Clopidogrel resistance in dual antiplatelet therapy after carotid stenting

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

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Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism

Case Reports in Medicine ◽

10.1155/2016/2312078 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Ashwad Afzal ◽

Bimal Patel ◽

Neel Patel ◽

Sudhakar Sattur ◽

Vinod Patel

Keyword(s):

Myocardial Infarction ◽

Antiplatelet Therapy ◽

Stent Thrombosis ◽

Dual Antiplatelet Therapy ◽

Coronary Intervention ◽

Drug Eluting Stents ◽

Clopidogrel Resistance ◽

St Segment Elevation ◽

Cyp2c19 Polymorphism ◽

Drug Eluting

Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism.

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Is Extended Duration of Dual Antiplatelet Therapy After Carotid Stenting Beneficial?

Medicine ◽

10.1097/md.0000000000001355 ◽

2015 ◽

Vol 94 (40) ◽

pp. e1355 ◽

Cited By ~ 1

Author(s):

Kai-Ming Jhang ◽

Jing-Yang Huang ◽

Oswald Ndi Nfor ◽

Zhi-Hong Jian ◽

Yu-Chun Tung ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Carotid Stenting ◽

Extended Duration

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SAFETY AND EFFICACY OF DUAL ANTIPLATELET THERAPY IN CAROTID STENTING IN ACUTE ISCHEMIC STROKE PATIENTS WITH TANDEM CAROTID LESIONS WHO UNDERWENT ENDOVASCULAR THROMBECTOMY

10.26226/morressier.5ab8f561d462b8029238cf1d ◽

2018 ◽

Author(s):

SONU BHASKAR

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Carotid Stenting ◽

Stroke Patients ◽

Endovascular Thrombectomy ◽

Safety And Efficacy

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Dual Antiplatelet Therapy after Carotid Stenting: Lessons from ‘Big Brother’

European Journal of Vascular and Endovascular Surgery ◽

10.1016/j.ejvs.2015.02.004 ◽

2015 ◽

Vol 49 (6) ◽

pp. 621-622 ◽

Cited By ~ 1

Author(s):

P. De Rango

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Carotid Stenting ◽

Big Brother

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Abstract TMP9: Use of Immediate Dual Antiplatelet Therapy in Carotid Stenting for Tandem Occlusion Stroke is Associated With Acceptable Symptomatic Intracranial Haemorrhage Rates

Stroke ◽

10.1161/str.51.suppl_1.tmp9 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Fiona S Lau ◽

Amer Mitchelle ◽

Andrew Cheung ◽

Jason Wenderoth ◽

Cecilia Cappelen-Smith ◽

...

Keyword(s):

Antiplatelet Therapy ◽

Functional Outcomes ◽

Intracranial Haemorrhage ◽

Dual Antiplatelet Therapy ◽

Carotid Stenting ◽

Anterior Circulation ◽

Stent Patency ◽

Stroke Study ◽

Tandem Occlusion ◽

Acute Stent Thrombosis

Introduction: Observational studies have shown conflicting data on safety and efficacy of carotid stenting in the setting of acute ischemic stroke. We evaluated our stent patency, functional outcomes and symptomatic intracranial haemorrhage rates in acute strokes with tandem occlusions treated with endovascular thrombectomy and concurrent carotid stenting. Methods: Prospectively maintained EVT databases at two comprehensive stroke centres were interrogated for patients with anterior circulation tandem occlusion stroke who were treated with EVT and extracranial carotid artery stenting. Intracranial haemorrhage on post-operative CT & MRI brain was assessed on European Cooperative Acute Stroke Study II criteria. Stent patency was assessed on CTA 12-24 hours post-operatively. Clinical and neuroimaging endpoints were modified treatment in cerebral ischaemia (mTICI) score, stent patency, any intracranial haemorrhage, symptomatic intracranial haemorrhage (sICH), and 90-day modified Rankin Scale (mRS). Results: Between 2016 and 2019, 105 patients were identified (mean age 70 years, 78% male, median NIHSS 15). Median time to reperfusion was 9.26 hours, with 97.1% achieving mTICI 2b/3. Immediate dual antiplatelet therapy was used in 102 (97.1%) patients. Good functional outcomes (mRS 0-2) were achieved in 53 (51%) patients. Acute stent thrombosis occurred in 12 (11.4%) patients with 7 (58.3%) still achieving good functional outcomes. Any intracranial haemorrhage occurred in 46 (44%) of all patients. Symptomatic intracranial haemorrhage occurred in 8 (7.6%). All sICH patients had 90-day mRS of 3-6. Conclusion: Acute tandem occlusion stroke patients present complex management challenges. Despite immediate dual antiplatelet therapy, acute stent occlusions may still occur. Symptomatic intracranial haemorrhage rates are acceptable in these complex patients, however, all patients with sICH had poorer outcomes.

