Direct Oral Anticoagulants Versus Vitamin-K Antagonist After PCIs in Patients With AF: A Meta-analysis of Cardiac Ischemic Events.

BACKGROUND: Clinical trials have assessed the effect of direct oral antagonists (DOACs) in patients with atrial fibrillation (AF) after percutaneous coronary interventions (PCI). Studies were designed to test the effect on bleeding incidence, but concerns related to safety on ischemic events remain. METHODS: We performed a meta-analysis with currently available studies involving DOACs versus Vitamin-K antagonist (VKA) in patients with AF after PCI. The primary endpoint was the incidence of cardiac ischemic events, including myocardial infarction and stent thrombosis. Secondary endpoints were the incidence of stroke, all-cause mortality, and major bleeding. RESULTS: Eleven thousand twenty-three patients were included in the analysis: 5510 receiving DOACs and 5513 VKA. A total of 190 cases of myocardial infarction were registered in patients treated with DOACs and 177 in patients on VKA, and no statistical difference was noted [relative risk (RR): 1.07 95% confidence interval (CI) 0.88-1.31]. The incidence of stent thrombosis was very low with no differences between both treatment strategies (RR: 1.14 95% CI 0.76-1.71). The incidence of cardiac ischemic events was the same in patients receiving DOACs or VKA (HR 1.09 95% CI 0.91-1.30). No differences were observed in the incidence of stroke (RR: 0.86 95% CI 0.61-1.23) or mortality (RR: 1.09, 95% CI 0.90-1.31). Treatment with DOACs was associated with 34% reduction in major bleeding (RR: 0.66, 95% CI 0.54-0.81). CONCLUSIONS: Treatment with DOACs in patients with AF after a PCI do not increase the risk of cardiac ischemic events, stroke, or death and reduce the incidence of major bleeding by 34% as compared with VKA.

MGuard mesh-covered stent for treatment of ST-segment elevation myocardial infarction with high thrombus burden despite manual aspiration.

OBJECTIVES: To assess the usefulness of the MGuard stent in patients with ST-segment elevation myocardial infarction (STEMI) in whom a high thrombus burden persists after manual aspiration. BACKGROUND: In some patients with STEMI, a high thrombus burden may persist after manual aspiration. These patients may be at high risk of distal embolization and therefore impaired myocardial reperfusion. The MGuard is a novel mesh-covered stent designed to minimize thrombus embolization. METHODS: Single-arm, prospective registry of patients with STEMI and high thrombus burden after aggressive thrombus aspiration treated with the MGuard stent. High thrombus burden was defined as thrombus burden grade 4 or 5 according to the TIMI score. Lesions with a side branch ≥2 mm and patients with cardiogenic shock were not included. The study end-points were proportion of final TIMI 3 flow, normal myocardial blush, and complete ST-segment resolution. RESULTS: Fifty-six patients were included. After MGuard stent implantation >85% of cases had thrombus score = 0. Final TIMI 3 flow was achieved in 82% of cases, normal myocardial blush in 55%, and complete ST-segment resolution in 59%. Occlusion of a side branch (<2 mm) occurred in 2 cases (3.5%), embolization to a distal branch in 5 cases (8.9%), and transient no-reflow in 4 cases (7.1%). Major adverse cardiac events rate at 9 months was 3.6%, including 1 definite acute stent thrombosis and 1 target-vessel revascularization. CONCLUSIONS: The MGuard stent may be useful to prevent distal embolization in patients with STEMI and high thrombus burden despite mechanical aspiration.

Effects of cangrelor in coronary artery disease patients with and without diabetes mellitus: an in vitro pharmacodynamic investigation.

