ticagrelor and Dyspnea

The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).

Topics: Acute Coronary Syndrome; Asian People; Clopidogrel; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Thrombosis; Ticagrelor; Treatment Outcome

The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Thrombosis; Ticagrelor; Treatment Outcome

For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. Because the genetic polymorphism of CYP2C19 gene leads to clopidogrel resistance, guidelines for antiplatelet recommendations in CYP2C19 of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizers (PM) are clear. However, there is no clear recommendation as to whether ticagrelor or double dose clopidogrel is the best antiplatelet regimen for CYP2C19 of intermediate metabolizers (IM). To evaluate the efficacy and safety of ticagrelor (combined with aspirin) and high-dose clopidogrel (combined with aspirin) in patients after PCI with CYP2C19 loss-of-function (LOF) alleles.. We searched the following databases to select RCTs of comparing ticagrelor with high-dose clopidogrel in patients after PCI with CYP2C19 LOF alleles: CNKI, Wanfang Data, PubMed, Clinical trials, Cochrane, Web of Science and Embase. Major adverse cardiovascular events (MACEs), platelet function and TIMI bleeding event were defined as the outcomes. revman 5.3 software was used to perform meta-analysis.. A total of 14 RCTs with 2351 patients were enrolled. Meta-analysis showed that compared with high-dose clopidogrel, ticagrelor had reduced incidence of MACEs (OR = 0.32, 95% Cl: 0.23-0.44, p < 0.00001), stent thrombosis (OR: 0.24, 95%CI: 0.13-0.44, p < 0.00001), myocardial infarction OR: 0.42, 95%CI: 0.22-0.80, p = 0.008), revascularization (OR: 0.29, 95%CI: 0.10-0.82, p = 0.02) and unstable angina (OR: 0.47, 95%CI: 0.29-0.77, p = 0.003) in patients after PCI with CYP2C19 LOF alleles. A subgroup analysis showed that ticagrelor reduced the risk of MACEs compared with high-dose clopidogrel regardless of the type of metabolizer. Compared with high-dose clopidogrel, ticagrelor significantly reduced the risk of MACE with longer follow-up period (more than 3 months) without increasing the risk of bleeding (OR: 0.89, 95%CI: 0.53-1.49, p = 0.30), while elevated dyspnoea (OR: 5.62, 95%CI: 3.07-10.28, p < 0.00001).. For patients carrying CYP2C19 LOF alleles after PCI, ticagrelor may be better than high-dose clopidogrel in reducing the risk of MACEs, while dyspnoea incidents should be alerted.

Topics: Acute Coronary Syndrome; Aspirin; Clopidogrel; Cytochrome P-450 CYP2C19; Dyspnea; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor; Treatment Outcome

Ticagrelor and prasugrel are two third-generation oral P2Y. We systematically searched the PubMed, Cochrane Central Register of Controlled Trials databases, ClinicalTrials.gov and Web of Science for randomized control trials (RCTs) comparing ticagrelor or prasugrel with clopidogrel until July 2019. The primary outcome was the incidence of dyspnea. The risk ratios (RR) and 95% confidence intervals (CI) were estimated using meta-analysis.. We included 25 RCTs involving 63,484 patients in this meta-analysis, including 21 studies on ticagrelor and 4 studies on prasugrel. Compared to the clopidogrel group, third-generation oral P2Y. Ticagrelor has a higher risk of dyspnea than clopidogrel, which was not observed in patients using prasugrel.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Clopidogrel; Dyspnea; Female; Humans; Incidence; Male; Middle Aged; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Ticagrelor; Young Adult

Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines. It is an antiplatelet agent with a unique mechanism of action, allowing a direct and reversible competitive inhibition of P2Y. This review is a comprehensive and thorough summary of the most important findings on ticagrelor. Pharmacokinetics, pharmacogenetics, drug-drug interactions, adverse effects, efficacy in specific patient populations and off-label properties of ticagrelor are discussed in this paper. Moreover, the results from pivotal clinical trials are presented.. Introduction of ticagrelor, a first directly-acting and reversible P2Y

Topics: Acute Coronary Syndrome; Adenosine; Cytochrome P-450 CYP2C19; Drug Interactions; Dyspnea; Half-Life; Hemorrhage; Humans; Pharmacogenetics; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor

