Ticagrelor related dyspnea in patients with acute coronary syndromes: Incidence and implication on ticagrelor withdrawn

Sánchez-Galian, María J.; Flores-Blanco, Pedro J.; Gómez-Molina, Miriam; Guerrero-Pérez, Esther; Cambronero-Sánchez, Francisco; Sánchez‐Martínez, Marianela; Valdés, Mariano; Manzano‐Fernández, Sergio

doi:10.1016/j.ijcard.2015.03.417

Cited by 14 publications

(12 citation statements)

References 5 publications

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“…Almost all cases of Ticagrelor related dyspnea occurred in the first week after the initiation of drug; dyspnea was paroxysmal and mild in intensity. In our study 96% of patients had milder paroxysmal dyspnea and was present in first week of treatment which is similar to the results in study done by Maria J. et al 6 Significant discrepancy in dyspnea while comparing our study with PLATO Trial can be attributed to regional variations as shown in various studies conducted across the globe covering western world to Asia Pacific. Incidents of dyspnea were higher in Asian patients in all previous studies and this may be because of difference in genetics, race & other regional factors.…”

Section: Parametersupporting

confidence: 89%

“…There was no significant difference in the incidence of dyspnea observed between Estate study and our study. (21% vs. 19.5%; p valve 0.701) By comparing our data with study done by Maria J, et al, 6 both studies showed non-significant difference in the incidence of dyspnea (19.5% vs. 14% respectively; p valve 0.181). Almost all cases of Ticagrelor related dyspnea occurred in the first week after the initiation of drug; dyspnea was paroxysmal and mild in intensity.…”

Section: Parametersupporting

confidence: 68%

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Evaluation on the Safety of Ticagrelor Among Indian Acute Coronary Syndrome (Acs) Patients Undergoing Percutaneous Coronary Intervention

G.H¹,

Jain²,

Dabral³

et al. 2018

jebmh

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BACKGROUNDTicagrelor is the novel class of anti-platelet drugs, has a simpler and faster metabolism (rapid onset of action), high potency and most importantly reversibility. The latter makes this drug safer in patients with bleeding complications. With this background, we studied the safety and tolerability of ticagrelor in Indian patients with acute coronary syndrome undergoing PCI. Primary Objective was to find out the assessment of bleeding events (major, minor or minimal) in acute coronary syndrome patients on Ticagrelor undergoing PCI. Secondary objective was to assess the incidence of dyspnea and other adverse events during 6months follow up. MATERIALS AND METHODSThis was single center, prospective, observational study involving 200 patients hospitalized in Medanta, The Medicity, Hospital, Gurgaon because of ACS undergoing PCI and were treated with Ticagrelor (180mg loading dose and 90mg thereafter) between December 2015 to May 2016. Study Design: Prospective Observational Study. RESULTSTotal bleeding was observed in 29 (14.5%) patients, in which major bleeding was seen in 08 (4%) patients, minor bleeding was seen in 07 (3.5%) patients, minimal bleeding was observed in 13 (6.5%) patients, and fatal bleeding was seen in 01 (0.5%) patient Upper Gastro-Intestinal Bleeding (UGIB) was most commonly seen, followed by ecchymosis, lower gastrointestinal bleeding, haematuria, nasal bleeding, haemoptysis and intracranial haemorrhage. Dyspnea was observed in 39 (19.5%) patients among whom only 02 (1%) required discontinuation of study drug. CONCLUSIONStudy showed that Ticagrelor is a safe newer antiplatelet drug. Since chance of bleeding was significantly higher in females and diabetics, care should be taken in these patients with high risk for bleeding. Also, incidence of major bleeding and myocardial infarction was seen significantly less in our patients as compared to western counter parts. As our study was small observational study, these conclusions need to be confirmed with larger randomized trials in Indian patients.

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Section: Parametersupporting

confidence: 89%

Section: Parametersupporting

confidence: 68%

Evaluation on the Safety of Ticagrelor Among Indian Acute Coronary Syndrome (Acs) Patients Undergoing Percutaneous Coronary Intervention

G.H¹,

Jain²,

Dabral³

et al. 2018

jebmh

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“…22 The rates of discontinuation of ticagrelor due to dyspnoea have varied considerably in previous studies, ranging from 0.9% in the PLATO trial to 14.3% in a retrospective cohort study. 7,[23][24][25][26] Discontinuation of ticagrelor due to dyspnoea at 1 year in our study was infrequent but occurred more commonly when compared to those treated with clopidogrel (3.3% vs 0%, P < 0.0001). The reason for the variation in the reported rates of dyspnoea-related discontinuation is likely to be multifactorial.…”

Section: Discussionmentioning

confidence: 94%

Contemporary antiplatelet therapy in acute coronary syndromes: are there differences in outcomes and discontinuation between clopidogrel and ticagrelor?

