Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Incidence and predictors of radial artery occlusion following transradial coronary angiography: the proRadial trial.

OBJECTIVES: This study investigated the contemporary incidence and predictors of radial artery occlusion as well as the effectiveness of antithrombotic treatment for radial artery occlusion following transradial coronary angiography. BACKGROUND: The radial artery is the standard access for coronary angiography and even complex interventions. Postprocedural radial artery occlusion is still a common and significant complication. METHODS: This prospective study enrolled 2004 patients following transradial coronary angiography. After sheath removal, hemostasis was obtained in a standardized fashion. Radial artery patency was evaluated by duplex ultrasonography in all patients. In case of occlusion, oral anticoagulation was recommended and patients were scheduled for a 30-day follow-up including Doppler ultrasonography. RESULTS: A new-diagnosed radial occlusion was found in 4.6% of patients. The strongest independent predictors of radial occlusion were female sex and active smoking status. In the subgroup of patients with percutaneous coronary interventions, female sex followed by sheath size > 6 French were the strongest predictors of radial occlusion. 76 of 93 patients with radial occlusion received an oral anticoagulation for 30 days. However, reperfusion at 30 days was found in 32% of patients on oral anticoagulation. CONCLUSION: The incidence of radial artery occlusion following coronary angiography in contemporary practice appears with 4.6% to be lower as compared to previous cohorts. Female sex and smoking status are the strongest independent predictors of radial occlusion followed by procedural variables. The limited effectiveness of oral anticoagulation for treatment of radial artery occlusion suggests a primarily traumatic than thrombotic mechanism of this complication.

Impact of On-Clopidogrel Platelet Reactivity on Incidence of Peri-Interventional Bleeding in Patients Undergoing Transcatheter Aortic Valve Implantation.

Dual anti-platelet therapy (DAPT) with clopidogrel and acetylsalicylic acid (ASA) has previously been recommended after transcatheter aortic valve implantation (TAVI) and is still the standard of care in patients who underwent coronary stent placement within 3 months prior to TAVI. This study sought to evaluate whether on-treatment platelet reactivity is a predictor for the occurrence of bleeding events after TAVI. This study enrolled 484 patients undergoing TAVI from November 2013 until April 2018. Patients were either on long-term DAPT with clopidogrel and ASA or received loading doses of both drugs before TAVI, reflecting the standard of care at the time of the patient's enrollment. Platelet reactivity was determined by multi-electrode impedance aggregometry before TAVI, at days 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification. Bleeding events were seen in 199 (41.1%) patients. The most frequent were BARC 2 bleeding cases (24.2%), followed by BARC 1 (6.0%), BARC 3b (5.2%), and BARC 3a (4.5%) cases. Low on-clopidogrel platelet reactivity before TAVI was present in 243 patients, of which 44.4% had a bleeding event. In contrast, the incidence of bleeding was 30.5% in the 95 patients with high on-clopidogrel platelet reactivity. Multivariate logistic regression analysis identified low/normal/high on-clopidogrel platelet reactivity (OR: 0.533; CI: 0.309-0.917; p = 0.023) and use of oral anticoagulation (OR: 1.766; CI: 1.209-2.581; p = 0.003) as strongest predictors for peri-interventional bleeding events. These findings support current recommendations advocating against the routine use of dual antiplatelet therapy following TAVI.

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p < 0.001) and more extensive coronary artery disease (p = 0.001). Results for intrinsic (p = 0.80) and on-clopidogrel platelet reactivity (p = 0.81) did not differ between quartiles of Lp(a) levels. Flow cytometry analyses of expression of different platelet surface proteins (CD41, CD62P or PAC-1) confirmed these findings. Correlation analyses of levels of Lp(a) with any of the tested platelet activation markers did not show any correlation. The present data do not support the hypothesis of an interaction of Lp(a) with platelet reactivity.

Prevalence and Causes of Myocardial Infarction with Non-Obstructive Coronary Arteries in a Contemporary Cohort of Patients with Suspected Myocardial Infarction.