Platelets from patients with diabetes mellitus (DM) are hyper-reactive and whether cangrelor, a potent intravenous P2Y(12) receptor blocker, has differential pharmacodynamic (PD) effects according DM status is unknown. The aim of this investigation was to evaluate the in vitro PD effects of cangrelor in coronary artery disease (CAD) patients with and without DM. This prospective study enrolled 120 clopidogrel-naïve patients with CAD on aspirin therapy. PD assessments using cangrelor (500 nmol/l) in vitro included vasodilator-stimulated phosphoprotein assay to obtain the P2Y(12) reactivity index (PRI), and multiple electrode aggregometry (MEA). In a 20 patients subgroup, dose-dependent response was assessed following exposure to escalating concentrations (baseline, 5, 50, 500 and 5,000 nmol/l); thrombin generation processes were evaluated by thromboelastography (TEG). PD data were evaluable in 103 patients. No differences in baseline PD parameters were observed in DM (n = 48) and non-DM (n = 45) subjects. Cangrelor reduced PRI values irrespective of DM status (p < 0.0001), yielding no difference in patients with and without DM (16.1 ± 12.3 vs. 16.8 ± 11.3; p = 0.346). All MEA values were significantly reduced, although this was of greater magnitude with purinergic compared to non-purinergic agonists. A trend analysis showed a dose-dependent effect on platelet inhibition, with no interaction due to DM status, whereas no significant dose-dependent effect was observed for TEG-derived parameters. Therefore, in vitro cangrelor provides potent and dose-dependent blockade of the platelet P2Y(12) receptor, with no differential effect in DM and non-DM patients. In addition, in vitro cangrelor exerts moderate inhibitory effects on non-purinergic platelet signaling pathways, without modulating platelet-derived thrombin generation processes.

Recommendation on the nomenclature for anticoagulants: updated communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Commitee on the Control of Anticoagulation.

Oral anticoagulation therapy has evolved beyond vitamin K antagonists to include oral direct thrombin inhibitors and factor Xa inhibitors. Collectively known as "direct oral anticoagulants," this class of medications represents the current standard of care for the prevention and treatment of common thrombotic disorders, including atrial fibrillation and venous thromboembolism. Medications that target factors XI/XIa and XII/XIIa are currently under investigation for several thrombotic and nonthrombotic conditions. Given that these emerging medications will likely have distinct risk-benefit profiles to the current direct oral anticoagulants, may have different routes of administration, and could be used for unique clinical conditions (e.g., hereditary angioedema), the International Society on Thrombosis and Haemostasis Subcommittee on Control of Anticoagulation assembled a writing group to make recommendations on the nomenclature of anticoagulant medications. With input from the broader thrombosis community, the writing group recommends that anticoagulant medications be described by the route of administration and specific targets (e.g., oral factor XIa inhibitor).

Amphilimus- Versus Everolimus-Eluting Stents in Patients With Diabetes Mellitus: 5-Year Follow-Up of the RESERVOIR Trial.

The amphilimus-eluting stent (AES) is a thin-strut polymer-free stent that releases sirolimus formulated with a carrier from abluminal grooves. The RESERVOIR trial compared AES vs everolimus-eluting stents (EES) in patients with diabetes mellitus (DM) and showed non-inferior neointimal hyperplasia suppression at 9 months follow-up. The aim of this study was to assess comparative clinical outcomes at 5 years. The endpoints analyzed for this extended follow-up were target-vessel failure (TVF), target-vessel revascularization (TVR) and target-lesion revascularization (TLR). At 5-years, AES vs EES had similar risk of TVF (HR 0.54, 95% CI 0.20-1.47, p = 0.23), TVR (HR 0.36, 95% CI 0.12-1.14, p = 0.08) and TLR (HR 0.43, 95%CI 0.11-1.67, p = 0.22). Landmark analyses between 1 and 5 years also showed no significant differences between groups.

Coronary endothelial and microvascular function distal to polymer-free and endothelial cell-capturing drug-eluting stents. The randomized FUNCOMBO trial.

