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We evaluated the effects of myocardial perfusion after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) on gender-based mortality rates. Research has demonstrated a gender-specific response of cardiomyocytes to ischemia and a potential increase in myocardial salvage in women compared with men. Myocardial blush grade (MBG), an angiographic surrogate of myocardial perfusion, is an independent predictor of early and late survival after AMI. Whether the incidence and prognosis of myocardial perfusion differs according to gender among patients with AMI undergoing PCI is unknown. MBG and short- and long-term mortality were evaluated in 1,301 patients (male = 935; female = 366) with AMI randomized to primary angioplasty ± abciximab versus stent ± abciximab. Following PCI, >96% of patients achieved final Thrombolysis In Myocardial Infarction 3 flow, of which MBG 2/3 was present in 58.3% of women versus 51.1% of men (p = 0.02). Worse MBG was an independent predictor of mortality in women at 30 days (7.4% for MBG 0/1 vs 2.4% for MBG 2/3, p = 0.04) and at 1-year (11.0% for MBG 0/1 vs 3.4% for MBG 2/3, p = 0.01); however, MBG was not associated with differences in mortality for men. In conclusion, impaired myocardial perfusion following PCI for AMI, indicated by worse MBG, is an independent predictor of early and late mortality in women but not in men. These findings imply an enhanced survival benefit from restoring myocardial perfusion for women compared with men during primary angioplasty and may have clinical implications for interventional strategies in women.

Both ST-segment resolution (STR) and myocardial blush grade (MBG) have prognostic utility after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. We sought to clarify how frequently MBG and STR provide discordant measures of reperfusion success and to determine the independent prognostic significance of each on long-term outcomes.In HORIZONS-AMI, core laboratory measures of both MBG and STR were assessed in 2,367 patients undergoing primary PCI. Four groups were identified based on MBG (grades 2/3 vs 0/1) and STR (≥50% vs50%). A multivariable model identified predictors of death and major adverse cardiac events at 3 years.Myocardial blush grade 2/3 was achieved in 77.7% of patients, and STR ≥50% was achieved in 75.1% of patients. Myocardial blush grade and STR were discordant in 765 patients (30.9%). By multivariable analysis, MBG 2/3 compared with 0/1 was an independent predictor of lower mortality at 3 years (4.4% vs 8.4%, adjusted hazard ratio [HR] = 0.57 [0.39, 0.82], P = .003). In contrast, STR ≥50% compared with50% was not associated with mortality (5.1% vs 5.9%, adjusted HR = 1.11 [0.68, 1.56], P = .89). However, repeated revascularization at 3 years was less frequent when STR ≥50% (12.4% vs 17.6%, adjusted HR = 0.74 [0.58, 0.95], P = .02). In contrast, MBG 2/3 vs 0/1 was not associated with reduced repeated revascularization (13.6% vs 14.1%, adjusted HR = 1.02 [0.79, 1.33], P = .85).In HORIZONS-AMI, MBG and STR after primary PCI were concordant in only 70% of patients and provided complementary prognostic information. Myocardial blush grade predicted long-term survival, whereas STR predicted freedom from repeated revascularization.

Previous studies have suggested that angiographically detected persistent contrast staining (PSS) at follow-up may predict subsequent very late stent thrombosis. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial in patients with ST-segment elevation myocardial infarctions. All follow-up angiograms (1,330 lesions in 1,115 patients, median time 13.3 months) without major cardiovascular events before follow-up angiography were analyzed at a core laboratory blinded to clinical events for the presence of PSS (defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter). Corresponding follow-up intravascular ultrasound (IVUS) data (275 lesions in 248 patients) were also evaluated to assess the mechanisms of PSS. PSS was present in 23 patients (2.1%) at follow-up and was not more common with paclitaxel-eluting than with bare-metal stents. All 6 PSS patients with follow-up IVUS had stent malapposition (vs 41.2% malapposition in the follow-up IVUS cohort). Comparing poststent and follow-up IVUS, 2 patients had late acquired and 4 had persistent malapposition; all 6 showed positive vessel remodeling from baseline to follow-up (mean vessel area 22.0 ± 8.0 to 32.4 ± 11.7 mm(2), p = 0.07). During 3-year follow-up, stent thrombosis developed in no patient with PSS compared with 8 PSS-negative patients (0% vs 0.8%, p = 0.68). The rates of revascularization and major adverse cardiovascular events were also not increased in PSS patients. In conclusion, in the large-scale HORIZONS-AMI trial, PSS at angiographic follow-up was infrequent and was associated with late stent malapposition and positive remodeling but was independent of stent type. Identification of PSS was not associated with subsequent stent thrombosis.

The present substudy from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial assessed the outcomes and their relation to different antithrombotic regimens in patients with previous coronary artery bypass grafting (CABG) treated with primary percutaneous coronary intervention. Of 3,599 patients with information regarding a history of CABG, 105 (2.9%) had previously undergone CABG. Of these 105 patients, 46 were randomized to heparin plus a glycoprotein IIb/IIIa inhibitor and 59 to bivalirudin. The patients with versus without previous CABG were less frequently triaged to primary percutaneous coronary intervention (83.8% vs 93.2%, p = 0.0002) and had a longer door-to-balloon time (median 1.9 vs 1.6 hours, p = 0.047), lower rates of final Thrombolysis In Myocardial Infarction flow grade 2 to 3 in the intervened vessel (92.6% vs 97.8%, p = 0.007), and less frequent rates of complete or partial ST-segment resolution (66.3% vs 77.6%, p = 0.019). At 3 years, previous CABG was associated with a significantly greater incidence of major adverse cardiovascular events (36.4% vs 21.4%, p0.001) owing to greater rates of mortality (11.2% vs 6.7%, p = 0.08), reinfarction (11.6% vs 7.1%, p = 0.09), stroke (5.1% vs 1.8%, p = 0.013), and ischemic target vessel revascularization (23.6% vs 12.9%, p = 0.005). The outcomes did not differ significantly as a function of the antithrombotic regimen. On multivariate analysis, previous CABG was an independent predictor of 3-year ischemic stroke (hazard ratio 3.57, 95% confidence interval 1.09 to 11.66). Intervention on the saphenous vein graft versus the native vessel predicted 3-year major adverse cardiovascular events (hazard ratio 2.69, 95% confidence interval 1.17 to 6.19). In the HORIZONS-AMI trial, previous CABG was associated with a delay to mechanical reperfusion and lower rates of percutaneous coronary intervention and patency of the infarct related vessel along with worse clinical outcomes.

The clinical features and prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and no significant coronary artery disease (CAD) have not been well studied. We examined the outcomes of patients with STEMI in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial according to the presence or absence of significant CAD. "No-CAD" was defined by the absence of any lesion with a diameter stenosis of ≥30% on quantitative coronary angiography of the baseline coronary angiogram. Of 3,602 patients, 127 (3.5%) had no-CAD. Of these, 86 (67.7%) had angiographically normal coronary arteries, and 41 (32.3%) had mild disease (diameter stenosis

Background The impact of acute stent malapposition ( ASM ) on long‐term clinical outcomes in patients undergoing percutaneous coronary intervention is still controversial. We sought to evaluate predictors and long‐term clinical outcomes of ASM . Methods and Results ADAPT ‐ DES (Assessment of Dual Antiplatelet Therapy With Drug‐Eluting Stents) was a prospective multicenter study of 8663 patients undergoing percutaneous coronary intervention using drug‐eluting stents. In a prespecified intravascular ultrasound–guided substudy, 2072 patients with 2446 culprit lesions had post–percutaneous coronary intervention intravascular ultrasound and were classified according to the presence or absence of ASM . After intravascular ultrasound–guided percutaneous coronary intervention, the overall prevalence of ASM after successful drug‐eluting stents implantation was 14.4% per patient and 12.6% per lesion. Compared to lesions without ASM , lesions with ASM had larger in‐stent lumen areas, larger stent areas, and larger in‐stent vessel areas. A larger mean plaque area along with more attenuated plaque was observed in lesions with ASM versus lesions without ASM . Lesions with ASM had greater proximal and distal reference lumen areas and more distal, but not proximal, reference calcium compared to lesions without ASM . At 2‐year follow‐up, there was no significant difference in the incidence of cardiac death; myocardial infarction; early, late, or very late stent thrombosis; or clinically driven target lesion revascularization in patients with ASM versus those without ASM . Furthermore, ASM was not an independent predictor of 2‐year major adverse cardiac events or target lesion revascularization even when forced into the multivariate model. Conclusions In patients treated with intravascular ultrasound–guided drug‐eluting stents implantation, ASM was not associated with adverse clinical events during long‐term follow‐up including, but not limited to, stent thrombosis. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 00638794.

