Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

Bonaca, Marc P.; Bhatt, Deepak L.; Cohen, Marc; Steg, Philippe Gabriel; Storey, Robert F.; Jensen, Eva C.; Magnani, Giulia; Bansilal, Sameer; Fish, Mary Polly; Im, KyungAh; Bengtsson, Olof; Ophuis, Ton Oude; Budaj, Andrzej; Théroux, Pierre; Ruda, Mikhail; Hamm, Christian; Goto, Shinya; Špinar, Jindřich; Nicolau, José Carlos; Kiss, Róbert Gábor; Murphy, Sabina A.; Wiviott, Stephen D.; Held, Peter; Braunwald, Eugene; Sabatine, Marc S.

doi:10.1056/nejmoa1500857

Cited by 1,621 publications

(1,190 citation statements)

References 28 publications

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“…In PLATO, treatment with ticagrelor 90 mg twice daily, compared with clopidogrel 75 mg once daily, for patients with ACS resulted in fewer ischemic complications and ST (9.8% vs. 11.7%, HR 0.84, 95% CI 0.77-0.92) but more frequent bleeding (non-CABG related) at 12 months (4.5% vs. 3.8%, p = 0.03) [26]. In PEGASUS-TIMI 54, patients randomized 1 to 3 years after MI with additional high risk features to either DAPT (with ticagrelor 60 mg or 90 mg twice daily) or continued aspirin monotherapy resulted in a 1.2% to 1.3% absolute reduction in the primary composite endpoint of cardiovascular death, MI, or stroke and a 1.2% to 1.5% absolute increase in major bleeding, with no excess in fatal bleeding or intracranial hemorrhage [27].…”

Section: Resultsmentioning

confidence: 99%

Duration of dual antiplatelet therapy following drug‐eluting stent implantation: A systemic review and meta‐analysis of randomized controlled trials with longer follow up

Sharma

Agrawal

Garg

et al. 2017

Cathet Cardio Intervent

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Objective To evaluate the long term efficacy and safety of long duration DAPT (L‐DAPT) compared to short duration DAPT (S‐DAPT) after drug‐eluting stent (DES) implantation. Methods We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the clinical impact of L‐DAPT versus S‐DAPT after DES and have mean follow up period of at least 2 years or longer. Primary end point was stent thrombosis (ST). Secondary endpoints were all‐cause mortality, cardiac mortality, myocardial infarction (MI), target vessel revascularization (TVR), thrombolysis in myocardial infarction (TIMI) major bleeding and stroke. Event rates were compared using a random effects model. Results We identified five RCTs in which 19,760 patients were randomized to S‐DAPT (N = 9,810) and L‐DAPT (n = 9,950), respectively. Compared with L‐DAPT, S‐DAPT was associated with higher rate of MI (odds ratio [OR] 1.48, 95% confidence interval [CI] [1.04, 2.10]). There were no significant differences between S‐DAPT and L‐DAPT in terms of all cause mortality, cardiac mortality, ST, TVR or stroke (OR 0.90, 95% CI [0.73, 1.12]; OR 1.02, 95% CI [0.80, 1.30]; OR 1.59, 95% CI [0.77, 3.27]; OR 0.87 95% CI [0.67, 1.14]; and OR 1.08 95% CI [0.81, 1.46], respectively). However, rate of TIMI major bleeding was significantly lower with S‐DAPT compared to L‐DAPT (OR 0.64, 95% CI [0.41, 0.99]). Conclusions In the present analysis of RCTs with longer follow up (2 years or longer), S‐DAPT compared with L‐DAPT, was associated with higher rate of MI and lower rate of major bleeding without any significant difference in the rates of all cause mortality, cardiac mortality, ST, TVR, and stroke.

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Section: Resultsmentioning

confidence: 99%

Duration of dual antiplatelet therapy following drug‐eluting stent implantation: A systemic review and meta‐analysis of randomized controlled trials with longer follow up

Sharma

Agrawal

Garg

et al. 2017

Cathet Cardio Intervent

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“…Novel techniques like proteomics of platelet releasates (181) and platelet RNA-profiling (182) could help to better understand specific anti-inflammatory effects of antiplatelet therapies. Furthermore, testing of platelet function and inflammatory markers over time might help to identify patients at risk, who need a more pronounced and prolonged platelet inhibition beyond current guidelines as demonstrated by recent RCTs (191,192). An effective combination therapy of anti-platelet drugs and drugs with anti-inflammatory capacities might represent a promising approach and should be investigated for individualised therapeutic concepts in the future.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Müller¹,

Chatterjee²,

Rath³

et al. 2015

Thromb Haemost

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SummaryPlatelets play a pivotal role in chronic inflammation leading to progression of atherosclerosis and acute coronary events. Recent discoveries on novel mechanisms and platelet-dependent inflammatory targets underpin the role of platelets to maintain a chronic inflammatory condition in cardiovascular disease. There is strong and clinically relevant crosslink between chronic inflammation and platelet activation. Antiplatelet therapy is a cornerstone in the prevention and treatment of acute cardiovascular events. The benefit of antiplatelet agents has mainly been attributed to their direct anti-aggregatory impact. Some anti-inflammatory off-target effects have also been described. However, it is unclear whether these effects are secondary due to inhibition of platelet activation or are caused by direct distinct mechanisms interfering with inflammatory pathways. This article will highlight novel platelet associated targets that contribute to inflammation in cardiovascular disease and elucidate mechanisms by which currently available antiplatelet agents evolve anti-inflammatory capacities, in particular by carving out the differential mechanisms directly or indirectly affecting platelet mediated inflammation. It will further illustrate the prognostic impact of antiplatelet therapies by reducing inflammatory marker release in recent cardiovascular trials.

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“…The duration of the preferred antithrombotic regimen is another important aspect of choosing the right regimen for the right patient, for whom prolonged treatment with DAPT reduces ischemic end points at the cost of increased bleeding, as exhibited in the PEGASUS TIMI‐54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54)51 study. The 2017 ESC guideline states that prolonged duration of DAPT may be considered for patients at high thrombotic risk, such as those undergoing complex PCI or those implanted with a bioresorbable vascular scaffold,38 and particularly for those who have tolerated DAPT without a bleeding complication 38…”

Section: Discussionmentioning

confidence: 99%

More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy—Current Data and Future Directions

Spinthakis

Farag

Rocca

et al. 2018

JAHA

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Long-Term Use of Ticagrelor in Patients with Prior Myocardial Infarction

Cited by 1,621 publications

References 28 publications

Duration of dual antiplatelet therapy following drug‐eluting stent implantation: A systemic review and meta‐analysis of randomized controlled trials with longer follow up

Duration of dual antiplatelet therapy following drug‐eluting stent implantation: A systemic review and meta‐analysis of randomized controlled trials with longer follow up

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual Antiplatelet Therapy—Current Data and Future Directions

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