Months Of Clopidogrel Therapy Research Articles

Risks and Benefits of Dual Antiplatelet Therapy Beyond 12 Months After Coronary Stenting: A Prospective Randomized Cohort Study.

The optimal duration of dual antiplatelet therapy (DAT) after coronary stenting remains poorly define. The aim of this study was to evaluate the impact of longer than 24 months DAT in patients who received drug-eluting and bare-metal stents.A total of 1010 individuals who underwent elective, urgent or emergency coronary angioplasty with intended stent implantation at reference or specialized cardiac hospitals were randomized to receive long-term and short-term DAT to determine the benefits and adverse effects of long-term DAT. Total of 508 patients were randomized to long-term and 502 patients to <1 year DAT, and all of them were followed for more than 36 months for major adverse cardiac and cerebvascular events and bleeding major adverse cardiac and cerebvascular events (MACCE)Mean age of the 1010 patients (364 women and 646 men) was 60 years. Stent reocclusion occurred in 15 patients. Mean Syntax score was 23.00 ± 5.08 for whole samples, 25.00 ± 5.27 in 28 patients with MACCE and 23 ± 5.00 in 982 patients without MACCE (P = 0.057). According to all specified bleeding definitions, clopidogrel therapy for >12 months was not associated with a greater risk of hemorrhage. A regimen of >12 months of clopidogrel therapy in patients who had received drug-eluting or bare-metal stents did not differ significantly from a regimen of <12 months on clopidogrel with regard to MACCE.Long-term DAT might not significantly affect the reduction in the risk of death from any cause, myocardial infarction, or stroke, and not associated with minor or major bleeding events.

Late-Breaking Clinical Trial Abstracts

### Late-Breaking Clinical Trials: Risk and Benefit of Dual Antiplatelet Therapy #### Increased Risk of Ischemic Events Upon Discontinuation of Prasugrel After 12 or 30 Months of Therapy Following Placement of the Taxus Liberte Paclitaxel-Eluting Coronary Stent Kirk N Garratt1, Ronald D Jenkins2, Thomas K Pow3, W. Douglas Weaver4, Laura Mauri5, De J Kereiakes6, Kenneth J Winters7, Thomas Christen8, Dominic J Allocco8, David P Lee9; 1Cardiac Interventions, Lenox Hill Heart and Vascular Institute, New York, NY; 2Cardiac Interventions, Heart Clinics Northwest, Coeur d'Alene, ID; 3Cardiac Interventions, Great Lakes Heart Institute, St Joseph, MI; 4Cardiology, Henry Ford Hosp, Detroit, MI; 5Div of Cardiovascular Medicine, Brigham and Women's Hosp, Boston, MA; 6Cardiology, The Christ Hosp Heart and Vascular Cntr/The Lindner Rsch Cntr, Cincinnati, OH; 7Lilly Rsch Laboratories, Eli Lily and Company, Indianapolis, IN; 8Clinical Sciences, Boston Scientific, Marlborough, MA; 9Cardiovascular Medicine Clinic, Standford, Stanford, CA Introduction : The TAXUS Liberte Post-approval Study (TL-PAS) studied long-term clinical outcomes for the TL stent in conjunction with the use of prasugrel and aspirin. A portion of patients from TL-PAS contributed to the Dual Anti-Platelet Therapy (DAPT) trial. Methods : Eligible and consecutive patients in the United States treated with TL stents were enrolled into TL-PAS (N=4199). Those meeting inclusion and exclusion criteria were recruited for participation in the DAPT trial (N=3904). Patients received open-label prasugrel plus aspirin for 12 months after stent placement. At 12 months, patients without ischemic or bleeding events continued aspirin therapy and were randomized 1:1 to continued blinded treatment with either prasugrel or placebo for an additional 18 months (N=2202). At 30 months, study drugs were discontinued, and aspirin was continued through at least 33 months after stent placement. Events were adjudicated by a clinical events committee and monitored by the TL-PAS Data Monitoring Committee (DMC). Results : Nearly 3 years following randomization, the DMC noted a significant increase …

Duration of dual antiplatelet therapy following percutaneous coronary intervention on re-hospitalization for acute coronary syndrome

BackgroundThe optimal duration of dual antiplatelet therapy after percutaneous coronary intervention (PCI) remains uncertain. The objective of this study was to examine the association between duration of dual antiplatelet therapy and re-hospitalization for acute coronary syndrome (ACS) in ACS patients who underwent PCI.MethodsWe identified 975 newly diagnosed ACS patients who underwent PCI between July, 2007 and June, 2009, at a medical center in Taiwan. Cox proportional hazard models were used to examine the association between duration of dual antiplatelet therapy (9 months, 12 months and 15 months) and risks of re-hospitalization for ACS.ResultsAt a mean follow-up of 2.3 years, we found that use of clopidogrel for ≥ 12 months was associated with a decreased risk of re-hospitalization for ACS (adjusted HR 0.59, 95% CI 0.36-0.95; p = 0.03). However, use of clopidogrel for ≥ 15 months was not associated with a decreased risk of re-hospitalization for ACS (adjusted HR 0.57, 95% CI 0.29-1.13; p = 0.11). Similar results were found in patients who implanted drug-eluting stents (DES), for whom at least 12 months of clopidogrel therapy is especially critical.ConclusionThe benefit of ≥ 12 months of clopidogrel use in reducing the risk of re-hospitalization for ACS was significant among ACS patients who underwent PCI and was especially critical for those who implanted DES.

