This study sought to investigate the effect of treatment delay on microvascular reperfusion in ST-segment elevation myocardial infarction (STEMI) patients from the large, multicenter, prospective ...HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial.
Despite restoration of epicardial blood flow during primary percutaneous coronary intervention (PCI), one-third of patients do not obtain myocardial perfusion due to impairment in the microvascular circulation.
We examined the effect of symptom onset-to-balloon time (SBT) and door-to-balloon time (DBT) on myocardial reperfusion during primary PCI in STEMI, utilizing resolution of ST-segment elevation (STR) and the myocardial blush grade (MBG). The primary analysis was the relationships between SBT ≤2, >2 to 4, and >4 h and DBT ≤1, >1 to 1.5, >1.5 to 2, and >2 h with MBG and STR. Clinical risk was assessed using a modified version of the Thrombolysis In Myocardial Infarction risk score for STEMI.
In 2,056 patients, absent microvascular perfusion (MBG 0/1) and STR (STR <30%) after primary PCI was significantly more common in patients with longer SBT, in patients with both low and high clinical risk profiles. By multivariable analysis, SBT (p < 0.0001), anterior infarction (p < 0.0001), reference vessel diameter (p = 0.005), lesion minimum lumen diameter (p < 0.0001), hyperlipidemia (p = 0.03), and current smoking (p = 0.001) were independent predictors of MBG 0/1, whereas SBT (p = 0.007), anterior infarction (p < 0.0001), and history of renal insufficiency (p = 0.0002) were independent predictors of absent STR. DBT (p < 0.0001) was an independent predictor of MBG 0/1. MBG 0/1 and STR<30% identified patients with increased 3-year mortality.
The present study suggests that delay in mechanical reperfusion therapy during STEMI is associated with greater injury to the microcirculation.
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.
Reinfarction after primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction has negative consequences. Little is known about reinfarction after ...drug-eluting stents and bivalirudin anticoagulation. We, therefore, sought to determine the incidence, predictors, and implications of reinfarction after primary percutaneous coronary intervention in the contemporary era.
Outcomes were assessed in 3202 patients undergoing stent implantation for ST-segment-elevation myocardial infarction in the Harmonizing Outcomes with RevascularIZatiON and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. Independent predictors of reinfarction and mortality were identified by Cox proportional hazards modeling. The cumulative incidence of reinfarction was 1.8% at 30 days, 4.0% at 1 year, and 6.9% at 3 years. Definite stent thrombosis was responsible for 76.3% of reinfarctions occurring within 30 days and 52.0% of all reinfarctions within 3 years. Independent predictors of reinfarction were current smoking, Killip class ≥2, baseline thrombocytosis, multivessel disease, symptom onset-to-balloon time, and total stent length. Randomization to bivalirudin versus heparin plus a glycoprotein IIb/IIIa inhibitor and use of drug-eluting versus bare metal stents were not significant predictors of reinfarction. Reinfarction was a powerful independent predictor of subsequent cardiac mortality (hazard ratio 95% confidence interval=7.65 4.47-13.09; P<0.0001) and all-cause mortality (hazard ratio 95% confidence interval=2.88 1.74-4.78; P<0.0001).
Despite advances in pharmacotherapy and stents, reinfarction after primary percutaneous coronary intervention is not infrequent, in the contemporary era is most often attributable to stent thrombosis, and is strongly associated with subsequent cardiac and all-cause mortality. Further enhancements in drugs and devices to prevent reinfarction are needed to improve outcomes in high-risk patients with ST-segment-elevation myocardial infarction.
http://www.clinicaltrials.gov. Unique identifier: NCT00433966.