INTRODUCTION AND OBJECTIVES: The vasomotor function of new-generation drug-eluting stents designed to enhance stent healing and reendothelialization is unknown. This study aimed to compare the endothelial function of the infarct-related artery (IRA) treated with bioactive circulating endothelial progenitor cell-capturing sirolimus-eluting stents (COMBO) vs polymer-free biolimus-eluting stents (BioFreedom) in ST-segment elevation myocardial infarction patients at 6 months. Secondary objectives were to compare the microcirculatory function of the IRA and stent healing at 6 months. METHODS: Sixty patients were randomized to bioactive sirolimus-eluting stent vs polymer-free biolimus-eluting stents implantation. At 6 months, patients underwent coronary angiography with vasomotor, microcirculatory and optical coherence tomography examinations. Endothelial dysfunction of the distal coronary segment was defined as ≥ 4% vasoconstriction to intracoronary acetylcholine infusion. RESULTS: Endothelial dysfunction was similarly observed between groups (64.0% vs 62.5%, respectively; P=.913). Mean lumen diameter decreased by 16.0 ±20.2% vs 16.1 ±21.6% during acetylcholine infusion (P=.983). Microcirculatory function was similar in the 2 groups: coronary flow reserve was 3.23 ±1.77 vs 3.23±1.62 (P=.992) and the index of microcirculatory resistance was 24.8±16.8 vs 21.3±12.0 (P=.440). Optical coherence tomography findings were similar: uncovered struts (2.3% vs 3.2%; P=.466), malapposed struts (0.1% vs 0.3%; P=.519) and major evaginations (7.1% vs 5.6%; P=.708) were observed in few cases. CONCLUSIONS: Endothelial dysfunction of the IRA was frequent and was similarly observed with new-generation drug-eluting stents designed to enhance stent reendothelialization at 6 months. Endothelial dysfunction was observed despite almost preserved microcirculatory function and complete stent coverage. Larger and clinically powered studies are needed to assess the role of residual endothelial dysfunction in ST-segment elevation myocardial infarction patients. Registered in ClinicalTrials.gov: NCT04202172.

Antithrombotic strategies in elderly patients with atrial fibrillation revascularized with drug-eluting stents: PACO-PCI (EPIC-15) registry.

BACKGROUND: We sought to investigate the antithrombotic regimens applied and their prognostic effects in patients over 75 years old with atrial fibrillation (AF) after revascularization with drug-eluting stents (DES). METHODS: Retrospective registry in 20 centers including patients over 75 years with AF treated with DES. A primary endpoint of MACCE and a co-primary endpoint of major bleeding by ISTH criteria were considered at 12 months. RESULTS: A total of 1249 patients (81.1 ±â€¯4.2 years, 33.1% women, 66.6% ACS, 30.6% complex PCI) were included. Triple antithrombotic therapy (TAT) was prescribed in 81.7% and dual antithrombotic therapy (DAT) in 18.3%. TAT was based on direct oral anticoagulants (DOAC) in 48.4% and maintained for only 1 month in 52.2%, and DAT included DOAC in 70.6%. Primary endpoint of MACCE was met in 9.6% and primary endpoint of major bleeding in 9.4%. TAT was significantly associated with more bleeding (10.2% vs. 6.1%, p = 0.04) but less MACCE (8.7% vs. 13.6%, p = 0.02) than DAT and the use of DOAC was significantly associated to less bleeding (8% vs. 11.1%, p = 0.03) and similar MACCE (9.8% vs. 9.4%, p = 0.8). TAT over 1 month or with VKA was associated with more major bleeding but comparable MACCE rates. CONCLUSIONS: Despite advanced age TAT prevails, but duration over 1 month or the use of other agent than Apixaban are associated with increased bleeding without additional MACCE prevention. DAT reduces bleeding but with a trade-off in terms of ischemic events. DOAC use was significantly associated to less bleeding and similar MACCE rates.

Coronary vasomotor function and myocardial flow with bioresorbable vascular scaffolds or everolimus-eluting metallic stents: a randomised trial.

