anticoagulants at discharge, and the lack of a statin prescription. Previous stroke was the only independent predictor of late discontinuation. Patients with early discontinuation experienced a greater incidence of major adverse cardiac events (28.6% vs 13.7%, p <0.001) and ST (7.6% vs 3.4%, p = 0.038). All-cause mortality (13.4% vs 4.7%, p <0.001) and cardiovascular death (5% vs 1.2%, p = 0.007) were significantly more frequent among patients with early discontinuation. In patients with late discontinuation, a nonstatistically significant increase was seen in major adverse cardiac events (20% vs 13.3%, p = 0.128) and ST (6.2% vs 3.2%, p = 0.275). In conclusion, premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death.
Objectives We designed a randomized trial exploiting optical coherence tomography (OCT) to assess coverage and apposition of overlapping bare-metal stents (BMS) and drug-eluting stents (DES) in human ...coronary arteries. Background Overlapping DES impair healing in animals. Optical coherence tomography allows accurate in vivo assessment of stent strut coverage and apposition. Methods Seventy-seven patients with long coronary stenoses were randomized to overlapping sirolimus-eluting stents (SES), paclitaxel-eluting stents (PES), zotarolimus-eluting stents (ZES), or BMS. The primary goal of the study was to determine the rate of uncovered/malapposed struts in overlap versus nonoverlap segments, according to stent type, at 6-month follow-up with OCT. Results A total of 53,047 struts were analyzed. The rate of uncovered/malapposed struts was 1.5 ± 3.4% and 0.6 ± 2.7% in overlap versus nonoverlap BMS (p = NS), respectively, and 4.3 ± 11% and 3.6 ± 8% in overlap versus nonoverlap DES (p = NS), respectively. There were no differences in the rates of uncovered/malapposed struts between overlapping BMS and DES, likely due to low frequency of uncovered/malapposed struts in ZES (0.1 ± 0.4%), which offset the higher rates observed in SES (6.7 ± 9.6%) and PES (6.7 ± 16.5%, p < 0.05). Overlap segments showed greater neointimal volume obstruction versus nonoverlap segments in all DES (p < 0.05 for all DES types). Strut-level neointimal thickness at overlap and nonoverlap segments were lowest in SES (0.16 ± 0.1 mm and 0.12 ± 0.1 mm, respectively) compared with PES (0.27 ± 0.1 mm and 0.20 ± 0.1 mm, respectively), ZES (0.40 ± 0.16 mm and 0.33 ± 0.13 mm, respectively), and BMS (0.55 ± 0.31 mm and 0.53 ± 0.25 mm, respectively, p < 0.05). Conclusions As assessed by OCT the impact of DES on vascular healing was similar at overlapping and nonoverlapping sites. However, strut malapposition, coverage pattern, and neointimal hyperplasia differ significantly according to DES type. (Optical Coherence Tomography for Drug Eluting Stent Safety ODESSA; NCT00693030 )
Randomized controlled trials assessing new drugs and devices tend to exclude subjects who are at greatest risk. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial ...Infarction (HORIZONS-AMI) trial incorporated broader inclusion criteria in an attempt to include a more representative spectrum of patients presenting with ST-segment elevation myocardial infarction (STEMI). To identify the differences between this modern trial and the real world, we analyzed the characteristics and outcomes of patients with STEMI who were screened but not enrolled at a high-volume recruiting center. Of 318 consecutive patients with STEMI who were screened, 200 (62.9%) were randomized, and 118 (37.1%) were excluded. The baseline characteristics and 30-day and 1-year clinical outcomes were compared in the 2 groups. The excluded patients had numerous high-risk features compared to those randomized, including being older (67.0 ± 12.8 vs 63.0 ± 11.4 years, p = 0.004), more often had had a previous MI (34.7% vs 8.0%, p <0.001), Killip class III-IV (27.4% vs 4.0%, p <0.001), and lower hemoglobin (13.4 ± 2.3 vs 14.8 ± 1.5 g/dl, p <0.001). The excluded patients had markedly greater 30-day and 1-year rates of all-cause mortality (17.4% vs 2.0%, p <0.001, and 27.6% vs 2.5%, p <0.001, respectively), major adverse cardiovascular events (death, MI, ischemia-driven target vessel revascularization, and stroke), major bleeding, and net adverse clinical events (major adverse cardiovascular events or major bleeding). On multivariate analysis, Killip class III-IV at presentation, age, left ventricular ejection fraction, and final Thrombolysis In Myocardial Infarction flow grade 3 were independent predictors of outcome. In conclusion, despite the broadened entry criteria of the HORIZONS-AMI trial, 37.1% of all patients presenting with STEMI at a center with a high rate of enrollment were judged to be ineligible and were excluded. The excluded patients had a significantly greater risk profile and markedly increased mortality and adverse events compared to the trial-eligible group.