Pre–percutaneous coronary intervention (PCI) Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow has been identified as a predictor of final TIMI grade 3 flow and better survival. Yet ...pharmacologic strategies increasing the rates of pre-PCI TIMI grade 3 flow resulted in more bleeding, without a benefit in survival. The aim of this study was to identify the predictors and implications of spontaneous reperfusion before primary PCI in patients with ST-segment elevation myocardial infarction. The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) and Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trials were combined, and the predictors of core laboratory–determined baseline TIMI grade 3 flow and 1-year outcomes were analyzed according to baseline TIMI flow. Baseline TIMI grade 3 flow was present in 932 of 5,332 patients (17.5%). The independent predictors of baseline TIMI grade 3 flow were diabetes, longer delay to PCI, smoking, and more extensive coronary disease. Patients with compared to those without baseline TIMI grade 3 flow had significantly higher rates of post-PCI TIMI grade 3 flow (99.1% vs 91.4%, p <0.0001) and lower 1-year all-cause mortality (2.7% vs 4.3%, p = 0.02). By multivariate analysis, baseline TIMI grade 3 flow (hazard ratio 1.65, 95% confidence interval 1.01 to 2.71, p = 0.046) and final TIMI grade 3 flow (hazard ratio 3.67, 95% confidence interval 2.45 to 5.48, p <0.001) were significant independent predictors of 1-year survival. In conclusion, TIMI grade 3 flow is present in about 1 in every 6 patients before PCI and paradoxically is more common in patients with higher risk characteristics. TIMI grade 3 flow before as well as after PCI is an independent predictor of greater 1-year survival. These data should inform future trials of ST-segment elevation myocardial infarction with respect to improvement in outcomes.
Our objective was to evaluate the impact of door-to-balloon time (DBT) on mortality depending on clinical risk and time to presentation.
DBT affects the mortality rate in ST-segment elevation ...myocardial infarction treated with primary percutaneous coronary intervention, but the impact may vary across subgroups.
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.
The 1-year mortality rate was lower in patients with short versus long DBT (< or = 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 (< or = 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.
Short DBTs (< or = 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.
We sought to examine if the risk conferred by high on-treatment platelet reactivity (HPR) varies based upon clinical presentation. We examined the relation between HPR (P2Y12 reaction units >208) and ...adverse ischemic and bleeding events among patients with and without acute coronary syndromes (ACS) from ADAPT-DES; 51.7% of patients had ACS. After clopidogrel loading, ACS patients had higher P2Y12 reaction units and a greater prevalence of HPR based on VerifyNow P2Y12 assay. Of 92 definite or probable stent thrombosis (ST) events at 2 years, 65.2% occurred among patients with ACS. HPR was independently associated with ST in ACS patients (adjusted hazard ratio 2.29, 95% confidence interval 1.32 to 3.98) but not with clinically relevant bleeding. Although no statistical interactions between ACS status and these associations were observed, non-ACS patients exhibited an attenuated association between HPR and ST, and an inverse association between HPR and clinically relevant bleeding. HPR was similarly associated with myocardial infarction, but not with overall mortality in ACS and non-ACS patients. In conclusion, the majority of ST events in the 2 years after drug-eluting stent placement occurred in ACS patients; HPR was strongly associated with ST in these patients. These data support current recommendations for using more potent antiplatelet therapies in ACS patients.
Background Target vessel revascularization (TVR) may compromise the benefits of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction (STEMI) We set out to identify ...the predictors and examine the impact of TVR after STEMI in patients receiving a coronary stent. Methods In HORIZONS-AMI, 3,602 patients with STEMI were randomized to bivalirudin versus heparin and a glycoprotein IIb/IIIa inhibitor. Stents were implanted in 3,202 patients (2,982 were randomized to bare-metal stents versus paclitaxel-eluting stents, and 220 received nonrandomized stents). Results Target vessel revascularization occurred in 219 patients (6.9%) at 1 year and in 437 patients (14.4%) at 3 years. Target vessel revascularization was ischemia-driven in 418 cases (95.7%). Target vessel revascularization was due to restenosis in 219 patients (50.1%), definite stent thrombosis in 124 (28.4%), and disease progression in 94 (21.5%). Independent predictors of TVR were more extensive coronary artery disease, smaller vessel size, longer lesion length and the number of stents implanted, post–percutaneous coronary intervention diameter stenosis, symptom onset to balloon time, treatment with bare-metal stents rather than paclitaxel-eluting stents, and scheduled angiographic follow-up. Target vessel revascularization was an independent predictor of subsequent myocardial infarction (hazard ratio HR 5.25, P < .0001), ST (HR 5.98, P < .0001), and major bleeding (HR 5.25, P < .0001) but not mortality (HR 0.88, P = .61). Conclusions In HORIZONS-AMI, TVR within 3 years after stent implantation was performed in ~1 of every 7 patients and was associated with more extensive coronary disease, more complex procedures, and bare metal stents. Target vessel revascularization was often due to stent thrombosis and disease progression as well as restenosis and was strongly associated with adverse outcomes but not mortality.