AIMS: The aim of this study was to compare the hyperaemic flow and vasomotor response to endothelium-dependent stimuli between bioresorbable vascular scaffolds (BVS) and metallic everolimus-eluting stents (EES) at 13 months. METHODS AND RESULTS: Seventy non-diabetic patients aiming to achieve complete revascularisation were randomised 1:1 to BVS or EES implantation. At 13 months, invasive coronary angiography was performed using intracoronary pressure and Doppler ultrasound measurements at rest and maximal hyperaemia. A vasomotor test to endothelium-dependent (acetylcholine) and independent (nitroglycerine) stimuli and optical coherence tomography (OCT) were also performed. Fifty-nine patients (30 BVS and 29 EES) underwent 13-month examination. Doppler ultrasound average peak velocity (49.0±17.5 vs 49.3±18.3 cm/sec; p=0.95), coronary blood flow (97.4±53.5 vs 88.3±46.7 ml/min; p=0.51), coronary flow reserve (2.6±0.9 vs 2.7±0.8; p=0.84) and fractional flow reserve (0.92±0.06 vs 0.94±0.04; p=0.17) were similar between the groups. The vasomotor test showed vasoconstriction response to acetylcholine in 75.6% proximal and 72.2% distal peri-scaffold segments without differences between study devices. BVS had larger in-scaffold vasoconstriction than EES (60.0% vs 27.6%; p=0.01) despite similar neointima response as assessed by OCT. CONCLUSIONS: BVS and EES had similar microcirculatory response to hyperaemia and predominant vasoconstrictive response in the peri-scaffold segments to endothelium-dependent stimuli. However, BVS exhibited larger vasoconstriction to endothelium-dependent stimuli in the scaffold segment.

Long-term prognostic impact of non-invasive follow-up with computed tomography angiography in patients with left main coronary artery stenting.

BACKGROUND: Left main coronary artery (LMCA) stenting is an evolving technique. Whether follow-up computed tomography angiography (CTA) might have clinical impact in these patients is controversial. The aim of present study is to compare clinical outcomes of patients with LMCA stenting followed with CTA versus patients with conventional clinical follow-up. METHODS: From 2003 to 2014 all consecutive patients with unprotected LMCA stenosis treated with single DES implantation were prospectively included. Since 2009 all patients underwent CTA at 6-month after LMCA stenting. Therefore, the non-CTA group included all patients treated from 2003 to 2009 and the CTA group included patients treated from 2009 to 2014. Patients with 6-month cardiac events, renal dysfunction or atrial fibrillation were excluded. All patients underwent at least 2-year clinical follow-up. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, and LMCA revascularization. RESULTS: A total of 236 patients were included (119 in the non-CTA and 117 in the CTA group). Nine event-free patients presented with in-stent restenosis as assessed by CTA at 6 months; 5 had angiographic confirmation and were revascularized. At 2 years, the primary end-point was observed in 15.1% and 7.3% of patients of the non-CTA and CTA groups, respectively (P=0.07). All-cause mortality was higher in the non-CTA group (8.4% vs. 2.6%; P=0.05). Euroscore and CTA were found independent predictors of the primary end-point in the multivariate analysis. CONCLUSIONS: Elective 6-month CTA after LMCA stenting is associated with better outcomes compared to conventional clinical follow-up.

In Vivo Evaluation of the Synergic Effect of Metformin and mTOR Inhibitors on the Endothelial Healing of Drug-eluting Stents in Diabetic Patients.

INTRODUCTION AND OBJECTIVES: Recent animal studies have shown metformin (MF) to impair endothelialization of drug-eluting stents (DES). The aim of this study was to evaluate the effect of MF on the healing of DES in human coronary arteries of patients with diabetes mellitus by optical coherence tomography (OCT). METHODS: The RESERVOIR trial randomized 116 lesions in 112 patients with diabetes mellitus to amphilimus- or everolimus-eluting stents and included mandatory OCT at 9 months of follow-up. Patients were divided in 3 groups according to the glucose-lowering agents received: a) no MF; b) MF in noninsulin treated patients, and c) MF in insulin-treated patients. The primary safety endpoint was the rate of uncovered stents. RESULTS: Seventeen patients with 19 lesions did not receive MF, whereas MF was administered to 53 noninsulin treated patients (54 lesions) and 28 insulin-treated patients (28 lesions). Baseline characteristics were comparable, although noninsulin treated patients who received MF had better glycemic control (P < .01). By OCT, rates of uncovered struts were comparable between groups (3.07±4.80% vs 2.23±4.73% vs 3.43±6.69%, respectively; P = .48). Multivariate models confirmed that MF had no effect on the healing of DES (OR, 1.49, 95%CI, 0.71-3.08; P = .29). Similarly, quantitative angiography showed no effect of MF on late lumen loss, whereas patients treated with exogenous insulin had greater late lumen loss (P = .02). CONCLUSIONS: Metformin use does not impair endothelial healing of DES in patients with both insulin- and noninsulin-treated diabetes mellitus. According to these results, MF should not be discouraged in these patients.

