Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of ...which may improve reperfusion success, reduce infarct size, and enhance event-free survival.
To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size.
Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis.
Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection.
Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events.
Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% 152/240 vs 61.9% 148/239, respectively; absolute difference, 1.4% 95% confidence interval, -7.7% to 10.5%; P = .78), and left ventricular infarct size was similar in both groups (median, 12.0% n = 229 vs 9.5% n = 208, respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66).
A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.
The aim of this study was to determine the risk period for increased stent thrombosis (ST) after percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS) and whether ...this increased risk is related to high platelet reactivity (HPR).
ST risk after PCI is higher among patients with ACS than those with stable ischemic heart disease. When ST risk is highest in patients with ACS and how that is affected by HPR is unknown.
Using the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry, ST rates during 2-year follow-up post-PCI with drug-eluting stents were compared among patients presenting with ACS (myocardial infarction MI or unstable angina) or stable ischemic heart disease (non-ACS). Landmark analyses were done at 30 days and 1 year post-PCI. Platelet reactivity on aspirin and clopidogrel post-PCI was assessed using VerifyNow assays.
Of 8,582 patients, 2,063 presented with MI, 2,370 with unstable angina, and 4,149 with non-ACS. Incidence rates of HPR were 48.0%, 43.3%, and 39.8%, respectively (p < 0.001). Within the first 30 days post-PCI, patients presenting with MI had increased ST risk compared with patients with non-ACS (hazard ratio HR: 4.52; 95% confidence interval CI: 2.01 to 10.14; p < 0.001). After 30 days, relative ST risks were progressively lower and no longer significant between groups (31 days to 1 year post-PCI: HR: 1.97; 95% CI: 0.80 to 4.85; >1 year post-PCI: HR: 0.89; 95% CI: 0.27 to 2.92). The elevated ST risk in patients with MI within 30 days was largely confined to those with HPR on clopidogrel (HR: 5.77; 95% CI: 2.13 to 15.63; p < 0.001).
Among patients undergoing PCI, rates of ST during 2-year follow-up were highest in those with MI and lowest in those with non-ACS. Increased ST risk in patients with MI was greatest in the first 30 days post-PCI and was observed predominantly among those with increased HPR on clopidogrel. These findings emphasize the importance of adequate P2Y
inhibition after MI, especially within the first 30 days after stent implantation.
Abstract Background Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse ...and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis. Methods PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002–12/2010). Studies were selected if including ≥ 2000 patients undergoing stenting or reporting on ≥ 25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate 95% confidence intervals), and consistency of predictors was formally appraised. Results A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22 months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently. Conclusions Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.
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).
A 600-mg loading dose of clopidogrel compared with 300 mg provides more rapid and potent inhibition of platelet activation.
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.
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 (p(interaction) = 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).
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).
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.
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<0.0001), and distal edge stent expansion (RR=1.11; 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).
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.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.
Door-to-Balloon Time With Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction Impacts Late Cardiac Mortality in High-Risk Patients and Patients Presenting Early After the Onset ...of Symptoms
Bruce R. Brodie, Charles Hansen, Thomas D. Stuckey, Scott Richter, Debra S. VerSteeg, Navin Gupta, William E. Downey, Mark Pulsipher
The impact of delays in door-to-balloon time on late cardiac survival after primary percutaneous coronary intervention (PCI) has not been studied. Consecutive patients treated with primary PCI were followed up for seven years. Prolonged door-to-balloon times were associated with higher hospital mortality and late mortality. Prolonged door-to-balloon times were associated with higher late mortality in high-risk but not low-risk patients and in patients presenting early but not late after the onset of symptoms. These findings have implications for the triage of patients for primary PCI.
The purpose of this study was to evaluate the impact of door-to-balloon time with primary percutaneous coronary intervention (PCI) on late cardiac mortality.
The impact of door-to-balloon time on outcomes is controversial, and the impact on late mortality has not been studied.
Consecutive patients (n = 2,322) treated with primary PCI from 1984 to 2003 were prospectively identified and followed up for a median of 83 months.
