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Outcomes with increased length of dual antiplatelet therapy after PCI  

20 Dec, 14 | by Alistair Lindsay

The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is uncertain. Although observational studies have suggested DAPT for longer than a year post-PCI reduces ischemic events, other studies suggest longer durations of DAPT confer no benefits despite increased bleeding risk. This randomized controlled trial evaluated patient outcomes with 12-months vs 30-months of DAPT after PCI. A total of 22866 patients after PCI with a drug-eluting stent (approximately 40% in the context of an ACS) were enrolled. After 12 months of standard DAPT (with either clopidogrel or prasugrel alongside aspirin) a total of 9961 patients who had tolerated DAPT without complications and who had not undergone any further procedures were randomly assigned to continue receiving DAPT treatment or to aspirin and placebo for an additional 18 months. more…

Smoking and antiplatelet agents – smoke and mirrors or something more?

22 Nov, 13 | by Alistair Lindsay

Many antiplatelet therapies are prodrugs that require metabolic activation.  It has been hypothesized that smoking may activate this metabolic conversion for some antiplatelets (i.e. clopidogrel) more than others (i.e. prasugrel and ticagrelor).  In this systematic review and meta-analysis, the authors identified 9 randomized controlled trials of clopidogrel, prasugrel, or ticagrelor which examined outcomes among subgroups of smokers and non-smokers.  In the studies of clopidogrel, smokers on clopidogrel saw a 25% reduction in the primary composite outcome of cardiovascular death, MI, and stroke compared with patients in the control group (RR 0.75, 95% CI 0.67 – 0.83).  However, in non-smokers there was only an 8% reduction in the primary end point (RR 0.92, 95% CI 0.87 – 0.98).  Similarly, greater risk reduction was observed for smokers on ticagrelor or prasugrel when compared to clopidogrel while risk reduction was similar for all three drugs in non-smokers. more…

Triple therapy post-PCI? WOEST clarifies

22 May, 13 | by Alistair Lindsay

20-30% of patients taking oral anticoagulants also have ischaemic heart disease that requires treatment by percutaneous coronary intervention (PCI), thereby necessitating dual anti-platelet therapy to prevent stent thrombosis. However, the combination of dual anti-platelet therapy (DAP) and anti-coagulants is associated with a high annual risk of fatal and non-fatal bleeding episodes. This study hypothesised that in patients who must continue with oral anti-coagulants, clopidogrel alone would reduce the risk of bleeding – while not increasing the risk of thrombotic events – compared to clopidogrel and aspirin. more…

RAPID GENE shows utility of bedside genetic testing

31 Jul, 12 | by Alistair Lindsay

The CYP2C19*2 allele is a common genetic variant that has been associated with a significantly increased risk of major cardiovascular events and stent thrombosis following percutaneous coronary intervention (PCI).  In this study a novel point-of-care genetic test was used to identify carriers of the CYP2C19*2 allele and to tailor a pharmacogenetic appriach to dual antiplatelet treatment after PCI. more…

Bedside genetic test identifies non-responders to Clopidogrel

25 Apr, 12 | by Alistair Lindsay

Clopidogrel is an inactive prodrug that requires hepatic bioactivation via several cytochrome P450 enzymes, including CYP2C19. A number of different alleles of CYP2C19 have been identified; depending on the allele present the enzymatic activity of CYP2C19 can be normal, or reduced. more…

Genetic factors related to early stent thrombosis

22 Nov, 11 | by Alistair Lindsay

Dual anti-platelet therapy (DAPT) reduces cardiovascular events after PCI by more than 80%.  However, stent thrombosis can occur in 0.5% to 4% of patients within the first year following PCI, with the majority occurring in the first month.  Cayla et al. performed a case-control study using a candidate gene approach – looking in particular at genetic variations previously associated with clopidogrel pharmocogenetics and arterial thrombosis – in order to determine their impact on early stent thrombosis, in addition to established clinical and angiographic factors. more…

High Residual Platelet Reactivity Predicts Future Cardiovascular Events

2 Oct, 11 | by Alistair Lindsay

With the increased use of platelet function testing, high residual platelet reactivity (HRPR) has been found to associate with a high risk of ischaemic events following percutaenous coronary intervention (PCI).  However, few data exist for patients with acute coronary syndromes (ACS).  To this end, the Responsiveness to Clopidogrel and Stent Thrombosis 2-ACS (RECLOSE 2-ACS) study investigated the hypothesis that HRPR after clopidogrel loading is an independent prognostic marker of risk of long-term thrombotic events in ACS patients undergoing an invasive procedure, even when the long-term antithrombotic treatment was adjusted according to the results of the platelet function tests. more…

No benefit from platelet testing post PCI

10 Apr, 11 | by Alistair Lindsay

Clopidogrel is a prodrug that needs to be converted into an active metabolite in order to be active, however wide interindividual variability has been noted both in the concentration of active metabolite and also platelet responsiveness.  The GRAVITAS (Gauging Responsiveness with A VerifyNow assay – Impact on Thrombosis and Safety) aimed to investigate the effect of high-dose vs standard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI. more…

Clopidogrel and Asprin ACTIVEly prevent stroke

21 Jun, 09 | by Alistair Lindsay

The ACTIVE Trial (Atrial Fibrillation Clopidogrel Trial with Irbesartan for the Prevention of Vascular Events) was designed to assess the role of clopidogrel and aspirin in the prevention of stroke and other vascular events in patients with atrial fibrillation (AF). ACTIVE W has already reported and compared clopidogrel + aspirin with a vitamin K antagonist. The ACTIVE A trial, the results of which are discussed here, compared combination therapy with clopidogrel and aspirin versus aspirin alone in patients with AF who were considered unsuitable for a Vitamin K antagonist. more…

Prasugrel proves powerful in STEMI

14 Mar, 09 | by Alistair Lindsay

Prasugrel is novel third-generation thienopyridine which is a more potent blocker of the platelet P2Y12 receptor than clopidogrel.The TRITON-TIMI 38 (Trial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibition with prasugrel – Thrombolysis in Myocardial Infarction 38) study compared clopidogrel with prasugrel in the setting of ST elevation myocardial infarction (STEMI). more…

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