Temporal trends in frequency, management and outcomes of coronary perforations.

BACKGROUND: Coronary perforations (CP) have been described as a rare but potentially fatal complication in percutaneous coronary interventions (PCI). Our aim is to compare temporal trends in frequency, management and outcomes of coronary perforations (CP). METHODS: All cases of CP recorded in our prospective institutional percutaneous coronary intervention (PCI) registry from 2003 to 2015 were included. Patients were divided in 2 groups according to the time frame in which the CP occurred: the early period (before 2009, when the chronic total occlusions and primary PCI programs started) and the current period. The primary endpoint was the composite of in-hospital serious adverse events, including final TIMI flow 0-1, cardiac tamponade, emergent cardiac surgery or death. RESULTS: Overall, 88 CP occurred in 17,566 procedures (0.50%). Of these, 17 (0.26%) occurred during the early period and 71 (0.64%) during the current period (P<0.001). CP management differed between groups, with less CP sealed by intracoronary devices in the early period than in the current one (23.5% vs. 47.9%, P=0.068). Moreover, patients with CP during the early period experienced more in-hospital serious adverse events (69% vs. 31% respectively, OR 3.18, 95% CI: 1.07-9.45, P=0.037). CONCLUSIONS: Expansion of indications and complexity of PCI in the current era may be associated with an increased frequency of CP. However, progress in technical and device management of CP have led to an improvement in the prognosis of this feared complication.

Long-Term Coronary Functional Assessment of the Infarct-Related Artery Treated With Everolimus-Eluting Bioresorbable Scaffolds or Everolimus-Eluting Metallic Stents: Insights of the TROFI II Trial.

OBJECTIVES: The study sought to compare the vasomotor and microcirculatory function of the infarct-related artery (IRA) between bioresorbable vascular scaffolds (BVS) and everolimus-eluting stents (EES) at 3 years. BACKGROUND: The ABSORB STEMI TROFI II study showed similar outcomes between BVS and EES in the context of ST-segment elevation myocardial infarction at 3 years. METHODS: Sixty-three consecutive event-free patients of the randomized TROFI II study were screened to undergo coronary angiography with vasomotor, microcirculatory, and optical coherence tomography (OCT) examination at 3 years. Vasomotion was defined as >4% change in mean lumen diameter to acetylcholine (ACH) and nitroglycerin as assessed by quantitative angiography. Microcirculatory examination was performed with pressure or thermodilution techniques. RESULTS: A total of 38 patients (20 BVS and 18 EES) were included. At 3 years, ≥60% of patients exhibited paradoxical vasoconstriction to ACH in the periscaffold or stent segments. Vasoconstriction to ACH and vasodilatation to nitroglycerin were more often observed in the scaffold or stent segment with BVS than with EES (77.8% vs. 25.0%; p = 0.008 and 61.1% vs. 18.8%; p = 0.018). The IRA-depending microcirculation showed similar index of resistance (23.8 vs. 22.4; p = 0.781), coronary flow reserve (2.4 vs. 1.9; p = 0.523), fractional flow reserve (0.91 vs. 0.93; p = 0.317), and absolute flow (135.5 ml/min vs. 147.3 ml/min; p = 0.791). OCT showed remaining strut footprints and larger number of intraluminal scaffold dismantling (26.3% vs. 0%; p = 0.049) in the BVS group. CONCLUSIONS: Both endothelium-dependent and -independent vasomotion of the IRA were more evident with BVS, as compared with EES, at 3 years. Functional microcirculatory parameters were mostly adequate and similar between BVS and EES. Clinical implications of these findings warrant further investigations.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

OBJECTIVES: The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). BACKGROUND: The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. METHODS: This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. RESULTS: A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. CONCLUSIONS: AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Predictive ability of bleeding risk scores in the routine clinical practice.

