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.

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.

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.

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).

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.

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.

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.

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.

Clinical outcomes of transcatheter aortic valve implantation: from learning curve to proficiency.

OBJECTIVE: The use of transcatheter aortic valve implantation (TAVI) is growing rapidly in countries with a predominantly elderly population, posing a huge challenge to healthcare systems worldwide. The increment of human and economic resource consumption imposes a careful monitoring of clinical outcomes and cost-benefit balance, and this article is aimed at analysing clinical outcomes related to the TAVI learning curve. METHODS: Outcomes of 177 consecutive transfemoral TAVI procedures performed in 5 years by a single team were analysed by the Cumulative Sum of failures method (CUSUM) according to the clinical events comprised in the Valve Academic Research Consortium (VARC-2) safety end point and the VARC-2 definition of device success. Margins for events acceptance were extrapolated from landmark trials that tested both balloon or self-expandable percutaneous valves. RESULTS: 30-day and 1-year survival rates were 97.2% and 89.9%, respectively. Achievement of the primary end point (number of cases needed to provide the acceptable margin of the composite end point of any death, stroke, myocardial infarction, life-threatening bleeding, major vascular complications, stage 2-3 acute kidney injury and valve-related dysfunction requiring a repeat procedure) required the performance of 54 cases, while the learning curve to achieve 'device success' identified 32 cases to reach the expected proficiency. In this experience, the baseline clinical risk as assessed by the Society of Thoracic Surgeons (STS) score determined the long-term survival rather than the adverse events related to the learning curve. CONCLUSIONS: A relatively large number of cases are required to achieve clinical outcomes comparable to those reported in high-volume centres and controlled trials. According to our national workload standards, this represents more than 2 years of continuous activity.

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.

Impact of Sex on 2-Year Clinical Outcomes in Patients Treated With 6-Month or 24-Month Dual-Antiplatelet Therapy Duration: A Pre-Specified Analysis From the PRODIGY Trial.

OBJECTIVES: The aim of this study was to assess the impact of sex on 2-year outcomes after percutaneous coronary intervention (PCI) in patients randomly allocated to 24-month versus 6-month dual-antiplatelet therapy (DAPT). BACKGROUND: The optimal duration of DAPT after PCI is highly debated. Whether sex per se should drive decision making on DAPT duration remains unclear. METHODS: The primary efficacy endpoint of PRODIGY (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study) 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 Bleeding Academic Research Consortium criteria. RESULTS: Women (n = 459 [23.3%]) were older and more likely to have hypertension, lower creatinine clearance, and acute coronary syndrome but had a lower severity of coronary artery disease. After adjustment, prolonged DAPT, compared with 6-month treatment, did not reduce the primary endpoint in both men (adjusted hazard ratio: 1.080; 95% confidence interval: 0.766 to 1.522; p = 0.661) and women (adjusted hazard ratio: 1.013; 95% confidence interval: 0.588 to 1.748; p = 0.962) (interaction p = 0.785). No sex disparity was identified across multiple secondary ischemic endpoints, including overall or cardiovascular mortality, myocardial infarction, and stent thrombosis. There was also no clear sex-related effect on clinically relevant bleeding, including Bleeding Academic Research Consortium type 3 or 5, TIMI (Thrombolysis in Myocardial Infarction), and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) scales. CONCLUSIONS: The present findings suggest that men and women undergoing PCI have similar adjusted 2-year ischemic and bleeding outcomes, despite being characterized by different clinical presentation. Sex failed to emerge as a treatment modifier with respect to DAPT duration, suggesting that decision making on DAPT duration in female patients should weigh ischemic versus bleeding risks.

Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial.

Importance: Patients with concomitant peripheral arterial disease (PAD) experience worse cardiovascular outcomes after percutaneous coronary intervention (PCI). Objective: To assess the efficacy and safety of prolonged (24 months) vs short (≤6 months) dual antiplatelet therapy (DAPT) in patients with PAD undergoing PCI. Design, Setting, and Participants: This subanalysis of the randomized Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) trial assessed unselected patients from tertiary care hospitals with stable coronary artery disease or acute coronary syndromes with or without concomitant PAD from December 2006 to December 2008. Data analysis was performed from January 7 to April 4, 2016. Interventions: Percutaneous coronary intervention. Main Outcomes and Measures: Rates of the primary efficacy end point, composite of death, myocardial infarction, or cerebrovascular accidents, and occurrence of the key safety end point, a composite of Bleeding Academic Research Consortium type 2, 3, or 5. Results: This analysis comprised 246 and 1724 patients with and without PAD, respectively. In the patients with PAD, mean (SD) age was 73.2 (9.2) in the prolonged group and 75.7 (8.7) years in the short DAPT group, and 97 (82.2%) were male in the prolonged group and 92 (71.9%) were male in the short DAPT group. In the patients without PAD, mean (SD) age was 67.1 (11.2) years in the prolonged group and 66.8 (11.3) years in the short DAPT group, and 667 (76.8%) were male in the prolonged group and 655 (76.6%) were male in the short DAPT group. Status of PAD was associated with a higher risk of death and ischemic events (hazard ratio [HR], 2.80; 95% CI, 2.05-3.83; P < .001). Prolonged vs short DAPT conveyed a lower risk of the primary efficacy end point in patients with PAD (19 [16.1%] vs 35 [27.3%]; HR, 0.54; 95% CI, 0.31-0.95; P = .03) but not in patients without PAD (81 [9.3%] vs 63 [7.4%]; HR, 1.28; 95% CI, 0.92-1.77; P = .15), with positive interaction (P = .01). The risk of definite or probable stent thrombosis was significantly lower in patients with PAD treated with prolonged compared with short DAPT (HR, 0.07; 95% CI, 0-1.21; P = .01). Bleeding Academic Research Consortium type 2, 3, or 5 bleeding occurred in 6 patients with PAD (5.2%) receiving prolonged DAPT relative to 8 (6.9%) of those receiving short DAPT (HR, 0.77; 95% CI, 0.27-2.21; P = .62), with a significant interaction (P = .04) compared with patients without PAD. Conclusions and Relevance: Peripheral artery disease confers a poor prognosis in patients undergoing PCI in the setting of stable coronary artery disease or acute coronary syndromes. Prolonged DAPT lowers the risk of ischemic events with no apparent bleeding liability in this high-risk group. Trial Registration: clinicaltrials.gov Identifier: NCT00611286.

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.

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.