Ticagrelor has been acknowledged as a new oral antagonist of P2Y12-adenosine diphosphate receptor, as a strategy with more rapid onset as well as more significant platelet inhibition function in acute coronary syndrome (ACS) patients. The clinical benefit of ticagrelor compared with clopidogrel remains controversial. The current meta-analysis was conducted to better evaluate the role of ticagrelor in comparison of clopidogrel in treating ACS patients.. The publications involving the safety as well as the efficacy of clopidogrel versus ticagrelor were screened and identified updated to June 2018. After rigorous review, eligible randomized controlled trials (RCTs) were extracted and propensity score matching (PSM) analysis was conducted. To analyze the summary odds ratios (ORs) of the endpoints of interest, we applied Meta-analysis Revman 5.3 software.. There were a total of 10 studies that met our inclusion criteria, of which the risk of bleeding rate (P = 0.43), MI (P = 0.14), and stroke (P = 0.70) had no association with significant differences between patients receiving ticagrelor or clopidogrel. Nonetheless, higher rate of dyspnea was observed in ticagrelor group (OR = 1.87, 95% CI: 1.70-2.05, P<0.00001 = .. Our present findings suggest similar efficacy and safety profiles for clopidogrel and ticagrelor Ticagrelor should be considered as a valuable option to reduce the risk of bleeding, MI and stroke, whereas potentially increases the incidence of dyspnea. Given the metabolic process, ticagrelor may be a valid and even more potent antiplatelet drug than clopidogrel, as an alternative strategy in treating patients with clopidogrel intolerance or resistance.

Topics: Acute Coronary Syndrome; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Factors; Ticagrelor; Treatment Outcome

The occurrence of dyspnoea in acute coronary syndrome (ACS) patients has always been considered a challenging diagnostic and therapeutic clinical scenario. P2Y12 platelet receptor inhibitors (i.e., clopidogrel, prasugrel and ticagrelor) are currently the cornerstone of treatment of ACS patients. Thus, in the last few years, the potential association between ACS and dyspnoea has also become more challenging with the increasing use of ticagrelor in these patients due to its beneficial effects on ischaemic event prevention and mortality, since ticagrelor can induce dyspnoea as a side effect. The present article is intended to review the current literature regarding dyspnoea occurrence in ACS patients, especially those treated with ticagrelor, and to propose ticagrelor-associated dyspnoea management recommendations based on current knowledge.

Topics: Acute Coronary Syndrome; Adenosine; Dyspnea; Humans; Purinergic P2Y Receptor Antagonists; Ticagrelor

Oral reversible platelet P2Y12 receptor inhibitors (ticagrelor and elinogrel) cause double-digit rates of dyspnea, while irreversible oral antiplatelet drugs (aspirin, ticlopidoine, clopidogrel, and prasugrel) or intravenous glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, or tirofiban) do not increase the incidence of dyspnea in randomized trials. Dyspnea after oral reversible antiplatelet agents remains unexplained. A transfusion-related acute lung injury (TRALI) hypothesis has been proposed. The dyspnea risks after cangrelor, an intravenous reversible antiplatelet agent, are not well defined but may offer a universal mechanism linking TRALI, dyspnea, and reversible platelet inhibition.. We analyzed safety data from recent head-to-head randomized trials with reversible antiplatelet agents (ticagrelor, elinogrel, and cangrelor) compared to irreversible (clopidogrel/placebo) comparators.. All three reversible antiplatelet agents cause excess dyspnea. In contrast to the high double-digit rates after oral ticagrelor or elinogrel, the dyspnea risks after intravenous cangrelor were smaller (<2%) but still consistently and significantly higher than in the corresponding control arms.. The clinical utility of reversible antiplatelet strategies has been challenged. Despite a potential advantage of fewer bleeding events during heart surgery, reversible antiplatelet agents carry the risk of potential autoimmune reactions manifesting as dyspnea. Repeated binding and unbinding cycles, impaired platelet turnover, and lung sequestration or apoptosis of overloaded destructive platelets are among the potential mechanism(s) responsible for dyspnea after reversible antiplatelet agents.

Topics: Acute Lung Injury; Adenosine; Adenosine Monophosphate; Administration, Oral; Clopidogrel; Dyspnea; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Sulfonamides; Ticagrelor; Ticlopidine; Transfusion Reaction

The dual antiplatelet therapy with acetylsalicylic acid and clopidogrel has been the mainstay of both acute and chronic phase coronary artery disease, reducing importantly the risk of adverse events. Despite a correct compliance, a non-negligible rate of adverse events still happens. New compounds, with improved properties, are now clinically available (such as prasugrel or ticagrelor) or under advanced development. The aim of the present review is the description of these new compounds, particularly prasugrel and ticagrelor.

