Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention.

BACKGROUND: The dual-antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive harm (score <2) or benefit (score ≥2) from prolonged DAPT after percutaneous coronary intervention (PCI). OBJECTIVE: To evaluate the safety and efficacy of DAPT duration according to DAPT score. DESIGN: Retrospective assessment of DAPT score-guided treatment duration in a randomized clinical trial. (ClinicalTrials.gov: NCT00611286). SETTING: PCI patients. PATIENTS: 1970 patients undergoing PCI. INTERVENTION: DAPT (aspirin and clopidogrel) for 24 versus 6 months. MEASUREMENTS: Primary efficacy outcomes were death, myocardial infarction, or cerebrovascular accident. The primary safety outcome was type 3 or 5 bleeding according to the Bleeding Academic Research Consortium definition. Outcomes were assessed between 6 and 24 months. RESULTS: 884 patients (44.9%) had a DAPT score of at least 2, and 1086 (55.1%) had a score less than 2. The reduction in the primary efficacy outcome with 24- versus 6-month DAPT was greater in patients with high scores (risk difference [RD] for score ≥2, -2.05 percentage points [95% CI, -5.04 to 0.95 percentage points]; RD for score <2, 2.91 percentage points [CI, -0.43 to 6.25 percentage points]; P = 0.030). However, the difference by score for the primary efficacy outcome varied by stent type; prolonged DAPT with high scores was effective only in patients receiving paclitaxel-eluting stents (RD, -7.55 percentage points [CI, -12.85 to -2.25 percentage points]). The increase in the primary safety outcome with 24- versus 6-month DAPT was greater in patients with low scores (RD for score ≥2, 0.20 percentage point [CI, -1.20 to 1.60 percentage points]; RD for score <2, 2.58 percentage points [CI, 0.71 to 4.46 percentage points]; P = 0.046). LIMITATION: Retrospective calculation of the DAPT score. CONCLUSION: Prolonged DAPT resulted in harm in patients with low DAPT scores undergoing PCI but reduced risk for ischemic events in patients with high scores receiving paclitaxel-eluting stents. Whether prolonged DAPT benefits patients with high scores treated with contemporary drug-eluting stents requires further study. PRIMARY FUNDING SOURCE: None.

Rationale and design of the Hunting for the off-target propertIes of Ticagrelor on Endothelial function and other Circulating biomarkers in Humans (HI-TECH) trial.

BACKGROUND: Among the 3 approved oral P2Y12 inhibitors for the treatment for patients with acute coronary syndrome (ACS), ticagrelor, but not prasugrel or clopidogrel, has been associated with off-target properties, such as improved endothelial-dependent vasomotion and increased adenosine plasma levels. METHODS: The HI-TECH study (NCT02587260) is a multinational, randomized, open-label, crossover study with a Latin squares design, conducted at 5 European sites, in which patients free from recurrent ischemic or bleeding events ≥30 days after a qualifying ACS were allocated to sequentially receive a 30 ± 5-day treatment with prasugrel, clopidogrel, and ticagrelor in random order. The primary objective was to evaluate whether ticagrelor, at treatment steady state (ie, after 30 ± 5 days of drug administration), as compared with both clopidogrel and prasugrel, is associated with an improved endothelial function, assessed with peripheral arterial tonometry. Thirty-six patients undergoing evaluable endothelial function assessment for each of the assigned P2Y12 inhibitor were needed to provide 90% power to detect a 10% relative change of the reactive hyperemia index in the ticagrelor group. CONCLUSION: The HI-TECH study is the first randomized, crossover study aiming to ascertain whether ticagrelor, when administered at approved regimen in post-ACS patients, improves endothelial function as compared with both clopidogrel and prasugrel.

Impact of chronic kidney disease on 2-year clinical outcomes in patients treated with 6-month or 24-month DAPT duration: An analysis from the PRODIGY trial.