Background— Patients with peripheral arterial disease (PAD) have high rates of adverse cardiovascular events after percutaneous coronary intervention and may additionally have heightened platelet reactivity. This study assessed the relationship between platelet reactivity and clinical outcomes after percutaneous coronary interventions among subjects with and without PAD. Methods and Results— ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. Platelet reactivity was assessed by the VerifyNow point-of-care assay; high on-treatment platelet reactivity (HPR) was defined as P2Y12 reaction units >208. A propensity-adjusted multivariable analysis was performed to determine the relationship between PAD, platelet reactivity, and subsequent adverse events (definite or probable stent thrombosis, all-cause mortality, myocardial infarction, and clinically relevant bleeding). Among 8582 patients, 10.2% had a history of PAD. Patients with PAD were older and more likely to have comorbid conditions; however, mean P2Y12 reaction units and HPR were not significantly different between PAD and no PAD groups. Patients with PAD had higher 2-year rates of all-cause mortality, myocardial infarction, stent thrombosis, and clinically relevant bleeding. Associations between HPR and adverse events were similar in PAD and no PAD groups, without evidence of interaction; however, adverse event rates were highest among subjects with both PAD and HPR. In a propensity-adjusted multivariable model, both PAD and HPR were independent predictors of myocardial infarction at 2 years. Conclusions— A history of PAD was associated with ischemic and bleeding outcomes 2 years after successful coronary drug-eluting stent implantation; however, these associations did not seem to be directly mediated by heightened platelet reactivity. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

We sought to examine the relation between various degrees of renal function and coronary plaque morphology by grayscale and virtual histology intravascular ultrasound (IVUS). ADAPT-DES was a prospective, multicenter registry of 8,582 consecutive patients treated using coronary drug-eluting stents with a prespecified grayscale and virtual histology-IVUS substudy. A lesion-level analysis of study participants was performed by comparing IVUS parameters of culprit and nonculprit lesions across tertiles of estimated creatinine clearance (CrCl). Preintervention IVUS imaging of 762 patients identified 898 culprit and 752 nonculprit native coronary artery lesions. Patients in the lowest CrCl tertile were older, more often women, and more often presented with stable angina. Compared with the middle and upper tertiles, the lowest tertile was significantly associated with culprit lesion smaller mean external elastic membrane cross-sectional area (12.9 vs 14.2 mm 3 /mm vs 14.9 mm 3 /mm, p 3 /mm vs 5.8 mm 3 /mm vs 6.1 mm 3 /mm, p = 0.002), and more dense calcium volume (11.5% vs 10.2% vs 9.7%, p = 0.02). Similar trends were found in the nonculprit lesions. Plaque rupture was least common in patients in the lowest tertile. On multivariable analysis, independent predictors of greater dense calcium volume were lower CrCl, hyperlipidemia, female gender, and presentation without ST-segment elevation myocardial infarction. In conclusion, in the present large-scale IVUS study diminishing renal function was associated with increased coronary calcification and decreased coronary vessel and lumen sizes, with a graded response according to the reduction in CrCl. In addition, these patients were more likely to present with stable angina versus patients with normal renal function who were more likely to present with an acute coronary syndrome.

The aim of this study was to evaluate the prevalence and long-term clinical impact of tissue protrusion (TP) after stent implantation.Stent implantation may be associated with tissue (plaque or thrombus) protrusion, especially in unstable lesions, but its clinical impact is unknown.ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective multicenter study of 8,663 patients undergoing percutaneous coronary intervention (PCI) using drug-eluting stents. In a pre-specified intravascular ultrasound (IVUS) substudy, 2,072 patients with 2,446 culprit lesions underwent post-PCI IVUS (among whom some also underwent pre-PCI IVUS) and were classified according to the presence or absence of post-stent TP.After PCI, 34.3% of lesions displayed TP on IVUS. Median maximum TP was 0.7 mm(2) (interquartile range: 0.5 to 1.2 mm(2)) in area and 3.0 mm (interquartile range: 1.4 to 6.7 mm) in length. Patients with TP more often presented with ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction but less often with unstable angina or stable ischemic heart disease. In 893 culprit lesions that were also examined pre-PCI, TP was associated with larger reference luminal area, greater plaque burden, and more plaque ruptures, attenuated plaque, and virtual histology thin-cap fibroatheromas. Because a larger stent or post-dilation balloon was used, post-PCI luminal area was significantly larger in lesions with versus without TP. At 2-year follow-up, there was less clinically driven target lesion revascularization in lesions with TP and no significant difference in major adverse cardiac events (defined as cardiac death, myocardial infarction, or stent thrombosis) in patients with versus without TP.IVUS-detected TP after drug-eluting stent implantation was not associated with worse long-term clinical outcomes, in part because of greater stent expansion in lesions with TP.

Major bleeding complications in STEMI patients result in significant mortality, morbidity and healthcare cost. Identification of patients at increased risk of bleeding is therefore essential. New biomarkers might be of incremental value to identify patients at risk for bleeding after primary PCI. A total of 26 biomarkers were measured at enrolment and analyzed at a central core laboratory in 464 STEMI patients in the HORIZONS-AMI trial. We investigated the relationship between tertiles of biomarker and in hospital non-CABG major bleeding. In hospital non-CABG major bleeding occurred in 3.7 % of patients (n = 17). Increasing levels of cystatin C and D-dimer at admission were associated with higher rates of in hospital major bleeding. After adjustment for a risk score for bleeding, the odds ratio for in hospital major bleeding was 3.13 for cystatin C > 2.04 mg/L (p = 0.046) and 3.28 for ESAM > 34 ng/mL (p = 0.037). In this exploratory analysis of the HORIZONS-AMI biomarker substudy, high cystatin C and ESAM levels were associated with a higher risk of major bleeding. Larger studies are warranted to confirm the prognostic value of cystatin C and ESAM for major bleeding in STEMI patients.

Objectives The purpose of this study was to evaluate the frequency and predictors of stent thrombosis (ST) after stenting for ST-segment elevation myocardial infarction (STEMI). Background Stent thrombosis remains a major concern with STEMI patients treated with primary percutaneous coronary intervention. Methods Consecutive patients (N = 1,640) undergoing stenting for STEMI were prospectively enrolled in our database and followed for 1 to 15 years. Bare-metal stents were implanted from 1995 to 2002, and drug-eluting and bare-metal stents were implanted from 2003 to 2009. Stent thrombosis was defined as definite or probable. Results Our population had a high risk profile, including a high incidence of Killip class III to IV (11.5%) and STEMI due to ST (10.2%). Stent thrombosis occurred in 124 patients, including 42 with early ST (0 to 30 days), 35 with late ST (31 days to 1 year), and 47 with very late ST (>1 year). The frequency of ST was 2.7% at 30 days, 5.2% at 1 year, and 8.3% at 5 years. Independent predictors of early or late ST were STEMI due to ST (hazard ratio [HR]: 4.38, 95% confidence interval [CI]: 2.27 to 8.45), small stent size (HR: 2.44, 95% CI: 1.49 to 4.00), Killip class III to IV (HR: 2.39, 95% CI: 1.30 to 4.40), and reperfusion time ≤2 h (HR: 2.09, 95% CI: 1.03 to 4.24). Drug-eluting stent was the only independent predictor of very late ST (HR: 3.73, 95% CI: 1.81 to 7.88). Conclusions Stent thrombosis after primary percutaneous coronary intervention is relatively frequent and continues to increase out to 5 years. New strategies are needed to prevent ST in STEMI patients, and targeted therapies are needed in patients identified at highest risk.