Topics: Adenosine; Adenosine Monophosphate; Clinical Trials, Phase III as Topic; Coronary Artery Disease; Double-Blind Method; Dyspnea; Hemorrhage; Humans; Multicenter Studies as Topic; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Receptors, Proteinase-Activated; Thiophenes; Ticagrelor; Treatment Outcome

Dyspnea has been consecutively reported in some trials evaluating new P2Y₁₂ inhibitors.. We aimed to review and quantify the global risk of dyspnea of recent P2Y₁₂ inhibitor drugs, and evaluate its association with the reversibility profile of P2Y₁₂ inhibitors.. A database search (March 2013) retrieved randomized controlled trials (RCTs) comparing new antiplatelet drugs (ticagrelor, prasugrel, cangrelor, elinogrel) with clopidogrel. The primary outcome was the incidence of dyspnea. Placebo-controlled trials were excluded. Meta-analysis was performed and estimates were expressed as risk ratio (RR) and 95% confidence intervals (95% CIs). Dyspnea incidence was evaluated according to the reversibility profile of P2Y₁₂ antagonists.. We found eight RCTs including 41,289 patients. Prasugrel was not associated with an increased risk of dyspnea (RR 1.09, 95% CI 0.93-1.27), whereas ticagrelor (RR 1.95, 95% CI 1.37-2.77), cangrelor (RR 2.42, 95% CI 1.36-4.33), and elinogrel (RR 3.25, 95% CI 1.57-6.72) showed an increased risk of dyspnea. Reversible inhibitors significantly increased the risk of dyspnea compared with the irreversible inhibitor, prasugrel, through adjusted indirect comparison (RR 1.99, 95% CI 1.40-2.82).. The reversible P2Y₁₂ antagonists ticagrelor, cangrelor, and elinogrel have an increased incidence of dyspnea in increasing order when compared with irreversible P2Y₁₂ inhibitors such as clopidogrel or prasugrel.

Topics: Adenosine; Adenosine Monophosphate; Clopidogrel; Dyspnea; Humans; Incidence; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Quinazolinones; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Sulfonamides; Thiophenes; Ticagrelor; Ticlopidine

Ticagrelor, a recently approved platelet antagonist indicated for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS), has been reported to cause dyspnea in more than 13% of patients. Dyspnea is not a clinically relevant adverse event with other medications indicated for ACS. One suggested mechanism of ticagrelor-induced dyspnea involves an increase in systemic adenosine concentrations through adenosine deaminase inhibition. Dyspnea, a subjective finding resulting from physiologic and sensory mechanisms, may be a consequence of increased systemic adenosine concentrations, leading to amplified and prolonged receptor activity. Current literature suggests, however, that pulmonary status is not compromised, with no reduction of efficacy seen in patients with ticagrelor-induced dyspnea, thus allowing clinicians to continue therapy without reservation. Still, patients with a history of asthma and chronic obstructive pulmonary disease may be more susceptible to ticagrelor-induced dyspnea, potentially leading to nonadherence and exacerbations of morbidity. Therefore, it is paramount that health care providers continually monitor these patients with the aims of maintaining medication therapy adherence and providing relevant options if dyspnea becomes intolerable.

Topics: Adenosine; Dyspnea; Humans; Platelet Aggregation Inhibitors; Ticagrelor

Ticagrelor, an oral P2Y(12) receptor antagonist used as part of dual antiplatelet therapy in the treatment of acute coronary syndromes (ACS), has many favorable characteristics when compared with the more frequently used P2Y(12) receptor antagonist clopidogrel. Ticagrelor binds reversibly, with a rapid onset and offset of action, and produces high levels of platelet inhibition without variation secondary to genetic polymorphism. Ticagrelor produces increased platelet inhibition and an overall reduction in adverse cardiac events compared with clopidogrel. Clinically relevant side effects include an increase in non-CABG-related bleeding events as well as off-target adverse effects including ventricular pauses and dyspnea.. This article details ticagrelor's pharmacokinetic and pharmacodynamic characteristics, development and chemical properties. The authors review relevant clinical trials looking at the efficiency and safety of ticagrelor focusing predominantly on the management of patients with ACS. Finally, the review article concludes with discussion of ticagrelor's current role and future integration into clinical practice.. Ticagrelor is a promising P2Y(12) receptor antagonist with characteristics that offer advantages for patients beyond those currently demonstrated by other P2Y(12) receptor antagonists. The challenge for prescribers is to identify those most likely to benefit from ticagrelor treatment while minimizing unnecessary bleeding events for 'real-world' ACS patients.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine

Ticagrelor is a novel, non-thienopyridine ADP inhibitor that reversibly blocks the P2Y(12) receptor, preventing platelet activation and aggregation. It is the first ADP inhibitor to show a mortality benefit in patients with acute coronary syndromes (ACS). Its major safety concern, as with the other ADP blockers, is bleeding. Other common adverse effects of ticagrelor such as dyspnea and ventricular pauses appear to be mild and self-limited.. The pharmacological properties of ticagrelor compared with clopidogrel are explored in this article. In addition, the relevant clinical trials in which ticagrelor was investigated are described, with an emphasis on efficacy and safety end points.. Although some patients suffer from dyspnea when administered with ticagrelor, there is no evidence of any untoward effects on the cardiovascular or pulmonary systems. Given that the majority of these episodes are mild to moderate and self-limiting, patients should be encouraged to continue the medication, as symptoms may resolve. Furthermore, patients with underlying heart failure or lung disease do not appear to be at an increased risk of developing ticagrelor-induced dyspnea. Its overall mortality benefit among patients with ACS, along with its ability to inhibit platelet aggregation more rapidly and consistently, makes it the preferred agent over clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Factors; Ticagrelor; Ticlopidine