OBJECTIVES: To assess whether moderate-to-severe CKD is a treatment modifier for benefit or harm in patients randomly allocated to 24-month versus 6-month DAPT. BACKGROUND: It is still unclear whether chronic kidney disease CKD should impact on the decision-making on optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). METHODS AND RESULTS: PRODIGY trial randomized 1970 all-comer patients at 24-month versus 6-month DAPT after PCI. Patients with moderate-to-severe CKD (n = 604; 30.7%) were older, more likely to be women, to have hypertension, diabetes, prior MI or PCI, with higher severity of coronary artery disease (CAD), but were less frequently smokers or presenting with stable CAD. After adjustment, the 2-year rates of primary endpoint (composite of death, myocardial infarction and cerebrovascular accident), as well as bleeding and net adverse clinical events were higher in patients with moderate-to-severe CKD. DAPT prolongation at 24-month did not reduce the primary endpoint in both CKD (adj. HR: 0.957; 95% CI 0.652-1.407; P = 0.825) and no-CKD (adj. HR: 1.341; 95% CI 0.861-2.086; P = 0.194) groups (Pint = 0.249), but increased bleeding in both groups (CKD: adj. HR: 1.999; 95% CI 1.100-3.632; P = 0.023; no-CKD: adj. HR: 2.880; 95% CI 1.558-5.326; P = 0.001; Pint = 0.407). CONCLUSIONS: Moderate-to-severe CKD did not modify the effect of a prolonged or shortened DAPT duration in largely unselected patients undergoing stent implantation. Our analysis suggests that CKD should not be a major driver in the decision-making on the duration of DAPT after stent implantation. This exploratory study is underpowered and should be considered hypothesis-generating only. © 2017 Wiley Periodicals, Inc.

Long-Term Use of Ticagrelor in Patients with Coronary Artery Disease.

PURPOSE OF REVIEW: This review aims to summarize and discuss safety and effectiveness of the long-term use of ticagrelor in patients with coronary artery disease (CAD). RECENT FINDINGS: Ticagrelor is an orally administered, direct, and reversible inhibitor of the P2Y12-platelet receptor. Long-term use of ticagrelor in patients with previous myocardial infarction (MI) has been investigated in the PEGASUS-TIMI-54 trial. Overall, 21,162 patients with a spontaneous MI 1 to 3 years before randomization were randomly assigned to ticagrelor 90 mg bid, ticagrelor 60 mg bid, or placebo. Compared with placebo, both doses of ticagrelor showed that they were capable of significantly reducing the primary efficacy endpoint, although with a significant increase in TIMI major bleeding. Intracranial hemorrhage or fatal bleeding did not differ across groups. These findings establish clear benefit of DAPT extension with ticagrelor beyond 1 year of treatment, which comes with a tradeoff of clinically meaningful bleeding. Altogether, current evidence suggests that the duration of DAPT remains a patient-by-patient decision based on thrombotic and bleeding risk profiles.

Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial.

BACKGROUND: Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. METHODS AND RESULTS: In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. CONCLUSIONS: The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

Coronary stent selection and optimal course of dual antiplatelet therapy in patients at high bleeding or thrombotic risk: navigating between limited evidence and clinical concerns.

PURPOSE OF REVIEW: Optimal duration of dual antiplatelet therapy (DAPT) after coronary revascularization, in particular after drug-eluting stent (DES) implantation, is a matter of ongoing debate. RECENT FINDINGS: First generation of DES, as compared with bare metal stents (BMS), reduce restenosis rates but increase very late stent thrombosis rates, thus requiring a prolonged course of DAPT. As a consequence, patients with high thrombotic and/or bleeding risk: have been systematically excluded from randomized trials comparing DES versus BMS; remain 'uncertain' DES candidates; should preferentially undergo BMS implantation at the time of percutaneous coronary intervention instead of DES. The Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates (ZEUS) trial is the first randomized study that demonstrated the superiority of the Zotarolimus-eluting Endeavor Sprint versus BMS in uncertain DES candidates who followed a personalized DAPT duration, which was tailored to patients's, not stent's, characteristics. SUMMARY: The results of the ZEUS trial may support a paradigm shift in our current understanding of the most proper use of DES in practice and should trigger further research in patients at high bleeding or thrombotic risk, who have been so far largely deprived of the potential benefit provided by DES.

