Survival curves were generated using the Kaplan\Meier technique, as well as the difference between organizations was assessed with a log\rank check. the difference between combined data. Success curves were produced using the Kaplan\Meier technique, as well as the difference between organizations was assessed with a log\rank check. The univariable and multivariable analyses to judge the 3rd party contribution of medical and angiographic factors to the principal end point had been performed from the Cox proportional risks model. The factors that reached the best significance in the univariable evaluation were regarded as in the ultimate multivariable model to avoid overfitting. Risk ratios (HR) and their 95% CI had been calculated. All testing were 2\tailed. To be able to minimize the bias due to the nonrandomized character from the scholarly research and the chance of overfitting, a propensity rating evaluation was performed utilizing a logistic regression model that the possibility for HPR was determined for each individual; variables introduced in to the propensity rating model were age group (years), man sex, diabetes mellitus, earlier coronary artery bypass graft, earlier myocardial infarction (MI), chronic kidney disease, remaining ventricular ejection small fraction <0.40, ACS, remaining anterior descending artery CTO, and 3\vessel disease. Model discrimination was assessed using the goodness\of\in shape and C\statistic with Hosmer and Lemeshow check. Thereafter, a Cox multivariable evaluation was performed using the propensity rating as a continuing covariate. A ValueValueValueValue
Age group (per con)1.08 (1.05C1.11)<0.0011.07 (1.04C1.10)<0.001Male sex0.42 (0.24C0.74)0.003Diabetes mellitus3.39 (2.04C5.64)<0.0012.86 (1.70C4.80)<0.001Previous MI1.68 (0.99C2.85)0.051Previous CABG2.54 (1.46C4.41)0.001Chronic kidney disease4.51 (2.57C7.92)<0.001ACS1.70 (0.99C2.90)0.053LVEF <0.407.06 (3.88C12.85)<0.0015.27 (2.87C9.65)<0.001Left anterior descending artery CTO1.81 (1.09C3.02)0.022Three\vessel disease1.67 (0.98C2.84)0.058Successful CTO\PCI0.33 (0.20C0.56)<0.001Complete Revascularization0.20 (0.12C0.34)<0.0010.31 (0.18C0.54)<0.001HPR on clopidogrel not switched3.46 (1.97C6.07)<0.0012.37 (1.33C4.20)0.003HPR on clopidogrel switched1.39 (0.60C3.25)0.436New P2Y12 antagonist therapy0.84 (0.46C1.52)0.578Year index0.99 (0.85C1.16)0.980Second generation DES0.90 (0.56C1.46)0.697 Open up in another window ACS indicates severe coronary symptoms; CABG, coronary artery bypass graft; CTO, chronic total occlusion; DES, medication\eluting stent; HPR, high platelet reactivity; LVEF, remaining ventricular ejection small fraction; MI, myocardial infarction; PCI, percutaneous coronary treatment. Discussion The primary findings of the analysis could be summarized the following: (1) HPR to ADP in individuals going through CTO\PCI was connected with very long\term cardiac mortality; (2) HPR on clopidogrel treatment could possibly be effectively overcome by switching to fresh P2Y12 receptor inhibitors as demonstrated by platelet function lab testing; (3) HPR of non-responders, whose therapy have been escalated to prasugrel and ticagrelor or transformed between these medicines efficiently, was simply no significantly linked to very long\term cardiac mortality much longer. To our understanding, this is the first research to measure the lengthy\term prognosis of individuals going through CTO\PCI and handled with a customized antiplatelet therapy predicated on platelet function tests in the brand new antiplatelet period. Several observational research and randomized managed trials possess explored the effect of platelet hyperreactivity on cardiovascular event prices in different medical settings, with conflicting results often.12, 22, 23, 24, 25, 26, 27 Specifically, outcomes of previous randomized controlled tests that didn't establish clinical improvements after treatment modifications predicated on platelet function tests had a solid impact traveling clinical practice recommendations that usually do not currently recommend