BACKGROUND: Previous predictive models of bleeding in acute coronary syndromes (ACSs) used different definitions of bleeding and some of them come from populations lacking important predictors of haemorrhagic complications. Our group previously developed a predictive model of bleeding (PMB), including clinically meaningful variables, providing an optimal predictive ability. We aimed to compare the ability of this PMB with the main available bleeding risk scores for predicting major bleeding according to different definitions in non-selected ACS patients from daily clinical practice. METHODS: All ACS patients admitted to the Coronary Care Unit were prospectively included. CRUSADE, Mehran and ACTION bleeding risk scores were calculated for each patient. In-hospital bleeding was recorded using the CRUSADE, TIMI, Mehran, ACTION and BARC definitions. For reasons of clinical relevance, BARC 3 and 5 categories were considered severe BARC bleeding for this study. The predictive ability of the PMB and other bleeding risk scores was assessed by binary logistic regression, ROC curves and areas under the curves (AUCs). RESULTS: We included 1976 patients. Mean age was 62.1 years. Almost all patients underwent angiography, 65% of them by the radial approach. The incidence of major bleeding was: CRUSADE bleeding 3.9% (77/1976); Mehran bleeding 4.8% (94/1976); ACTION bleeding 3.9% (78/1976); and BARC 3/5 bleeding 2.4% (48/1976). The PMB showed the best ability for predicting major bleeding regardless of the definition used. The differences were specially significant for predicting BARC 3/5 bleeding (AUC: PMB 0.87, Mehran score 0.68, CRUSADE score 0.70 and ACTION score 0.70). The predictive ability of CRUSADE, ACTION and Mehran scores was similar for all the definitions analysed. CONCLUSIONS: Current bleeding risk scores showed a similar predictive ability for major bleeding regardless of the definitions used. Including other clinically meaningful predictors of bleeding into the new PMB significantly improved its predictive ability in the clinical scenario of ACS.

Impact of smoking on long-term outcomes in patients with atherosclerotic vascular disease treated with aspirin or clopidogrel: insights from the CAPRIE trial (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events).

OBJECTIVES: The goal of this study was to investigate the differential efficacy of clopidogrel or aspirin monotherapy according to smoking status in patients with atherosclerotic vascular disease. BACKGROUND: Smoking enhances clopidogrel-induced platelet inhibition, which may explain the higher relative benefit among smokers observed in trials evaluating dual antiplatelet therapy. Whether smoking has an impact on clinical outcomes in patients requiring a single antiplatelet agent remains unknown. METHODS: This was a post-hoc analysis of the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events) trial that compared clopidogrel and aspirin monotherapy in patients (N = 19,184) with atherosclerotic vascular disease. RESULTS: Current smokers (n = 5,688) had an increased risk of ischemic events compared with never smokers (n = 4,135; hazard ratio [HR]: 1.24 [95% confidence interval (CI): 1.08 to 1.42]) and ex-smokers (n = 9,381; HR: 1.32 [95% CI: 1.18 to 1.47]) (p < 0.001). Clopidogrel was associated with a reduction in ischemic events among current smokers (8.3% vs. 10.8%; HR: 0.76 [95% CI: 0.64 to 0.90]), whereas no benefit over aspirin was seen in the combined group of ex-smokers/never-smoked patients (10.4% vs. 10.6%; HR: 0.99 [95% CI: 0.89 to 1.10]; p = 0.01 for interaction). Among current smokers, clopidogrel also reduced myocardial infarction, vascular death, and death from any cause compared with aspirin. No interaction between smoking status and study treatment was observed for bleeding events. CONCLUSIONS: In a post-hoc analysis of the CAPRIE population, current smokers appeared to have enhanced benefit with clopidogrel therapy for secondary prevention compared with aspirin. These results should be considered hypothesis generating for future prospective studies assessing the impact of specific platelet-inhibiting strategies according to smoking status.

Longitudinal deformation of drug-eluting stents: evaluation by multislice computed tomography.