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.
DES might have greatest utility in patients who would benefit most from their antirestenotic properties.
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.
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.
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).
Whereas survival after lytic therapy for myocardial infarction is strongly dependent on early administration, it is unknown whether the otherwise excellent outcomes in patients undergoing primary ...PTCA for acute myocardial infarction, in whom TIMI-3 flow rates of >90% may be achieved, can be further improved by early reperfusion.
Among 2507 patients enrolled in 4 PAMI trials undergoing primary PTCA, spontaneous reperfusion (TIMI-3 flow) was present in 16% at initial angiography. Compared with patients without TIMI-3 flow, those with TIMI-3 flow before PTCA had greater left ventricular ejection fraction (57+/-10% versus 53+/-11%, P=0.003) and were less likely to present in heart failure (7.0% versus 11.6%, P=0.009). Patients with initial TIMI-3 flow had significantly lower in-hospital rates of mortality, new-onset heart failure, and hypotension and had a shorter hospital stay. Cumulative 6-month mortality was 0.5% in patients with initial TIMI-3 flow, 2.8% with TIMI-2 flow, and 4.4% with initial TIMI-0/1 flow (P=0.009). By multivariate analysis, TIMI-3 flow before PTCA was an independent determinant of survival (odds ratio 2.1, P=0.04), even when corrected for by postprocedural TIMI-3 flow.
Patients undergoing primary PTCA in whom TIMI-3 flow is present before angioplasty present with greater clinical and angiographic evidence of myocardial salvage, are less likely to develop complications related to left ventricular failure, and have improved early and late survival. These data warrant prospective randomized trials of pharmacological strategies to promote early reperfusion before definitive mechanical intervention in acute myocardial infarction.
Whether the association between platelet count (PC) and thrombotic and bleeding risk is independent of or varies by residual platelet reactivity to antiplatelet therapies is unclear. We sought to ...investigate the independent and combined effects of PC and platelet reactivity on thrombotic and bleeding risk after coronary artery implantation of drug-eluting stents (DES). Patients enrolled in the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents study were stratified by PC tertiles. The study cohort comprised 8,402 patients. By linear regression analysis, lower PC was strongly and independently associated with higher platelet reactive units (PRUs) on clopidogrel. After multivariable adjustment (including PRU and aspirin reactive units), high, but not low, PC tertile was independently associated with higher risk of thrombotic complications, including spontaneous myocardial infarction and stent thrombosis. Although no independent association was observed between PC tertiles and hemorrhagic risk, both high and low PC tertiles were associated with increased risk for all-cause mortality. After stratification of PC tertiles by tertiles of PRUs, the crude risk of thrombotic complications was highest in patients in the high PC and high PRU tertiles. By multivariable adjustment, PRU increases were uniformly associated with higher risk of thrombotic events across PC tertiles, without evidence of interaction. In conclusion, higher PCs and higher PRUs act independently and synergistically in determining thrombotic risk. Alongside PRU, PCs could be a simple hematological parameter to consider for risk stratification and in tailoring duration and potency of pharmacologic platelet inhibition after DES implantation.
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