Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies

Gurbel, Paul A.; Bliden, Kevin P.; Butler, Kathleen; Antonino, Mark J.; Wei, Cheryl; Teng, Renli; Rasmussen, Lars Hvilsted; Storey, Robert F.; Nielsen, Tonny; Eikelboom, John W.; Sabe-Affaki, Georges; Husted, Steen; Kereiakes, Dean J.; Henderson, David A.; Patel, Dharmendra V.; Tantry, Udaya S.

doi:10.1161/circulationaha.109.919456

Cited by 430 publications

(285 citation statements)

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“…One major and three minor bleeding events occurred either during or after ticagrelor therapy, while no bleeding events were reported for patients taking clopidogrel. Only five serious adverse events (MI, hypotension, atrial fibrillation, and bradycardia) were reported during this study and they all occurred either during or after ticagrelor therapy [28]. Although switching agents might be able to significantly reduce platelet aggregation, this may not translate to a reduction in clinical outcomes such as MACE.…”

Section: Discussionmentioning

confidence: 89%

“…Compassionate use of prasugrel was able to be obtained for four of the patients and adequate platelet inhibition was observed in all of the patients after four weeks [27]. The RESPOND trial was a crossover designed trial in 98 patients comparing both responders and non-responders of clopidogrel to ticagrelor which is an oral reversible P2Y 12 inhibitor [28]. Ticagrelor was able to significantly inhibit more platelet aggregation than clopidogrel in non-responders (p<0.05) and platelet aggregation fell significantly when patients were switched from clopidogrel to ticagrelor (p<0.0001).…”

Section: Discussionmentioning

confidence: 99%

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Characterization and Evaluation of Clopidogrel Response Testing in a Community Hospital Setting

Lalama¹

2011

J Clinic Experiment Cardiol

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Purpose: To describe how VerifyNow P2Y 12 testing for clopidogrel response is being utilized at a community hospital.Methods: A retrospective chart review was conducted at a 411-bed community hospital in patients who tested positive for poor clopidogrel response.Results: There were 95 positive P2Y 12 tests evaluated in this study. Positive P2Y 12 tests were obtained 40.0% of the time for cardiovascular indications, 28.4% for neurologic indications, 1.1% for hematologic indications, and 30.5% were obtained to evaluate patients prior to surgery. The medication regimens of 38.8% of patients did not change as a result of a positive test for poor clopidogrel response. The clopidogrel dose was increased in 16.3% of patients, and clopidogrel was discontinued in 10.2% of patients positive for poor clopidogrel response not undergoing surgical evaluation. Rehospitalization rates of non-surgical patients for recurrent thrombosis or bleeding at 90 days were highest for patients who had an additional antiplatelet agent or anticoagulant added due to poor clopidogrel response. The lowest rehospitalization rate was seen in patients switched to an alternative agent. Conclusions:The most common findings after a positive P2Y 12 test in non-surgical patients were no change in therapy and increasing the dose of clopidogrel. Adding an additional antiplatelet agent or anticoagulant was associated with the highest risk of rehospitalization.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Characterization and Evaluation of Clopidogrel Response Testing in a Community Hospital Setting

Lalama¹

2011

J Clinic Experiment Cardiol

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“…Third, because clopidogrel and eptifibatide 18‐ versus 2‐hour infusion increased bleeding,8 we did not randomize patients to ticagrelor and eptifibatide 18‐ versus 2‐hour infusion. Fourth, because it has been demonstrated23 that the vasodilator‐stimulated phosphoprotein assay had minor differences as compared with the LTA measurements, we did not perform the vasodilator‐stimulated phosphoprotein assay to measure platelet reactivity index. Instead, multiple platelet function tests were performed in duplicates.…”

Section: Discussionmentioning

confidence: 99%

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

Marian

Alli

Solaiman

et al. 2017

JAHA

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BackgroundIn patients with non‐ST‐segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2‐hour infusion is unknown.Methods and ResultsA total of 70 P2Y12‐naïve patients, with high‐risk non‐ST‐segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2‐hour infusion (group 2). Levels of IPA with ADP, thrombin receptor‐activating peptide, collagen, and high on‐treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point, IPA with ADP 20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 (P<0.001 for noninferiority). High on‐treatment platelet reactivity with ADP was zero at 2, 6, and 24 hours in both groups. IPA levels with ADP, thrombin receptor‐activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively; P<0.01).ConclusionsTicagrelor and eptifibatide bolus maximally inhibited platelet aggregation at 2 hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2‐hour infusion and might decrease bleeding complications.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01919723.

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“…This study also showed that switching patients from clopidogrel to ticagrelor result in rapid, higher and consistent IPA. 21 …”

Section: Ticagrelor: Clinical Developmentmentioning

confidence: 99%

Ticagrelor: molecular discovery to clinical evidence

Sinha

2012

Indian Heart Journal

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1.Acute coronary syndrome e global and Indian perspective Cardiovascular death (CVD) is one of the leading causes in the non-communicable disease (NCD) deaths. According to WHO estimates around 17 million people die of CVD each year, 1 out of which coronary heart disease (CHD) accounts for 7.1 million deaths. Developing countries like India are witnessing economic transition, urbanization and industrialization resulting in major lifestyle changes like increased tobacco use, physical inactivity and unhealthy diet, that has lead to a dramatic increase in CVD and CHD. 2 In Indian context, there are many challenges in managing patients of ACS. ACS patients in India die younger and sicker with average age at 57 years, almost 10e15 years younger than in west. Moreover, they carry high risk factor profile that includes Diabetes, Hypertension, Smoking and Dyslipidemia and close to 20% patients suffer from a 2nd heart attack in India. 3 As per CREATE registry 60% of patients in India were of STEMI whereas as per global registry data 40% patients were of STEMI. This implies that patients admitted to Indian hospitals with acute coronary syndromes are likely to have a worse prognosis than those in developed countries. In spite of being at high risk, in India, <10% ACS patients are managed through PCI with less than 15% receiving DAPT. 3 Experience in the developed world has shown that significant reductions in CAD prevalence and mortality can be

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Response to Ticagrelor in Clopidogrel Nonresponders and Responders and Effect of Switching Therapies

Cited by 430 publications

References 24 publications

Characterization and Evaluation of Clopidogrel Response Testing in a Community Hospital Setting

Characterization and Evaluation of Clopidogrel Response Testing in a Community Hospital Setting

Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention

Ticagrelor: molecular discovery to clinical evidence

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