***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background —High on-treatment platelet reactivity ( HTPR ) is associated with adverse outcomes . We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs . Methods and Results —Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay , defining HTPR as area under the curve > 450 . Those with HTPR were r and omized to prasugrel ( 10 mg/day ) or high-dose clopidogrel ( 150 mg/day ) for 2 weeks and then crossed-over to , respectively , clopidogrel and prasugrel , repeating the P2Y12 assay at the end of each cycle . Clinical follow-up ( until 3 months ) and CYP2C19 genotyping was performed in all patients . The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel . Thirty-two patients were r and omized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel . Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was ( 325.8 versus 478.5 area under the curve , P=0.028 ) . No patient treated with prasugrel exhibited HTPR , whereas 9 ( 28.1 % ) receiving high-dose clopidogrel still had prevalence of HTPR ( P=0.001 ) . Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable . Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 ( 56.3 % ) CYP2C19 * 2 noncarriers ( HTPR in 12.5 % versus 0 , P=0.274 ) , whereas it was significantly worse in the 14 ( 43.7 % ) carriers ( HTPR in 43.7 % versus 0 , P=0.003 ) . Conclusions —HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype . Conversely , high-dose clopidogrel can address HTPR only in CYP2C19 * 2 noncarriers . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01465828 Background We investigated the pharmacodynamic effect of cilostazol addition ( 100 mg twice , Triple ) or clopidogrel doubling ( 150 mg daily , Double ) on st and ard dual antiplatelet therapy in type 2 diabetes mellitus ( T2DM ) patients with clopidogrel resistance undergoing a percutaneous coronary intervention .  Methods and results This was a prospect i ve , r and omized , cross-over platelet function study . Percent inhibition less than 20 % was used as the cutoff value of clopidogrel resistance . After percutaneous coronary intervention , a total of 50 T2DM patients with clopidogrel resistance were assigned to receive cilostazol 100 mg twice daily or clopidogrel 150 mg daily for 28 days ; afterwards , they received cross-over treatment for another 28 days . Eight patients were excluded because of side effects and follow-up loss . The platelet function test using VerifyNow was performed at three time points : at baseline ( T0 ) , 28 days after r and omization ( T1 ) , and 28 days after cross-over treatment (T2).A total of 42 T2DM patients completed the study protocol . The clopidogrel resistance improved significantly following cilostazol addition or clopidogrel doubling treatment compared with baseline ( 52.9±27.0 in Triple , 45.4±16.8 % in Double , P<0.001 in both ) . This effect continued after cross-over treatment ( 58.1±26.1 and 41.0±20.0 % , respectively , both P<0.05 ) . A head-to-head comparison between two groups showed a lower P2Y12 reaction unit ( PRU ) and higher percentage of platelet inhibition in the Triple than those in the Double group ( PRU , 138.7±88.2 vs. 198.8±19.5 , P=0.049 ; % platelet inhibition , 58.1±26.1 vs. 40.97±20.0 , P=0.048 ) . Conclusion Adjunctive treatment with cilostazol in T2DM patients on st and ard dual antiplatelet therapy might be a more effective strategy for overcoming clopidogrel resistance than clopidogrel doubling treatment Aims Patients with diabetes mellitus ( DM ) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM . Prasugrel , a more potent antiplatelet agent , is associated with greater reductions in ischaemic events compared with clopidogrel , particularly in patients with DM . The aim of this study was to perform serial pharmacodynamic assessment s of prasugrel with high-dose clopidogrel in patients with DM . Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospect i ve , r and omized , double-blind , crossover study in patients with type 2 DM and coronary artery disease ( CAD ) . Patients ( n= 35 ) were r and omly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose ( MD ) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period . Platelet function was assessed by VerifyNow ® P2Y12 assay , light transmission aggregometry , and vasodilator-stimulated phosphoprotein phosphorylation at 0 , 1 , 4 , and 24 h and 7 days . Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD ( least squares mean , 89.3 vs. 27.7 % , P < 0.0001 ; primary endpoint ) . The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days ( P < 0.0001 ) . Similar results were obtained using all other platelet function measures . Prasugrel result ed in fewer poor responders at all time points irrespective of definition used . Conclusion In patients with type 2 DM and CAD , st and ard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel . Clinical trial identifier : www . clinical trials.gov — OBJECTIVES The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic ( PD ) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease ( CAD ) and high-on-treatment platelet reactivity ( HTPR ) while on st and ard-dose clopidogrel before percutaneous coronary intervention ( PCI ) . BACKGROUND Patients with HTPR are at increased risk of adverse cardiovascular events after PCI . High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms , including antithrombotic effects . METHODS The ACHIDO ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity ) study was a r and omized PD study of high-dose ( 80 mg ) atorvastatin in addition to double-dose ( 150 mg ) clopidogrel ( atorvastatin group , n = 38 ) versus double-dose clopidogrel alone ( control group , n = 38 ) in patients with HTPR . HTPR was defined as P2Y(12 ) reaction units ( PRU ) ≥235 by the VerifyNow P2Y12 assay . Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days . RESULTS Patients r and omized to atorvastatin had lower PRU values ( 188 ± 48 vs. 223 ± 53 PRU , p < 0.01 ; primary endpoint ) and HTPR rates ( 16 % vs. 42 % , p < 0.01 ) at 30 days than patients in the control group . Statin treatment ( odds ratio [ OR ] : 3.8 , p = 0.011 ) , baseline PRU < 298 ( OR : 10.7 , p = 0.0001 ) , noncarrier status of CYP2C19 * 2 loss-of-function allele ( OR : 2.9 , p = 0.043 ) , and age ( OR : 0.94 , p = 0.032 ) were variables significantly associated with optimal PD response ( PRU < 235 ) at 30 days . No correlations were found between PRU and lipid fractions . CONCLUSIONS High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI  ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ ACHIDO ] ; NCT01335048 ) In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background — The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation ( IPA ) .  Prasugrel is a new thienopyridine that is more potent than st and ard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease . The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown . Methods and Results — Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation – Thrombolysis in Myocardial Infa rct ion 44 ( PRINCIPLE-TIMI 44 ) was a r and omized , double-blind , 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention . The primary end point of the loading-dose phase ( prasugrel 60 mg versus clopidogrel 600 mg ) was IPA with 20 & mgr;mol/L ADP at 6 hours . Patients with percutaneous coronary intervention entered the maintenance-dose phase , a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug . In this study , 201 subjects were r and omized . IPA at 6 hours was significantly higher in subjects receiving prasugrel ( mean±SD , 74.8±13.0 % ) compared with clopidogrel ( 31.8±21.1 % ; P<0.0001 ) . During the maintenance-dose phase , IPA with 20 & mgr;mol/L ADP was higher in subjects receiving prasugrel ( 61.3±17.8 % ) compared with clopidogrel ( 46.1±21.3 % ; P<0.0001 ) . Results were consistent across all key secondary end points ; significant differences emerged by 30 minutes and persisted across all time points . Conclusions — Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention , loading with 60 mg prasugrel result ed in greater platelet inhibition than a 600-mg clopidogrel loading dose . Maintenance therapy with prasugrel 10 mg/d result ed in a greater antiplatelet effect than 150 mg/d clopidogrel Background —Optimal platelet inhibition is an important therapeutic adjunct in patients acute myocardial infa rct ion ( AMI ) undergoing coronary stenting . Whether adjunctive cilostazol to dual antiplatelet therapy ( triple antiplatelet therapy ) can inhibit enhanced platelet reactivity in patients with AMI yet has not 
    Output:
    
Even when DDC was compared with either ticagrelor or prasugrel or TAPT , still no significant difference was observed in terms of bleeding outcomes .
Conclusions In patients with CAD , adverse clinical outcomes were not significantly different when DDC was compared to the other antiplatelet regimens .
In addition , bleeding events were also similarly manifested when DDC was compared to DAPT , TAPT or ticagrelor/prasugrel