BACKGROUND: A significant proportion of patients presenting with acute myocardial infarction (MI) has no coronary obstruction at coronary angiography and no other obvious non-coronary pathophysiology causing MI. These patients are classified as MI with non-obstructive coronary arteries (MINOCA). Data on incidence and predictors of MINOCA are still limited. METHODS: This study enrolled patients presenting symptoms suggestive of MI and undergoing a comprehensive cardiac work-up including an early invasive strategy. Patients with non-obstructive coronary arteries and without other obvious reasons for MI were scheduled for further work-up including magnetic resonance or intraluminal imaging. MINOCA was diagnosed according to the current European Society of Cardiology guidelines. RESULTS: From the 1532 patients enrolled, 730 had available coronary imaging and 546 were diagnosed with MI. No significant coronary obstructions were found in 117 patients with MI. After the exclusion of 6 patients with acute myocarditis or takotsubo-syndrome as well as 88 with type II MI, 23 patients were diagnosed with MINOCA (4% of all MIs). Among these 23 patients, the most common etiology of MINOCA was thromboembolic events followed by coronary spasm. Female sex, the absence of hypercholesterolemia, and a normal left-ventricular ejection fraction were independently predictive for MINOCA compared to patients with other causes of MI. CONCLUSION: More than 20% of patients presenting with acute MI showed no significant coronary obstruction. About 4% of these patients were diagnosed with MINOCA. Female sex, a lower cardiovascular risk profile, and normal left-ventricular function were predictive for MINOCA.

Long-term results after PCI of unprotected distal left main coronary artery stenosis: the Bifurcations Bad Krozingen (BBK)-Left Main Registry.

AIMS: Percutaneous coronary intervention (PCI) of unprotected distal left main stenosis (UDLM) is increasingly performed as an alternative to surgical treatment. The optimal strategy for stenting in this setting is still a matter of debate. Therefore, this analysis investigated the long-term clinical outcome of a single- versus a double-stenting strategy for treatment of UDLM. METHODS AND RESULTS: From a large registry, 867 consecutive patients with UDLM undergoing either single or double stenting with drug-eluting stents (DES) were identified. Follow-up was up to 10 (median 3.1, interquartile range 1.1-5.3) years. Primary endpoint was MACE consisting of all-cause death, myocardial infarction, or target lesion re-intervention (TLR). Secondary clinical endpoints included these single endpoints and stent thrombosis. MACE occurred in 41.5% after single and in 49.0% after double stenting (P = 0.03). TLR was lower after single (17.4%) as compared to double stenting (27.2%; P < 0.01). Between single and double stenting, there were no significant differences for death (26.4 versus 23.3%; P = 0.31), death or myocardial infarction (29.1 versus 27.2%; P = 0.55), or definite/probable stent thrombosis (1.3 versus 2.1%; P = 0.42). CONCLUSIONS: Compared with single stenting, double stenting was associated with a significantly higher long-term risk of MACE. This was driven by a higher incidence of TLR, whereas the risk of death, MI, or stent thrombosis was similar between the two strategies.

A Randomized Trial to Assess Regional Left Ventricular Function After Stent Implantation in Chronic Total Occlusion: The REVASC Trial.

OBJECTIVES: The aim of this study was to investigate whether percutaneous coronary intervention (PCI) of chronic total occlusions (CTOs) improves left ventricular function. BACKGROUND: The benefit of PCI in CTOs is still controversial. METHODS: Patients with CTOs who were candidates for PCI were eligible for the study and were randomized to PCI or no PCI of CTO. Relevant coexisting non-CTO lesions were treated as indicated. Patients underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary endpoint was the change in segmental wall thickening (SWT) in the CTO territory. Secondary endpoints were improvement of regional wall motion and changes in left ventricular volumes and ejection fraction. Furthermore, major adverse coronary events after 12 months were assessed. RESULTS: The CTO PCI group comprised 101 patients and the no CTO PCI group 104 patients. The change in SWT did not differ between the CTO PCI (4.1% [interquartile range: 14.6 to 19.3]) and no CTO PCI (6.0% [interquartile range: 8.6 to 6.0]) groups (p = 0.57). Similar results were obtained for other indexes of regional and global left ventricular function. Subgroup analysis revealed that only in patients without major non-CTO lesions (basal SYNTAX [Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery] score ≤13) CTO PCI was associated with larger improvement in SWT than no CTO PCI (p for interaction = 0.002). Driven by repeat intervention, major adverse coronary event rates at 12 months were significantly lower in the CTO PCI group (16.3% vs. 5.9%; p = 0.02). CONCLUSIONS: No benefit was seen for CTO PCI in terms of the primary endpoint, SWT, or other indexes of left ventricular function. CTO PCI resulted in clinical benefit over no CTO PCI, as evidenced by reduced major adverse coronary event rates at 12 months.