The use of drug-eluting stents (DESs) in primary percutaneous coronary intervention (PPCI) has shown early benefit over bare-metal stents (BMSs) in decreasing adverse cardiac events. However, there are concerns regarding the increased risk of late and very late stent thrombosis (ST) after DES use. With the paucity of ST events individual trials may have been underpowered to detect significant differences. We sought to perform a meta-analysis to evaluate the available literature examining the outcomes of DESs and BMSs in PPCI after ≥3 years of follow-up. We analyzed 8 randomized clinical trials (RCTs) and 5 observational studies comparing DESs to BMSs in PPCI. Clinical end-point data were analyzed for RCTs and observational studies separately using random-effect models. RCTs included 5,797 patients in whom first-generation DESs (sirolimus- or paclitaxel-eluting stents) were compared to BMS control arms. Patients receiving DESs had a significantly lower risk of target lesion revascularization (odds ratio [OR] 0.48, confidence interval [CI] 0.37 to 0.61), target vessel revascularization (OR 0.53, CI 0.42 to 0.66), and accordingly major adverse cardiac events (OR 0.69; CI 0.56 to 0.84). Incidence of ST was not different between groups (OR 1.02, CI 0.76 to 1.37). There was no significant difference in mortality (OR 0.88, CI 0.68 to 1.12) or recurrent myocardial infarction (OR 0.97; CI 0.61 to 1.54). Among observational studies (n = 4,650) fewer studies reported on target lesion revascularization and target vessel revascularization, but the trend remained in favor of DESs. A small but statistically significant increase in ST was noted with DES use (OR 1.62, CI 1.18 to 2.21) at ≥3 years of follow up, without evidence of recurrent myocardial infarction. Those receiving DESs had a significantly lower mortality compared to those receiving BMSs (OR, 0.65, 95% CI 0.53 to 0.80, p

Background— Intravascular ultrasound (IVUS)-attenuated plaque is characterized by absence of ultrasound signal behind hypoehcoic plaque and is seen almost exclusively in acute coronary syndromes. Methods and Results— We analyzed poststenting and 13-month follow-up IVUS in 186 patients (195 lesions) with acute myocardial infarction who underwent primary percutaneous coronary intervention. The primary prespecified IVUS end point was the in-stent percent net volume obstruction at follow-up. Overall, 70.3% of lesions contained attenuated plaques at baseline. During follow-up, attenuation scores decreased significantly, behind paclitaxel-eluting stents (PES) (14.1 [11.9, 16.3] to 7.7 [5.4, 9.9], P P P =0.02). There was a greater calcium increase in attenuated than nonattenuated plaques in both PES (Δcalcium score of 4.4 [3.3, 5.5] versus 1.6 [0.9, 2.3], P P =0.001). PES implantation into attenuated plaques was particularly associated with late acquired stent malapposition (36.8% versus 15.4% compared with nonattenuated plaques treated with PES, P =0.03). Changes in attenuation scores correlated with changes in calcium scores both in PES (Pearson correlation coefficient=−0.456, P P =0.0006). In 3 years of follow-up, target lesion revascularization was significantly less in patients with attenuated plaque at baseline (6.0% versus 17.4% in patient without attenuated plaques, P =0.019). Conclusions— Attenuated plaques evolved into calcified plaques after stent implantation. Attenuated plaque is associated with late acquired stent malapposition and related less target lesion revascularization (consistent with less neointimal hyperplasia), especially after PES implantation in patients with acute myocardial infarction. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00433966.

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 +/- A 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted

HORIZONS-AMI was a prospective dual-arm randomized trial of different antithrombotic regimens and stent types in patients with ST-segment elevation myocardial infarction. A formal intravascular ultrasound (IVUS) substudy enrolled 464 patients with baseline and 13-month follow-up at 36 centers. Of them, 318 patients with 355 lesions were evaluated for this study. Angiographic restenosis occurred in 45 of 355 lesions (12.7%). Bare-metal stent use (45.5% vs 21.2%, p0.001) and diabetes mellitus (29.5% vs 10.9%, p0.001) were more prevalent in patients with versus without restenosis. Postprocedure IVUS minimum lumen area (5.6 mm(2), 5.0 to 6.1, vs 6.7 mm(2), 6.5 to 6.9, p0.001), minimum stent area (5.7 mm(2), 5.1 to 6.3, vs 6.9 mm(2), 6.6 to 7.1, p0.001), and reference average lumen area (7.7 mm(2), 6.8 to 8.6, vs 9.7 mm(2), 9.3 to 10.1, p0.001) were smaller in restenotic versus nonrestenotic lesions. By multivariable analysis, minimum stent area was an independent predictor of angiographic restenosis (odds ratio 0.75, 95% confidence interval 0.61 to 0.93, p = 0.009) in addition to diabetes, bare-metal stent use, and longer stent length. Attenuated plaque behind the stent struts had a trend to predict less binary restenosis (p = 0.07). In conclusion, a smaller IVUS minimum stent area was an independent predictor of angiographic restenosis after primary percutaneous intervention in patients with ST-segment elevation myocardial infarction, similar to patients with stable coronary artery disease.

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remains in dispute, particularly after 12 months. The DAPT Score was developed from the DAPT trial to identify pts who may benefit the most from extended therapy. We sought to assess the

Background— The relationship between white blood cell count (WBCc) and mortality in patients with ST-segment–elevation acute myocardial infarction treated with percutaneous coronary intervention is poorly understood. Furthermore, whether there is a relationship between WBCc and risk of noncardiac mortality and bleeding after percutaneous coronary intervention is unknown. Methods and Results— The baseline WBCc was available in 3193 of 3345 patients (95.5%) who underwent percutaneous coronary intervention in the Harmonizing Outcome With Revascularization and Stent in Acute Myocardial Infarction (HORIZONS-AMI) trial. In a propensity-adjusted multivariable analysis, WBCc was an independent predictor of 1-year cardiac mortality (hazard ratio, 1.15; 95% confidence interval, 1.09 to 1.22), noncardiac mortality (hazard ratio, 1.19; 95% confidence interval, 1.10 to 1.29), and major bleeding (hazard ratio, 1.08; 95% confidence interval, 1.04 to 1.12). After adjustment for baseline creatinine phosphokinase levels and left ventricular ejection fraction, WBCc remained an independent predictor of 1-year all-cause mortality and cardiac mortality. In patients matched for baseline creatinine phosphokinase levels at hospital admission, the median peak creatinine phosphokinase level was significantly higher in patients with high WBCc (>11 000 per 1 mm 3 ) compared with low WBCc (1851 U/L [range, 880-3307 U/L] versus 1241 U/L [range, 540 to 2,78], respectively; P Conclusions— In patients with ST-segment–elevation acute myocardial infarction undergoing percutaneous coronary intervention, elevated baseline WBCc is an independent predictor of infarct size, as assessed by peak creatinine phosphokinase level, and of 1-year cardiac mortality, noncardiac mortality, and major bleeding. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov . Unique identifier: NCT00433966.

Objectives We investigated the outcomes of switching to bivalirudin after initial administration of heparin in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Background Unfractionated heparin (UFH) is frequently administered early in ST-segment elevation myocardial infarction. Whether the benefits of bivalirudin documented in the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial persist in patients previously administered UFH is unknown. Methods We analyzed the outcomes of the 2,357 patients from HORIZONS-AMI treated with UFH before enrollment according to their subsequent randomization to bivalirudin (switch group, n = 1,178) or UFH plus a glycoprotein IIb/IIIa inhibitor (control group, n = 1,179). Results At 30 days, major bleeding occurred in 7.6% of the switch group versus 12.3% of the control group (p = 0.0001). Switch patients had lower 30-day rates of cardiac mortality (1.6% vs. 2.9%, p = 0.04). At 2-year follow-up, switch patients experienced lower rates of major bleeding (8.4% vs. 13.0%, p = 0.0003), cardiac mortality (2.3% vs. 3.8%, p = 0.04), and reinfarction (4.0% vs. 7.1%, p = 0.0002). Two-year rates of definite/probable stent thrombosis were similar in switch and control patients (3.1% vs. 4.3%, p = 0.17). Conclusions In ST-segment elevation myocardial infarction patients who receive early treatment with UFH, switching to bivalirudin before primary percutaneous coronary intervention results in reduced rates of major bleeding and improved early and late cardiac survival.

