On-Treatment Platelet Reactivity and Ischemic Outcomes in Patients With Diabetes Mellitus: Two-Year Results From ADAPT-DES.

Background Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR-associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. 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. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point-of-care assay. Cox multivariable analysis was used to assess whether HPR-associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin-treated diabetes mellitus (ITDM), non-ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2-year rates of MACE in patients with and without diabetes mellitus (Pinteraction=0.36). A significant interaction was present between HPR and non-insulin-treated diabetes mellitus versus ITDM for 2-year MACE (adjusted hazard ratio [HR] for non-ITDM, 2.28 [95% CI, 1.39-3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70-1.50]; Pinteraction=0.01). Conclusions HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower-risk non-ITDM patients than in higher-risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).

Genotype-Guided Use of P2Y12 Inhibitors: A Review of Current State of the Art.

The pharmacodynamics of the purinergic receptor type Y, subtype 12 (P2Y12) inhibitors has evolved. Our understanding of the metabolism of P2Y12 inhibitors has revealed polymorphisms that impact drug metabolism and antiplatelet efficacy, leading to genetic testing guided therapy. In addition, assays of platelet function and biochemistry have provided insight into our understanding of the efficacy of "antiplatelet" therapy, identifying patients with high or low platelet reactivity on P2Y12 therapy. Despite the data, the implementation of these testing modalities has not gained mainstream adoption across hospital systems. Given differences in potency between the three clinically available P2Y12 inhibitors, the balance between thrombotic and bleeding complications must be carefully considered, especially for the large proportion of patients at higher risk for bleeding. Here we review the current data for genetic and functional testing, risk assessment strategies, and guidelines for P2Y12 inhibitors guided therapy.

Right Ventricular Myocardial Infarction Complicated by Cardiac Arrest: Utilization of Extracorporeal Membrane Oxygenation.

A 44-year-old male with an out-of-hospital cardiac arrest due to an acute left ventricular (LV) inferoposterior wall myocardial infarction (MI) involving the right ventricle (RV) is presented. This case highlights the challenges in the management of patients with cardiac arrest, indications for use of ventricular assist devices, potential effects of LV assist devices on the RV in the setting of RV MI, and culprit versus complete coronary artery revascularization in these patients.

Inherited Variants in SCARB1 Cause Severe Early-Onset Coronary Artery Disease.

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

OBJECTIVES: 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). BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 P2Y12 inhibition after MI, especially within the first 30 days after stent implantation.

Extracorporeal Cardiopulmonary Resuscitation (ECPR) for Out-of-Hospital Cardiac Arrest due to Pulseless Ventricular Tachycardia/Fibrillation.

BACKGROUND: Survival rates for out-of-hospital cardiac arrest are very low and neurologic recovery is poor. Innovative strategies have been developed to improve outcomes. A collaborative extracorporeal cardiopulmonary resuscitation (ECPR) program for out-of-hospital refractory pulseless ventricular tachycardia (VT) and/or ventricular fibrillation (VF) has been developed between The Ohio State University Wexner Medical Center and Columbus Division of Fire. METHODS: From August 15, 2017, to June 1, 2019, there were 86 patients that were evaluated in the field for cardiac arrest in which 42 (49%) had refractory pulseless VT and/or VF resulting from different underlying pathologies and were placed on an automated cardiopulmonary resuscitation device; from these 42 patients, 16 (38%) met final inclusion criteria for ECPR and were placed on extracorporeal membrane oxygenation (ECMO) in the cardiac catheterization laboratory (CCL). RESULTS: From the 16 patients who underwent ECPR, 4 (25%) survived to hospital discharge with cerebral perfusion category 1 or 2. Survivors tended to be younger (48.0 ± 16.7 vs. 59.3 ± 12.7 years); however, this difference was not statistically significant (p=0.28) likely due to a small number of patients. Overall, 38% of patients underwent percutaneous coronary intervention (PCI). No significant difference was found between survivors and nonsurvivors in emergency medical services dispatch to CCL arrival time, lactate in CCL, coronary artery disease severity, undergoing PCI, and pre-ECMO PaO2, pH, and hemoglobin. Recovery was seen in different underlying pathologies. CONCLUSION: ECPR for out-of-hospital refractory VT/VF cardiac arrest demonstrated encouraging outcomes. Younger patients may have a greater chance of survival, perhaps the need to be more aggressive in this subgroup of patients.

Extracorporeal Cardiopulmonary Resuscitation for Management of Out-of-Hospital Cardiac Arrest in a Patient with Fulminant Myocarditis.