BACKGROUND: Some modifications introduced in the design of the new generation of drug-eluting stent (DES) to improve their flexibility may entail a reduction in their longitudinal strength. This study sought to evaluate the longitudinal deformation of DESs by multislice computed tomography (MSCT). METHODS: This study included DESs that could have been potentially deformed by mechanical actions such as: (1) catheter impingement; (2) postdilation; (3) kissing balloon; and (4) intravascular imaging after implantation. Patients on atrial fibrillation or with overlapping stents were excluded. All patients underwent stent length evaluation by MSCT 9-12 months after implantation. RESULTS: Forty-five stents were included: 15 platinum chromium (PtCr-DES), 15 cobalt chromium (CoCr-DES), and 15 stainless-steel (SS-DES). The relative longitudinal deformation by stent type was 6.93 ± 5.82% for PtCr-DES, 6.19 ± 5.79% for CoCr- DES, and 4.03 ± 4.07% for SS-DES (P=.31). Among the mechanical actions studied, only catheter impingement was related to longitudinal stent deformation (P<.01). After adjustment, only catheter impingement (P<.01) and nominal stent length (P=.049) were independently related to longitudinal deformation. There were no stent fractures. CONCLUSIONS: Longitudinal deformation of DESs is common in all the studied platforms when subject to longitudinal forces. Guiding catheter impingement is the only mechanical action significantly associated with DES shortening.

Multislice CT for assessing in-stent dimensions after left main coronary artery stenting: a comparison with three dimensional intravascular ultrasound.

OBJECTIVE: To evaluate the agreement between multislice CT (MSCT) and intravascular ultrasound (IVUS) to assess the in-stent lumen diameters and lumen areas of left main coronary artery (LMCA) stents. DESIGN: Prospective, observational single centre study. SETTING: A single tertiary referral centre. PATIENTS: Consecutive patients with LMCA stenting excluding patients with atrial fibrillation and chronic renal failure. INTERVENTIONS: MSCT and IVUS imaging at 9-12 months follow-up were performed for all patients. MAIN OUTCOME MEASURES: Agreement between MSCT and IVUS minimum luminal area (MLA) and minimum luminal diameter (MLD). A receiver operating characteristic (ROC) curve was plotted to find the MSCT cut-off point to diagnose binary restenosis equivalent to 6 mm(2) by IVUS. RESULTS: 52 patients were analysed. Passing-Bablok regression analysis obtained a ß coefficient of 0.786 (0.586 to 1.071) for MLA and 1.250 (0.936 to 1.667) for MLD, ruling out proportional bias. The α coefficient was -3.588 (-8.686 to -0.178) for MLA and -1.713 (-3.583 to -0.257) for MLD, indicating an underestimation trend of MSCT. The ROC curve identified an MLA ≤ 4.7 mm(2) as the best threshold to assess in-stent restenosis by MSCT. CONCLUSIONS: Agreement between MSCT and IVUS to assess in-stent MLA and MLD for LMCA stenting is good. An MLA of 4.7 mm(2) by MSCT is the best threshold to assess binary restenosis. MSCT imaging can be considered in selected patients to assess LMCA in-stent restenosis.

Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways.

Clopidogrel response varies according to the presence of genetic polymorphisms. The CYP2C19*2 allele has been associated with impaired response; conflicting results have been reported for CYP2C19*17, ABCB1, and PON1 genotypes. We assessed the impact of CYP2C19, PON1, and ABCB1 polymorphisms on clopidogrel and prasugrel pharmacodynamic (PD) and pharmacokinetic (PK) parameters. Aspirin-treated patients (N=194) with coronary artery disease from two independent, prospective, randomised, multi-centre studies comparing clopidogrel (75 mg) and prasugrel (10 mg) were genotyped and classified by predicted CYP2C19 metaboliser phenotype (ultra metabolisers [UM] = *17 carriers; extensive metabolisers [EM] = *1/1 homozygotes; reduced metabolisers [RM] = *2 carriers). ABCB1 T/T and C/T polymorphisms and PON1 A/A, A/G and G/G polymorphisms were also genotyped. PD parameters were assessed using VerifyNow® P2Y12 and vasodilator stimulated phosphoprotein (VASP) expressed as platelet reactivity index (PRI) after 14 days of maintenance dosing. Clopidogrel and prasugrel active metabolite (AM) exposure was calculated in a cohort of 96 patients. For clopidogrel, genetic variants in CYP2C19, but not ABCB1 or PON1, affected PK and PD. For prasugrel, none of the measured genetic variants affected PK or PD. Compared with clopidogrel, platelet inhibition with prasugrel was greater even in the CYP2C19 UM phenotype. Prasugrel generated more AM and achieved greater platelet inhibition than clopidogrel irrespective of CYP2C19, ABCB1, and PON1 polymorphisms. The lack of effect from genetic variants on prasugrel AM generation or antiplatelet activity is consistent with previous studies in healthy volunteers and is consistent with improved efficacy in acute coronary syndrome patients managed with percutaneous coronary intervention.

