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GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin.

ABSTRACT: BACKGROUND:There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world. METHODS:We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and either high-dose tirofiban or double-bolus eptifibatide (double AAD plus small molecules group, n=666). The primary end point (incidence of composite ischemic events within one year) included death, acute myocardial infarction, unstable angina, stent thrombosis or repeat PCI or coronary bypass surgery (related to the target vessel PCI failure) and was modelled by Cox's regression. RESULTS:There were 89 composite ischemic events: 24 (11.6%) in double AAD alone and 65 (9.8%) in double AAD plus small molecules groups (log-rank test: p=0.36). Incidences by type of ischemic events were similar between the 2 groups. Based on 21 potential covariates fitted simultaneously, adjusted hazard ratios (HR and 95% confidence intervals) showed that age (HR 1.03, 1.01-1.06, p=0.01), diabetes (HR 1.68, 1.01-2.79, p=0.05) and intra aortic balloon pump (HR 5.12, 2.36-11.10, p=0.0001) were significant risk factors whereas thrombolysis by tenecteplase (HR 0.35, 0.13-0.98, p=0.05) and having had hypertension or anti-hypertensive treatment (HR 0.58, 0.36-0.93, p=0.03) were significant protectors for events. Whether small molecules were present provided a non significant additional benefit as compared to double AAD alone (HR 0.83, 0.51-1.36, p=0.46). Pre-PCI CK-MB were not useful to predict events (HR 1.01, 0.99-1.01, p=0.17). CONCLUSIONS:In clinical world patients undergoing PCI (rescue plus primary <13%) while on double AAD, based on clopidogrel plus aspirin, small molecules (tirofiban or eptifibatide) provided no additive long-term protection against the occurrence of composite ischemic events whereas thrombolysis by tenecteplase did.

SUBMITTER: Schiariti M

PROVIDER: S-EPMC2948151 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin.

Schiariti Michele M Saladini Angela A Papalia Francesco F Grillo Placido P Nesta Cristina C Cuturello Domenico D Missiroli Bindo B Puddu Paolo Emilio PE

The open cardiovascular medicine journal 20100720

<h4>Background</h4>There is some controversy as to whether tirofiban or eptifibatide, two small anti-aggregating drugs (AAD), may reduce the incidence of composite ischemic events within one year in patients undergoing percutaneous coronary intervention (PCI) in the real clinical world.<h4>Methods</h4>We compared consecutive patients on oral double AAD (with clopidogrel and aspirin) who underwent PCI (n=207) and patients who were on single AAD and received a second AAD, just prior to PCI, and ei ...[more]

PMID: 20922049

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Project description:Background and Purpose- The role of aspirin plus clopidogrel (A+C) therapy compared with aspirin monotherapy in patients presenting with acute ischemic stroke (IS) or transient ischemic attack remains uncertain. We conducted this study to determine the optimal period of efficacy and safety of A+C compared with aspirin monotherapy. Methods- Ten randomized controlled trials (15 434 patients) were selected using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) (inception June 2018) comparing A+C with aspirin monotherapy in patients with transient ischemic attack or IS. The primary efficacy outcome was recurrent IS, and the primary safety outcome was major bleeding. The secondary outcomes were major adverse cardiovascular events (composite of stroke, myocardial infarction, and cardiovascular mortality) and all-cause mortality. We stratified analysis based on the short- (≤1 month), intermediate- (≤3 month), and long-term (>3 month) A+C therapy. Effects were estimated as relative risk (RR) with 95% CI. Results- A+C significantly reduced the risk of recurrent IS at short-term (RR, 0.53; 95% CI, 0.37-0.78) and intermediate-term (RR, 0.72; 95% CI, 0.58-0.90) durations. Similarly, major adverse cardiovascular event was significantly reduced by short-term (RR, 0.68; 95% CI, 0.60-0.78) and intermediate-term (RR, 0.76; 95% CI, 0.61-0.94) A+C therapy. However, long-term A+C did not yield beneficial effect in terms of recurrent IS (RR, 0.81; 95% CI, 0.63-1.04) and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.71-1.07). Intermediate-term (RR, 2.58; 95% CI, 1.19-5.60) and long-term (RR, 1.87; 95% CI, 1.36-2.56) A+C regimens significantly increased the risk of major bleeding as opposed to short-term A+C (RR, 1.82; 95% CI, 0.91-3.62). Excessive all-cause mortality was limited to long-term A+C (RR, 1.45; 95% CI, 1.10-1.93). Conclusions- Short-term A+C is more effective and equally safe in comparison to aspirin alone in patients with acute IS or transient ischemic attack.