A 68-year-old male with a witnessed out-of-hospital cardiac arrest while jogging who was managed with extracorporeal cardiopulmonary resuscitation (ECPR) is presented. The patient was found to be in refractory ventricular fibrillation by emergency medical service personnel and underwent advanced cardiac life support (ACLS) protocol with placement of an automated chest compression device. He was emergently transported to the cardiac catheterization laboratory. Due to refractory ventricular fibrillation, he was placed on venoarterial extracorporeal membranous oxygenation (VA-ECMO). Coronary angiography at that time showed nonobstructive coronary artery disease. Management with VA-ECMO and other supportive measures were continued for 5 days, after which a cardiac magnetic resonance imaging was performed with findings consistent with acute myocarditis. His condition substantially improved, and he was discharged from the hospital with good neurologic and functional status. Fulminant myocarditis is often fatal, but aggressive supportive measures with novel ECPR protocols may result in recovery, as it happened in this case.

Floppy mitral valve/mitral valve prolapse: A complex entity with multiple genotypes and phenotypes.

Floppy mitral valve/mitral valve prolapse (FMV/MVP) is a common valvular abnormality affecting 2% to 3% of the general population. It occurs in a heterogeneous group of patients with varying and age dependent expressions. FMV/MVP can be familial or sporadic, isolated (called non-syndromic) or as a part of a well-defined syndrome of heritable connective tissue disorders or other diseases. A wide range of phenotypic expression exists ranging from asymptomatic to non-specific symptoms related to neuroendocrine or autonomic nervous system functional abnormalities, varying degrees of mitral regurgitation that may require interventional therapy, heart failure, infective endocarditis, cardiac arrhythmias and/or sudden cardiac death. FMV/MVP is predominantly considered a heritable disorder with clinical manifestations not present at birth, but appearing later in life. Though a variant gene may initiate the development of FMV/MVP, precise phenotypic expression may be related to multiple other molecular, genetic and epigenetic factors that modify the final expression of the disease. A better understanding of these mechanisms will help to better define the natural history of the disease, inhibit disease progression and even prevent the phenotypic expression of FMV/MVP.

Impact of high on-treatment platelet reactivity on outcomes following PCI in patients on hemodialysis: An ADAPT-DES substudy.

OBJECTIVES: We sought to compare clinical outcomes after percutaneous coronary intervention (PCI) in patients on versus not on hemodialysis (HD) and examine whether high on-treatment platelet reactivity (HPR) further impacts outcomes among patients on HD. BACKGROUND: Both chronic kidney disease (CKD) and HPR are predictors of major adverse cardiac events (MACE) after PCI. METHODS: Two-year outcomes of patients from the prospective, multicenter ADAPT-DES study (N = 8,582) were analyzed according to HD status at enrollment. All patients underwent platelet function testing with the VerifyNow assay; HPR on clopidogrel was defined as P2Y12 reaction units (PRU) >208. RESULTS: Compared with non-HD patients, patients on HD (n = 85) had significantly higher baseline PRU (median 254 vs. 188, p = .001) and more frequently had HPR (61.7% vs. 42.5%, p < .001). HD was associated with increased 2-year rates of MACE (death, myocardial infarction (MI) or definite stent thrombosis (ST); 23.4% vs. 10.7%, p < .001). HD was also strongly associated with 2-year overall mortality, cardiac death, MI, target vessel revascularization, major bleeding, stroke and ST. Following adjustment for HPR and other covariates, HD was independently associated with overall mortality, MI, ST, and major bleeding at 2 years. The relationship between HD status and 2-year MACE was consistent in patients with and without HPR (Pinteraction = .78). CONCLUSIONS: Nearly two-thirds of patients on HD exhibited HPR on clopidogrel, and both HD and HPR were independently associated with 2-year adverse outcomes after DES implantation. However, the deleterious impact of HD on clinical outcomes was present in both patients with and without HPR.

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.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

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.

Relationship Between Intravascular Ultrasound Guidance and Clinical Outcomes After Drug-Eluting Stents.

Background In the large-scale ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents), drug-eluting stent implantation with intravascular ultrasound (IVUS) guidance was associated with a reduction in 1-year rates of stent thrombosis, myocardial infarction (MI), and major adverse cardiac events (cardiac death, MI, or stent thrombosis) compared with angiography guidance alone. We assessed whether the benefits of IVUS guidance were maintained, reduced, or increased at 2 years. Methods and Results ADAPT-DES was a prospective, multicenter, nonrandomized all-comers study of 8582 consecutive patients at 11 US and German sites designed to determine the frequency, timing, and correlates of adverse events after drug-eluting stents. Propensity-adjusted multivariable analysis was performed to examine the impact of IVUS guidance on 2-year outcomes. IVUS guidance (n=3361; 39%) compared with angiography guidance (n=5221; 61%) was associated with reduced 2-year adjudicated rates of (1) major adverse cardiac events (cardiac death, MI, or stent thrombosis; 4.9% versus 7.5%; adjusted hazard ratio, 0.72; 95% CI, 0.59-0.89; P=0.003), (2) definite/probable stent thrombosis (0.55% versus 1.16%; adjusted hazard ratio, 0.40; 95% CI, 0.22-0.73; P=0.003), and (3) MI (3.5% versus 5.6%; adjusted hazard ratio, 0.65; 95% CI, 0.51-0.83; P=0.0006). By landmark analysis, IVUS guidance compared with angiography guidance was also associated with significantly reduced rates of major adverse cardiac events, MI, stent thrombosis, and clinically driven target lesion revascularization between 1 and 2 years after drug-eluting stent implantation. The number needed to treat with IVUS guidance to prevent 1 major adverse cardiac event was reduced from 64 (42-137) at 1 year to 41 (29-69) at 2 years. Conclusions In ADAPT-DES, the early improvement in event-free survival after drug-eluting stent implantation with IVUS guidance compared with angiography guidance was further increased with longer term follow-up to 2 years. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00638794.