schedule evaluation of platelet reactivity. The GRAVITAS (Gauging Responsiveness having a VerifyNow P2Y12 Assay: Effect on Thrombosis and Protection) research showed the shortcoming of a dual dosage of clopidogrel to totally overcome HPR and improve results; furthermore, the populace was underpowered as well as the follow\up period was brief (6?weeks). Result in\PCI (Tests Platelet Reactivity In Individuals Going through Elective Stent Positioning on Clopidogrel to steer Substitute Therapy With Prasugrel) research didn't demonstrate a 6\month success benefit in individuals with HPR turned to prasugrel for an extremely low noticed ischemic event price inside a low\risk human population that was actually underpowered. The ARCTIC (Two times Randomization of the Monitoring Adjusted Antiplatelet Treatment Pitched against a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Two times Antiplatelet Therapy) trial prolonged the follow\up time for you to 12?weeks and included 27% of ACS but only 9.3% of individuals.Baseline Characteristics Click here for more data document.(95K, pdf) Acknowledgments We are grateful to Paola Fabio and Baldini Torrini, (A.R. relating to light transmitting aggregometry outcomes: ideal platelet reactivity (82%) and HPR (18%). Opportinity for the adenosine diphosphate check had been 4416% versus 776%, respectively. Three\yr survival was considerably higher in the perfect platelet reactivity group weighed against HPR individuals (95.30.8% versus 86.22.8%; check or Mann\Whitney rank\amount check were used to check differences among constant variables. A combined check was used to check the difference between combined data. Success curves were produced using the Kaplan\Meier technique, as well as the difference between organizations was assessed with a log\rank check. The univariable and multivariable analyses to judge the 3rd party contribution of medical and angiographic factors to the principal end point had been performed from the Cox proportional risks model. The factors that reached the best significance in the univariable evaluation were regarded as in the ultimate multivariable model to avoid overfitting. Risk ratios (HR) and their 95% CI had been calculated. All testing were 2\tailed. To be able to minimize the bias due to the nonrandomized character of the analysis and the chance of overfitting, a propensity rating evaluation was performed utilizing a logistic regression model that the possibility for HPR was determined for each individual; variables introduced in to the propensity rating model were age group (years), man sex, diabetes mellitus, earlier coronary artery bypass graft, earlier myocardial infarction (MI), chronic kidney disease, remaining ventricular ejection small fraction <0.40, ACS, remaining anterior descending artery CTO, and 3\vessel disease. Model discrimination was evaluated using the C\statistic and goodness\of\match with Hosmer and Lemeshow check. Thereafter, a Cox multivariable evaluation was performed using the propensity rating as a continuing covariate. A ValueValueValueValue
Age group (per con)1.08 (1.05C1.11)<0.0011.07 (1.04C1.10)<0.001Male sex0.42 (0.24C0.74)0.003Diabetes mellitus3.39 (2.04C5.64)<0.0012.86 (1.70C4.80)<0.001Previous MI1.68 (0.99C2.85)0.051Previous CABG2.54 (1.46C4.41)0.001Chronic kidney disease4.51 (2.57C7.92)<0.001ACS1.70 (0.99C2.90)0.053LVEF <0.407.06 (3.88C12.85)<0.0015.27 (2.87C9.65)<0.001Left anterior descending artery CTO1.81 (1.09C3.02)0.022Three\vessel disease1.67 (0.98C2.84)0.058Successful CTO\PCI0.33 (0.20C0.56)<0.001Complete Revascularization0.20 (0.12C0.34)<0.0010.31 (0.18C0.54)<0.001HPR on clopidogrel not switched3.46 (1.97C6.07)<0.0012.37 (1.33C4.20)0.003HPR on clopidogrel switched1.39 (0.60C3.25)0.436New P2Y12 antagonist therapy0.84 (0.46C1.52)0.578Year index0.99 (0.85C1.16)0.980Second generation DES0.90 (0.56C1.46)0.697 Open up in another window ACS indicates severe coronary symptoms; CABG, coronary artery bypass graft; CTO, chronic total occlusion; DES, medication\eluting stent; HPR, high platelet