Two-Year Outcomes After First- or Second-Generation Drug-Eluting or Bare-Metal Stent Implantation in All-Comer Patients Undergoing Percutaneous Coronary Intervention: A Pre-Specified Analysis From the PRODIGY Study (PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY)

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001). Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

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Short- Versus Long-Term Duration of Dual-Antiplatelet Therapy After Coronary Stenting

Background— The optimal duration of dual-antiplatelet therapy and the risk-benefit ratio for long-term dual-antiplatelet therapy after coronary stenting remain poorly defined. We evaluated the impact of up to 6 versus 24 months of dual-antiplatelet therapy in a broad all-comers patient population receiving a balanced proportion of Food and Drug Administration–approved drug-eluting or bare-metal stents. Methods and Results— We randomly assigned 2013 patients to receive bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting stent implantation. At 30 days, patients in each stent group were randomly allocated to receive up to 6 or 24 months of clopidogrel therapy in addition to aspirin. The primary end point was a composite of death of any cause, myocardial infarction, or cerebrovascular accident. The cumulative risk of the primary outcome at 2 years was 10.1% with 24-month dual-antiplatelet therapy compared with 10.0% with 6-month dual-antiplatelet therapy (hazard ratio, 0.98; 95% confidence interval, 0.74–1.29; P =0.91). The individual risks of death, myocardial infarction, cerebrovascular accident, or stent thrombosis did not differ between the study groups; however, there was a consistently greater risk of hemorrhage in the 24-month clopidogrel group according to all prespecified bleeding definitions, including the recently proposed Bleeding Academic Research Consortium classification. Conclusions— A regimen of 24 months of clopidogrel therapy in patients who had received a balanced mixture of drug-eluting or bare-metal stents was not significantly more effective than a 6-month clopidogrel regimen in reducing the composite of death due to any cause, myocardial infarction, or cerebrovascular accident. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00611286.

Clopidogrel tapering as a strategy to attenuate platelet rebound phenomenon in patients with bare-metal stents

Early clustering of adverse cardiovascular events after abrupt cessation of clopidogrel has been reported in patients with acute coronary syndromes. A platelet rebound phenomenon may contribute to this increased thrombotic risk and a gradual drug tapering may attenuate this proposed platelet effect. Accordingly, we aimed to assess the effect of clopidogrel tapering on platelet reactivity. Twenty patients who underwent elective percutaneous coronary interventions with bare metal stents receiving 3months of clopidogrel therapy (75mg daily) were randomized to either of two discontinuation strategies: (1) Off group-abrupt drug cessation or (2) Tapering group-receiving clopidogrel 75mg every other day for 4weeks duration. Light transmission aggregometry, induced by ADP (5 and 10μM) and collagen, was measured at four time-points (at baseline and 2, 4 and 6weeks after randomization). In the off group, there was an early rise in platelet reactivity at 2weeks after abrupt drug cessation compared to baseline, as measured by ADP 5μmol/l (39.6±2.8 vs. 67.9±6.0, P<0.001). The tapering regimen suppressed this rebound platelet aggregation by ADP 5μmol/l at 2weeks (P=0.001) and 4weeks (P=0.001). Similar results were found with ADP 10μmol/l and collagen agonists. Abrupt cessation of clopidogrel results in an early rise in platelet aggregability in patients with BMS that is attenuated by a tapering regimen. Clopidogrel administration every other day may achieve similar levels of platelet inhibition as full dose therapy. Further investigations evaluating clopidogrel tapering strategies and their potential clinical impact are warranted.

Randomized comparison of 6- versus 24-month clopidogrel therapy after balancing anti-intimal hyperplasia stent potency in all-comer patients undergoing percutaneous coronary intervention: Design and rationale for the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia study (PRODIGY)

The optimal duration of clopidogrel therapy after coronary stenting is debated because of the scarcity of randomized controlled trials and inconsistencies arising from registry data. Although prolonged clopidogrel therapy after bare metal stenting is regarded as an effective secondary prevention measure, the safety profile of drug-eluting stents itself has been questioned in patients not receiving ≥ 12 months of dual-antiplatelet therapy. Twenty-four months of clopidogrel therapy after coronary stenting reduces the composite of death, myocardial infarction, or stroke compared with 6 months of treatment. PRODIGY is an unblinded, multicenter, 4-by-2 randomized trial. All-comer patients with indication to coronary stenting are randomly treated-balancing randomization-with bare metal stent (no active late loss inhibition), Endeavor Sprint zotarolimus-eluting stent (Medtronic, Santa Rosa, CA) (mild late loss inhibition), Taxus paclitaxel-eluting stent (Boston Scientific, Natick, MA) (moderate late loss inhibition), or Xience V everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) (high late loss inhibition). At 30 days, patients in each stent group are randomly allocated to receive 24 or up to 6 months of clopidogrel therapy-primary end point randomization. With 1,700 individuals, this study will have >80% power to detect a 40% difference in the primary end point after sample size augmentation of 5% and a background event rate of 8%. The PRODIGY trial aims to assess whether 24 months of clopidogrel therapy improves cardiovascular outcomes after coronary intervention in a broad all-comer patient population receiving a balanced mixture of stents with various anti-intimal hyperplasia potency.

Response to Letter Regarding Article, “Increased Risk of Bleeding in Patients on Clopidogrel Therapy After Drug-Eluting Stents Implantation: Insights From the HMO Research Network-Stent Registry (HMORN-Stent)”

We agree with Drs Lozano, Garcia, and Barriales that dual antiplatelet therapy should be recommended for 12 months after drug-eluting stent (DES) placement. We also agree with ACC/AHA PCI guidelines that included a provision of 12 months of clopidogrel therapy for patients not at high risk of bleeding.1 As shown in our report, the lower risk of ischemic complications on dual antiplatelet therapy (DAPT) must be balanced with the increased bleeding risk.2 Accordingly, a multidimensional approach is needed to address the risks and benefits of DAPT that takes into account the following: (1) appropriate patient selection to maximize the benefit while …