Impact of Reticulated Platelets on the Antiplatelet Effect of the Intravenous P2Y12-Receptor Inhibitor Cangrelor.

BACKGROUND: Reticulated platelets are associated with impaired antiplatelet response to irreversibly acting P2Y12-receptor inhibitors. However, the impact of reticluated platelets (RP) on the reversibly acting injectable P2Y12-receptor inhibitor cangrelor is unknown. Thus, this study sought to investigate the influence of RP on cangrelor and transitioning strategies to oral P2Y12-receptor inhibitors. METHODS: This study randomized 110 patients undergoing elective percutaneous coronary intervention with use of cangrelor to different oral transitioning strategies loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). ADP-induced platelet reactivity was assessed by impedance aggregometry. Reticulated platelets were analysed by an automated whole blood flow cytometry and described as immature platelet count. RESULTS: There was no correlation of reticulated platelets and ADP-induced platelet reactivity in patients under treatment with cangrelor (r = 0.06, p = 0.47). This finding was consistent in all three transitioning strategies. On day 1 following treatment with cangrelor, the correlation of reticulated platelets and platelet reactivity was detectable again in patients receiving thienopyridines but not ticagrelor (all patients r = 0.37, p < 0.001; clopidogrel: r = 0.59, p = 0.01; prasugrel: r = 0.47, p < 0.001; ticagrelor r = 0.22, p = 0.13). CONCLUSION: Platelet inhibition is not influenced by levels of reticulated platelets during infusion of cangrelor independent of oral P2Y12-receptor inhibitor transitioning strategy. These findings underline the potency of cangrelor as immediate and reversibly acting P2Y12-receptor inhibitor.

Impact of proximal radiopaque coronary bypass graft markers on postbypass surgery coronary angiography.

BACKGROUND: Implantation of radiopaque bypass graft markers during coronary artery bypass surgery (CABG) has the potential of facilitating subsequent coronary angiography. This study sought to investigate the impact of proximal coronary bypass graft markers on angiographic outcomes during subsequent coronary angiography in a large cohort. METHODS AND RESULTS: Between 2005 and 2016, we enrolled 1378 patients (331 with and 1047 without bypass graft markers) with a history of CABG who underwent their first subsequent coronary angiography at our institution. Primary endpoints were radiation time and absolute amount of contrast media used. In unadjusted analyses, radiation time, duration of angiography, dose area product, and the amount of contrast agent were significantly lower in patients with proximal bypass graft markers (P < .001). After full adjustment, proximal coronary bypass graft markers remained a significant predictor for less radiation time and a lower consumption of contrast agent but not for dose area product, which was mainly associated with body mass index and sex. Bypass graft markers were not associated with a lower graft patency. CONCLUSIONS: Radiopaque coronary bypass graft markers can improve the detection of bypass grafts during subsequent coronary angiography and are associated with a lower radiation time and less consumption of contrast agent. Thus, this easy and cost-efficient technique might significantly reduce the risk of coronary angiography after CABG.

Risk of discontinuation of clopidogrel after 1 month following bare-metal stents: a propensity-score adjusted comparison with continued administration of clopidogrel after drug-eluting stents.