reactivity; LVEF, remaining ventricular ejection small fraction; MI, myocardial infarction; PCI, percutaneous coronary treatment. Discussion The primary findings of the analysis could be summarized the following: (1) HPR to ADP in individuals going through CTO\PCI was connected with very long\term cardiac mortality; (2) HPR on clopidogrel treatment could possibly be effectively overcome by switching to fresh P2Y12 receptor inhibitors as demonstrated by platelet function lab testing; (3) HPR of non-responders, whose therapy have been efficiently escalated to prasugrel and ticagrelor or transformed between these medicines, was no more significantly linked to lengthy\term cardiac mortality. To your knowledge, this is the first research to measure the lengthy\term prognosis of individuals going through CTO\PCI and handled with a customized antiplatelet therapy predicated on platelet function tests in the brand new antiplatelet period. Several observational research and randomized managed trials possess explored the effect of platelet hyperreactivity on cardiovascular event prices in different medical settings, frequently with conflicting outcomes.12, 22, 23, 24, 25, 26, 27 Specifically, outcomes of previous randomized controlled tests that didn't establish clinical improvements after treatment modifications based on platelet function screening had a strong impact driving clinical practice recommendations that do not currently recommend program assessment of platelet reactivity. The GRAVITAS (Gauging Responsiveness having a VerifyNow P2Y12 Assay: Impact on Thrombosis and Security) study showed the inability of a double dose of clopidogrel to completely overcome HPR and improve results; furthermore, the population was underpowered and the follow\up time was short (6?weeks). Result in\PCI (Screening Platelet Reactivity In Individuals Undergoing Elective Stent Placement on Clopidogrel to Guide Alternate Therapy With Prasugrel) study failed to demonstrate a 6\month survival benefit in individuals with HPR switched to prasugrel for a very low observed ischemic event rate inside a low\risk populace that was actually underpowered. The ARCTIC (Two times Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Two times Antiplatelet Therapy) trial prolonged the follow\up time to 12?weeks and included 27% of ACS but only 9.3% of individuals were discharged home on prasugrel in the monitoring group. In the ANTARCTIC (Tailored Antiplatelet Therapy Versus Recommended Dose of Prasugrel) trial, individuals included were older >75?years and all presented with ACS: with this large\risk populace, platelet function monitoring did not improve 1\12 months ischemic or security outcomes. More recently, in TROPICAL\ACS, guided de\escalation of antiplatelet treatment was noninferior to standard treatment with prasugrel after PCI in terms.All these randomized controlled tests have been conducted with different platelet function assays and thresholds; hypothetically, the results acquired with 1 of these checks could not become transferred to the others. In our study, platelet aggregation was assessed by LTA, a laboratory assay considered as a gold standard past years but currently replaced by other tests (VerifyNow, VASP, and Multiplate) because of the lack of standardization between institutions.32 HPR to ADP was found in 18% of the study populace, mainly older and diabetic patients, consistently with previous data.11, 17, 18 The clinical benefit demonstrated by prasugrel in diabetic individuals21, the earlier availability of this agent, and the better compliance of individuals explain the prevalence of this prescription; ticagrelor was primarily prescribed in case of contraindications to prasugrel therapy. (18%). Means for the adenosine diphosphate test were 4416% versus 776%, respectively. Three\12 months survival was significantly higher in the optimal platelet reactivity group compared with HPR individuals (95.30.8% versus 86.22.8%; test or Mann\Whitney rank\sum test were used to test differences among continuous variables. A