Incidence, prognostic impact, and optimal definition of contrast-induced acute kidney injury in consecutive patients with stable or unstable coronary artery disease undergoing percutaneous coronary intervention. insights from the all-comer PRODIGY trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is associated with poor outcome. Whether this association differs in stable coronary artery disease (CAD) as compared to acute coronary syndrome (ACS) patients is unknown. Definitions and Methods: PRODIGY trial patients were defined as stable CAD or ACS according to the initial presentation. CI-AKI was defined as an increase (Δ) of serum creatinine (SCr) ≥25% above baseline. Two endpoints were considered: all-cause death and the composite of death, stroke, or myocardial infarction (MI). The interaction between CI-AKI, clinical setting, and the impact of increasing ΔSCr% cut-offs were also explored. RESULTS: Two thousand three patients were enrolled in the PRODIGY trial, 85 patients were excluded for missing SCr data, leading to a population of 1,918 patients. CI-AKI incidence was 6.7% in stable CAD and 12.2% in ACS patients. CI-AKI was associated with all-cause mortality [adjusted hazard ratio (aHR) of 2.05, 95% confidence interval (CI) 1.38-3.05, P < 0.001] and the composite of death, stroke, or MI [aHR of 1.49, 95% CI 1.13-1.97, P < 0.001]. The risk of CI-AKI for the composite endpoint was higher in stable CAD, P for interaction: 0.048. A ΔSCr of 35% was associated with the highest aHR for all-cause mortality: 2.34 [95% CI, 1.46-3.76, P < 0.001] and the composite of death, stroke, or MI: 1.70 [95% CI, 1.20-2.40, P > 0.001]. CONCLUSIONS: In a large, contemporary, all-comers percutaneous coronary intervention population, CI-AKI was associated with an increased risk of all-cause death and the composite of death, stroke, or MI. While CI-AKI is more common in ACS than in stable CAD patients, its adjusted prognostic impact on the composite endpoint appears to be more pronounced in patients with stable CAD.

Unexpected Pulmonary Embolism Late After Recovery from Mild COVID-19?

SARS-CoV-2 infection is associated with an increased risk of venous thromboembolism (VTE), which is common during active illness but unusual in milder cases and after healing. We describe a case of bilateral acute pulmonary embolism occurring 3 months after recovery from a paucisymptomatic SARS-CoV-2 infection. The only VTE risk factor demonstrable was a history of previous SARS-CoV-2 infection, with laboratory signs of residual low-grade inflammation. Clinicians should be aware of VTE as a potential cause of sudden dyspnoea after COVID-19 resolution, especially in the presence of persistent systemic inflammation. LEARNING POINTS: Venous thromboembolism may occur after COVID-19, even in milder SARS-CoV-2 infections and late after coronavirus clearance.Laboratory signs of systemic inflammation are clues for suspecting venous thromboembolism as a cause of sudden dyspnoea in patients with low risk scores for pulmonary embolism but with previous COVID-19 infection.

Sacubitril/Valsartan to Treat Heart Failure in a Patient with Relapsing Hairy Cell Leukaemia: Case Report.

Experience with angiotensin-receptor neprilysin inhibitors (ARNI) in oncologic patients with heart failure (HF) is limited. We report a case of ARNI started as first-choice therapy in a patient with relapsing hairy cell leukaemia (HCL) and HF with depressed left ventricular ejection fraction (LVEF). A middle-aged male, previously treated with rituximab for HCL, was scheduled for cardiologic screening before starting a new antineoplastic therapy for cancer relapse. The patient had symptomatic HF with reduced LVEF and high NT-proBNP levels. In this patient, early ARNI treatment was well tolerated and produced a rapid and durable improvement of symptoms, LVEF and NT-proBNP levels. Consequently, the oncologic team could start an experimental treatment with obinutuzumab, with complete HCL remission. In conclusion, in this patient with HCL and HF, ARNI therapy was safe and effective, contributing to undelayed cancer treatment.

Role of Response-to-Diuretic in Predicting Prognosis in Discharged Heart Failure Patients After an Acute Decompensation.

