Sara Ariotti

Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial.

OBJECTIVES This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. BACKGROUND DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns. METHODS The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization. RESULTS Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups. CONCLUSIONS Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy

Background Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent‐Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24‐ and 6‐month dual antiplatelet therapy groups. Methods and Results Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS−BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS‐BLED. Major bleeding and transfusions were higher in the 24‐ versus 6‐month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (P int=0.05 and P int=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24‐month rather than 6‐month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively. Conclusions Our analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all‐comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long‐term dual antiplatelet therapy regimen. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.

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.

Duration of dual antiplatelet therapy after drug-eluting stent implantation: will we ever reach a consensus?

This editorial refers to ‘ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting’, by S. Schulz-Schupke et al. , on page doi:10.1093/eurheartj/ehu523. ‘Well? Shall we go?’—‘Yes, lets go’. ‘They do not move.’Waiting for Godot, by Samuel Beckett, Combined treatment with aspirin and a P2Y12 inhibitor, the so-called dual antiplatelet therapy (DAPT) regimen, exerts protection against ischaemic myocardial recurrences via a double mechanism of action. First, it prevents sudden thrombotic occlusion of previously implanted stent(s) in the coronary arteries, thereby reducing the risk of stent thrombosis that occurs as a result of inflammation during healing.1,2 Since the vast majority of stent thrombosis cases are known to occur within the first weeks after stent implantation, an arbitrary 30 day to 6 weeks duration of DAPT has been investigated and a 30 day duration of therapy has become the standard of care approach after uncoated stent implantation. Secondly, DAPT has also been shown to mitigate the risk of subsequent myocardial infarction in patients not previously treated with coronary stents or arising from non-previously stented coronary segments.3,4 While the capability of DAPT to limit the progression of atherosclerosis per se has never been demonstrated, it remains likely—even if not proven—that DAPT protects the patient from the consequences of spontaneous coronary plaque rupture. The reasons why long-term prolongation of DAPT is debated, despite its unquestionable value, are two-fold. Long-term DAPT carries a time-dependent risk of major and clinically relevant bleeding complications, which affects morbidity and mortality at least as much as ischaemic recurrences.4–7 Moreover, the advent of drug-eluting stents (DES) has prompted attention …

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.