The relationship between diabetes mellitus and coronary artery disease is well established. The percentage of patients participating in clinical trials of percutaneous coronary intervention who have diabetes is quickly rising. Diabetic patients have a worse prognosis than nondiabetic patients, with generally greater rates of death, myocardial infarction and need for target lesion and vessel revascularization. Stenting has improved the outcome of diabetic patients receiving percutaneous coronary intervention. Compared with bare-metal stents, the use of drug-eluting stents in diabetic patients has resulted in a significant reduction in late lumen loss, binary restenosis, and clinically driven target vessel revascularization. The safety and efficacy of drug-eluting stents in diabetic patients is now well established; they are the preferred option in this subgroup in the absence of contraindications. New stent designs, polymers and drugs are resulting in better outcomes overall, but more research is required ...

Objectives The purpose of this study was to assess the frequency of very late stent thrombosis (VLST) after stenting with bare-metal stents (BMS) and drug-eluting stents (DES) for ST-segment elevation myocardial infarction (STEMI). Background Stent thrombosis occurs more frequently after stenting for STEMI than after elective stenting, but there are little data regarding VLST. Methods Consecutive patients (n = 1,463) who underwent stenting for STEMI were prospectively enrolled in our database. BMS were implanted exclusively from 1995 to 2002, and DES and BMS were implanted from 2003 to 2009. Follow-up was obtained at 1 to 15 years. Results BMS patients (n = 1,095) were older and had more shock, whereas DES patients (n = 368) had more diabetes and smaller vessels. Stent thrombosis occurred in 107 patients, of which 42 were VLST (>1 year). Stent thrombosis continued to increase to at least 11 years with BMS and to at least 4.5 years with DES. Stent thrombosis rates with BMS versus DES were similar at 1 year (5.1% and 4.0%, respectively) but increased more with DES after the first year (1.9%/year vs. 0.6%/year, respectively). Landmark analysis (>1 year) found DES had a higher frequency of VLST (p Conclusions VLST after primary PCI for STEMI occurs with relatively high frequency to at least 11 years with BMS and to at least 4.5 years with DES. Very late stent thrombosis and reinfarction (>1 year) were more frequent with DES. New strategies are needed to manage this problem.

Objectives We sought to identify patients with ST-segment elevation myocardial infarction most likely to benefit from drug-eluting stents (DES), and to evaluate the impact of routine angiographic follow-up on the apparent differences between stent types. Background DES might have greatest utility in patients who would benefit most from their antirestenotic properties. Methods We randomly assigned 3,006 patients with ST-segment elevation myocardial infarction to paclitaxel-eluting stents (PES) or to bare-metal stents (BMS). Events were assessed at 12 months and 24 months, with a subset undergoing routine angiographic follow-up at 13 months. Using well-known risk factors for restenosis and target lesion revascularization (TLR), risk groups were formed to examine the absolute differences between PES and BMS. Results Compared with BMS, PES reduced TLR at 12 months from 7.4% to 4.5% (p = 0.003). Insulin-treated diabetes mellitus (hazard ratio: 3.12), reference vessel diameter ≤3.0 mm (hazard ratio: 2.89), and lesion length ≥30 mm (hazard ratio: 2.49) were independent predictors of 12-month TLR after BMS. In patients with 2 or 3 of these baseline risk factors, PES compared with BMS markedly reduced 12-month TLR (19.8% vs. 8.1%, p = 0.003). In patients with 1 of these risk factors, the 12-month rates of TLR were modestly reduced by PES (7.3% vs. 4.3%, p = 0.02). The 12-month TLR rates were low and similar for both stents in patients with 0 risk factors (3.3% vs. 3.2%, p = 0.93). Routine 13-month angiographic follow-up resulted in a marked increase in TLR procedures (more so with BMS) so that the absolute incremental benefit of PES compared with BMS doubled from 2.9% at 12 months to 6.0% at 24 months, a difference evident in all risk strata. Conclusions Patients at high risk for TLR after BMS in ST-segment elevation myocardial infarction for whom DES are of greatest benefit may be identified. Conversely, DES may be of less clinical benefit for patients at lower risk for TLR after BMS. Routine angiographic follow-up increases the perceived clinical benefits of DES, and must be avoided to accurately estimate absolute treatment effects. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966 )

Background— The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear. Methods and Results— The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm 2 best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62). Conclusions— The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Objectives Our objective was to evaluate the impact of door-to-balloon time (DBT) on mortality depending on clinical risk and time to presentation. Background DBT affects the mortality rate in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, but the impact may vary across subgroups. Methods The CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trials evaluated stent and antithrombotic therapy in patients undergoing primary percutaneous coronary intervention. We studied the impact of DBT on mortality in 4,548 patients based on time to presentation and clinical risk. Results The 1-year mortality rate was lower in patients with short versus long DBT (≤90 min vs. >90 min, 3.1% vs. 4.3%, p = 0.045). Short DBTs were associated with a lower mortality rate in patients with early presentation (≤90 min: 1.9% vs. 3.8%, p = 0.029) but not those with later presentation (>90 min: 4.0% vs. 4.6%, p = 0.47). Short DBTs showed similar trends for a lower mortality rate in high-risk (5.7% vs. 7.4%, p = 0.12) and low-risk (1.1% vs. 1.6%, p = 0.25) patients. Short DBTs had similar relative risk reductions in patients with early presentation in high-risk (3.7% vs. 7.0%, p = 0.08) and low-risk (0.8% vs. 1.5%, p = 0.32) patients, although the absolute benefit was greatest in high-risk patients. Conclusions Short DBTs (≤90 min) are associated with a lower mortality rate in patients with early presentation but have less impact on the mortality rate in patients presenting later. The absolute mortality rate reduction with short DBT is greatest in high-risk patients presenting early. These data may be helpful in designing triage strategies for reperfusion therapy in patients presenting to non–percutaneous coronary intervention hospitals.

The aim of this study was to assess the impact of baseline anemia on the outcomes of patients with ST elevation myocardial infarctions who underwent primary percutaneous coronary intervention in relation to contemporary adjunctive antithrombotic therapy and gender. In the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, patients were randomized to bivalirudin alone or to unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor before primary percutaneous coronary intervention. Outcomes were assessed at 30 days and 1 year according to anemia and gender. Baseline anemia was present in 331 of 3,153 patients (10.5%). Patients with versus without baseline anemia had a more than twofold increase in major bleeding at 30 days (13.5% vs 6.7%, p

Background: Mechanisms underlying the association between myocardial bridge (MB)-stenting and in-stent restenosis (ISR) are still unclear. Objective: To assess the impact of MB on ISR using intravascular ultrasound (IVUS). Methods: In the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, 100 left anterior descending artery (LAD) culprit lesions (79 treated with paclitaxel-eluting stents [PES] and 21 treated with bare metal stents) were imaged with serial IVUS immediately postprocedure and at 13 months. Results: At baseline the LAD stent extended into the MB segment beyond the culprit lesion in seven patients (MB-stent group). In the remaining 93 patients the LAD stent was implanted only in the culprit lesion without extending into the MB segment (non-MB-stent group). In PES-treated lesions intimal hyperplasia (IH) was greater in MB-stent group than in non-MB-stent group (1.0 [0.9, 1.3] mm2 vs. 0.4 [0.2, 0.7] mm2, P = 0.007). When comparing the MB-stent segment with the non-MB-stent segment in the MB-stent group treated with PES, a significant reduction in lumen area was observed in only the MB-stent segment, owing to an augmented IH within the MB-stent segment (1.56 [1.40, 1.91] mm2 vs. 0.77 [0.55, 1.23] mm2 for non-MB-stent segment, P = 0.08), not significant stent recoil (Δstent area). At follow-up, the minimum lumen area was smaller in the MB-stent group than in the non-MB-stent group (2.9 [2.5, 4.2] mm2 vs. 5.2 [4.1, 6.7] mm2, P = 0.02). Conclusions: Increased incidence of ISR associated with MB-stenting may be attributable to enhanced IH, specific to stented MB segment, not to chronic stent recoil. (J Interven Cardiol 2010;23:114-122)