BACKGROUND: The diuretic response has been shown to be a robust independent marker of cardiovascular outcomes in acute heart failure (ADHF) patients. The objectives of this clinical research, will aim are to: a) include diuresis in the formula for diuretic response (R-to-D); b) add to R-to-D the value of a pre-discharged determination of galectin-3 and BNP in predicting mid-term clinical outcome. METHODS: Consecutive patients discharged alive after an ADHF were enrolled. All patients underwent BNP and galectin-3, a 6 min walk test and an echocardiogram together with diuresis and body weight during diuretic administration. Death by any cause, cardiac transplantation and worsening HF requiring readmission to the hospital were considered cardiovascular events. RESULTS: 141 patients (98 males, age 73.8) were analysed (follow-up 17 months). During the follow-up 45 (31.9%) events were scheduled (19 cardiac deaths, 26 re-hospitalisation for HF). Patients who experienced CV-event had a worst renal function (p = 0.003), an higher BNP (p = 0.006) and galectin-3 (p = 0.008). At multivariate analysis, only R-to-D, galectin-3 and BNP showed a significant correlation with worst clinical prognosis (respectively p = 0.043; OR 6.01; p = 0.01; OR 8.9; p = 0.02 OR 10.38), independently of age and renal function. Kaplan-Meier curves depicted a powerful stratification using an R-to-D <1.2 kg/40 mg furosemide (log rank 10.96; p = 0.0009). Adding R-to-D<1.2 mg/40 mg furosemide to galectin-3>17.6 pg/mL and BNP>500 pg/mL the predictive value improved (log rank 23.59; p = 0.0001). CONCLUSION: Adding R-to-D to Gal-3 and BNP, a single pre-discharge strategy testing seemed to obtain a satisfactorily predictive value in alive HF patients discharged after an ADHF episode.

Early versus newer generation devices for transcatheter aortic valve implantation in routine clinical practice: a propensity score matched analysis.

Aim: Contemporary data comparing early versus newer generation transcatheter heart valve (THV) devices in routine clinical practice are lacking. We sought to compare the safety and efficacy of early versus newer generation THVs in unselected patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: We performed a propensity score matched analysis of patients undergoing transfemoral TAVI at a single centre with early versus newer generation devices between 2007 and 2016. Patients were matched for balloon-expandable versus self-expandable valves and Society of Thoracic Surgeons score. The primary end point was the Valve Academic Research Consortium (VARC)-2 early safety composite end point at 30 days. Among the 391 matched pairs, no differences between early (21.2%) and newer generation (20.8%) THVs regarding the early safety composite end point (HR 0.98, 95% CI 0.72 to 1.33, P=0.88) were observed. The rates of valve embolisation (0.8% vs 4.2%, P=0.005), bleeding events (24.8% vs 32.0%, P=0.028) and moderate-to-severe paravalvular regurgitation (PVR) (3.1% vs 12.1%, P<0.001) were lower among patients receiving newer generation devices. Conversely, patients treated with early generation THVs less frequently experienced annulus rupture (0% vs 2.0%, P=0.008). Conclusion: Newer compared with early generation THV devices were associated with a lower rate of valve embolisation, PVR and bleeding events.

Effects of Ticagrelor, Prasugrel, or Clopidogrel on Endothelial Function and Other Vascular Biomarkers: A Randomized Crossover Study.

OBJECTIVES: The study sought to assess whether treatment with ticagrelor, as compared with prasugrel and clopidogrel, improves endothelium-dependent dilation throughout the course of the treatment and other vascular biomarkers, including systemic adenosine plasma levels. BACKGROUND: The in vivo off-target effects of ticagrelor in post-acute coronary syndrome (ACS) patients remain poorly characterized. METHODS: Fifty-four stable post-ACS patients were sequentially exposed to each of the 3 oral P2Y12 inhibitors following a 3-period balanced Latin square crossover design with 4 weeks per treatment in 5 European centers. The primary endpoint was the assessment of endothelial function with pulse amplitude tonometry and expressed as reactive hyperemia index at treatment steady state. Secondary endpoints included reactive hyperemia index after loading or before maintenance regimen, systemic adenosine plasma levels, a wide set of vascular biomarkers, and ticagrelor or AR-C124910XX plasma levels throughout each ticagrelor period. In 9 patients, the evaluation of endothelial function was performed simultaneously by pulse amplitude tonometry and flow-mediated dilation. RESULTS: Reactive hyperemia index did not differ after ticagrelor (1.970 ± 0.535) as compared with prasugrel (2.007 ± 0.640; p = 0.557) or clopidogrel (2.072 ± 0.646; p = 0.685), nor did systemic adenosine plasma levels or vascular biomarkers at any time points. P2Y12 platelet reactivity units were lower after ticagrelor as compared with clopidogrel at all time points and after maintenance dose as compared with prasugrel. Flow-mediated dilation did not differ after the maintenance dose of ticagrelor as compared with clopidogrel and prasugrel. CONCLUSIONS: Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260).

