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.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

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.

BACKGROUND: Whether the consequences of diabetes mellitus (DM) are worse for women than for men treated with drug-eluting stents (DES) and antiplatelet therapy remain unclear. METHODS: Patients 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. RESULTS: Out 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). CONCLUSIONS: In 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.

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).

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.

Sex Differences in the Clinical Impact of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents: Results From the ADAPT-DES Study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

BACKGROUND: Sex differences in the outcomes after percutaneous coronary intervention with drug-eluting stents and in the response to clopidogrel therapy have been reported; however, the differential risk of high platelet reactivity (HPR) on clopidogrel in women versus men is unknown. METHODS AND RESULTS: We compared 8448 patients enrolled in the ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) according to sex and the presence/absence of HPR on clopidogrel (defined as P2Y12 reactivity units >208). Study end points were definite and probable stent thrombosis (ST), clinically relevant bleeding, all-cause mortality, myocardial infarction, and major adverse cardiac events (comprising mortality, myocardial infarction, and target lesion revascularization). HPR was more common among women (1118/2163, 51.7%) than men (2491/6285, 39.6%). HPR was associated with a roughly double risk of 1-year ST in both women and men (women with versus without HPR: 1.4% versus 0.7%; hazard ratio [HR], 2.02; 95% confidence interval [CI], 0.82-4.95; P=0.12; and men: 1.2% versus 0.5%; HR, 2.42; 95% CI, 1.36-4.30; P=0.002; Pinteraction=0.73). HPR was associated with almost half the rate of clinically relevant bleeding in women (women: HPR versus no HPR, 5.3% versus 9.8%; HR, 0.54; 95% CI, 0.40-0.74; P<0.001), whereas men had similar rates of bleeding regardless of HPR status (men: HPR versus no HPR, 5.7% versus 5.9%; HR, 0.96; 95% CI, 0.78-1.18; P=0.70; Pinteraction=0.003). In propensity-adjusted models, HPR was an independent predictor of ST and myocardial infarction in men; although both associations were nonsignificant among women, no interaction was observed in the associations between HPR and either ST or myocardial infarction. Conversely, HPR was an independent predictor of reduced bleeding only in women (women: adjusted HR, 0.58; 95% CI, 0.41-0.82; P=0.002; and men: adjusted HR, 0.83; 95% CI, 0.65-1.04; P=0.11; Pinteraction=0.01). CONCLUSIONS: In the current analysis, the associated risk of HPR for ST was similar in both sexes. However, HPR was associated with significantly reduced bleeding only among women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Relation Between Renal Function and Coronary Plaque Morphology (from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Virtual Histology-Intravascular Ultrasound Substudy).

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 mm3/mm vs 14.9 mm3/mm, p <0.0001), smaller mean lumen cross-sectional area (5.5 mm3/mm vs 5.8 mm3/mm vs 6.1 mm3/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.

Predictors and Long-Term Clinical Impact of Acute Stent Malapposition: An Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Intravascular Ultrasound Substudy.

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: NCT00638794.

Impact of Anemia on Platelet Reactivity and Ischemic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

Anemic patients remain at increased risk of ischemic and bleeding events. Whether the effects of hemoglobin levels on thrombotic and bleeding risk are independent of platelet reactivity on clopidogrel, however, remains unknown. Patients from the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents study were categorized by the presence of anemia at baseline, defined according the World Health Organization criteria. Platelet reactivity was measured with VerifyNow assay; high platelet reactivity (HPR) on clopidogrel was defined as platelet reactive units value >208. Of 8,413 patients included in the study cohort, 1,816 (21.6%) had anemia. HPR was more prevalent in patients with anemia (58.3% vs 38.4%; p <0.001), an association that persisted after multivariate adjustment (adjusted odds ratio: 2.04; 95% confidence interval [CI]: 1.82 to 2.29; p <0.0001). Patients with anemia had higher 2-year rates of major adverse cardiac events (9.5% vs 5.6%; p <0.0001), major bleeding (11.8% vs 7.7%; p <0.0001), and all-cause mortality (4.0% vs 1.4%; p <0.0001); however, after adjustment for baseline clinical confounders, including HPR, anemia was no longer significantly associated with major adverse cardiac events but was still independently associated with all-cause mortality (adjusted HR 1.61, 95% CI 1.23 to 2.12; p <0.0001) and major bleeding (adjusted HR 1.42, 95% CI 1.20 to 1.68; p <0.0001). The effect of HPR on clinical outcomes was uniform according to anemia status, without evidence of interaction. In conclusion, anemia independently correlated with HPR. After percutaneous coronary intervention with drug-eluting stents, anemia at baseline was significantly associated with higher 2-year hemorrhagic and mortality risk; conversely, its association with ischemic risk was attenuated after multivariate adjustment, including HPR.