In patients at high risk for bleeding undergoing percutaneous coronary intervention (PCI) the use of bare-metal-stent (BMS) is considered an option that allows discontinuation of clopidogrel after 4 weeks. We sought to investigate the risk of early discontinuation of clopidogrel in patients with BMS as compared with a 6-month course of clopidogrel after DES in patients with or without high on-treatment platelet reactivity (HTPR). In 765 consecutive patients undergoing PCI after loading with clopidogrel 600 mg, HTPR was tested by optical aggregometry and defined as residual platelet reactivity > 14%. On top of aspirin 100 mg, patients received clopidogrel 75 mg for 4 weeks after BMS or 6 months after DES. The primary endpoint was all-cause mortality or myocardial infarction (MI) during 1 year. The 1-year incidence of death or MI was 3.5% with BMS (n = 484), 0.9% with DES and no HTPR (n = 211), and 7.1% with DES and HTPR (n = 70; p = 0.03). Landmark analyses for the first 6 months demonstrated that the risk of patients receiving BMS was similar as in patients receiving a DES with HTPR during this period (2.3 vs. 2.9%) but lowest in patients receiving a DES without HTPR (0.5%). The incidence of bleeding was similar in all three groups. These findings did not change after propensity score adjustment for stent type. After discontinuation of clopidogrel at 1 month, patients treated with BMS are at higher risk for death or MI than patients treated with a DES and sufficiently responding to clopidogrel planned for 6 months.ClinicalTrials.gov number NCT00457236.

On-clopidogrel platelet reactivity as predictor for long-term clinical outcome in patients after planned discontinuation of clopidogrel.

It is unknown whether the known association of high on-treatment platelet reactivity (HTPR) with worse clinical outcome in patients on clopidogrel following coronary stent implantation persists after planned discontinuation of clopidogrel. This study investigated the association of HTPR with major ischaemic events after planned discontinuation of clopidogrel. Consecutive patients undergoing elective coronary stent implantation after loading with clopidogrel 600 mg were followed for up to seven years (n=765). Platelet reactivity was tested on day 1 after coronary intervention. Clopidogrel was continued for six months after implantation of drug-eluting stents and for one month if only bare-metal stents were used. The combined primary endpoint was death of any cause or non-fatal myocardial infarction (MACE). HTPR was found in 217 of 765 patients (28 %). During a median follow-up of 5.7 years, the primary endpoint occurred in 145 subjects after planned discontinuation of clopidogrel. Patients with HTPR showed a higher incidence of MACE after discontinuation of clopidogrel. There was a significant interaction of HTPR and time following discontinuation of clopidogrel beyond one year (p for interaction 0.08). Landmark analyses confirmed that the association of HTPR and MACE was only significant within the first year (HR: 2.93, 95 %-CI 1.13-7.60, p=0.03), but not beyond the first year following discontinuation of clopidogrel (HR: 1.19, 95 %-CI 0.82-1.72, p=0.37). In conclusion, patients with HTPR persist to be at high risk for death or myocardial infarction even following planned discontinuation of clopidogrel. However, this association was only significant for the first year following discontinuation of clopidogrel.

Randomized Comparison of Oral P2Y12-Receptor Inhibitor Loading Strategies for Transitioning From Cangrelor: The ExcelsiorLOAD2 Trial.

OBJECTIVES: This randomized trial tested whether early loading with prasugrel can provide sufficient platelet inhibition even when given at the start of a 2-h infusion of cangrelor. BACKGROUND: Effective platelet inhibition with intravenous cangrelor reduces the risk of ischemic complications during percutaneous coronary intervention (PCI). Transitioning to oral therapy with clopidogrel or prasugrel is only recommended after discontinuation of cangrelor due to drug interactions. Given the long half-life of prasugrel, this drug could achieve effective platelet inhibition even when given early under cangrelor and thereby prevent a transient gap in platelet inhibition. METHODS: This trial randomized 110 P2Y12-receptor blocker-naive patients undergoing PCI with use of cangrelor to loading with prasugrel 60 mg or ticagrelor 180 mg at the start of cangrelor (n = 45 each) or loading with clopidogrel 600 mg after discontinuation of cangrelor (n = 20). The primary endpoint was the proportion of patients without high on-treatment platelet reactivity 1 h after stopping cangrelor. RESULTS: The 3 groups were well balanced with respect to clinical parameters. One hour following discontinuation of cangrelor, the primary endpoint was seen in 65.0% of patients on clopidogrel versus 95.6% with ticagrelor and 93.3% with prasugrel (p for superiority of prasugrel vs. clopidogrel = 0.003; p of prasugrel vs. ticagrelor = 0.65). The 30-day incidence of ischemic and bleeding events was similar in all groups. CONCLUSIONS: Prasugrel 60 mg given at the start of a 2-h infusion of cangrelor can provide a sufficient platelet inhibition post-cangrelor. This approach prevents the transient gap in platelet inhibition seen with oral loading after discontinuation of cangrelor. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate - Advanced Loading Strategies [ExcelsiorLOAD2]; DRKS00009739).

Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy.

BACKGROUND: Previous data suggest that reticulated platelets significantly affect antiplatelet response to thienopyridines. It is unknown whether parameters describing reticulated platelets can predict antiplatelet response to thienopyridines. OBJECTIVES: The authors sought to determine the extent to which parameters describing reticulated platelets can predict antiplatelet response to thienopyridine loading compared with established predictors. METHODS: This study randomized 300 patients undergoing elective coronary stenting to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg. Adenosine diphosphate (ADP)-induced platelet reactivity was assessed by impedance aggregometry before loading (intrinsic platelet reactivity) and again on day 1 after loading. Multiple parameters of reticulated platelets were assessed by automated whole blood flow cytometry: absolute immature platelet count (IPC), immature platelet fraction, and highly fluorescent immature platelet fraction. RESULTS: Each parameter of reticulated platelets correlated significantly with ADP-induced platelet reactivity (p < 0.01 for all 3 parameters). In a multivariable model including all 3 parameters, only IPC remained a significant predictor of platelet reactivity (p < 0.001). In models adjusting each of the 3 parameters for known predictors of on-treatment platelet reactivity including cytochrome P450 2C19 (CYP2C19) polymorphisms, age, body mass index, diabetes, and intrinsic platelet reactivity, only IPC prevailed as an independent predictor (p = 0.001). In this model, IPC was the strongest predictor of on-treatment platelet reactivity followed by intrinsic platelet reactivity. CONCLUSIONS: IPC is the strongest independent platelet count-derived predictor of antiplatelet response to thienopyridine treatment. Given its easy availability, together with its even stronger association with on-treatment platelet reactivity compared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred predictor of antiplatelet response to thienopyridine treatment. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102).

Predictors of high-sensitivity cardiac troponin in stable patients undergoing coronary angiography.

AIMS: Elevated levels of high-sensitivity troponin are seen in a significant proportion of stable patients undergoing elective coronary assessment. Multiple variables have been associated with troponin levels. The present analysis sought to identify variables independently associated with elevations of troponin and their relative strength of association with this biomarker. METHODS AND RESULTS: Stable patients undergoing elective coronary angiography and echocardiographic assessment were enrolled. High-sensitivity troponin T (hsTnT) was determined before any diagnostic procedures. Multivariable linear regression models including angiographic and echocardiographic parameters were used to identify independent predictors of levels of troponin and to determine their relative contribution to levels of troponin. Out of 2,046 patients, 15% presented with levels of troponin above the upper reference limit of normal. In a combined analysis, gender followed by renal function, age, left ventricular ejection fraction, diabetes, and left ventricular mass showed the strongest association with levels of troponin. Coronary obstruction was also an independent predictor, but strength of association weakened following adjustment. CONCLUSIONS: Up to 15% of patients undergoing coronary assessment outside the setting of acute coronary syndromes present with elevated levels of cardiac troponin. These changes are independently associated with multiple clinical, laboratory, and imaging variables.

Validation of a P2Y12-receptor specific whole blood platelet aggregation assay.