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Dual Antiplatelet Therapy: Is More Better?

Internal Medicine News ◽

10.1016/s1097-8690(06)74048-3 ◽

2006 ◽

Vol 39 (16) ◽

pp. 39

Author(s):

JON O. EBBERT ◽

ERIC G. TANGALOS

Keyword(s):

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy

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Anticoagulation in addition to dual antiplatelet therapy has no impact on long-term follow-up after endovascular treatment of (sub)acute lower limb ischemia

VASA ◽

10.1024/0301-1526/a000786 ◽

2019 ◽

Vol 48 (4) ◽

pp. 321-329

Author(s):

Mariya Kronlage ◽

Erwin Blessing ◽

Oliver J. Müller ◽

Britta Heilmeier ◽

Hugo A. Katus ◽

...

Keyword(s):

Endovascular Treatment ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Limb Ischemia ◽

Bleeding Complications ◽

Severe Bleeding ◽

Short Term ◽

Long Term Follow Up

Summary. Background: To assess the impact of short- vs. long-term anticoagulation in addition to standard dual antiplatelet therapy (DAPT) upon endovascular treatment of (sub)acute thrombembolic occlusions of the lower extremity. Patient and methods: Retrospective analysis was conducted on 202 patients with a thrombembolic occlusion of lower extremities, followed by crirical limb ischemia that received endovascular treatment including thrombolysis, mechanical thrombectomy, or a combination of both between 2006 and 2015 at a single center. Following antithrombotic regimes were compared: 1) dual antiplatelet therapy, DAPT for 4 weeks (aspirin 100 mg/d and clopidogrel 75 mg/d) upon intervention, followed by a lifelong single antiplatelet therapy; 2) DAPT plus short term anticoagulation for 4 weeks, followed by a lifelong single antiplatelet therapy; 3) DAPT plus long term anticoagulation for > 4 weeks, followed by a lifelong anticoagulation. Results: Endovascular treatment was associated with high immediate revascularization (> 98 %), as well as overall and amputation-free survival rates (> 85 %), independent from the chosen anticoagulation regime in a two-year follow up, p > 0.05. Anticoagulation in addition to standard antiplatelet therapy had no significant effect on patency or freedom from target lesion revascularization (TLR) 24 months upon index procedure for both thrombotic and embolic occlusions. Severe bleeding complications occurred more often in the long-term anticoagulation group (9.3 % vs. 5.6 % (short-term group) and 6.5 % (DAPT group), p > 0.05). Conclusions: Our observational study demonstrates that the choice of an antithrombotic regime had no impact on the long-term follow-up after endovascular treatment of acute thrombembolic limb ischemia whereas prolonged anticoagulation was associated with a nominal increase in severe bleeding complications.

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TWILIGHT: A Randomized Trial of Ticagrelor Monotherapy Versus Ticagrelor Plus Aspirin Beginning at 3 Months in High-risk Patients Undergoing Percutaneous Coronary Intervention

US Cardiology Review ◽

10.15420/usc.2019.02 ◽

2020 ◽

Vol 14 ◽

Author(s):

Johny Nicolas ◽

Usman Baber ◽

Roxana Mehran

Keyword(s):

Percutaneous Coronary Intervention ◽

High Risk ◽

Antiplatelet Therapy ◽

Dual Antiplatelet Therapy ◽

Coronary Intervention ◽

Bleeding Events ◽

High Risk Patients ◽

Risk Of Death ◽

Percutaneous Coronary ◽

Risk Patients

A P2Y12 inhibitor-based monotherapy after a short period of dual antiplatelet therapy is emerging as a plausible strategy to decrease bleeding events in high-risk patients receiving dual antiplatelet therapy after percutaneous coronary intervention. Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT), a randomized double-blind trial, tested this approach by dropping aspirin at 3 months and continuing with ticagrelor monotherapy for an additional 12 months. The study enrolled 9,006 patients, of whom 7,119 who tolerated 3 months of dual antiplatelet therapy were randomized after 3 months into two arms: ticagrelor plus placebo and ticagrelor plus aspirin. The primary endpoint of interest, Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, occurred less frequently in the experimental arm (HR 0.56; 95% CI [0.45–0.68]; p<0.001), whereas the secondary endpoint of ischemic events was similar between the two arms (HR 0.99; 95% CI [0.78–1.25]). Transition from dual antiplatelet therapy consisting of ticagrelor plus aspirin to ticagrelor-based monotherapy in high-risk patients at 3 months after percutaneous coronary intervention resulted in a lower risk of bleeding events without an increase in risk of death, MI, or stroke.

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