Proximal LAD (PLAD) vessel diameter is rarely

Objectives The aim of this study was to assess the risk-benefit of enoxaparin (Sanofi-Aventis, Paris, France) in primary percutaneous coronary intervention (PCI). Background Randomized studies have demonstrated the superiority of enoxaparin over unfractionated heparin (UFH) in acute ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytics. Methods In the FINESSE (Facilitated INtervention with Enhanced Reperfusion Speed to Stop Events) trial—a double-blind, placebo-controlled study—2,452 patients with STEMI were randomized to primary PCI or facilitated PCI with abciximab alone or with half-dose reteplase. In this prospective FINESSE substudy, centers pre-specified use of either enoxaparin (0.5 mg/kg intravenous [IV], 0.3 mg/kg subcutaneous [SC]) or UFH (40 U/kg IV, 3,000 U maximum) with PCI. A logistic-regression model and a propensity multivariate model, both adjusted for baseline variables, were used to evaluate primary safety and secondary efficacy end points for enoxaparin versus UFH. Results Enoxaparin was administered to 759 patients and UFH to 1,693 patients. Nonintracranial Thrombolysis In Myocardial Infarction (TIMI) major/minor bleeding was not significantly different, but lower nonintracranial TIMI major bleeding was found with enoxaparin (2.6% vs. UFH 4.4%, logistic-regression adjusted odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.31 to 0.99, p = 0.045), whereas intracranial hemorrhage was similar (0.27% vs. 0.24%, adjusted OR: 1.03; 95% CI: 0.11 to 9.68, p = 0.980). Lower death, myocardial infarction, urgent revascularization, or refractory ischemia through 30 days was also associated with enoxaparin (5.3%) versus UFH (8.0%, adjusted OR: 0.47, 95% CI: 0.31 to 0.72, p = 0.0005) as was all-cause mortality through 90 days (3.8% vs. 5.6%, respectively, adjusted OR: 0.59, 95% CI: 0.35 to 0.99, p = 0.046). End points evaluating the net clinical benefit also significantly favored enoxaparin over UFH. Conclusions Enoxaparin seems to be associated with a lower risk of cardiovascular outcomes compared with UFH in patients with STEMI undergoing primary PCI. Confirmation of these findings in a randomized study is warranted. (A Study of Abciximab and Reteplase When Administered Prior to Catheterization After a Myocardial Infarction [Finesse]; NCT00046228)

Objectives This study compares outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients undergoing saphenous vein graft (SVG) intervention. Background The safety and efficacy of DES in patients undergoing SVG intervention is controversial. Methods The STENT (Strategic Transcatheter Evaluation of New Therapies) registry is a multicenter U.S. registry evaluating outcomes with DES. Our study population includes patients undergoing PCI of SVG lesions with DES (n = 785) or BMS (n = 343) who completed 9-month or 2-year follow-up. Outcomes were adjusted with propensity analyses. Results The DES patients had fewer emergent procedures but had smaller vessels and longer lesions. The DES patients had less death or myocardial infarction at 9 months (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.33 to 0.83, p = 0.006) and less death at 2 years (HR: 0.60, 95% CI: 0.36 to 0.98, p = 0.041). Target vessel revascularization (TVR) was less with DES at 9 months (7.2% vs. 10.0%, HR: 0.36, 95% CI: 0.22 to 0.61, p Conclusions Treatment of SVG lesions with DES vs. BMS is effective in reducing TVR at 9 months, although most of this advantage is lost at 2 years. The DES seem safe with less death or myocardial infarction, although selection bias might have affected these results. Our data suggest that DES might have short-term advantages over BMS in SVG lesions with diameter

ObjectivesWe hypothesized that patients most likely to benefit would be those at high risk with a shorter duration of acute ischemia and who required transfer for percutaneous coronary intervention (PCI).BackgroundThe FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) study failed to demonstrate an improvement in the 90-day composite clinical end point of early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or abciximab alone.MethodsWe performed a retrospective analysis of 2,452 patients in this double-blind, placebo-controlled study. Patients were stratified by Thrombolysis In Myocardial Infarction (TIMI) risk score for ST-segment elevation myocardial infarction (STEMI), presentation to a spoke (no PCI available) or hub site, and symptom-to-randomization time. Outcomes included the primary composite end point of death, ventricular fibrillation after 48 h, cardiogenic shock, and congestive heart failure through day 90 as well as 1-year mortality.ResultsMortality for all patients at 1 year was directly related to TIMI risk score (23 of 1,223 = 1.9% in patients with score

Objectives The aim of this report was to evaluate 12-month outcomes of facilitated percutaneous coronary intervention (PCI) in the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events) trial. Background Treatment delays remain common for patients with primary PCI leading to studies evaluating possible benefit of “facilitated” PCI. In the FINESSE trial, no reduction in the 90-day primary ischemic end point and an increase in bleeding were observed with both facilitated approaches, although modest favorable trends were seen for some patient subgroups. Methods A total of 2,452 patients with ST-segment elevation myocardial infarction (MI) and anticipated 1 to 4 h delay until catheterization were randomized to reduced-dose reteplase + abciximab, abciximab alone, or placebo, followed by expedited primary PCI. Placebo-treated patients received abciximab in the cath lab. One-year mortality was a pre-specified secondary end point. Results One-year mortalities in the 3 groups noted in the preceding text were 6.3%, 7.4%, and 7.0%, respectively (p = NS), representing 1.1%, 1.9%, and 2.5% increments since the 90-day outcome (p = 0.053 for combination treatment vs. primary PCI). A favorable trend with combination treatment was seen for patients with anterior MI (p = 0.09), but no other specified groups benefited or tended to benefit. Independent baseline correlates of 1-year mortality were systolic blood pressure 1, anterior MI, body mass index ≤25 kg/m2, heart rate >100 beats/min, and no statin use. Conclusions These results suggest that widespread utilization of the facilitated approaches tested cannot be justified, but that high-risk patient groups such as patients with anterior MI may deserve further study. (The FINESSE trial; NCT00046228 )

Objectives Our aim was to determine whether a 600-mg loading dose of clopidogrel compared with 300 mg results in improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Background A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation. Methods In the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI undergoing primary PCI were randomized to bivalirudin (n = 1,800) or unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (n = 1,802). Randomization was stratified by thienopyridine loading dose, which was determined before random assignment. Results Patients in the 600-mg (n = 2,158) compared with the 300-mg (n = 1,153) clopidogrel loading dose group had significantly lower 30-day unadjusted rates of mortality (1.9% vs. 3.1%, p = 0.03), reinfarction (1.3% vs. 2.3%, p = 0.02), and definite or probable stent thrombosis (1.7% vs. 2.8%, p = 0.04), without higher bleeding rates. Compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin monotherapy resulted in similar reductions in net adverse cardiac event rates within the 300-mg (15.2% vs. 12.3%) and 600-mg (10.4% vs. 7.3%) clopidogrel loading dose subgroups (pinteraction= 0.41). By multivariable analysis, a 600-mg clopidogrel loading dose was an independent predictor of lower rates of 30-day major adverse cardiac events (hazard ratio: 0.72 [95% confidence interval: 0.53 to 0.98], p = 0.04). Conclusions In patients with STEMI undergoing primary PCI with contemporary anticoagulation regimens, a 600-mg loading dose of clopidogrel may safely reduce 30-day ischemic adverse event rates compared with a 300-mg loading dose. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966)

Background— The safety and efficacy of drug-eluting stents (DES) among more generalized “real-world” patients than those enrolled in pivotal randomized controlled trials (RCTs) are controversial. We sought to perform a meta-analysis of DES studies to estimate the relative impact of DES versus bare metal stents (BMS) on safety and efficacy end points, particularly for non–Food and Drug Administration–labeled indications. Methods and Results— Comparative DES versus BMS studies published or presented through February 2008 with ≥100 total patients and reporting mortality data with cumulative follow-up of ≥1 year were identified. Data were abstracted from studies comparing DES with BMS; original source data were used when available. Data from 9470 patients in 22 RCTs and from 182 901 patients in 34 observational studies were included. RCT and observational data were analyzed separately. In RCTs, DES (compared with BMS) were associated with no detectable differences in overall mortality (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.81 to 1.15; P =0.72) or myocardial infarction (HR, 0.95; 95% CI, 0.79 to 1.13; P =0.54), with a significant 55% reduction in target vessel revascularization (HR, 0.45; 95% CI, 0.37 to 0.54; P Conclusions— In RCTs, no significant differences were observed in the long-term rates of death or myocardial infarction after DES or BMS use for either off-label or on-label indications. In real-world nonrandomized observational studies with greater numbers of patients but the admitted potential for selection bias and residual confounding, DES use was associated with reduced death and myocardial infarction. Both RCTs and observational studies demonstrated marked and comparable reductions in target vessel revascularization with DES compared with BMS. These data in aggregate suggest that DES are safe and efficacious in both on-label and off-label use but highlight differences between RCT and observational data comparing DES and BMS.