Impact of Sex on Comparative Outcomes of Radial Versus Femoral Access in Patients With Acute Coronary Syndromes Undergoing Invasive Management: Data From the Randomized MATRIX-Access Trial.

OBJECTIVES: This study sought to assess whether transradial access (TRA) compared with transfemoral access (TFA) is associated with consistent outcomes in male and female patients with acute coronary syndrome undergoing invasive management. BACKGROUND: There are limited and contrasting data about sex disparities for the safety and efficacy of TRA versus TFA for coronary intervention. METHODS: In the MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) program, 8,404 patients were randomized to TRA or TFA. The 30-day coprimary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE), defined as death, myocardial infarction, or stroke, and net adverse clinical events (NACE), defined as MACCE or major bleeding. RESULTS: Among 8,404 patients, 2,232 (26.6%) were women and 6,172 (73.4%) were men. MACCE and NACE were not significantly different between men and women after adjustment, but women had higher risk of access site bleeding (male vs. female rate ratio [RR]: 0.64; p = 0.0016), severe bleeding (RR: 0.17; p = 0.0012), and transfusion (RR: 0.56; p = 0.0089). When comparing radial versus femoral, there was no significant interaction for MACCE and NACE stratified by sex (pint = 0.15 and 0.18, respectively), although for both coprimary endpoints the benefit with TRA was relatively greater in women (RR: 0.73; p = 0.019; and RR: 0.73; p = 0.012, respectively). Similarly, there was no significant interaction between male and female patients for the individual endpoints of all-cause death (pint = 0.79), myocardial infarction (pint = 0.25), stroke (pint = 0.18), and Bleeding Academic Research Consortium type 3 or 5 (pint = 0.45). CONCLUSIONS: Women showed a higher risk of severe bleeding and access site complications, and radial access was an effective method to reduce these complications as well as composite ischemic and ischemic or bleeding endpoints.

Ischaemic and bleeding outcomes in elderly patients undergoing a prolonged versus shortened duration of dual antiplatelet therapy after percutaneous coronary intervention: insights from the PRODIGY randomised trial.

AIMS: The aim of this study was to evaluate the efficacy and safety of 24-month vs. six-month dual antiplatelet therapy (DAPT) among elderly (≥75 years) and non-elderly patients (<75 years) undergoing percutaneous coronary intervention. METHODS AND RESULTS: The primary efficacy endpoint of the PRODIGY trial was the composite of death, myocardial infarction, or cerebrovascular accident at 24-month follow-up. The key safety endpoint was type 2, 3 or 5 bleeding according to the BARC criteria. Of 1,970 participants, 587 (29.8%) were elderly and had a higher risk of adverse events compared with younger patients. The risk of the primary endpoint was not significantly reduced with 24-month compared to six-month DAPT among both elderly (HR 0.80, 95% CI: 0.55-1.16, p=0.24) and non-elderly patients (HR 1.48, 95% CI: 0.95-2.30, p=0.08), although interaction testing was significant (p=0.036). A 24-month versus six-month DAPT significantly increased the risk of BARC type 2, 3 or 5 bleeding in both older (HR 1.90, 95% CI: 1.06-3.38, p=0.03) and younger patients (HR 2.54, 95% CI: 1.43-4.53, p=0.002, p-interaction=0.48). However, measures of absolute risk difference indicated a less favourable safety profile of prolonged DAPT for older rather than younger patients. CONCLUSIONS: In the PRODIGY trial, prolonging clopidogrel-based DAPT beyond six months in elderly patients increased the risk of bleeding, without affording a significant prevention of ischaemic events.