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

Dual-antiplatelet therapy (DAPT) with aspirin and oral P2Y12 adenosine diphosphatereceptor inhibitors is an evidence-based, guideline-recommended standard of care in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) (13). The pathobiological rationale for DAPT after PCI is to prevent atherothrombotic manifestations in the stented coronary segments before arterial healing and stent endothelialization are complete. However, although guidelines mandate a minimum course of 1 to 6 months after PCI, depending on clinical presentation and stent type (1, 3), the optimal duration of DAPT in the long term is controversial because the ischemic protection afforded by extended DAPT is largely offset by an increase in bleeding complications (4, 5). Prolonged DAPT has been estimated to prevent 8 myocardial infarctions per 1000 persons treated for 1 year, but at a cost of 6 major bleeding events (6, 7). In view of this tradeoff between efficacy and safety, as well as a possible lack of a mortality benefit due to an increase in noncardiovascular deaths with prolonged DAPT (4, 8), American and European guidelines recommend individualizing the duration of DAPT on the basis of ischemic versus bleeding risks (1, 3). This recommendation is also consistent with the results of a survey assessing contemporary clinical practice (9). The DAPT score is a new standardized tool to identify patients who would derive benefit or harm from prolonged DAPT (10, 11). However, the efficacy and safety of DAPT duration as guided by the score have not been assessed outside the derivation cohort included in the DAPT (Dual Antiplatelet Therapy) Study (ClinicalTrials.gov: NCT00977938), in which all patients received DAPT for 12 months and were then randomly assigned to continue thienopyridine treatment or placebo on a background of aspirin (8). We therefore sought to apply the DAPT score to PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study), which enrolled a broadly inclusive sample of patients randomly assigned to a prolonged (24 months) versus a short (6 months) DAPT regimen after PCI (12). Methods Details on study design and primary results of PRODIGY have been reported elsewhere (1214). Briefly, unselected patients undergoing PCI (n= 2013) were randomly assigned to receive 1 of 4 types of stent (bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting). At 30 days, 1970 patients were randomly allocated to either 6 or 24 months of DAPT. Randomization was stratified by center, ongoing ST-segment elevation myocardial infarction, presence or absence of diabetes mellitus, and presence or absence of in-stent restenosis. Selection criteria were broad in order to reflect routine clinical practice. The main exclusion criteria were known allergy to antiplatelet drugs, planned surgery within the next 24 months, history of bleeding diathesis, active bleeding or stroke in the previous 6 months, need for concomitant oral anticoagulation, pregnancy, and life expectancy less than 2 years. Treatment Protocol A maintenance dose of clopidogrel (75 mg/d) was administered for up to 6 or 24 months according to randomization. A low dose of aspirin (80 to 160 mg/d) was prescribed indefinitely in all patients. Study End Points The primary efficacy end point for this analysis was the composite of death, myocardial infarction, or cerebrovascular accident. Other efficacy outcomes included each component of the primary efficacy end point, cardiovascular death, and stent thrombosis according to the Academic Research Consortium criteria (15). The primary safety end point was a composite of type 3 or 5 bleeding according to the Bleeding Academic Research Consortium (BARC) definitions, including overt bleeding with a decrease in hemoglobin level of at least 3 g/dL; bleeding requiring transfusion, intravenous vasoactive agents, or surgical intervention for control; bleeding resulting in cardiac tamponade; and intracranial or intraocular bleeding. Other safety end points were BARC type 2, 3, or 5 bleeding as well as bleeding that met the Thrombolysis in Myocardial Infarction (TIMI) and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria. The BARC, TIMI, and GUSTO criteria are detailed in Appendix 1. A clinical events committee blinded to treatment allocation adjudicated all efficacy and safety events. Calculation of the DAPT Score We calculated the DAPT score for each patient included in PRODIGY, as previously reported (10). The score ranges from 2 to 10 and is calculated by assigning points according to characteristics related to the patient (0 for age <65 years, 1 for age 65 and <75 years, 2 for age 75 years, 1 for diabetes mellitus, 1 for current smokers, 1 for prior PCI or myocardial infarction, and 2 for history of congestive heart failure or left ventricular ejection fraction <30%) and the index procedure (1 for acute myocardial infarction at presentation, 2 for PCI of saphenous vein graft, 1 for implantation of a paclitaxel-eluting stent, and 1 for stent diameter <3 mm). Overall, a low score (<2) identifies patients for whom bleeding risks outweigh ischemic benefits, and a high score (2) identifies patients for whom ischemic benefits outweigh bleeding risks. A calculator for the score is available at www.daptstudy.org/for-clinicians/calchome.htm. Statistical Analysis For calculation of the DAPT score, missing values for left ventricular ejection fraction (n= 136) were estimated using multiple imputation (Appendix 2). The reported percentages are KaplanMeier estimates of cumulative incidence at 24 months. Because the randomized treatment between groups began to diverge at 6 months, a landmark analysis was performed between 6 and 24 months by censoring patients if they experienced the event of interest, died, or were lost to follow-up before 6 months (16). The efficacy and safety of prolonged versus short DAPT were assessed in categories of high and low DAPT score. To account for data censoring, the pseudovalue approach was used to calculate absolute risk differences (RDs) and 95% CIs between prolonged and short DAPT (17). The treatment effect of prolonged versus short DAPT between patients with high and low scores was compared using a Z test for interaction (18). The efficacy of prolonged versus short DAPT within the high and low score groups was also explored across stent types, with heterogeneity assessed by the Q statistic. Sensitivity analyses were conducted from 1 to 24 months after patients who received earlier-generation paclitaxel-eluting stents, which are associated with a higher risk for stent thrombosis and myocardial infarction, and those with missing values for left ventricular ejection fraction were excluded. A sensitivity analysis of safety outcomes accounting for the competing risk for death was also conducted (17). All P values were 2-sided, and those less than 0.05 indicated statistical significance. All analyses were done using Stata, version 13 (StataCorp). Further details on the statistical analysis are provided in Appendix 2. Institutional Review Board Approval The ethics committees of the participating centers independently approved the protocol, and all participants gave written informed consent. Role of the Funding Source This study received no funding. Results DAPT Score Distribution and Baseline Characteristics Of 1970 patients enrolled in PRODIGY, 884 (44.9%) had a high DAPT score (2) and 1086 (55.1%) had a low score (<2). The median score was 1 (interquartile range, 0 to 2; mean, 1.3 [SD, 1.5]) (Appendix Figure 1). Patients with high scores were younger and more likely to be male; to be smokers; and to have diabetes, prior myocardial infarction, prior coronary revascularization, congestive heart failure or left ventricular dysfunction, and acute myocardial infarction at presentation. They also were less likely to have arterial hypertension or peripheral artery disease and had higher estimated glomerular filtration rates (Table 1). Patients with high scores more frequently had PCI for saphenous vein graft disease or in-stent restenosis and had a greater mean stent diameter (Table 2). Baseline and periprocedural characteristics were similar within high and low score groups between patients assigned to 24 versus 6 months of DAPT (Appendix Tables 1 and 2). Appendix Figure 1. Distribution of the DAPT score. DAPT = dual-antiplatelet therapy. Table 1. Baseline Characteristics, by DAPT Score Table 2. Angiographic Characteristics, by DAPT Score* Appendix Table 1. Baseline Characteristics, by DAPT Score and Randomized Treatment Appendix Table 2. Angiographic Characteristics, by DAPT Score and Randomized Treatment Efficacy Outcomes With Prolonged Versus Short DAPT, by Score The reduction in the primary efficacy outcome of death, myocardial infarction, or cerebrovascular accident with 24 versus 6 months of DAPT was greater in patients with high scores than those with low scores (P for interaction= 0.030) (Figure, top). Figure. Riskbenefit assessment of a DAPT scoreguided strategy from 6 to 24 mo for the primary efficacy end point (top) and the primary safety end point (bottom). DAPT= dual-antiplatelet therapy. Among patients with high scores, the primary ischemic outcome occurred in 4.2% randomly assigned to 24-month DAPT compared with 6.2% randomly assigned to 6-month DAPT (RD, 2.05 percentage points [95% CI, 5.04 to 0.95 percentage points]) (Table 3 and Appendix Figure 2). Compared with short DAPT, prolonged DAPT was associated with fewer cardiac deaths and myocardial infarctions (RD, 2.01 percentage points [CI, 4.53 to 0.51 percentage points]). Definite, probable, or possible stent thrombosis was also significantly reduced in patients with high scores who received prolonged versus short DAPT (RD, 2.44 percentage points [CI, 4.70 to 0.19 percentage points]). Among patients with low

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.

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.

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.

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

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.