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

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

Impact of high on-aspirin platelet reactivity on outcomes following successful percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Whether high on-aspirin platelet reactivity (HAPR) confers an increased risk of adverse outcomes after percutaneous coronary intervention (PCI) remains unclear. We sought to examine the specific relationship between HAPR and clinical outcomes in ADAPT-DES. METHODS: A total of 8,526 "all-comer" patients in the ADAPT-DES registry who underwent placement of drug-eluting stents (DES) and were treated with aspirin and clopidogrel were assessed to measure platelet reactivity. HAPR was characterized as ≥550 aspirin reaction units and high on-clopidogrel platelet reactivity as >208 P2Y12 reaction units. Univariable and propensity-adjusted multivariable analyses were used to assess the relationship between HAPR and clinical outcomes. RESULTS: HAPR was present in 478 (5.6%) patients. Patients with HAPR were older and had more comorbid illnesses and more complex coronary anatomy. During 2-year follow-up, HAPR was not associated with increased rates of major adverse cardiac events (MACE), stent thrombosis, myocardial infarction, or all-cause mortality. In propensity-adjusted multivariable analyses, HAPR was not an independent predictor of MACE after successful PCI (multivariable adjusted hazard ratio: 1.04; 95% CI 0.64-1.69, P = .87). Nor was HAPR associated with reduced bleeding. Even among patients with concomitant high on-clopidogrel platelet reactivity, HAPR was not associated with worse ischemic outcomes (adjusted hazard ratio for 2-year MACE: 1.06; 95% CI 0.55-2.00, P = .87). CONCLUSIONS: HAPR was infrequently present in a large registry of patients undergoing PCI. There was no clear relationship between HAPR and 2-year clinical outcomes. Investigations of antiplatelet regimens without aspirin after DES implantation are ongoing and should inform future management of patients undergoing PCI.

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

OBJECTIVES: The 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. BACKGROUND: The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear. METHODS: Incidence, 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. RESULTS: Among 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). CONCLUSIONS: Higher 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).

Bleeding Complications Related to Right Heart Catheterization in the Setting of Elevated INR.

OBJECTIVES: Right heart catheterization (RHC) provides cardiovascular hemodynamic information in a variety of clinical settings. RHC performed in the setting of coagulopathy may have the potential to increase bleeding complications; however, data currently are limited. This study was undertaken to determine bleeding complications during RHC with an elevated international normalized ratio (INR) value. METHODS: A total of 312 patients who underwent RHC were retrospectively studied. Patients were divided into two groups: INR <1.8 (257 patients; median INR, 1.2; range, 0.8-1.7) and INR ≥1.8 (55 patients; median INR, 2.1; range, 1.8-4.0). There were 80 patients (31.1%) and 46 patients (83.6%) taking oral vitamin K antagonist (warfarin) in the INR <1.8 and ≥1.8 groups, respectively. RESULTS: Overall bleeding complications related to the procedure were extremely low, occurring in 2 patients (0.6%). All bleeding complications occurred in the INR <1.8 group, and both patients developed a small-sized hematoma requiring prolonged manual pressure without further intervention (0.8% vs 0.0% in the INR <1.8 vs INR ≥1.8 groups, respectively; P>.99). CONCLUSION: Bleeding complications associated with RHC were extremely low when performed by experienced operators in the cardiac catheterization laboratory. Furthermore, these complications were not related to an elevated INR, as bleeding occurred in patients with INR <1.8. Performing RHC in patients with an elevated INR in the therapeutic range did not increase bleeding compared to lower INR values.

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.

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

OBJECTIVES: In 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. BACKGROUND: The relationship between platelet reactivity and long-term adverse events following implantation of drug-eluting stents (DES) has been incompletely characterized. METHODS: The 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. RESULTS: A 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. CONCLUSIONS: The 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.