Role of stent type and of duration of dual antiplatelet therapy in patients with chronic kidney disease undergoing percutaneous coronary interventions. Is bare metal stent implantation still a justifiable choice? A post-hoc analysis of the all comer PRODIGY trial.

AIM: Chronic kidney disease (CKD) is a powerful predictor of major cardiovascular events and stent thrombosis (ST) in patients undergoing percutaneous coronary interventions (PCI). No randomized data are available to compare, and guide the selection of type of stent between bare metal (BMS) or drug eluting stent (DES) in this population. METHODS AND RESULTS: We performed a post-hoc analysis of the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY) trial, in which stable or unstable patients with coronary artery disease undergoing PCI were randomized 1:1:1:1 to receive BMS, paclitaxel- (PES), zotarolimus- (ZES-S), or everolimus- (EES) eluting stent. A total of 2003 patients were randomized, and 22 patients were excluded for missing serum creatinine leading to a final population of 1981 patients. Primary outcome was definite or probable ST. We also assessed MACE (myocardial infarction, stroke, or death), and all-cause death, as secondary outcome. CKD, defined with estimated glomerular filtration rate <60ml/min/1.73m(2), was found in 373 patients (18.8%). The incidence of ST at 2years was 5.1% in CKD and 2.1% in non-CKD patients (HR 2.57, 95% confidence interval (CI) 1.46 to 4.52, p<0.001). At multivariable regression we found that patients randomized to EES or ZES-S, but not PES, had lower risk of ST at two years as compared with BMS: adjusted HR=0.288, 95% CI [0.107-0.778, p=0.014] and HR=0.394, 95% CI [0.164-0.947, p=0.037] respectively. The number of patients needed to be treated to prevent 1 ST with an EES vs BMS was 20 in CKD and 50 in patients without CKD. EES patients had the lowest incident MACE events 26.4% as compared to BMS 35.1%, ZES-S 33.0%, or PES 35.7% patients, p=0.551. All-cause death was lowest in ZES-S group 10.6% as compared to BMS 18.1%, PES 25.5% and EES 14.9%, p=0.040. We found no significant interaction between DAPT duration (6 vs 24months) and stent type on primary outcome, PINT=0.47 for BMS, PINT=0.57 for PES, PINT=0.41 for ZES-S and PINT=0.28 for EES. CONCLUSIONS: In an all-comer population of patients with stable and unstable CAD, CKD at baseline was associated with a double risk of ST and MACE. CKD patients receiving EES had less than half risk of ST 2years after PCI as compared with BMS and PES. Our analysis suggests that 2nd generation limus-based stent should be favored over paclitaxel-based DES or BMS to reduce ST and MACE in CKD patients.

Phosphate- or Citrate-Buffered Tirofiban Versus Unfractionated Heparin and its Impact on Thrombocytopenia and Clinical Outcomes in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the PRISM Trial.