combined test was used to test the difference between combined data. Survival curves were generated using the Kaplan\Meier method, and the difference between groupings was assessed with a log\rank check. The univariable and multivariable analyses to judge the indie contribution of scientific and angiographic factors to the principal end point had been performed with the Cox proportional dangers model. The factors that reached the best significance on the univariable evaluation were regarded in the ultimate GSK2578215A multivariable model to avoid overfitting. Threat ratios (HR) and their 95% CI had been calculated. All exams were 2\tailed. To be able to minimize the bias due to the nonrandomized character of the analysis and the chance of overfitting, a propensity rating evaluation was performed utilizing a logistic regression model that the possibility for HPR was computed for each individual; variables introduced in to the propensity rating model were age group (years), man sex, diabetes mellitus, prior coronary artery bypass graft, prior myocardial infarction (MI), chronic kidney disease, still left ventricular ejection small fraction <0.40, ACS, still left anterior descending artery CTO, and 3\vessel disease. Model discrimination was evaluated using the C\statistic and goodness\of\suit with Hosmer and Lemeshow check. Thereafter, a Cox multivariable evaluation was performed using the propensity rating as a continuing covariate. A ValueValueValueValue
Age group (per con)1.08 (1.05C1.11)<0.0011.07 (1.04C1.10)<0.001Male sex0.42 (0.24C0.74)0.003Diabetes mellitus3.39 (2.04C5.64)<0.0012.86 (1.70C4.80)<0.001Previous MI1.68 (0.99C2.85)0.051Previous CABG2.54 (1.46C4.41)0.001Chronic kidney disease4.51 (2.57C7.92)<0.001ACS1.70 (0.99C2.90)0.053LVEF <0.407.06 (3.88C12.85)<0.0015.27 (2.87C9.65)<0.001Left anterior descending artery CTO1.81 (1.09C3.02)0.022Three\vessel disease1.67 (0.98C2.84)0.058Successful CTO\PCI0.33 (0.20C0.56)<0.001Complete Revascularization0.20 (0.12C0.34)<0.0010.31 (0.18C0.54)<0.001HPR on clopidogrel not switched3.46 (1.97C6.07)<0.0012.37 (1.33C4.20)0.003HPR on clopidogrel switched1.39 (0.60C3.25)0.436New P2Y12 antagonist therapy0.84 (0.46C1.52)0.578Year index0.99 (0.85C1.16)0.980Second generation DES0.90 (0.56C1.46)0.697 Open up in another window ACS indicates severe coronary symptoms; CABG, coronary artery bypass graft; CTO, chronic total occlusion; DES, medication\eluting stent; HPR, high platelet reactivity; LVEF, still left ventricular ejection small fraction; MI, myocardial infarction; PCI, percutaneous coronary involvement. Discussion The primary findings of the analysis could be summarized the following: (1) HPR to ADP in sufferers going through CTO\PCI was connected with longer\term cardiac mortality; (2) HPR on clopidogrel treatment could possibly be effectively overcome by switching to brand-new P2Y12 receptor inhibitors as proven by platelet function lab exams; (3) HPR of non-responders, whose therapy have been successfully escalated to prasugrel and ticagrelor or transformed between these medications, was no GSK2578215A more significantly linked to lengthy\term cardiac mortality. To your knowledge, this is the first research to measure the lengthy\term prognosis of sufferers going through CTO\PCI and maintained with a customized antiplatelet therapy predicated on platelet function tests in the brand new antiplatelet period. Several observational research and randomized managed trials have got explored the influence of platelet hyperreactivity on cardiovascular event prices in different scientific settings, frequently with conflicting outcomes.12, 22, 23, 24, 25, 26, 27 Specifically, outcomes of previous randomized controlled studies that didn’t establish clinical improvements after treatment changes predicated on platelet function tests had a solid impact traveling clinical practice suggestions that usually do not currently recommend schedule evaluation of platelet reactivity. The GRAVITAS (Gauging Responsiveness using a VerifyNow P2Y12 Assay: Effect on Thrombosis and