Relation Between Platelet Count and Platelet Reactivity to Thrombotic and Bleeding Risk: From the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents Study.

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.

Relationship Between Platelet Reactivity and Culprit Lesion Morphology: An Assessment From the ADAPT-DES Intravascular Ultrasound Substudy.

OBJECTIVES: This study evaluated the relationship between platelet reactivity and plaque morphology using grayscale and radiofrequency intravascular ultrasound (IVUS) virtual histology (VH). BACKGROUND: Recent studies have reported that high on-treatment platelet reactivity (HPR) is associated with higher plaque volume and the presence of multivessel disease; however, the association between HPR and plaque morphology has not been evaluated. METHODS: The ADAPT-DES (Dual AntiPlatelet Therapy With Drug Eluting Stents) intravascular ultrasound substudy was a prospective, multicenter, observational study of 8,582 patients undergoing percutaneous coronary intervention with drug-eluting stents in whom platelet reactivity on clopidogrel was assessed routinely. The current analysis included 909 culprit lesions from 773 patients with pre-intervention grayscale IVUS and IVUS-VH. HPR was defined as platelet reactivity >208 P2Y12 reaction unit in point-of-care P2Y12 testing by the VerifyNow assay, measured during steady-state platelet inhibition in patients receiving an antiplatelet agent. RESULTS: HPR was associated with 3-vessel coronary artery disease (31.0% vs. 24.4%; p = 0.04). The incidence of fibroatheroma was higher in patients with HPR than those without HPR (77.1% vs. 68.9%; p = 0.01). The HPR group had larger percent plaque and media volume (plaque and media/external elastic membrane volume: 58.1% [95% confidence interval (CI): 57.1% to 59.0%] vs. 56.6% [95% CI: 55.8% to 57.5%]; p = 0.03) and plaque burden at the minimum lumen site (76.7% [95% CI: 75.7% to 77.8%] vs. 75.0% [95% CI: 74.0% to 76.0%]; p = 0.02). Despite a similar prevalence of attenuated plaque, patients with HPR had longer culprit lesion attenuated plaque length (8.0 [95% CI: 7.0 to 9.1] mm vs. 6.5 [95% CI: 5.9 to 7.1] mm; p = 0.01). On multivariate analysis, the presence of angiographic calcium (odds ratio [OR]: 1.85: 95% CI: 1.33 to 2.56; p = 0.0002) and HPR (OR: 1.45; 95% CI: 1.05 to 2.01; p = 0.02) were independent predictors for a culprit lesion fibroatheroma. CONCLUSIONS: HPR was associated with increased culprit lesion atherosclerotic burden and adverse plaque morphology among patients undergoing percutaneous coronary intervention. Platelet reactivity might be associated with not only blood clot formation, but also severity of atherosclerosis. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794).

Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry.

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<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. 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.

Effect of obesity on coronary atherosclerosis and outcomes of percutaneous coronary intervention: grayscale and virtual histology intravascular ultrasound substudy of assessment of dual antiplatelet therapy with drug-eluting stents.

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.