In studies that compared the reversible P2Y12 inhibitor ticagrelor with the irreversible inhibitor clopidogrel, dyspnea was observed more frequently among ticagrelor-treated patients than among clopidogrel-treated patients. Because dyspnea was not associated with acidosis, pulmonary or cardiac dysfunction, alterations in the mechanisms and pathways of the sensation of dyspnea may be involved in its pathogenesis. It has been hypothesised that the sensation of dyspnea in ticagrelor-treated patients is triggered by adenosine, because ticagrelor inhibits its clearance, thereby increasing its concentration in the circulation. However, dipyridamole, a much stronger inhibitor of adenosine clearance than ticagrelor, usually does not cause dyspnea. We hypothesise that inhibition of P2Y12 on sensory neurons increases the sensation of dyspnea, particularly when reversible inhibitors are used. We base our hypothesis on the following considerations: 1) cangrelor and elinogrel, which, like ticagrelor, are reversible P2Y12 inhibitors, also increase the incidence of dyspnea; 2) it is biologically plausible that inhibition of P2Y12 on sensory neurons increases the sensation of dyspnea; 3) inhibition of P2Y12 on platelets (which do not have a nucleus) by clopidogrel is permanent, despite the once daily administration and the short plasma half-life of the inhibitor; 4) in contrast, inhibition of P2Y12 on neurons by clopidogrel may be temporary and transient, because neurons have a nucleus and can therefore rapidly replace the inhibited receptors with newly synthetised ones; 5) inhibition of P2Y12 on neurons by reversible inhibitors is permanent, because the plasma drug concentration is maintained high by repeated dosing, in order to ensure permanent inhibition of platelet P2Y12.

Topics: Adenosine; Clopidogrel; Dyspnea; Humans; Models, Biological; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Sensory Receptor Cells; Ticagrelor; Ticlopidine

Acute coronary syndromes (ACS) are the leading cause of mortality and one of the main reasons for hospital admissions in the developed nations. Due to high rates of mortality and reinfarction, ACS represent a major public health concern. Platelets play a central role in atherothrombosis, the main pathologic substrate in ACS. Sufficient inhibition of platelet aggregation is therefore one of the key targets in the treatment of ACS. Blockade of the P2Y12 subtype of adenosine diphosphate (ADP) receptor on platelet cell membranes has been established as a key mechanism of platelet inhibition. Clopidogrel, an ADP receptor antagonist and a second-generation thienopyridine, has been demonstrated to be of clinical benefit in patients with ACS when added to aspirin. A delayed onset of action due to two-step conversion to the active metabolite, irreversible binding to P2Y12 receptors, and broad interindividual variability in levels of platelet response are the main limitations of clopidogrel. Prasugrel, a novel third-generation thienopyridine, provides faster and stronger inhibition of platelet aggregation than clopigodrel. However, like the active metabolite of clopidogrel, prasugrel binds irreversibly to the P2Y12 ADP receptor site, causing inhibition of platelet aggregation for the life of the platelet. Although in a randomized, double-blind trial prasugrel demonstrated superiority for multiple cardiovascular endpoints compared with standard-dose clopidogrel, it was also associated with an increased bleeding risk, including fatal bleeding. This review discusses the optimal antiplatelet regimens for management of patients with ACS, with special focus on ticagrelor, the first oral agent in a new chemical class of nonthienopyridine antiplatelet agents termed cyclopentyltriazolo-pyrimidines. Faster and greater platelet inhibition than clopidogrel, quick recovery of platelet function, and high efficacy regardless of clopidogrel response status, are the obvious advantages of ticagrelor as compared with thienopyridines. The prospective, randomized Platelet Inhibition and Patient Outcomes trial has established the clinical utility, enhanced efficacy, and similar safety of ticagrelor as compared with clopidogrel in a wide range of patients with ACS managed with contemporary antithrombotic therapies and invasive strategies when indicated. Dyspnea, ventricular pauses ≥3 seconds, and elevation of serum creatinine and uric acid are the most common known adverse effects associ

Topics: Acute Coronary Syndrome; Adenosine; Aspirin; Blood Platelets; Clopidogrel; Dyspnea; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Receptors, Purinergic P2Y12; Ticagrelor; Ticlopidine; Treatment Outcome