Protection) study demonstrated the inability of the double dosage of clopidogrel to totally overcome HPR and improve final results; furthermore, the populace was underpowered as well as the follow\up period was brief (6?a few months). Cause\PCI (Tests Platelet Reactivity In Individuals Going through Elective Stent Positioning on Clopidogrel to steer Substitute Therapy With Prasugrel) research didn’t demonstrate a 6\month success benefit in individuals with HPR turned to prasugrel for an extremely low noticed ischemic event price inside a low\risk human population that was actually underpowered. The ARCTIC (Two times Randomization of the Monitoring Adjusted Antiplatelet Treatment GSK2578215A Pitched against a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Two times Antiplatelet Therapy) trial prolonged the follow\up time for you to 12?weeks and included 27% of ACS but only 9.3% of individuals were discharged house on prasugrel in the monitoring group. In the ANTARCTIC (Tailored Antiplatelet Therapy Versus Suggested Dosage of Prasugrel) trial, individuals included were old.CARDOnlus Basis, Florence, Italy) for his or her secretarial assistance. Notes (J Am Heart Assoc. versus 776%, respectively. Three\yr survival was considerably higher in the perfect platelet reactivity group weighed against HPR individuals (95.30.8% versus 86.22.8%; check or Mann\Whitney rank\amount check were used to check differences among constant variables. A combined check was used to check the difference between combined data. Success curves were produced using the Kaplan\Meier technique, as well as the difference between organizations was assessed with a log\rank check. The univariable and multivariable analyses to judge the 3rd party contribution of medical and angiographic factors to the principal end point had been performed from the Cox proportional risks model. The factors that reached the best significance in the univariable evaluation were regarded as in the ultimate multivariable model to avoid overfitting. Risk ratios (HR) and their 95% CI had been calculated. All testing were 2\tailed. To be able to minimize the bias due to the nonrandomized character of the analysis and the chance of overfitting, a propensity rating evaluation was performed utilizing a logistic regression model that the possibility for HPR was determined for each individual; variables introduced in to the propensity rating model were age group (years), man sex, diabetes mellitus, earlier coronary artery bypass graft, earlier myocardial infarction (MI), chronic kidney disease, remaining ventricular ejection small fraction <0.40, ACS, remaining anterior descending artery CTO, and 3\vessel disease. Model discrimination was evaluated using the C\statistic and goodness\of\match with Hosmer and Lemeshow check. Thereafter, a Cox multivariable evaluation was performed using the propensity rating as a continuing covariate. A ValueValueValueValue
Age group (per con)1.08 (1.05C1.11)<0.0011.07 (1.04C1.10)<0.001Male sex0.42 (0.24C0.74)0.003Diabetes mellitus3.39 (2.04C5.64)<0.0012.86 (1.70C4.80)<0.001Previous MI1.68 (0.99C2.85)0.051Previous CABG2.54 (1.46C4.41)0.001Chronic kidney disease4.51 (2.57C7.92)<0.001ACS1.70 (0.99C2.90)0.053LVEF <0.407.06 (3.88C12.85)<0.0015.27 (2.87C9.65)<0.001Left anterior descending artery CTO1.81 (1.09C3.02)0.022Three\vessel disease1.67 (0.98C2.84)0.058Successful CTO\PCI0.33 (0.20C0.56)<0.001Complete Revascularization0.20 (0.12C0.34)<0.0010.31 (0.18C0.54)<0.001HPR on clopidogrel not switched3.46 (1.97C6.07)<0.0012.37 (1.33C4.20)0.003HPR on clopidogrel switched1.39 (0.60C3.25)0.436New P2Y12 antagonist therapy0.84 (0.46C1.52)0.578Year index0.99 (0.85C1.16)0.980Second generation DES0.90 (0.56C1.46)0.697 Open up in another window ACS indicates severe coronary symptoms; CABG, coronary artery bypass graft; CTO, chronic total occlusion; DES, medication\eluting stent; HPR, high platelet reactivity; LVEF, remaining ventricular ejection small fraction; MI, myocardial infarction; PCI, percutaneous coronary treatment. Discussion The primary