Harding¹,

Holley

Wilkins

et al. 2017

Internal Medicine Journal

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“…14,15 Ticagrelor has to be dosed twice daily and causes dyspnea in 15% of patients, 16 an adverse event that is responsible for 55% of drug withdrawal. 17 Prasugrel cannot be administered to patients with a history of stroke or transient ischemic attacks and is not recommended for patients ≥75 years of age. 18 Current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for the use of antiplatelet therapy in acute coronary syndromes (2014), ST-elevation myocardial infarction (2013) and PCI (2011) continue to recommend the use of clopidogrel as a class I, level of evidence B drug.…”

Section: Alternatives To Clopidogrelmentioning

confidence: 99%

Pharmacogenetics of Clopidogrel

Pereira

Mayr

Shah

et al. 2016

Circ Cardiovasc Genet

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A 58-year-old male was presented with an ST-elevation inferior myocardial infarction. Emergency medical services administered 325 mg of aspirin and sublingual nitroglycerin en route to the emergency room.In the emergency room, the patient received 600 mg of clopidogrel and a heparin bolus. Coronary angiography revealed complete occlusion of the distal right coronary artery with thrombus. Intravenous eptifibatide was given at the start of the percutaneous coronary intervention (PCI). Intravascular ultrasound demonstrated significant soft atheroma and ruptured plaque in the distal right coronary artery at the crux. A drug-eluting stent was deployed with an excellent angiographic result.Postintervention, the patient's chest pain and ECG demonstrated complete resolution of the previous ischemic changes. Approximately 11 hours after being treated in the emergency room, the patient developed recurrent chest pain. He was restarted on eptifibatide and heparin, and repeat coronary angiography demonstrated total occlusion at the origin of the right coronary artery stent (Figure 1).Thrombectomy was performed, removing huge amounts of atherothrombotic material ( Figure 2). Intravascular ultrasound did not demonstrate stent edge dissection or stent malapposition.A drug-eluting stent with 1-mm overlap with the distal edge of the previous stent was deployed. The patient was felt to have failed clopidogrel therapy and was transitioned to prasugrel therapy. The patient was screened for genetic variants in CYP2C19, the gene encoding the cytochrome P450 enzyme CYP2C19 that metabolizes clopidogrel. Pharmacogenetic Test ResultsA Luminex assay using a polymerase chain reaction was used to test for the presence or absence of CYP2C19*17, *4, *8, *6, *9, *3, *10, *2, *7, and *5 alleles. Genetic testing revealed a genotype of CYP2C19 *1/*17 or heterozygosity for CYP2C19*17 (rs12248560). Prodrugs, such as clopidogrel, may be activated to the therapeutic metabolite to a greater degree by individuals, who carry the CYP2C19*17 allele.1 Genetic testing for CYP2C19 variants did not explain clopidogrel failure or the propensity for stent thrombosis in this patient, paradoxically the CYP2C19*17 allele should have potentially predisposed the patient to increased bleeding complications. Unlike patients with CYP2C19*17 genotype, patients who are CYP2C19 poor metabolizers, that is those who are carriers of CYP2C19 loss of function (LOF) variant alleles such as *2 or *3, have been shown to have a significantly increased risk for stent thrombosis. Clopidogrel PharmacogeneticsClopidogrel is a prodrug and is metabolized by CYP2C19 into active thiol metabolites by a 2-step oxidative biotransformation process. Only the active metabolite of clopidogrel targets the P2Y12 receptor for ADP on platelets. The most common LOF variant alleles are CYP2C19*2 and *3 alleles that result in nonfunctional proteins. The haplotype CYP2C19*2 comprises the variant rs4244285, which is a synonymous singlenucleotide polymorphism affecting the amino acid residue proline at pos...

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Ticagrelor related dyspnea in patients with acute coronary syndromes: Incidence and implication on ticagrelor withdrawn

Cited by 14 publications

References 5 publications

Evaluation on the Safety of Ticagrelor Among Indian Acute Coronary Syndrome (Acs) Patients Undergoing Percutaneous Coronary Intervention

Evaluation on the Safety of Ticagrelor Among Indian Acute Coronary Syndrome (Acs) Patients Undergoing Percutaneous Coronary Intervention

Contemporary antiplatelet therapy in acute coronary syndromes: are there differences in outcomes and discontinuation between clopidogrel and ticagrelor?

Pharmacogenetics of Clopidogrel

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