Recent randomised studies suggest that experimental oral reversible platelet P2Y12 receptor inhibitor, AZD6140, causes dyspnoea. This also raises similar concerns about the parent compound, and another adenosine triphosphate (ATP) analogue (AR-69931MX or cangrelor), which is currently in Phase 3 trial in patients undergoing coronary interventions. We analysed package inserts, and available clinical trials safety data for antiplatelet agents with regard to the incidence of dyspnoea. We found that dyspnoea is a very rare complication of the presently approved platelet inhibitors, mostly caused by underlying disease, rather than antiplatelet therapy per se. The main reasons for respiratory distress after oral (AZD6140), and intravenous (cangrelor) agents may be the development of mild asymptomatic thrombotic thrombocytopenic purpura, fluid retention and dyspnoea because of the reversible nature of these drugs. Also, these agents are ATP analogues, which rapidly metabolise to adenosine, a well-known bronchoprovocator causing dyspnoea as well. In summary, dyspnoea is seldom considered, there are no treatment algorithms when it does occur, plausible mechanisms exist and despite these plausible mechanisms, the true cause of dyspnoea in these exposed individuals is unknown. Additional pulmonary function testing, immunological investigations and platelet receptor studies are urgently needed to determine the cause of dyspnoea after AZD6140, and to point out how such serious adverse reactions can be prevented, or at least minimised, raising potential concerns about this drug.

Topics: Adenosine; Dyspnea; Humans; Platelet Aggregation Inhibitors; Ticagrelor

Nearly 20% of patients on ticagrelor experience dyspnea, which may lead to treatment discontinuation in up to one-third of cases.. The authors sought to evaluate the incidence, predictors, and outcomes of dyspnea-related ticagrelor discontinuation after percutaneous coronary intervention (PCI).. In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The occurrence of dyspnea associated with ticagrelor discontinuation was evaluated among all patients enrolled in the trial. A landmark analysis was performed at 3 months after PCI, that is, the time of randomization. Predictors of dyspnea-related ticagrelor discontinuation were obtained from multivariable Cox regression with stepwise selection of candidate variables.. The incidence of dyspnea-related ticagrelor discontinuation was 6.4% and 9.1% at 3 and 15 months after PCI, respectively. Independent predictors included Asian race (lower risk), smoking, prior PCI, hypercholesterolemia, prior coronary artery bypass, peripheral artery disease, obesity, and older age. Among 179 patients who discontinued ticagrelor because of dyspnea after randomization, ticagrelor monotherapy was not associated with a higher risk of subsequent ischemic events (composite of all-cause death, myocardial infarction, or stroke) compared with ticagrelor plus aspirin (5.0% vs 7.1%; P = 0.566).. In the TWILIGHT trial, dyspnea-related ticagrelor discontinuation occurred in almost 1 in 10 patients and tended to occur earlier rather than late after PCI. Several demographic and clinical conditions predicted its occurrence, and their assessment may help identify subjects at risk for therapy nonadherence.

Topics: Aspirin; Drug Therapy, Combination; Dyspnea; Hemorrhage; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

It was aimed at the plasma concentration detection of aminophylline under multi-walled carbon nanotube (MWNT) modified electrodes and the curative effect of aminophylline for ticagrelor-related dyspnea (TRD). 120 patients with TRD and coronary atherosclerotic heart disease (CAHD) in Wuhan Sixth Hospital Hospital were randomly divided into an intervention group and a control group, with 60 cases in each. The novel chitosan/gold nanoparticles-MWNTs (CTS/Au NPs-MWNTs) composite was prepared for studying the electrochemical behaviors of aminophylline on the electrodes. The clinical curative effect of aminophylline, as well as the levels of peripheral blood T lymphocyte subsets and inflammatory cytokines, was observed in the treatment of TRD. The actual plasma molar concentration of aminophylline was 23.6-47.8 μmol/L. After treatment, the total effective rate in the intervention group was higher than that in the control group significantly (95% VS 65%) (P<0.05). The forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) of the intervention group were better than those of the control group remarkably (P<0.05). The intervention group showed lower levels of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 as well as the higher IL-10 significantly in serum compared with the control group (P<0.05). After follow-up, there was no cardiovascular death in either group. The CTS/Au NPs-MWNTs could be used for detecting the plasma concentration of aminophylline in blood samples. Aminophylline could notably relieve the clinical symptoms, reduce the inflammatory response, and regulate the immunity of patients with good safety.

