Assessment Of Dual Antiplatelet Therapy With Drug-Eluting Stents Research Articles

Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: AnADAPT-DES Substudy.

This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD). The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined. The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5mg/dL or a relative increase of≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate<60mL/min/1.73m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding. Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted HR: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95%CI: 1.22-2.55; MI, HR: 1.67; 95%CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95%CI: 1.10-2.65; and major bleeding, HR: 1.38; 95%CI: 1.06-1.80). Compared with the CA-AKI-/CKD- group, the CA-AKI+/CKD- (HR: 1.83; 95%CI: 1.33-2.52), CA-AKI-/CKD+ (HR: 1.56; 95%CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95%CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95%CI: 1.65-4.31) groups were at higher risk of NACE. CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

Risk-Benefit of 1-Year DAPT After DES Implantation in Patients Stratified by Bleeding and Ischemic Risk

BackgroundAlthough a 1-year duration of dual antiplatelet therapy (DAPT) is used in many patients after drug-eluting stent (DES) implantation, the evidence supporting this duration is uncertain. ObjectivesThe authors investigated the risk-benefit profile of 1-year vs ≤6-month DAPT after DES using 2 novel scores to risk stratify bleeding and ischemic events. MethodsIschemic and bleeding risk scores were generated from ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), a multicenter, international, “all-comers” registry that enrolled 8,665 patients treated with DES. The risk-benefit profile of 1-year vs ≤6-month DAPT was then investigated across risk strata from an individual patient data pooled dataset of 7 randomized trials that enrolled 15,083 patients treated with DES. ResultsIn the derivation cohort, the ischemic score and the bleeding score had c-indexes of 0.76 and 0.66, respectively, and both were well calibrated. In the pooled dataset, no significant difference was apparent in any ischemic endpoint between 1-year and ≤6-month DAPT, regardless of the risk strata. In the overall dataset, there was no significant difference in the risk of clinically relevant bleeding between 1-year and ≤6-month DAPT; however, among 2,508 patients at increased risk of bleeding, 1-year compared with ≤6-month DAPT was associated with greater bleeding (HR: 2.80; 95% CI: 1.12-7.13) without a reduced risk of ischemic events in any risk strata, including those with acute coronary syndromes. These results were consistent in a network meta-analysis. ConclusionsIn the present large-scale study, compared with ≤6-month DAPT, a 1-year duration of DAPT was not associated with reduced adverse ischemic events in any risk strata (including acute coronary syndromes) but was associated with greater bleeding in patients at increased risk of bleeding.

Stent Thrombosis Risk Over Time on the Basis of Clinical Presentation and PlateletReactivity: Analysis From ADAPT-DES.

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 30days 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 30days 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 30days, relative ST risks were progressively lower and no longer significant between groups (31days 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 30days 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 30days post-PCI and was observed predominantly among those with increased HPR on clopidogrel. These findings emphasize the importance of adequate P2Y12 inhibition after MI, especially within the first 30days after stent implantation.

Association Between Hypertension, Platelet Reactivity, and the Risk of Adverse Events After Percutaneous Coronary Intervention (From the ADAPT-DES Study)