Objectives: This study compares outcomes with drug-eluting stents (DES) versus bare metal stents (BMS) in patients with ST-elevation myocardial infarction (STEMI). Background: DESs have been effective in elective percutaneous coronary intervention (PCI), but their safety and efficacy in patients with STEMI have not been well studied. Methods: The STENT Registry is a multicenter United States registry evaluating outcomes of DES. Our study population includes patients with STEMI treated with either a DES or BMS who completed 9-month or 2-year follow-up. Outcomes were adjusted using propensity score analysis. Results: DES patients were younger, had less prior infarction and prior bypass surgery, but had smaller vessels and longer lesions. After adjusting for differences in baseline variables, there were no significant differences between DES and BMS in death, reinfarction, or major adverse cardiac events (MACE). DES had lower rates of stent thrombosis at 9 months (1.0% vs. 2.7%, HR 0.40 [0.17–0.95]) and lower rates of target vessel revascularization (TVR) at 9 months (4.0% vs. 7.5%, HR 0.55 [0.34–0.88]) and 2 years (8.0% vs. 11.3%, HR 0.57 [0.35–0.92]). There was a nonsignificant increase in stent thrombosis with DES versus BMS from 1 to 2 years (1.1% vs. 0.3%, P = 0.28). Conclusions: Our data suggest that DES used with primary PCI for STEMI are more effective than BMS in reducing TVR and are safe for up to 2 years. Whether DES are safe beyond 2 years and whether the reduction in TVR is enough to justify their use in STEMI will have to wait for the results of large randomized trials. 2008 Wiley-Liss, Inc.

Objectives This study evaluates outcomes and complications in patients treated with drug-eluting stents (DES) for “off-label” indications. Background Drug-eluting stents have been effective in randomized trials, but their safety and efficacy for off-label indications has not been well studied. Methods The STENT (Strategic Transcatheter Evaluation of New Therapies) Registry is the largest multicenter U.S. registry evaluating outcomes of DES. Off-label indications included ostial, left main, long, bifurcation, and in-stent restenotic lesions, saphenous vein grafts, chronic total occlusions, small or large vessels, multilesion or multivessel percutaneous coronary interventions, and ST-segment elevation myocardial infarction. Outcomes were adjusted using Cox proportional hazards regression and propensity analyses. Results Drug-eluting stents were used in an off-label manner in 59% of patients. The patients who received off-label treatment were more often male, had a higher incidence of prior infarction and bypass surgery, and lower ejection fractions. Off-label versus “on-label” use of DES was associated with higher rates of death, myocardial infarction, target vessel revascularization, major adverse cardiac events, and stent thrombosis at 9 months and 2 years. Off-label use of DES compared with off-label use of bare-metal stents (BMS) had lower rates of death, myocardial infarction, target vessel revascularization, and major adverse cardiac events at 9 months and 2 years and lower rates of stent thrombosis at 9 months. Conclusions Off-label use of DES is associated with higher event rates compared with on-label use of DES, which is consistent with a higher risk clinical and lesion profile. However, event rates with off-label use of DES are lower compared with off-label use of BMS. Pending results from randomized trials, our data support the use of DES for off-label indications in selected patients.

Background Advances in coronary angioplasty and adjunct pharmacology have improved patient outcomes after primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI). However, several areas for improvement remain. Hemorrhagic complications, which are common in patients receiving intense anticoagulant and antiplatelet agents during primary PCI to suppress ischemia, have been strongly associated with early and late mortality. Moreover, restenosis after bare-metal stents (BMSs) frequently results in symptom recurrence and the need for repeat rehospitalization and revascularization procedures. Newer pharmacologic agents and drug-eluting stents may address both of these issues. Study Design In the HORIZONS-AMI trial, 3,602 patients with AMI undergoing primary PCI were prospectively randomized to unfractionated heparin plus routine use of glycoprotein (GP) IIb/IIIa inhibitors versus the direct thrombin inhibitor bivalirudin plus provisional use of GP IIb/IIIa inhibitors reserved for predefined thrombotic complications. In a second randomization, 3,011 eligible patients were randomly assigned to either a polymer-based paclitaxel-eluting stent or to an otherwise identical BMS. The study was powered for the assessment of sequential safety and efficacy end points for each specific randomization, with clinical end points assessed at 30 days, 1 year, and then annually for 5 years. Summary The ongoing HORIZONS-AMI trial will determine whether bivalirudin monotherapy reduces bleeding complications and improves overall event-free survival compared with unfractionated heparin plus the routine use of GP IIb/IIIa inhibitors in patients undergoing primary PCI for AMI. Furthermore, this study will determine whether paclitaxel-eluting stents safely reduce rates of ischemic target lesion revascularization compared with BMSs in the setting of primary PCI.

Udgivelsesdato: 2008-May-22 BACKGROUND: We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone (abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardial infarction, as compared with abciximab administered immediately before the procedure (primary PCI). METHODS: In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. RESULTS: A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49). CONCLUSIONS: Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228 [ClinicalTrials.gov].)

The current standard of care for anti-thrombotic therapy with primary PCI for acute ST elevation myocardial infarction (STEMI) is aspirin, clopidogrel, unfractionated heparin and platelet glycoprotein IIb/IIIa inhibitors. However, heparin and glycoprotein IIb/IIIa inhibitors are associated with a high incidence of bleeding, and many of the trials documenting benefit with this therapy were performed before the widespread use of stents and clopidogrel. Bivalirudin is a direct thrombin inhibitor which has been found to have similar efficacy with less bleeding compared with heparin plus glycoprotein IIb/IIIa inhibitors when used with elective PCI and with PCI for unstable angina and non-ST elevation myocardial infarction. The HORIZONS trial evaluated bivalirudin compared with unfractionated heparin and IIb/IIIa inhibitors in patients with STEMI treated with primary PCI and found similar MACE (major adverse cardiac events) with less bleeding and a lower incidence of net adverse clinical events (MACE or major bleeding) at 30 days. Mortality at 30 days was also significantly less with bivalirudin. These results make a strong case for the use of bivalirudin with primary PCI in the great majority of patients with STEMI, with the possible exception of patients with cardiogenic shock or stent thrombosis, and patients with a large thrombus burden or no re-flow following PCI. In the latter case, platelet glycoprotein IIb/IIIa inhibitors would be used as a bail-out strategy.

Objectives The purpose of this study was to compare the 9-month clinical outcomes of patients treated with paclitaxel-eluting stents (PES) or sirolimus-eluting stents (SES) for coronary artery stenosis. Background The STENT (Strategic Transcatheter Evaluation of New Therapies) registry is the first multicenter registry in the U.S. to collect long-term outcomes of drug-eluting stents from “real-world” practice. Methods Data on all percutaneous coronary interventions in 8 U.S. hospital centers were collected in the STENT registry between 2003 and 2005. In this prospective, nonrandomized, observational study, the choice of procedures was at the physicians’ discretion. Patients who only received a PES (n = 4,671) or SES (n = 4,555) and completed 9-month follow-up (93.8% of eligible) were included for analysis. Primary end points were death, myocardial infarction (MI), and target vessel revascularization (TVR) at 9 months. Secondary outcomes included major adverse cardiac events (MACE) (any of the 3 primary end points) and stent thrombosis. Results At 9 months, death, MI, and TVR occurred in 2.2%, 2.0%, and 4.1%, respectively, of the PES group and 2.5%, 2.2%, and 4.3%, respectively, of the SES group (p = NS); MACE occurred in 7.5% of the PES group and 8.0% of the SES group (p = 0.37). After adjustments for group differences in baseline characteristics, TVR (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.70 to 1.32; p = 0.26) and MACE (HR 0.95, 95% CI 0.81 to 1.12; p = 0.56) were similar for PES and SES. Stent thrombosis at 9 months occurred in 0.7% of both groups. Conclusions The results of this study show that clinical restenosis and MACE events after PES and SES procedures in “real-world” patients are infrequent and similar at 9 months.