Topics: Aminophylline; Chitosan; Dyspnea; Electrodes; Gold; Humans; Metal Nanoparticles; Nanotubes, Carbon; Ticagrelor

To evaluate long-term safety and efficacy of ticagrelor monotherapy in patients undergoing percutaneous coronary interventions (PCIs) in relation to chronic obstructive pulmonary disease (COPD) at baseline and the occurrence of dyspnoea reported as adverse event (AE) that may lead to treatment non-adherence.. This is a non-prespecified, post hoc analysis of the randomized GLOBAL LEADERS trial (n = 15 991), comparing the experimental strategy of 23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. Impact of COPD and dyspnoea AE (as a time-dependent covariate) on clinical outcomes was evaluated up to 2 years. The primary endpoint was a 2-year all-cause mortality or non-fatal, centrally adjudicated, new Q-wave myocardial infarction. The presence of COPD (n = 832) was the strongest clinical predictor of 2-year all-cause mortality after PCI [hazard ratio (HR) 2.84; 95% confidence interval (CI) 2.21-3.66; P adjusted = 0.001] in this cohort (n = 15 991). No differential treatment effects on 2-year clinical outcomes were found in patients with and without COPD (primary endpoint: HR 0.88; 95% CI 0.58-1.35; P = 0.562; P int = 0.952). Overall, at 2 years dyspnoea was reported as an AE in 2101 patients, more frequently among COPD patients, irrespective of treatment allocation (27.2% in experimental arm vs. 14.5% in reference arm, P = 0.001). Its occurrence was not associated with a higher rate of the primary endpoint (P adjusted = 0.640) in the experimental vs. the reference arm.. In this exploratory analysis, COPD negatively impacted long-term prognosis after PCI. Despite higher incidence of dyspnoea in the experimental arm, in particular among COPD patients, the safety of the experimental treatment strategy appeared not to be affected.. NCT01813435.

Topics: Aged; Coronary Artery Disease; Drug Administration Schedule; Dual Anti-Platelet Therapy; Dyspnea; Female; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Topics: Aged; Aspirin; Beverages; Caffeine; Double-Blind Method; Dual Anti-Platelet Therapy; Dyspnea; Female; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Ticagrelor; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Adenosine; Biomarkers; Cross-Over Studies; Drug Monitoring; Dyspnea; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Time Factors

Topics: Adenosine; Aged; Caffeine; Drug Monitoring; Dyspnea; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Reported Outcome Measures; Purinergic P2Y Receptor Antagonists; Ticagrelor

In the PEGASUS-TIMI 54 trial, treatment with ticagrelor reduced the incidence of cardiovascular death, myocardial infarction, or stroke by 15% to 16% among stable patients compared with placebo. However, more patients prematurely discontinued treatment with ticagrelor than with placebo.. To investigate the reasons and timing of discontinuation of treatment with ticagrelor among stable patients prior myocardial infarction.. In the PEGASUS-TIMI 54 trial, 21 162 stable outpatients with prior myocardial infarction were randomly assigned to 90 mg of ticagrelor twice daily, 60 mg of ticagrelor twice daily, or placebo, with all of the patients receiving a low dose of aspirin. These participants were followed up for a median of 33 months (study start date: October 2010; completion date: December 2014). Discontinuation of treatment was evaluated by treatment arm, cause, and timing. This analysis was initiated in May 2015.. Discontinuation of treatment.. Over 33 months, 32%, 29%, and 21% of patients receiving 90 mg of ticagrelor, 60 mg of ticagrelor, and placebo, respectively, discontinued treatment (P < .001). Discontinuation of treatment due to an adverse event occurred in 19%, 16%, and 9% of patients, respectively (P < .001). The most frequent adverse events leading to discontinuation of treatment were bleeding (with Kaplan-Meier event rates of 7.8%, 6.2%, and 1.5% of patients, respectively; P < .001) and dyspnea (6.5%, 4.6%, and 0.8% of patients, respectively; P < .001). Eighty-six percent of bleeding events that led to the discontinuation of treatment with ticagrelor were nonmajor, and 86% of adverse events due to dyspnea that led to discontinuation of treatment with ticagrelor were mild or moderate in severity. The discontinuation rates are annualized for patients who received 90 mg of ticagrelor twice daily (hazard ratio [HR], 2.00 [95% CI, 1.84-2.16] for the first year; HR, 1.12 [95% CI, 1.00-1.26] for the second and third years) and patients who received 60 mg of ticagrelor twice daily (HR, 1.59 [95% CI, 1.46-1.73] for the first year; HR, 1.18 [95% CI, 1.06-1.32] for the second and third years) compared with patients who received placebo.. When initiated among stable patients with prior myocardial infarction, discontinuation of treatment with ticagrelor was driven primarily by nonserious adverse events occurring primarily early after randomization. For patients completing 1 year of treatment, the subsequent discontinuation rate was low. These data demonstrate how adverse events considered "nonserious" by traditional trial criteria may have an effect on quality of life and, thus, may precipitate the discontinuation of treatments and underscore the need for patient education and counseling on the timing and nature of adverse effects with the aim of improving adherence when appropriate.. clinicaltrials.gov Identifier: NCT01225562.