Objectives This study investigated the role of uncovered stent struts on late stent thrombosis (LST) after drug-eluting stent (DES) implantation with optical coherence tomography (OCT). Background ...Autopsy studies have identified delayed healing and lack of endothelialization of DES struts as the hallmarks of LST. DES strut coverage has not previously been examined in vivo in patients with LST. Methods We studied 54 patients, including 18 with DES LST (median 615 days after implant) undergoing emergent percutaneous coronary interventions and 36 matched DES control subjects undergoing routine repeat OCT and intravascular ultrasound (IVUS) who did not experience LST for ≥3 years. Thrombus aspiration was performed during emergent percutaneous coronary intervention before OCT and IVUS assessment. Results By OCT, patients with LST—compared with control subjects—had a higher percentage of uncovered (median interquartile range) (12.27 5.50 to 23.33 vs. 4.14 3.00 to 6.22, p < 0.001) and malapposed (4.60 1.85 to 7.19 vs. 1.81 0.00 to 2.99, p < 0.001) struts. The mean neointimal thickness was similar in the 2 groups (0.23 ± 0.17 mm vs. 0.17 ± 0.09 mm, p = 0.28). By IVUS, stent expansion was comparable in the 2 groups, although positive remodeling was increased in patients with LST (mean vessel cross-section area 19.4 ± 5.8 mm2 vs. 15.1 ± 4.6 mm2 , p = 0.003). Thrombus aspiration demonstrated neutrophils and eosinophils in most cases. By multivariable analysis, the length of segment with uncovered stent struts by OCT and the remodeling index by IVUS were independent predictors of LST. Conclusions In this in vivo case-controlled study, the presence of uncovered stent struts as assessed by OCT and positive vessel remodeling as imaged by IVUS were associated with LST after DES.
Objectives We assessed the in vivo vascular response to a new generation of zotarolimus-eluting stents (ZES) with prolonged drug release (Resolute ZES-SR, Medtronic Vascular, Santa Rosa, California) ...compared with ZES with faster kinetics (Endeavor ZES-FR, Medtronic Vascular) by optical coherence tomography. Background Local drug release kinetics has been implicated with antirestenosis efficacy of drug-eluting stents. However, the impact of different release kinetics on vascular response of diseased human coronary arteries remains to be investigated. Methods The study population consisted of 43 patients with long lesions in native coronary vessels treated with multiple overlapping ZES. Twenty-one patients treated with ZES-SR were compared with 22 patients treated with ZES-FR from the ODESSA (Optical coherence tomography for DES SAfety) study. The primary endpoint was in-stent neointimal hyperplasia as assessed by optical coherence tomography at 6-month follow-up. Coprimary endpoints were the percentage of uncovered and malapposed struts. Results Strut-level median neointimal thickness was 0.11 mm (interquartile range IQR: 0.07 to 0.15 mm) in ZES-SR and 0.31 mm (IQR: 0.27 to 0.42 mm) in ZES-FR, respectively (p < 0.001). The 6-month rate of uncovered struts per patient was 7.38% (IQR: 3.06% to 12.72%) in ZES-SR and 0.00% (IQR: 0.00% to 0.00%) in ZES-FR (p < 0.001); rate of malapposed and uncovered struts was 1.47% (IQR: 0.32% to 4.23%) in ZES-SR and 0.00% (IQR: 0.00% to 0.00%) in ZES-FR (p < 0.001). Conclusions This study demonstrated the impact of different release kinetics on human in vivo vascular response to ZES implantation. The new generation of ZES-SR compared with ZES-FR had better suppression of the neointimal response but higher proportion of uncovered and malapposed struts at 6-month optical coherence tomography follow-up. (Optical Coherence Tomography in Long Lesions LongOCT; NCT01133925 )