Background The prognostic impact of baseline collateral flow of the infarct-related artery (IRA) in patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We sought to examine the impact of baseline collateral flow to the IRA on reperfusion success, infarct size, and clinical outcomes in patients undergoing primary PCI for acute myocardial infarction (AMI). Methods and Results Acute procedural, 30-day, and 6-month clinical outcomes were assessed after primary PCI among patients enrolled in the EMERALD trial (n = 501 with AMI within 6 hours of onset). Patients with collateral flow to the IRA (Rentrop grade 2 or 3) more commonly had prior stable angina, less commonly had failed thrombolysis and left anterior descending artery occlusion, and presented with less ST-segment elevation. Myocardial reperfusion assessed by ST-segment recovery and myocardial blush was similar in patients with and without baseline collateral flow to the IRA. Infarct size (assessed by technetium Tc 99m sestamibi) was similar among patients with and without baseline collateral flow in anterior infarction (mean 28.5% vs 31.2%, respectively; P = .59) and nonanterior infarction (12.5% vs 12.1%, respectively; P = .81). There were no differences in the rates of major adverse cardiac events at 30 days or 6 months according to baseline IRA collateral flow. Conclusions Among patients undergoing primary PCI for AMI within 6 hours of symptom onset, we found no significant relationship between baseline collateral flow and either reperfusion success, infarct size, or subsequent clinical outcomes.

The impact of time to treatment on outcomes after primary percutaneous coronary intervention (PCI) is controversial, and there are few data about time to treatment and infarct size. The EMERALD trial randomly assigned 501 high-risk patients with ST-elevation myocardial infarction undergoing primary PCI to stenting with or without GuardWire (Medtronic, Santa Rosa, California) distal protection. Infarct size using sestamibi imaging at 5 to 14 days and clinical outcomes were examined by time to treatment. There were no differences in outcomes between distal protection and control patients. Shorter time to reperfusion ( 3 to 4 vs >4 hours) was associated with smaller infarct size (2% vs 9% vs 12% vs 11%, p = 0.026), trends for better myocardial blush (p = 0.08), and lower 6-month mortality rates (0% vs 0% vs 2.4% vs 5.3%, p = 0.06). Incremental delays in reperfusion after 2 hours had little impact on infarct size. Shorter time to reperfusion impacted on infarct size in patients with anterior infarction (0% vs 17% vs 20.5% vs 30.5%, p = 0.026), but not nonanterior infarction (3% vs 7% vs 7.5% vs 10%, p = 0.23, p = 0.022 for interaction). In conclusion, very early reperfusion with primary PCI is associated with smaller infarct size and has a much greater impact in anterior versus nonanterior infarction. Incremental delays in reperfusion after 2 hours have less effect on infarct size. These data have implications regarding the triage of patients for primary PCI.

This study compared late survival after primary percutaneous coronary intervention (PCI) in patients with cardiogenic shock due to right ventricular (RV) infarction versus left ventricular (LV) pump failure. Consecutive patients with ST-elevation myocardial infarction treated with primary PCI (n = 2,496) were prospectively enrolled in a registry from 1984 to 2004. Cardiogenic shock occurred before PCI in 189 patients (7.6%). Shock was attributed to predominant RV infarction when there was right coronary artery occlusion with preserved LV function and increased right atrial pressure. Patients with shock due to RV infarction (n = 30) versus LV pump failure (n = 136) had fewer previous infarctions (10% vs 29%, p = 0.03), less multivessel disease (20% vs 47%, p = 0.007), higher right atrial pressure (21 vs 16 mm, p = 0.003), and better LV ejection fraction (57% vs 32%, p

Background— Intravascular ultrasound detects stent edge dissections after percutaneous coronary intervention that are not seen angiographically. This study investigated the association between stent edge dissections and clinical outcomes. Methods and Results— ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a large-scale, prospective, multicenter study of patients undergoing drug-eluting stent implantation. In this prospective substudy, 2062 patients (2433 lesions) were evaluated with intravascular ultrasound to characterize the morphological features and clinical outcomes of stent edge dissection after percutaneous coronary intervention. The prevalence of post–percutaneous coronary intervention stent edge dissection was 6.6% per lesion (161 of 2433). Calcified plaque at the proximal stent edge (relative risk [RR]=1.72; P =0.04) and proximal stent edge expansion (RR=1.18; P =0.004) were predictors for proximal dissection; attenuated plaque at the distal stent edge (RR=3.52; P =0.004), distal reference plaque burden (RR=1.56; P P =0.02) were predictors for distal dissection. At 1-year follow-up, target lesion revascularization was more common in lesions with versus without dissection (5.2% versus 2.7%; P =0.04). Multivariable analysis indicated that residual dissection was associated with target lesion revascularization at 1-year follow-up (RR=2.67; P =0.02). Among lesions with dissection, smaller effective lumen area increased the risk of target lesion revascularization at 1-year follow-up (cutoff value of 5.1 mm 2 ; P =0.05). Conclusions— Greater stent expansion and the presence of large, calcified, and/or attenuated plaques were independent predictors of stent edge dissection. Residual stent edge dissection, especially with a smaller effective lumen area, was associated with target lesion revascularization during 1-year follow-up after drug-eluting stent implantation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

Background— The frequency, causes, and impact of myocardial infarction (MI) after successful percutaneous coronary intervention have not been well studied. Methods and Results— The Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) study was a prospective, multicenter registry study of 8582 patients undergoing successful drug-eluting stent implantation at 11 centers in the United States and Germany. After excluding 128 patients with periprocedural MI, we investigated the pathogenesis, frequency, and long-term consequences of non-periprocedural MI in 8454 patients. MI during 2-year follow-up developed in 263 patients (3.3%) at a median (25th and 75th percentiles) time of 318 (129, 503) days. The 263 MIs were subclassified as spontaneous MI (n=78; 29.7%), secondary or indeterminate MI (n=64; 24.3%), stent thrombosis–related MI (n=63; 24.0%), and in-stent restenosis–related MI (n=58; 22.1%). Multivariable predictors of MI included clinical and angiographic factors (acute coronary syndromes presentation, diabetes mellitus, current smoker, multivessel disease, treatment of an in-stent restenotic lesion), laboratory findings (low baseline hemoglobin and reduced creatinine clearance), antiplatelet agent–related factors (higher on-treatment platelet P2Y12 receptor reactivity and premature thienopyridine discontinuation), and not being on a statin at discharge. Patients who experienced an MI during the follow-up period had significantly greater 2-year mortality than those without MI (17.3% [42 deaths] versus 3.4% [265 deaths], P P =0.03). Conclusions— The occurrence of a non-periprocedural MI within 2 years after successful drug-eluting stent implantation is relatively infrequent, but has numerous etiologies and is significantly associated with subsequent mortality. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

Background— Certain proton pump inhibitors (PPIs) interfere with clopidogrel metabolism, potentially attenuating P2Y12 receptor inhibition. Previous observational and randomized trials report conflicting results regarding the clinical significance of this pharmacological interaction. We examined the interaction between concomitant administration of PPI and clopidogrel on platelet reactivity and clinical outcomes in the large-scale, prospective Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents study. Methods and Results— On-treatment P2Y12 platelet reactivity testing was performed using the VerifyNow assay after clopidogrel loading and successful drug-eluting stent implantation at 11 sites in the United States and Germany. PPIs were prescribed at the discretion of treating physicians; patients were followed for 2 years. High platelet reactivity was defined as P2Y12 reactivity units >208. Of 8582 enrolled patients, 2697 (31.4%) were taking a PPI at the time of coronary intervention. After adjustment for differences in baseline characteristics, PPI use was independently associated with high platelet reactivity (odds ratio, 1.38: 95% confidence interval, 1.25–1.52, P =0.0001). A total of 2162 (25.2%) patients were prescribed a PPI at hospital discharge. In a propensity-adjusted multivariable analysis, discharge PPI use was independently associated with increased risk for postdischarge major adverse cardiac events (cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) at 2-year follow-up (hazard ratio, 1.21; 95% confidence interval, 1.04–1.42, P =0.02). Conclusions— In patients treated with clopidogrel after successful drug-eluting stents implantation, the concomitant administration of PPI was associated with high platelet reactivity and a greater rate of adverse outcomes during long-term follow-up. Additional studies are warranted to determine the risk–benefit ratio of PPIs in patients with drug-eluting stents treated with clopidogrel. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00433966.