findings of the analysis could be summarized the following: (1) HPR to ADP in individuals going through CTO\PCI was connected with very long\term cardiac mortality; (2) HPR on clopidogrel treatment could possibly be effectively overcome by switching to fresh P2Y12 receptor inhibitors as demonstrated by platelet function lab testing; (3) HPR of non-responders, whose therapy have been efficiently escalated to prasugrel and ticagrelor or transformed between these medicines, was no more significantly linked to lengthy\term cardiac mortality. To your knowledge, this is the first research to measure the lengthy\term prognosis of individuals going through CTO\PCI and handled with a customized antiplatelet therapy predicated on platelet function examining in the brand new antiplatelet period. Several observational research and randomized managed trials have got explored the influence of platelet hyperreactivity on cardiovascular event prices in different scientific settings, frequently with conflicting outcomes.12, 22, 23, 24, 25, 26, 27 Specifically, outcomes of previous randomized controlled studies that didn't establish clinical improvements after treatment changes predicated on platelet function assessment had a solid impact traveling clinical practice suggestions that usually do not currently recommend regimen evaluation of platelet reactivity. The GRAVITAS (Gauging Responsiveness using a VerifyNow P2Y12 Assay: Effect on Thrombosis and Basic safety) study demonstrated the inability of the double dosage of clopidogrel to totally overcome HPR and improve final results; furthermore, the populace was underpowered as well as the follow\up period was brief (6?a few months). Cause\PCI (Examining Platelet Reactivity In Sufferers Going through Elective Stent Positioning on Clopidogrel to steer Choice Therapy With Prasugrel) research didn't demonstrate a 6\month success benefit in sufferers with HPR turned to prasugrel for an extremely low noticed ischemic event price within a low\risk people that was also underpowered. The ARCTIC (Increase Randomization of the Monitoring Adjusted Antiplatelet Treatment Pitched against a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Increase Antiplatelet Therapy) trial expanded the follow\up time for you to 12?a few months and included 27% of ACS but only 9.3% of sufferers were discharged house on prasugrel in the monitoring group. In the ANTARCTIC (Tailored Antiplatelet Therapy Versus Suggested Dosage of Prasugrel) trial, sufferers included were old >75?years and everything offered ACS: within this great\risk people, platelet function monitoring didn’t improve 1\calendar year ischemic or basic safety outcomes. Recently, in TROPICAL\ACS, led de\escalation of antiplatelet treatment was noninferior to regular treatment with prasugrel after PCI with regards to net clinical advantage at 1?calendar year. Each one of these randomized managed trials have already been executed with different platelet function assays and thresholds; hypothetically, the full total benefits attained with 1.Three\year success was considerably higher in the perfect platelet reactivity group weighed against HPR sufferers (95.30.8% versus 86.22.8%; test or Mann\Whitney rank\sum test were used to test differences among continuous variables. and HPR (18%). Means for the adenosine diphosphate test were 4416% versus 776%, respectively. Three\12 months survival was significantly higher in the optimal platelet reactivity group compared with HPR patients (95.30.8% versus 86.22.8%; test or Mann\Whitney rank\sum test were used to test differences among continuous variables. A paired test was used to test the difference between paired data. Survival curves were generated using the Kaplan\Meier method, and the difference between groups was assessed by a log\rank test. The univariable and multivariable analyses to evaluate the impartial contribution of clinical and angiographic variables to the primary end point were performed by the Cox proportional hazards model. The variables that reached the highest