Objectives Using optical coherence tomography, we assessed the proportion of uncovered struts at 6-month follow-up in zotarolimus-eluting stents (ZES), specifically Endeavor (Medtronic ...CardioVascular, Santa Rosa, California) stents, and identical bare-metal stents (BMS) implanted in patients with ST-segment elevation myocardial infarction (STEMI). Background Sirolimus- and paclitaxel-eluting stents implanted in STEMI have been associated with delayed healing and incomplete strut coverage. ZES are associated with a more complete and uniform strut coverage in stable patients, but whether this holds true also after STEMI is unknown. Methods Forty-four patients with STEMI who underwent primary PCI were randomized to ZES or BMS (3:1 randomization). Angiographic, intravascular ultrasound, and optical coherence tomography follow-up was conducted at 6 months and clinical follow-up at 1 year. All images were analyzed by an independent core laboratory that was blind to stent assignments. Results There were no differences between ZES and BMS in percentage of uncovered struts (median: 0.00% interquartile range (IQR): 0.00% to 1.78% vs. 1.98% IQR: 0.21% to 7.33%, p = 0.13), maximum length of uncovered segments (0.00 IQR: 0.00 to 1.19 mm vs. 1.38 IQR: 0.65 to 3.30 mm, p = 0.10), percentage of malapposed struts (0.00% IQR: 0.00% to 0.23% vs. 0.15% IQR: 0.00% to 5.81%, p = 0.16), and maximum length of malapposed segments (0.00 IQR: 0.00 to 0.67 mm vs. 0.33 IQR: 0.00 to 2.55 mm, p = 0.20). Neointimal response was similar between ZES and BMS (332 IQR: 240 to 429 μm vs. 186 IQR: 136 to 348 μm, p = 0.99) and evenly distributed. No late acquired malapposition was observed in both groups. There were no deaths, myocardial infarction, or stent thromboses at 1 year. Conclusions This optical coherence tomography study found no difference in strut coverage and similar vessel response to ZES, when compared with identical BMS, implanted during primary percutaneous coronary intervention in STEMI patients. (Six-Month Coverage and Vessel Wall Response of the Zotarolimus Drug-Eluting Stent Implanted in AMI Assessed by Optical Coherence Tomography OCTAMI; NCT00704561 )
Abstract Advanced chronic kidney disease (CKD) is associated with poor outcomes in patients undergoing surgical aortic valve replacement while its prognostic role in transcatheter aortic valve ...implantation (TAVI) remains unclear. This study aimed to investigate outcomes in patients with advanced CKD undergoing TAVI. 1904 consecutive patients undergoing balloon-expandable TAVI in 33 centers between 2007-2012 were enrolled in the I talian T ranscatheter Balloon- E xpandable Valve Implantation R egistry (ITER). Advanced CKD was defined according to estimated glomerular filtration rate (eGFR): 15-29 mL/min/1.73m2 stage 4 (S4), <15 mL/min/1.73m2 stage 5 (S5). Edwards Sapien or Sapien-XT prosthesis were used. Primary end-point was all-cause mortality during follow-up. Secondary end-points were 30-days and FU major-adverse-cardiac-events (MACE), defined with VARC-2 criteria. 421 patients were staged S5 (n=74) or S4 (n=347). S5 patients were younger, had more frequently porcelain aorta and lower incidence of previous stroke. Peri-procedural and 30-days outcomes were similar in S5 and S4 patients. During a 670 (±466) days of FU, S5 patients suffered higher mortality rates (69% vs. 39%, p<0.01) and cardiac death (19% vs. 9%, p=0.02) compared to S4. Male sex (HR 1.6, 95%CI 1.2-2.2), LVEF<30% (HR 2.3, 95% CI: 1.3-4), atrial fibrillation (HR 1.4, 95%CI:1.0-1.9) and S5 CKD (HR 1.5, 95%CI: 1.0-2.1) were independent predictors of death. In conclusion, TAVI in pre-dialytic or dialytic patients (i.e. S5) is independently associated with poor outcomes with more than double risk of death compared to patients with stage 4 renal function. Conversely, in severe CKD (i.e. S4) a rigorous risk stratification is required to avoid the risk of futility risk.
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