Project description:OBJECTIVE:To assess the effectiveness and safety of dual agent antiplatelet therapy combining clopidogrel and aspirin to prevent recurrent thrombotic and bleeding events compared with aspirin alone in patients with acute minor ischaemic stroke or transient ischaemic attack (TIA). DESIGN:Systematic review and meta-analysis of randomised, placebo controlled trials. DATA SOURCES:Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, ClinicalTrials.gov, WHO website, PsycINFO, and grey literature up to 4 July 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS:Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. A third team member reviewed all final decisions, and the team resolved disagreements through discussion. When reports omitted data that were considered important, clarification and additional information was sought from the authors. The analysis was conducted in RevMan 5.3 and MAGICapp based on GRADE methodology. RESULTS:Three eligible trials involving 10?447 participants were identified. Compared with aspirin alone, dual antiplatelet therapy with clopidogrel and aspirin that was started within 24 hours of symptom onset reduced the risk of non-fatal recurrent stroke (relative risk 0.70, 95% confidence interval 0.61 to 0.80, I2=0%, absolute risk reduction 1.9%, high quality evidence), without apparent impact on all cause mortality (1.27, 0.73 to 2.23, I2=0%, moderate quality evidence) but with a likely increase in moderate or severe extracranial bleeding (1.71, 0.92 to 3.20, I2=32%, absolute risk increase 0.2%, moderate quality evidence). Most stroke events, and the separation in incidence curves between dual and single therapy arms, occurred within 10 days of randomisation; any benefit after 21 days is extremely unlikely. CONCLUSIONS:Dual antiplatelet therapy with clopidogrel and aspirin given within 24 hours after high risk TIA or minor ischaemic stroke reduces subsequent stroke by about 20 in 1000 population, with a possible increase in moderate to severe bleeding of 2 per 1000 population. Discontinuation of dual antiplatelet therapy within 21 days, and possibly as early as 10 days, of initiation is likely to maximise benefit and minimise harms.

Project description:ObjectiveTo test the hypothesis that ticagrelor plus aspirin is safe and superior to clopidogrel plus aspirin for reducing high platelet reactivity at 90 days and stroke recurrence in patients with minor stroke or transient ischaemic attack, particularly in carriers of the CYP2C19 loss-of-function allele and patients with large artery atherosclerosis.DesignOpen label, blinded endpoint, randomised controlled phase II trial.SettingProspective studies conducted at 26 centres in China, August 2015 to March 2017.Participants675 patients with acute minor stroke or transient ischaemic attack.InterventionTicagrelor (180 mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300 mg loading dose, 75 mg daily thereafter) on a background of aspirin (100 mg daily for the first 21 days) within 24 hours of symptom onset.Main outcome measuresPrimary outcome was the proportion of patients with high platelet reactivity at 90 days. High platelet reactivity was defined as P2Y12 reaction units of more than 208. Secondary outcomes included high platelet reactivity at 90 days (7 days either way) in patients carrying genetic variants that would affect clopidogrel metabolism, and any stroke (ischaemic or haemorrhagic) recurrence at 90 days (7 days either way), six months, and one year.ResultsAt 90 days, high platelet reactivity occurred in 35 (12.5%) of 280 patients in the ticagrelor/aspirin group and 86 (29.7%) of 290 patients in the clopidogrel/aspirin group (risk ratio 0.40; 95% confidence interval 0.28 to 0.56; P<0.001), and in 10.8% versus 35.4% (0.31; 0.18 to 0.49; P<0.001) of patients carrying CYP2C19 loss-of-function alleles. Stroke occurred in 21 (6.3%) of 336 patients in the ticagrelor/aspirin group and 30 (8.8%) of 339 patients in the clopidogrel/aspirin group (hazard ratio 0.70; 95% confidence interval 0.40 to 1.22; P=0.20). Patients with large artery atherosclerosis in the ticagrelor/aspirin group had a lower stroke recurrence at 90 days than those in the clopidogrel/aspirin group (6.0% v 13.1%; hazard ratio 0.45, 95% confidence interval 0.20 to 0.98; P=0.04). No difference was seen in the rates of major or minor haemorrhagic events between the ticagrelor/aspirin and clopidogrel/aspirin groups (4.8% v 3.5%; P=0.42).ConclusionPatients with minor stroke or transient ischaemic attack who are treated with ticagrelor plus aspirin have a lower proportion of high platelet reactivity than those who are treated with clopidogrel plus aspirin, particularly for those who are carriers of the CYP2C19 loss-of-function allele. The results of this study should be evaluated further in large scale, phase III trials and in different populations.Trial registrationClinicaltrials.gov NCT02506140.

Dataset Information

GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin.

Publications

GPIIb/IIIa Receptor Antagonism Using Small Molecules Provides no Additive Long-Term Protection after Percutaneous Coronary Intervention as Compared to Clopidogrel Plus Aspirin.

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