Impact of pentoxifylline on platelet function profiles in patients with type 2 diabetes mellitus and coronary artery disease on dual antiplatelet therapy with aspirin and clopidogrel.

OBJECTIVES: The aim of this study was to evaluate the impact of the phosphodiesterase (PDE) inhibitor pentoxifylline on platelet function profiles in patients receiving dual antiplatelet therapy (DAPT). BACKGROUND: Previous studies have shown that, in patients receiving DAPT, the adjunctive use of a PDE inhibitor enhances platelet inhibition, particularly in those presenting with diabetes mellitus (DM). However, the pharmacodynamic (PD) effects of the PDE inhibitor pentoxifylline on platelet function profiles in DM patients receiving DAPT are unknown. METHODS: This was a prospective, randomized, double-blind, parallel design study conducted in DM patients with stable coronary artery disease receiving DAPT. Patients were randomly assigned to either pentoxifylline 400 mg or placebo 3 times daily for 14 days. The PD effects were assessed by vasodilator-stimulated phosphoprotein phosphorylation assay, light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetric, Inc., San Diego, California), and multiple electrode aggregometry at baseline and 14 days. The PD effects were also assessed according the presence or absence of high on-treatment platelet reactivity status. RESULTS: A total of 40 patients were available for analysis. At 14 days, there were no differences in the P2Y(12) reactivity index as assessed by vasodilator-stimulated phosphoprotein phosphorylation between treatment groups (primary endpoint; p = 0.93). Intra-group comparisons also failed to show any differences between baseline and 14-day P2Y(12) reactivity index assessment in the placebo and pentoxifylline arms (p = 0.61). There were no significant inter- and intra-group differences in all other PD measures. The PD effects did not vary according the presence or absence of high on-treatment platelet reactivity. CONCLUSIONS: Adjunctive treatment with pentoxifylline is not associated with increased platelet inhibitory effects in DM patients with coronary artery disease receiving DAPT.

Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease.

OBJECTIVES: The aim of this study was to assess the association between genetic variants of the insulin receptor substrate (IRS)-1 gene, platelet function, and long-term outcomes in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease while on aspirin and clopidogrel therapy. BACKGROUND: The effects of pharmacogenetic determinants on platelet function and cardiovascular outcomes in type DM patients are unknown. METHODS: The association between IRS-1 genetic variants, platelet function, and the risk of major adverse cardiac events (MACE) at 2 years was assessed in 187 patients with type 2 DM and stable coronary artery disease on maintenance aspirin and clopidogrel therapy. RESULTS: Seven tag single nucleotide polymorphisms were selected. Individuals with high platelet reactivity were more frequent among carriers of the C allele (GC and CC genotypes; approximately 20% of population) of the rs956115 marker (44.4% vs. 20.5%; odds ratio: 3.1, 95% confidence interval [CI]: 1.44 to 6.67; p = 0.006). These patients were at higher risk of MACE (28.0% vs. 10.9%; hazard ratio: 2.90, 95% CI: 1.38 to 6.11; p = 0.005). The C allele carriers of the rs956115 marker were more commonly associated with a hyperreactive platelet phenotype. This was confirmed in an external validation cohort of patients with type 2 DM but not in an external validation cohort of patients without DM. Carriers of the C allele of the rs956115 marker also had a significantly higher risk of MACE compared with noncarriers (30.6% vs. 11.4%; hazard ratio: 2.88, 95% CI: 1.35 to 6.14; p = 0.006). CONCLUSIONS: Type 2 DM patients who are carriers of the C allele of the rs956115 marker of the IRS-1 gene have a hyperreactive platelet phenotype and increased risk of MACE.