significance at the univariable analysis were considered in the final multivariable model in order to avoid overfitting. Hazard ratios (HR) and their 95% CI were calculated. All assessments were 2\tailed. In order to minimize the bias because of the nonrandomized nature of the study and the possibility of overfitting, a propensity score analysis was performed using a logistic regression model from which the probability for HPR was calculated for each patient; variables introduced into the propensity score model were age (years), male sex, diabetes mellitus, previous coronary artery bypass graft, previous myocardial infarction (MI), chronic kidney disease, left ventricular ejection portion <0.40, ACS, left anterior descending artery CTO, and 3\vessel disease. Model discrimination was assessed with the C\statistic and goodness\of\fit with Hosmer and Lemeshow test. Thereafter, a Cox multivariable analysis was performed using the propensity score as a continuous covariate. A ValueValueValueValue
Age (per y)1.08 (1.05C1.11)<0.0011.07 (1.04C1.10)<0.001Male sex0.42 (0.24C0.74)0.003Diabetes mellitus3.39 (2.04C5.64)<0.0012.86 (1.70C4.80)<0.001Previous MI1.68 (0.99C2.85)0.051Previous CABG2.54 (1.46C4.41)0.001Chronic kidney disease4.51 (2.57C7.92)<0.001ACS1.70 (0.99C2.90)0.053LVEF <0.407.06 (3.88C12.85)<0.0015.27 (2.87C9.65)<0.001Left anterior descending artery CTO1.81 (1.09C3.02)0.022Three\vessel disease1.67 (0.98C2.84)0.058Successful CTO\PCI0.33 (0.20C0.56)<0.001Complete Revascularization0.20 (0.12C0.34)<0.0010.31 (0.18C0.54)<0.001HPR on clopidogrel not switched3.46 (1.97C6.07)<0.0012.37 (1.33C4.20)0.003HPR on clopidogrel switched1.39 (0.60C3.25)0.436New P2Y12 antagonist therapy0.84 (0.46C1.52)0.578Year index0.99 (0.85C1.16)0.980Second generation DES0.90 (0.56C1.46)0.697 Open in a separate window ACS indicates acute coronary syndrome; CABG, coronary artery bypass graft; CTO, chronic total occlusion; DES, drug\eluting stent; HPR, high platelet reactivity; LVEF, left ventricular ejection portion; MI, myocardial infarction; PCI, percutaneous coronary intervention. Discussion The main findings of the study can be summarized as follows: (1) HPR to ADP in patients undergoing CTO\PCI was associated with long\term cardiac mortality; (2) HPR on clopidogrel treatment could be successfully overcome by switching to new P2Y12 receptor inhibitors as shown by platelet function laboratory assessments; (3) HPR of nonresponders, whose therapy had been effectively escalated to prasugrel and ticagrelor or changed between these drugs, was no longer significantly related to long\term cardiac mortality. To our knowledge, this was the first study to assess the long\term prognosis of patients undergoing CTO\PCI and managed with a tailored antiplatelet therapy based on platelet function screening in the new antiplatelet era. Several observational studies and randomized controlled trials have explored the impact of platelet hyperreactivity on cardiovascular event rates in different clinical settings, often with conflicting results.12, 22, 23, 24, 25, 26, 27 In particular, results of previous randomized controlled trials that did not establish clinical improvements after treatment adjustments based on platelet function screening had a strong impact driving clinical practice guidelines that do not currently recommend program assessment of platelet reactivity. The GRAVITAS (Gauging Responsiveness with a VerifyNow P2Y12 Assay: Impact on Thrombosis and Security) study showed the inability of a double dose of clopidogrel GSK2578215A to completely overcome HPR and improve outcomes; furthermore, the population was underpowered and the follow\up time was short (6?months). TRIGGER\PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study failed to demonstrate a 6\month survival benefit in patients with HPR switched to prasugrel for a very low observed ischemic event rate PDGFRA in a low\risk population that was even underpowered. The ARCTIC (Double Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Double Antiplatelet Therapy) trial extended.