Background— Previous studies evaluating correlates of stent thrombosis (ST) have included mostly patients with bare metal stents and early-generation drug-eluting stents (DES) and have not systematically evaluated the role of intravascular ultrasound–guided stenting and high platelet reactivity on clopidogrel. The purpose of this study was to evaluate the frequency and correlates of ST in patients receiving DES, specifically examining the impact of risk factors modifiable by physician and patient behavior. Methods and Results— Assessment of Dual Anti-platelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a multicenter, prospective study in patients undergoing successful coronary intervention with DES in whom routine platelet reactivity testing was performed. Definite or probable ST occurred in 92 (1.1%) of 8582 patients within 2 years. Independent baseline correlates of ST included presentation with an acute coronary syndrome (hazard ratio [HR]=1.81, P =0.01), insulin-treated diabetes mellitus (HR=1.91, P =0.02), previous myocardial infarction (HR=1.75, P =0.02), and peripheral arterial disease (HR=2.01, P =0.01). Independent treatment-related correlates included use of early generation DES (HR=1.75, P =0.02), no procedural intravascular ultrasound guidance (HR=1.75, P =0.04), and premature discontinuation of dual antiplatelet therapy (HR=2.67, P =0.003); high platelet reactivity on clopidogrel trended as a correlate of ST (HR=1.49, P =0.08). The 2-year risk of ST ranged from 0.3% to 10.0% when 0 to 3 modifiable risk factors were present. Conclusions— After successful DES implantation, ST occurred within 2 years in 1.1% of patients and was strongly associated with fixed and modifiable risk factors. The frequency of ST may be reduced with intravascular ultrasound –guided stenting, assiduous adherence to dual antiplatelet therapy, and adequate P2Y12 platelet receptor inhibition. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

We aimed to construct a predictive model for one-year mortality in patients undergoing invasive coronary evaluation and to examine the impact of bivalirudin on survival according to the level of baseline risk.Compared to heparin plus GP IIb/IIIa inhibitors (HEP/GPI), bivalirudin decreases bleeding complications in a range of clinical presentations. The impact of preprocedural risk assessment on survival and whether this is modified by bivalirudin, has not been investigated in detail.We examined patient-level data from the REPLACE-2, ACUITY, and HORIZONS-AMI trials (n = 18,819) to construct a risk-adjusted mortality model using baseline clinical variables.One-year mortality occurred in 287 patients (3.1%) assigned to bivalirudin and 336 patients (3.6%) assigned to HEP/GPI (HR 0.85; 95% CI, 0.73-1.00; P = 0.048). Using 11 highly significant predictors of mortality, we developed an integer-risk score to classify patients into risk tertiles. High-risk patients had a rate of 1-year mortality over 9-fold greater than low-risk patients. Consequently, the absolute mortality reduction attributed to bivalirudin was more marked in high-risk patients: 3.1% (-0.8% to 7.0%) in the overall cohort, 4.8% (0.5% to 9.2%) in the PCI cohort (P-interaction versus intermediate and low risk categories, 0.09 and P = 0.02, respectively).In patients undergoing invasive coronary evaluation, 1-year mortality can be predicted using baseline variables. Bivalirudin treatment (versus HEP/GPI) conferred a survival benefit.

Background— Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. Methods and Results— We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively ( P Conclusions— HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

BACKGROUND Although smoking is a risk factor for coronary atherosclerosis, the age-related impact on lesion characteristics and plaque instability remains unclear. PATIENTS AND METHODS In ADAPT-DES, 780 patients with 916 culprit lesions were evaluated by preprocedural grayscale and virtual histology-intravascular ultrasound. RESULTS Current smokers (smoking within 1 month) more often presented with acute coronary syndrome (67 vs. 51 vs. 51%, P 1 month) or nonsmokers. In patients 65 or more years of age, current smokers (vs. nonsmokers) showed larger normalized volumes of plaque and media [8.6 (7.8-9.4) vs. 7.2 (6.8-7.7) mm/mm, P=0.016] and external elastic membrane [14.4 (13.2-15.5) vs. 12.8 (12.2-13.4) mm/mm, P=0.05]. At the minimal lumen area site, despite a greater plaque burden, the larger external elastic membrane area [14.4 (13.1-15.7) vs. 12.0 (11.3-12.7) mm, P=0.003] contributed toward preserving the minimal lumen area [2.6 (2.4-2.7) vs. 2.6 (2.5-2.7) mm, P=0.91] in current smokers (vs. nonsmokers) 65 or more years of age. Moreover, current smokers (vs. nonsmokers) 65 or more years of age showed a greater normalized necrotic core volume [1.19 (0.96-1.46) vs. 0.75 (0.66-0.85) mm/mm, P=0.0007], more thin-cap fibroatheromas (61 vs. 48%, P=0.04), and plaque ruptures (38 vs. 26%, P=0.051). Conversely, in patients younger than 65 years of age, there was no significant difference in culprit lesion morphology among current, former, and nonsmokers. CONCLUSION In patients 65 or more years (not in patients

Background— Obesity is a cardiovascular risk factor, but the obesity paradox in patients undergoing percutaneous coronary intervention is poorly understood. Methods and Results— Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter study of patients undergoing drug-eluting stent implantation. Overall, 780 patients (916 culprit lesions) were evaluated by grayscale and virtual histology–intravascular ultrasound pre–percutaneous coronary intervention. Poststenting intravascular ultrasound was done in 780 patients (894 treated lesions). Patients were divided into body mass index (BMI) tertiles. The high-BMI group had more diabetes mellitus, hypertension, and hyperlipidemia and more frequent plaque ruptures compared with the low-BMI group. At the minimal lumen area site, the high-BMI group had a larger plaque area (11.7 [11.0–12.4] versus 9.8 [9.3–10.4] mm 2 ) and a greater plaque burden (77.3% [76.1%–78.5%] versus 74.4% [73.1%–75.8%]) compared with the low-BMI group; however, a larger external elastic membrane area (14.6 [13.8–15.3] versus 12.7 [12.1–13.3] mm 2 ) resulted in a similar minimal lumen area compared with the low-BMI group. Post stenting, the high-BMI group had a significantly larger stent area versus the lower-BMI group. At 1-year follow-up, the high-BMI group was associated with less clinically driven target lesion revascularization compared with the low-BMI group in both the overall and the propensity-matched cohorts. Conclusions— A high BMI was associated with a greater plaque burden; however, a larger external elastic membrane preserved lumen dimensions and was associated with a larger stent area during intravascular ultrasound-guided stent implantation. Thus, despite more comorbidities, greater plaque burden, and more plaque rupture, a high BMI was not associated with worse outcomes after drug-eluting stent implantation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00638794.

Objectives The goal of this work was to determine whether rheolytic thrombectomy (RT) as an adjunct to primary percutaneous coronary intervention (PCI) reduces infarction size and improves myocardial perfusion during treatment of ST-segment elevation myocardial infarction (STEMI). Background Primary PCI for STEMI achieves brisk epicardial flow in most patients, but myocardial perfusion often remains suboptimal. Distal embolization of thrombus during treatment may be a contributing factor. Methods This prospective, multicenter trial enrolled 480 patients presenting within 12 h of symptom onset and randomized to treatment with RT as an adjunct to PCI (n = 240) or to PCI alone (n = 240). Visible thrombus was not required. The primary end point was infarct size measured by sestamibi imaging at 14 to 28 days. Secondary end points included final Thrombolysis In Myocardial Infarction (TIMI) flow grade, tissue myocardial perfusion (TMP) blush, ST-segment resolution, and major adverse cardiac events (MACE), defined as the occurrence of death, new Q-wave myocardial infarction, emergent coronary artery bypass grafting, target lesion revascularization, stroke, or stent thrombosis at 30 days. Results Final infarct size was higher in the adjunct RT group compared with PCI alone (9.8 ± 10.9% vs. 12.5 ± 12.13%; p = 0.03). Final TIMI flow grade 3 was lower in the adjunct RT group (91.8% vs. 97.0% in the PCI alone group; p Conclusions Despite effective thrombus removal, RT with primary PCI did not reduce infarct size or improve TIMI flow grade, TMP blush, ST-segment resolution, or 30-day MACE.