Hypertension is associated with vascular and endothelial dysfunction that may result in a greater propensity for reactive platelets to cause thrombosis. We sought to assess whether the risk of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in patients with on-clopidogrel residual high platelet reactivity (HPR) varies in patients with versus without hypertension. Assessment of dual antiplatelet therapy with drug eluting stents (ADAPT-DES) was a prospective, multicenter registry of patients successfully treated with coronary drug-eluting stents (DES). HPR was defined as P2Y12 reaction units (PRU) >208, as assessed by the VerifyNow point-of-care assay. Multivariable Cox proportional hazards regression was used to assess whether the adjusted association between HPR and 2-year risk of MACE (cardiac death, myocardial infarction [MI], or stent thrombosis) was different in patients with versus without hypertension. A total of 6833 of 8582 patients (79.6%) had a history of hypertension. Patients with compared with those without hypertension were older, more likely to have other cardiovascular risk factors, and had higher PRU (190.1 ± 97.3 vs 179.5 ± 94.3; p <0.0001). Patients with hypertension had significantly higher 2-year rates of MACE (7.0% vs 4.4%, p <0.001), all-cause death (4.2% vs 2.5%, p = 0.001), and MI (5.2% vs 3.2%, p <0.001), and had nominally higher rates of stent thrombosis (1.0% vs 0.5%, p = 0.059). A significant interaction was present between hypertension and HPR regarding 2-year MACE risk (adjusted hazard ratio for HPR vs no HPR 1.38, 95% confidence interval 1.14 to 1.68 for patients with hypertension vs 0.81, 95% confidence interval 0.50 to 1.33 for patients without hypertension, p = 0.046). In conclusion, following successful PCI with DES, 2-year MACE rates are increased in patients with both hypertension and residual HPR on clopidogrel. HPR had a greater effect on the risk of adverse events among patients with versus without hypertension.

Derivation and external validation of a novel risk score for prediction of 30-day mortality after percutaneous coronary intervention.

Early mortality after percutaneous coronary intervention (PCI) is relatively rare. Current risk prediction models for this event are outdated. We sought to derive a 30-day mortality risk score after PCI. The score was derived from a pooled database of 21 randomised clinical trials using a logistic regression model incorporating clinical and angiographic variables. The score was validated in a separate unrestricted study population, the Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents (ADAPT-DES) registry. Of 32,882 eligible patients, 75% had data for all 19 variables used for score derivation. The independent predictors of 30-day mortality were age, presentation with ACS, diabetes mellitus, use of first-generation drug-eluting stents, left main or left anterior descending artery lesion, prior myocardial infarction (MI), and suboptimal flow in the artery before or after PCI. The median [interquartile range] score in the derivation cohort was 5 [3, 6] and overall mortality was 0.49%, ranging from 0.08% to 1.64% with scores of 0-16. The 30-day mortality rate was approximately tenfold higher in patients with a score at or above versus below the median of 5 (0.86% versus 0.08%, p<0.0001). Discrimination in both cohorts was very good (C statistic=0.848 and 0.828, respectively), and calibration was satisfactory. A novel risk score incorporating eight readily available clinical and angiographic variables had high discrimination for 30-day death after PCI across a wide range of clinical scenarios.

Adverse events in patients with high platelet reactivity following successful chronic total occlusion PCI: The Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study

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.

Prediction of Ischemic and Bleeding Events Using the Dual Antiplatelet Therapy Score in an Unrestricted Percutaneous Coronary Intervention Population.

The dual antiplatelet therapy (DAPT) risk score was developed from the DAPT trial to inform the optimal duration of DAPT after percutaneous coronary intervention. We assessed the performance of the DAPT score in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with drug-eluting stents) all-comers registry and tested the utility of additional predictors of adverse events. Outcomes between 1 and 2 years were examined according to DAPT score ≥2 versus <2, adjusted for DAPT continuation as a time-dependent variable. To assess the incremental utility of variables not included in the DAPT score, baseline high platelet reactivity was added to the ischemia model, and high platelet reactivity, baseline hemoglobin, and warfarin use 1 year after percutaneous coronary intervention were added to the bleeding model. Among 8582 patients enrolled in ADAPT-DES, 5397 were event-free after 1 year. Between 1 and 2 years, ischemic (myocardial infarction or stent thrombosis) and bleeding events occurred in 75 (1.5%) and 124 (2.3%) patients, respectively. Patients with higher DAPT scores (≥2 versus <2) had higher rates of myocardial infarction or stent thrombosis (1.9% versus 1.1%; P=0.01) and similar rates of bleeding (2.2% versus 2.4%, respectively; P=0.79). For the prediction of myocardial infarction or stent thrombosis, bleeding and death, DAPT score ≥2 had sensitivities of 57%, 41%, and 56%, respectively; specificities of 58%, 57%, and 58%, respectively; positive predictive values of 1.9%, 2.2%, and 2.1%, respectively; and negative predictive values of 99%, 98%, and 99%, respectively. Addition of baseline high platelet reactivity to the DAPT score did not improve discrimination for ischemic events. Addition of high platelet reactivity and 2 other bleeding covariates to the DAPT score marginally improved discrimination. In ADAPT-DES, the DAPT score was predictive of ischemic events between 1 and 2 years after drug-eluting stents. Prediction of bleeding improved marginally after addition of variables not incorporated in the DAPT score.