OBJECTIVES: The aim of this study was to investigate whether the 2 tirofiban formulations tested in the early and late phases of the PRISM (Platelet Receptor Inhibitor in Ischemic Syndrome Management) trial might differ with respect to risk for thrombocytopenia and clinical outcomes compared with unfractionated heparin (UFH). BACKGROUND: Citrate-buffered tirofiban is currently marketed as brand-name drug. However, tirofiban has recently been promoted in some countries as a generic drug with different formulations, such as phosphate-buffered product. METHODS: In the PRISM trial 3,232 patients were randomly assigned to receive tirofiban or UFH. In the early phase, 879 patients were allocated to phosphate-buffered tirofiban and 874 patients to UFH group. After a protocol amendment due to a study drug instability report, citrate-buffered tirofiban replaced the phosphate-buffered formulation. Therefore, in the late phase, 737 and 742 patients were treated with citrate-buffered tirofiban and UFH, respectively. RESULTS: The relative risk for thrombocytopenia (nadir <90,000/mm(3) or <100,000/mm(3)) was increased in patients treated with phosphate-buffered tirofiban in the early phase (odds ratio [OR]: 3.51; 95% confidence interval [CI]: 1.15 to 10.73; p = 0.027; and OR: 2.83; 95% CI: 1.11 to 7.22; p = 0.029, respectively) but not in patients treated with citrate-buffered tirofiban in the late phase (OR: 1.01; 95% CI: 0.20 to 5.05; p = 0.987; and OR: 0.99; 95% CI: 0.26 to 3.45; p = 0.991, respectively). Using a combined definition of thrombocytopenia (nadir <150,000/mm(3) or a decrease ≥50%), the randomization period significantly modified the effect of the treatment (tirofiban vs. UFH) on platelet decrease (p for interaction = 0.024). Thrombocytopenia was associated with a 5- to 10-fold increased risk for TIMI (Thrombolysis In Myocardial Infarction) bleeding and a 2-fold increased risk for net adverse cardiovascular events. CONCLUSIONS: Phosphate-buffered tirofiban, currently marketed as a generic drug, is associated with a higher rate of thrombocytopenia with a potentially increased risk for adverse clinical outcomes compared with citrate-buffered tirofiban.

Radial versus femoral approach in STEMI: what do we know so far?

Radial approach has been used since 1989 to perform coronary angiography as an alternative to femoral access. During past decades, the development of dedicated equipment has led to high efficacy also in complex procedures. ST elevation myocardial infarction (STEMI) is known to be a high bleeding risk setting and in turn bleeding events can negatively impact on outcomes. Observational studies have demonstrated feasibility, efficacy and safety of radial approach when compared to femoral access in STEMI patients, with benefit in bleeding rates. These advantages have also been described in specific populations such as in the elderly and in patients with cardiogenic shock. Some large randomized trials have been conducted to assess outcomes of transradial access versus transfemoral access, with RIVAL and MATRIX representing the largest two studies. The RIVAL documented a significant reduction in access site-related complications in the global population of acute coronary syndrome (ACS) patients, with also lower mortality and net clinical adverse events (NACE), mainly driven by significant reduction of bleeding and all-cause mortality, in the STEMI sub-group. Overall, the MATRIX trial confirmed that radial access decreased bleeding and all-cause death thus reducing the rate of NACE and supporting the transradial access as the one to be preferred in ACS patients. Clinical advantages of radial access have been also tested in smaller randomized trials corroborating the evidence of radial access as a highly recommendable alternative to femoral access in the setting of primary percutaneous coronary intervention (p-PCI). The current evidence suggests that radial access should become the default access for patients with ACS undergoing invasive management.

Left main or proximal left anterior descending coronary artery disease location identifies high-risk patients deriving potentially greater benefit from prolonged dual antiplatelet therapy duration.

AIMS: It is currently unclear if the location of coronary artery disease affects decision making with regard to dual antiplatelet therapy (DAPT). We investigated if the presence of at least 30% luminal narrowing in the left main (LM) and/or proximal left anterior descending (pLAD) coronary arteries on angiography is an outcome modifier with respect to DAPT duration. METHODS AND RESULTS: In the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia (PRODIGY) study, 953 (54.3%) patients with and 801 (45.7%) without LM/pLAD lumen narrowing at the qualifying coronary intervention were randomised to six or 24 months of DAPT. Twenty-four month as compared to six-month DAPT reduced the occurrence of definite, probable or possible stent thrombosis by 50% in patients with (2.8% vs. 5.6%; HR 0.45, 95% CI: 0.23-0.89; p=0.02) but not in those without LM/pLAD lumen narrowing, with a highly significant interaction testing (PINT= 0.002). This result remained consistent irrespective of whether stenting was (PINT: 0.01) or was not (PINT: 0.02) performed in the LM/pLAD. CONCLUSIONS: Left main and/or proximal LAD lumen narrowing may be a treatment modifier with respect to the duration of DAPT. Patients fulfilling these angiographic characteristics seem to benefit from a prolonged dual antiplatelet treatment. Trial registration: ClinicalTrials.gov Identifier: NCT00611286