Testing of P2Y12-receptor antagonist effects can support clinical decision-making. However, most platelet function assays use only ADP as agonist which is not P2Y12-receptor specific. For this reason P2Y12-receptor specific assays have been developed by adding prostaglandin E1 (PGE1) to reduce ADP-induced platelet activation via the P2Y1-receptor. The present study sought to evaluate a P2Y12-receptor specific assay for determination of pharmacodynamic and clinical outcomes. This study enrolled 400 patients undergoing coronary stenting after loading with clopidogrel or prasugrel. ADP-induced platelet reactivity was assessed by whole blood aggregometry at multiple time points with a standard ADP assay (ADPtest) and a P2Y12-receptor specific assay (ADPtest HS, both run on Multiplate Analyzer, Roche Diagnostics). Patients were clinically followed for 1 month and all events adjudicated by an independent committee. In total, 2084 pairs of test results of ADPtest and ADPtest HS were available showing a strong correlation between results of both assays (r = 0.96, p < 0.001). These findings prevailed in multiple prespecified subgroups (e.g., age; body mass index; diabetes). Calculated cutoffs for ADPtest HS and the established cutoffs of ADPtest showed a substantial agreement for prediction of ischemic and hemorrhagic events with a Cohen's κ of 0.66 and 0.66, respectively. The P2Y12-receptor specific ADPtest HS assay appears similarly predictive for pharmacodynamic and clinical outcomes as compared to the established ADPtest assay indicating its applicability for clinical use. Further evaluation in large cohorts is needed to determine if P2Y12-receptor specific testing offers any advantage for prediction of clinical outcome.

Randomized Comparison of Different Thienopyridine Loading Strategies in Patients Undergoing Elective Coronary Intervention: The ExcelsiorLOAD Trial.

OBJECTIVES: This randomized trial investigated to what extent loading with prasugrel can provide a more rapid peri-interventional antiplatelet effect than clopidogrel 600 mg. BACKGROUND: Effective platelet inhibition at the start of a percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. With clopidogrel administered immediately before a PCI, effective platelet inhibition is delayed by 2 h. Prasugrel has the potential of shortening this period. METHODS: We randomly assigned 300 P2Y12 receptor blocker-naive patients undergoing an elective PCI to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg immediately before the PCI. Platelet function was assessed serially by impedance aggregometry. The primary endpoint was the proportion of patients with high on-treatment platelet reactivity at 60 min after loading defined as ≥468 aggregation units × minute (Multiplate Analyzer, Roche Diagnostics, Mannheim, Germany). RESULTS: The 3 groups were well balanced with respect to clinical and angiographic characteristics. At 60 min, 33% of the patients assigned to prasugrel 60 mg, 37% of patients assigned to prasugrel 30 mg, but 55% of those assigned to clopidogrel had high on-treatment platelet reactivity (p < 0.001). At any time point starting from 30 min, prasugrel 60 mg achieved significantly lower platelet reactivity than clopidogrel. Platelet reactivity at 60 min after prasugrel was not significantly different from that at 120 min after clopidogrel (p = 0.18). Prasugrel 30 mg had an intermediate effect. The 30-day incidence of bleeding events was not different among the 3 groups. CONCLUSIONS: From 30 min onward, prasugrel 60 mg achieved a stronger platelet inhibition than clopidogrel loading in stable patients undergoing a PCI. Compared with clopidogrel, prasugrel 60 mg was associated with a twice as fast onset of platelet inhibition. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition during Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102).

Long-term outcomes of routine versus provisional T-stenting for de novo coronary bifurcation lesions: five-year results of the Bifurcations Bad Krozingen I study.

AIMS: Previously, we reported that the nine-month angiographic result after treatment of coronary bifurcation lesions with provisional T-stenting was not significantly different from that with routine T-stenting. To compare long-term clinical outcomes of the two stenting strategies, we extended the follow-up of our study on bifurcation stenting. METHODS AND RESULTS: One hundred and one patients with coronary bifurcation lesions had been randomly assigned to provisional T-stenting and 101 to routine T-stenting, using sirolimus-eluting stents. We performed complete five-year follow-up. The primary efficacy endpoint was the incidence of target lesion revascularisation (TLR), and the primary safety endpoint was the incidence of definite/probable stent thrombosis (ST). We also monitored death, myocardial infarction (MI) and MACE (composite of death, MI and TLR). The cumulative five-year incidence of TLR in the provisional T-stenting arm was not significantly different from that in the routine T-stenting arm (16.2% vs. 16.3%, p=0.97). The same was true for MACE (22.8% vs. 22.9%, p=0.91), the composite of death and MI (9.9% vs. 13.9%, p=0.40), and ST (2.0% vs. 5.1%; p=0.25). CONCLUSIONS: During five-year follow-up, routine T-stenting offered no advantage over provisional T-stenting with respect to TLR or MACE. ClinicalTrials.gov Identifier: NCT00288535