Sex-based differences in bleeding and long term adverse events after percutaneous coronary intervention for acute myocardial infarction: three year results from the HORIZONS-AMI trial.

BACKGROUND: Studies have shown sex-based disparities in ST-segment elevation myocardial infarction (STEMI) management and prognosis. We sought to compare women and men undergoing primary percutaneous coronary intervention (PCI) for STEMI in a large, prospective, contemporary context. METHODS: The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial randomized 3,602 patients (23.4% women and 76.6% men) with STEMI presenting within 12 hr of onset of symptoms to bivalirudin or heparin plus glycoprotein IIb/IIIa inhibitors and to PCI with drug-eluting or bare metal stents. RESULTS: Compared with men, women presented later after symptom onset and were more often treated with medical management alone (6.9% vs. 4.7%; P = 0.01). Women had significantly higher rates of 3-year major adverse cardiac events (MACE) and major bleeding. After adjusting for baseline differences, female sex remained an independent predictor of major bleeding (hazard ratio [HR] 1.81, 95% confidence interval [CI] 1.41-2.33; P < 0.0001) but not of MACE (HR 1.09; 95% CI 0.91-1.32; P = 0.35). CONCLUSIONS: This study found that women with STEMI are at increased risk of bleeding as compared to men. While female sex may not directly contribute to increased risk of MACE, it is, however, associated with the presence of comorbidities that increase the risk of ischemic events long-term. Further dedicated studies are needed to confirm these findings and to assess strategies to optimize both the initial emergent treatment and long-term management in this high-risk subset. © 2014 Wiley Periodicals, Inc.

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).

OBJECTIVES: 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. BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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).

Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: the assessment of dual antiplatelet therapy with drug-eluting stents (ADAPT-DES) study.

BACKGROUND: Prior small to modest-sized studies suggest a benefit of intravascular ultrasound (IVUS) guidance in noncomplex lesions. Whether IVUS guidance is associated with improved clinical outcomes after drug-eluting stent (DES) implantation in an unrestricted patient population is unknown. METHODS AND RESULTS: Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter, nonrandomized "all-comers" study of 8583 consecutive patients at 11 international centers designed to determine the frequency, timing, and correlates of stent thrombosis and adverse clinical events after DES. Propensity-adjusted multivariable analysis was performed to examine the relationship between IVUS guidance and 1-year outcomes. IVUS was utilized in 3349 patients (39%), and larger-diameter devices, longer stents, and/or higher inflation pressures were used in 74% of IVUS-guided cases. IVUS guidance compared with angiography guidance was associated with reduced 1-year rates of definite/probable stent thrombosis (0.6% [18 events] versus 1.0% [53 events]; adjusted hazard radio, 0.40; 95% confidence interval, 0.21-0.73; P=0.003), myocardial infarction (2.5% versus 3.7%; adjusted hazard radio, 0.66; 95% confidence interval, 0.49-0.88; P=0.004), and composite adjudicated major adverse cardiac events (ie, cardiac death, myocardial infarction, or stent thrombosis) (3.1% versus 4.7%; adjusted hazard radio, 0.70; 95% confidence interval, 0.55-0.88; P=0.002). The benefits of IVUS were especially evident in patients with acute coronary syndromes and complex lesions, although significant reductions in major adverse cardiac events were present in all patient subgroups those with including stable angina and single-vessel disease. CONCLUSIONS: In ADAPT-DES, the largest study of IVUS use to date, IVUS guidance was associated with a reduction in stent thrombosis, myocardial infarction, and major adverse cardiac events within 1 year after DES implantation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Variation in hospital length of stay in patients with acute myocardial infarction undergoing primary angioplasty and the need to change the diagnostic-related group system.

Our findings show significant variation in length of hospital stay among patients with acute myocardial infarction treated with primary percutaneous coronary intervention; length of stay can be predicted from baseline clinical and angiographic characteristics. Our investigation suggests the need for a multi-tier diagnostic-related group system for patients with acute myocardial infarction treated with percutaneous coronary intervention.