Platelet Reactivity and Risk of Ischemic Stroke After Coronary Drug-Eluting Stent Implantation: From the ADAPT-DES Study

ObjectivesThe authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation. BackgroundThe association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. MethodsIncidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation. ResultsAmong 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001). ConclusionsHigher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)

Sex differences in the effect of diabetes mellitus on platelet reactivity and coronary thrombosis: From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents (ADAPT-DES) study

BackgroundWhether the consequences of diabetes mellitus (DM) are worse for women than for men treated with drug-eluting stents (DES) and antiplatelet therapy remain unclear. MethodsPatients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were stratified according to sex and DM status. We investigated the sex-specific effect of DM on high on-clopidogrel platelet reactivity (HPR), defined as a P2Y12 reaction units ≥208, and the adjusted association of DM on the 2-year risk for coronary thrombotic events (CTE), defined as spontaneous myocardial infarction or definite or probable stent thrombosis. ResultsOut of 8582 patients included in the study, 829 were women with DM (9.6%) and 1954 were men with DM (16.2%). The prevalence of insulin-treated DM (ITDM) was greater in women (p<0.0001). By multivariable logistic regression, DM was associated with a greater likelihood of HPR that was uniform between sexes (pint=0.88). Following adjustment for baseline variables and HPR, in women a stepwise increase in risk for CTEs was observed in the transition from no DM to non–ITDM (NITDM) (adjusted hazard ratio [adjHR]: 1.31; 95% CI: 0.78–2.18) to ITDM (adjHR: 2.69; 95% CI: 1.23–3.45). This increase in risk associated with subtypes of DM was of smaller magnitude in men (for NITDM, adjHR: 1.04; 95% CI: 0.77–1.39; for ITDM, adjHR: 1.46; 95% CI: 1.05–2.03; pint=0.016). ConclusionsIn a population treated with DES and antiplatelet therapy, the risk for CTE associated with DM seems to be greater in women and was independent of HPR.

Comparison of plaque morphology between peripheral and coronary artery disease (from the CLARITY and ADAPT-DES IVUS substudies)

The aim of this study was to help understand the different outcomes when treating peripheral arterial disease (PAD) versus coronary artery disease (CAD). We compared plaque morphology between PAD and CAD using intravascular ultrasound. Complete Lesion Assessment with ffR and IVUS TechnologY (CLARITY) was a prospective, multicenter trial that enrolled 50 PAD patients with a lower extremity wound fed by a tibial or a peroneal artery with diameter stenosis more than 50%. Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents (ADAPT-DES) was a prospective, multicenter, registry that enrolled 8582 CAD patients. We compared preintervention intravascular ultrasound findings in 42 PAD lesions from CLARITY versus 79 matched CAD lesions from ADAPT-DES. Compared with CAD lesions, PAD lesions had (i) smaller mean vessel, plaque, and lumen volumes; (ii) twice the lesion length; (iii) greater maximum superficial calcium arc and plaque eccentricity (i.e. there was more concentric plaque) measured at the minimum lumen area site; (iv) calcium arc and plaque eccentricity were positively correlated to plaque burden in both PAD and CAD lesions; and (v) calcium arc and the presence of concentric plaque were greater in PAD compared with CAD independent of the degree of plaque burden. Compared with CAD lesions, PAD lesions in a tibial or a peroneal artery were longer; had more concentric, diffuse, and calcified plaque; and had smaller vessel volumes.