Topics: Adenosine; Dyspnea; Hemorrhage; Humans; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Quality of Life; Secondary Prevention; Stroke; Ticagrelor

Ticagrelor treatment has the side effect of increased incidence of dyspnea. Adenosine-induced dyspnea is augmented by ticagrelor and can be alleviated with the adenosine antagonist theophylline. Caffeine is a closely related xanthine derivative.. The primary objective of the TROCADERO is to evaluate the effect of caffeine versus placebo on ticagrelor-associated dyspnea, measured by the visual analog scale area under the curve in patients with ongoing ticagrelor treatment after an acute coronary syndrome event.. After a run-in period of 1 to 7 days of absence of caffeine intake, acute coronary syndrome patients with ticagrelor-induced dyspnea (planned inclusion 416) are randomized in a blinded fashion to either caffeine 200 mg twice daily or matching placebo with a treatment duration of 1 week. The primary efficacy end point is change in visual analog scale area under the curve for dyspnea, and the primary safety end point is occurrence of high on-treatment platelet reactivity measured by the VerifyNow P2Y12 assay.. This trial will determine if adenosine antagonism by caffeine can alleviate ticagrelor-related dyspnea, without impairing the antiplatelet effect of ticagrelor.

Topics: Acute Coronary Syndrome; Adenosine; Caffeine; Dose-Response Relationship, Drug; Double-Blind Method; Dyspnea; Electrocardiography; Purinergic P1 Receptor Antagonists; Purinergic P2Y Receptor Antagonists; Ticagrelor

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients.. In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results.. In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Dyspnea; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Platelet Aggregation Inhibitors; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; Time Factors; Treatment Outcome

AIMS To describe the incidence of dyspnoea and its associations with demographic characteristics and clinical outcomes in patients with acute coronary syndromes (ACS) treated with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) study. METHODS AND RESULTS In the PLATO study, 18 624 patients were randomized to receive either clopidogrel [300-600 mg loading dose (LD), 75 mg daily] or ticagrelor (180 mg LD, 90 mg b.i.d.). The occurrence of reported dyspnoea adverse events (AEs) was analysed in the 18 421 patients who received at least one dose of study medication in relation to demographic characteristics, clinical outcomes and other associations of patients with and without dyspnoea. A total of 1339 ticagrelor-treated patients (14.5%) and 798 clopidogrel-treated patients (8.7%) had a dyspnoea AE following randomization, with respectively 39 (0.4%) and 24 (0.3%) classified as severe in intensity. Excluding dyspnoea AEs occurring after the secondary endpoint of myocardial infarction (MI), the yearly rates of the efficacy endpoints in dyspnoea AE patients in the ticagrelor and clopidogrel groups were: for the primary composite of CV death, MI, and stroke, 8.8 and 10.4% (unadjusted P = 0.25; adjusted P = 0.54); for CV death, 3.1 and 4.8% (unadjusted P = 0.024; adjusted P = 0.18); and for total death 3.7 and 6.2% (unadjusted P = 0.004; adjusted P = 0.06), respectively. CONCLUSIONS Ticagrelor-related dyspnoea is usually mild or moderate in intensity and does not appear to be associated with differences concerning any efficacy or safety outcomes with ticagrelor compared with clopidogrel therapy in ACS patients.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Double-Blind Method; Dyspnea; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Ticlopidine; Treatment Outcome

We prospectively assessed cardiac and pulmonary function in patients with stable coronary artery disease (CAD) treated with ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease) study.. Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes. Dyspnea develops in some patients treated with ticagrelor, and it is not known whether this is associated with changes in cardiac or pulmonary function.. In all, 123 stable aspirin-treated CAD patients randomly received either ticagrelor (180 mg load, then 90 mg twice daily; n=57), clopidogrel (600 mg load, then 75 mg daily; n=54), or placebo (n=12) for 6 weeks in a double-blind, double-dummy design. Electrocardiography, echocardiography, serum N-terminal pro-brain natriuretic peptide, and pulmonary function tests were performed before (baseline) and 6 weeks after drug administration and/or after development of dyspnea.. After drug administration, dyspnea was reported by 38.6%, 9.3%, and 8.3% of patients in the ticagrelor, clopidogrel, and placebo groups, respectively (p<0.001). Most instances were mild and/or lasted<24 h, although 3 patients discontinued ticagrelor because of dyspnea. Eight of 22 and 17 of 22 ticagrelor-treated patients experiencing dyspnea did so within 24 h and 1 week, respectively, after drug administration. In all treatment groups, and in ticagrelor-treated patients with dyspnea, there were no significant changes between baseline and 6 weeks in any of the cardiac or pulmonary function parameters.. Dyspnea is commonly associated with ticagrelor therapy, but was not associated in this study with any adverse change in cardiac or pulmonary function. (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ONSET/OFFSET]; NCT00528411).