Prolonged door-to-balloon times (0 to 1.4 h vs. 1.5 to 1.9 h vs. 2.0 to 2.9 h vs. ≥3.0 h) were associated with higher in-hospital mortality (4.9% vs. 6.1% vs. 8.0% vs. 12.2%, p < 0.0001) and late mortality (12.6% vs. 16.4% vs. 20.4% vs. 27.1% at 7 years, p < 0.0001) and were an independent predictor of late mortality by Cox regression (p = 0.0004). Prolonged door-to-balloon times (≥2 h vs. <2 h) were associated with higher late mortality in high-risk patients (32.5% vs. 21.5%; hazard ratio HR, 1.53; 95% confidence interval CI, 1.22 to 1.90; p = 0.0002) but not in low-risk patients (10.8% vs. 9.2%; HR, 1.13; 95% CI, 0.78 to 1.64; p = 0.53) and in patients presenting early (≤3 h) (24.7% vs. 15.0%; HR, 1.54; 95% CI, 1.24 to 1.90; p = 0.0001) but not late (>3 h) (21.1% vs. 18.5%; HR, 0.95; 95% CI, 0.62 to 1.45; p = 0.80).
Delays in door-to-balloon time impact late survival in high-risk but not low-risk patients and in patients presenting early but not late after the onset of symptoms. These findings have implications for the triage of patients for primary PCI.
The panel focused largely on the management of this complex disease and derived prudent, practical, and contemporary treatment strategies for the many subgroups of patients comprising the broad HCM ...disease spectrum. Because of the relatively low prevalence of HCM in general cardiologic practice (50), its diverse presentation, and mechanisms of death and disability and skewed patterns of patient referral (7,11,13,36-38,42,51-59), the level of evidence governing management decisions for drugs or devices has often been derived from non-randomized and retrospective investigations. Large-scale controlled and randomized study designs, such as those that have provided important answers regarding the management of coronary artery disease (CAD) and congestive heart failure (60-62), have generally not been available in HCM as a result of these factors. ...treatment strategies have necessarily evolved based on available data that have frequently been observational in design, sometimes obtained in relatively small patient groups, or derived from the accumulated clinical experience of individual investigators, and reasonable inferences drawn from other cardiac diseases.
Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) typically requires a greater number of stents and longer stent length than non-CTO PCI, placing these patients at greater risk ...for adverse ischemic events. We sought to determine whether the association between high platelet reactivity (HPR) and the risk of ischemic events is stronger after CTO than non-CTO PCI.
Patients undergoing successful PCI in the multicenter ADAPT-DES study were stratified according to whether they underwent PCI of a CTO. HPR was defined as VerifyNow platelet reaction units >208. The study primary endpoint was the 2-year risk target vessel failure (TVF defined as cardiac death, myocardial infarction, or target lesion revascularization).
CTO PCI was performed in 400 of 8448 patients. HPR was present in 34.5% of CTO PCI patients and 43.1% of non-CTO PCI patients (P = .0007). Patients undergoing CTO PCI with versus without HPR had significantly higher 2-year rates of TVF (15.0% versus 8.3%, P = .04) without significant differences in bleeding. HPR was an independent predictor of 2-year TVF (adjusted HR 1.16, 95% CI 1.02-1.34, P = .03) whereas CTO PCI was not (adjusted HR 0.89, 95% CI 0.65-1.22, P = .48). There was a significant interaction between CTO versus non-CTO PCI and PRU as a continuous variable for 2-year TVF (Pinteraction = 0.02).
In ADAPT-DES, HPR was associated with an increased 2-year risk of TVF after PCI, an association that was at least as strong after CTO PCI compared with non-CTO PCI.
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 <0.0001) and at 1 year (14.8% vs 7.2%, p <0.0001), an association that on multivariate analysis was independent of gender. Mortality was significantly higher in men with versus without baseline anemia (4.6% vs 1.8% at 30 days, p = 0.003; 8.9% vs 3.0% at 1 year, p <0.0001) but not in women (5.3% vs 3.6% at 30 days, p = 0.42; 7.5% vs 5.9% at 1 year, p = 0.54). On multivariate analysis, anemia independently predicted 1-year all-cause mortality in men but not in women. Bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor resulted in twofold lower rates of all-cause and cardiac mortality and major bleeding in patients without but not in those with baseline anemia. In conclusion, baseline anemia was associated with increased major bleeding and death in patients with ST elevation myocardial infarctions who underwent primary PCI but was a stronger predictor of early and late mortality in men than in women. Paradoxically, in this post hoc analysis, the reductions in major bleeding and mortality in ST elevation myocardial infarction afforded by bivalirudin occurred primarily in patients without baseline anemia.
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