Impact of Aspirin and Clopidogrel Hyporesponsiveness in Patients Treated With Drug-Eluting Stents: 2-Year Results of a Prospective, Multicenter Registry Study

ObjectivesIn this analysis of 2-year outcomes in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) study, the authors sought to examine the independent associations between platelet reactivity to both aspirin and clopidogrel and subsequent outcomes. BackgroundThe relationship between platelet reactivity and long-term adverse events following implantation of drug-eluting stents (DES) has been incompletely characterized. MethodsThe ADAPT-DES study was a multicenter registry of patients undergoing routine platelet function testing following percutaneous coronary intervention with DES. The primary study endpoint was definite or probable stent thrombosis (ST); other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. ResultsA total of 8,582 patients were enrolled between 2008 and 2010; 46.3% of patients were on dual antiplatelet therapy at 2 years without discontinuation. At 2 years, definite or probable ST occurred in 92 patients (1.07%). In patients treated with dual antiplatelet therapy continuously for 2 years, high platelet reactivity on clopidogrel was independently associated with definite or probable ST (adjusted hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.27 to 3.67; p = 0.003), myocardial infarction (adjusted HR: 1.35; 95% CI: 1.05 to 1.74; p = 0.02), freedom from clinically relevant bleeding (adjusted HR: 0.74; 95% CI: 0.62 to 0.90; p = 0.002), and all-cause mortality (adjusted HR: 1.36; 95% CI: 1.01 to 1.85; p = 0.04). Between years 1 and 2, high platelet reactivity was not associated with the very late ST and in patients on aspirin monotherapy, aspirin hyporesponsiveness was not associated with adverse outcomes. ConclusionsThe present study confirms the strong relationship of high platelet reactivity on clopidogrel to 2-year ischemic and bleeding outcomes after DES. The majority of stent-related events occurred within the first year.

Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study)

Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

Platelet Reactivity and Clinical Outcomes After Coronary Artery Implantation of Drug-Eluting Stents in Subjects With Peripheral Arterial Disease: Analysis From the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

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. 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. 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. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

The Impact of Timing of Ischemic and Hemorrhagic Events on Mortality After Percutaneous Coronary Intervention: The ADAPT-DES Study.

The aim of this study was to understand the impact of the timing of ischemic and hemorrhagic events after percutaneous coronary intervention (PCI) with drug-eluting stents on subsequent mortality. These events have been strongly associated with subsequent death. In the multicenter, prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents) study, patients at 11 clinical sites with successful PCI with drug-eluting stents underwent assessment of platelet function and were followed for 2 years. Events occurring after PCI-definite or probable stent thrombosis (ST), myocardial infarction (MI) not related to ST, and clinically relevant bleeding (CB)-were classified as early (≤30 days), late (31 to 365days), or very late (>365 days). Mortality within 30 days of each event was estimated by Kaplan-Meier methodology. Cox regression multivariate modeling was used to analyze the relationship between each event (as a time-updated variable) and mortality over the entire study period. Among 8,582 patients, 1,060 (12.4%) had events-691 (8.1%) had CB, 294 (3.4%) had MI, and 75 (0.9%) had ST-and 7,522 (87.6%) had no events. The highest risk was associated with early ST (38.5% mortality at 30 days after the event), whereas very late MI (7.5%) and late CB (7.3%) were less dangerous. By multivariate analysis, each event was independently predictive of death, with hazard ratios of 2.4, 1.8, and 11.4, respectively (p< 0.0001). Approximately 1 in 8 patients successfully undergoing PCI with drug-eluting stents had CB, MI, or ST during the ensuing 2 years. These events are associated with an increased hazard of mortality, particularly within the first 30 days following the event, warranting efforts to prevent their occurrence.

Prevalence and Clinical Impact of Tissue Protrusion After Stent Implantation

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 whomsome 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-termclinical outcomes, in part because of greater stent expansion in lesions with TP.

Prevalence, Features, and Prognostic Importance of Edge Dissection After Drug-Eluting Stent Implantation: An ADAPT-DES Intravascular Ultrasound Substudy.

