| 11. |
- Angiolillo, Dominick J., et al.
(författare)
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International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-7322 .- 1524-4539. ; 136:20, s. 1955-
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Tidskriftsartikel (refereegranskat)abstract
- Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors.
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| 12. |
- Bhatt, Deepak L., et al.
(författare)
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Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial
- 2019
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 394:10204, s. 1169-1180
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor.Methods The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria:a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).Findings Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, p(interaction)=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p<0.0001), and fatal bleeding in 6 (0.1%) of 5536 patients with ticagrelor and 6 (0.1%) of 5564 with placebo (1.13 [0.36-3.50], p=0.83). Intracranial haemorrhage occurred in 33 (0.6%) and 31 (0.6%) patients (1.21 [0.74-1.97], p=0.45). Ticagrelor improved net clinical benefit:519/5558 (9.3%) versus 617/5596 (11.0%), HR=0.85, 95% CI 0.75-0.95, p=0.005, in contrast to patients without PCI where it did not, p(interaction)=0.012. Benefit was present irrespective of time from most recent PCI.Interpretation In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk.
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| 13. |
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| 14. |
- Cannon, Christopher P., et al.
(författare)
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Design and Rationale of the RE-DUAL PCI Trial : A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting
- 2016
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 39:10, s. 555-564
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Tidskriftsartikel (refereegranskat)abstract
- Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize similar to 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.
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| 15. |
- Cornel, Jan H., et al.
(författare)
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Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy For Medically Managed Patients With Non-St-Segment Elevation Acute Coronary Syndromes
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Background--The relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention. Methods and Results--We analyzed 2428medicallymanaged acute coronary syndromes patients fromthe Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major orminor bleeding. Exploratory analyses used 3-level composites that incorporatedmild andminimalGUSTOand TIMI events.Continuousmeasures of PRUs (per 10-unit decrease)were not independently associatedwith the 2-levelGUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites.However, the PRUcut point of 75 differentiated bleeding riskwith the 3-level composites ofGUSTO(26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001). Conclusions--Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.
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| 16. |
- Costa, Francesco, et al.
(författare)
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Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score : a pooled analysis of individual-patient datasets from clinical trials
- 2017
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10073, s. 1025-1034
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y(12) inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0.73 (95% CI 0.61-0.85) in the derivation cohort, and 0.70 (0.65-0.74) in the PLATO trial validation cohort and 0.66 (0.61-0.71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score >= 25), but not in those with lower risk profiles (p(interaction)=0.007), and exerted a significant ischaemic benefit only in this latter group.Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.
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| 17. |
- Costa, Francesco, et al.
(författare)
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Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting
- 2019
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 73:7, s. 741-754
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDComplex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short-or long-term DAPT should be prioritized.OBJECTIVESThis study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.METHODSComplex PCI was defined as $ 3 stents implanted and/or $ 3 lesions treated, bifurcation stenting and/or stent length > 60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high ($ 25) or nonhigh (< 25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.RESULTSAmong 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference:-3.86%; 95% confidence interval:-7.71 to thorn0.06) and noncomplex PCI strata (absolute risk difference:-1.14%; 95% confidence interval:-2.26 to-0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.CONCLUSIONS Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.
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| 18. |
- Dellborg, Mikael, 1954, et al.
(författare)
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Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.
- 2019
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Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 5:4, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60mg b.i.d. initiated up to 2years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Of the 21162 patients enrolled in PEGASUS-TIMI 54, 10779 patients were included in the primary analysis for this study, randomized to ticagrelor 60mg (n=5388) or matching placebo (n=5391). The cumulative proportions of patients with events at 36months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P=0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P=0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P<0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P=0.58).In PEGASUS-TIMI 54, treatment with ticagrelor 60mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60mg in this population.http://www.clinicaltrials.gov NCT01225562.
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| 19. |
- Fanaroff, Alexander C., et al.
(författare)
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Antithrombotic agents for secondary prevention after acute coronary syndromes : A systematic review and network meta-analysis
- 2017
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 241, s. 87-96
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nine oral antithrombotic medications currently available in the United States and Europe have been studied in clinical trials for secondary prevention of cardiac events following acute coronary syndrome (ACS). Few combinations of these medications have been directly compared, and studies have used multiple different comparator regimens.Methods: We performed a systematic review and network meta-analysis of randomized controlled trials evaluating one or more available oral antithrombotic therapies in patients with ACS or prior myocardial infarction (MI). Co-primary outcomes were all-cause and cardiovascular mortality compared with imputed placebo and aspirin monotherapy.Results: Forty-seven studies (196,057 subjects) met inclusion criteria and were included in the systematic review. Almost all studies tested either aspirin monotherapy compared with placebo or a combination of antithrombotic agents that included aspirin. Nearly all regimens reduced all-cause and cardiovascular mortality compared with imputed placebo. However, compared with imputed aspirin monotherapy, only combination therapy with aspirin plus ticagrelor was associated with lower cardiovascular mortality (OR 0.80, 95% CI 0.68-0.93), and triple therapy with aspirin, clopidogrel, and very low dose rivaroxaban was associated with lower all-cause mortality (OR 0.67, 95% CI 0.49-0.90). Major bleeding was increased 45-95% with dual antithrombotic therapy, and 2-6-fold with triple therapy.Conclusion: Few combinations of antithrombotic therapy were associated with a reduction inmortality compared with aspirin monotherapy, highlighting the difficulty in clinical interpretation of composite ischemic endpoints. Future studies may need to focus on limiting the number of antithrombotic therapies tested in combination to best balance ischemic event reduction and bleeding.
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| 20. |
- Golwala, Harsh B., et al.
(författare)
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Safety and efficacy of dual vs. triple antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention : a systematic review andmeta-analysis of randomized clinical trials
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:19, s. 1726-
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Forskningsöversikt (refereegranskat)abstract
- Aims: Of patients with atrial fibrillation (AF), approximately 10% undergo percutaneous coronary intervention (PCI). We studied the safety and efficacy of dual vs. triple antithrombotic therapy (DAT vs. TAT) in this population.Methods and results: A systematic review and meta-analysis was conducted using PubMed, Embase, EBSCO, Cochrane database of systematic reviews, Web of Science, and relevant meeting abstracts for Phase 3, randomized trials that compared DAT vs. TAT in patients with AF following PCI. Four trials including 5317 patients were included, of whom 3039 (57%) received DAT. Compared with the TAT arm, Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding showed a reduction by 47% in the DAT arm [4.3% vs. 9.0%; hazard ratio (HR) 0.53, 95% credible interval (CrI) 0.36–0.85, I2 = 42.9%]. In addition, there was no difference in the trial-defined major adverse cardiac events (MACE) (10.4% vs. 10.0%, HR 0.85, 95% CrI 0.48–1.29, I2 = 58.4%), or in individual outcomes of all-cause mortality, cardiac death, myocardial infarction, stent thrombosis, or stroke between the two arms.Conclusion: Compared with TAT, DAT shows a reduction in TIMI major or minor bleeding by 47% with comparable outcomes of MACE. Our findings support the concept that DAT may be a better option than TAT in many patients with AF following PCI.
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