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.

Coronary Thrombosis and Major Bleeding After PCI With Drug-Eluting Stents: Risk Scores From PARIS

BackgroundDual-antiplatelet therapy with aspirin and clopidogrel after percutaneous coronary intervention reduces the risk for coronary thrombotic events (CTEs) at the expense of increasing risk for major bleeding (MB). Metrics to accurately predict the occurrence of each respective event and inform clinical decision making are lacking. ObjectivesThe aim of this study was to develop and validate separate models to predict risks for out-of-hospital thrombotic and bleeding events after percutaneous coronary intervention with drug-eluting stents. MethodsUsing data from 4,190 patients treated with drug-eluting stents and enrolled in the PARIS (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients) registry, separate risk scores were developed to predict CTE (defined as the composite of stent thrombosis or myocardial infarction) and MB (defined as the occurrence of a Bleeding Academic Research Consortium type 3 or 5 bleed). External validation was performed in the ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) registry. ResultsOver 2 years, CTEs occurred in 151 patients (3.8%) and MB in 133 (3.3%). Independent predictors of CTEs included acute coronary syndrome, prior revascularization, diabetes mellitus, renal dysfunction, and current smoking. Independent predictors of MB included older age, body mass index, triple therapy at discharge, anemia, current smoking, and renal dysfunction. Each model displayed moderate levels of discrimination and adequate calibration. ConclusionsSimple risk scores of baseline clinical variables may be useful to predict risks for ischemic and bleeding events after PCI with DES, thereby facilitating clinical decisions surrounding the optimal duration of DAPT. (Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients [PARIS]; NCT00998127)

Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention?: "Window" Analysis From the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents).

This study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation. Patients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes. In the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU). The PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality. In this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).

Etiology, Frequency, and Clinical Outcomes of Myocardial Infarction After Successful Drug-Eluting Stent Implantation: Two-Year Follow-Up From the ADAPT-DES Study.

The frequency, causes, and impact of myocardial infarction (MI) after successful percutaneous coronary intervention have not been well studied. 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<0.001). By multivariable analysis, the adjusted hazard ratio (95% confidence interval) for subsequent mortality during follow-up was 2.17 (1.06, 4.45) in patients with versus without a non-periprocedural MI (P=0.03). 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. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Incidence, Predictors, and Impact of Post-Discharge Bleeding After Percutaneous Coronary Intervention

BackgroundThe incidence, predictors, and prognostic impact of post-discharge bleeding (PDB) after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation are unclear. ObjectivesThis study sought to characterize the determinants and consequences of PDB after PCI. MethodsThe prospective ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) study was used to determine the incidence and predictors of clinically relevant bleeding events occurring within 2 years after hospital discharge. The effect of PDB on subsequent 2-year all-cause mortality was estimated by time-adjusted Cox proportional hazards regression. ResultsAmong 8,582 “all-comers” who underwent successful PCI with DES in the ADAPT-DES study, PDB occurred in 535 of 8,577 hospital survivors (6.2%) at a median time of 300 days (interquartile range: 130 to 509 days) post-discharge. Gastrointestinal bleeding (61.7%) was the most frequent source of PDB. Predictors of PDB included older age, lower baseline hemoglobin, lower platelet reactivity on clopidogrel, and use of chronic oral anticoagulation therapy. PDB was associated with higher crude rates of all-cause mortality (13.0% vs. 3.2%; p < 0.0001). Following multivariable adjustment, PDB was strongly associated with 2-year mortality (hazard ratio [HR]: 5.03; p < 0.0001), with an effect size greater than that of post-discharge myocardial infarction (PDMI) (HR: 1.92; p = 0.009). ConclusionsAfter successful PCI with DES in an unrestricted patient population, PDB is not uncommon and has a strong relationship with subsequent all-cause mortality, greater that that associated with PDMI. Efforts to reduce PDB may further improve prognosis after successful DES implantation. (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794)