Topics: Adenosine; Aged; Aspirin; Clopidogrel; Coronary Disease; Double-Blind Method; Dyspnea; Female; Heart; Humans; Lung; Male; Middle Aged; Platelet Aggregation Inhibitors; Prospective Studies; Ticagrelor; Ticlopidine

Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel.. In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.. At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.. In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872.)

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Double-Blind Method; Dyspnea; Electrocardiography; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Stroke; Ticagrelor; Ticlopidine

This study aimed to define the association between altitude and ticagrelor-associated dyspnea in patients with acute coronary syndrome (ACS).. We studied consecutive patients with de novo ACS who were admitted to two centers at a low altitude (18 and 25 m, n = 65) and two centers at a high altitude (1313 and 1041 m, n = 136). We managed them with ticagrelor between May 2017 and September 2017. Patients with ACS underwent an interventional procedure within <90 minutes in those with ST elevation and within <3 hours in those without ST elevation. We recorded the incidence of dyspnea in patients with ACS receiving ticagrelor therapy.. The mean age was 59.5 ± 10 years, and the mean ejection fraction was 43% ± 18%. A total of 110 (56.7%) patients had ST elevation and 84 (43.3%) did not. There were no significant differences in cardiac risk factors, concurrent medications, or procedural variables between the two groups. Dyspnea developed during hospitalization in 53 (38%) patients from high-altitude centers and in 13 (20%) patients from low-altitude centers (66 patients represented 32% of the total ACS cohort).. Dyspnea is a common multifactorial symptom in patients following development of ACS. Ticagrelor-induced dyspnea appears to be associated with altitude.

Topics: Acute Coronary Syndrome; Aged; Altitude; Dyspnea; Humans; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Dyspnea; Humans; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Ticagrelor is a frequently prescribed platelet aggregation inhibitor used in patients with acute coronary syndrome. A rare side effect is severe dyspnoea.. A 76 year old woman experiences severe shortness of breath three weeks after percutaneous coronary intervention because of acute myocardial infarction. Physical examination and additional investigation showed no pulmonary or cardiac explanation for her complaints. Shortly after cessation of ticagrelor, her complaints disappeared.. Ticagrelor-related severe dyspnoea in post-myocardial infarction patients is a diagnosis by exclusion of other reasonable causes of dyspnoea. Unfamiliarity with this side effect can lead to excess diagnostics and unnecessary referrals.

Topics: Acute Coronary Syndrome; Aged; Dyspnea; Female; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor; Treatment Outcome

Dyspnoea often occurs in patients with acute coronary syndrome (ACS) treated with ticagrelor compared with other anti-platelet agents and is a cause of drug discontinuation. We aimed to explore the contribution of central apnoeas (CA) and chemoreflex sensitization to ticagrelor-related dyspnoea in patients with ACS.. Sixty consecutive patients with ACS, preserved left ventricular ejection fraction, and no history of obstructive sleep apnoea, treated either with ticagrelor 90 mg b.i.d. (n = 30) or prasugrel 10 mg o.d. (n = 30) were consecutively enrolled. One week after ACS, all patients underwent two-dimensional Doppler echocardiography, pulmonary static/dynamic testing, carbon monoxide diffusion capacity assessment, 24-h cardiorespiratory monitoring for hypopnoea-apnoea detection, and evaluation of the chemosensitivity to hypercapnia by rebreathing technique. No differences were found in baseline demographic and clinical characteristics, echocardiographic, and pulmonary data between the two groups. Patients on ticagrelor, when compared with those on prasugrel, reported more frequently dyspnoea (43.3% vs. 6.7%, P = 0.001; severe dyspnoea 23.3% vs. 0%, P = 0.005), and showed higher apnoea-hypopnoea index (AHI) and central apnoea index (CAI) during the day, the night and the entire 24-h period (all P < 0.001). Similarly, they showed a higher chemosensitivity to hypercapnia (P = 0.001). Among patients treated with ticagrelor, those referring dyspnoea had the highest AHI, CAI, and chemosensitivity to hypercapnia (all P < 0.05).. Central apnoeas are a likely mechanism of dyspnoea and should be screened for in patients treated with ticagrelor. A drug-related sensitization of the chemoreflex may be the cause of ventilatory instability and breathlessness in this setting.

Topics: Acute Coronary Syndrome; Dyspnea; Humans; Platelet Aggregation Inhibitors; Sleep Apnea, Central; Stroke Volume; Ticagrelor; Ventricular Function, Left

Topics: Adenosine Monophosphate; Aged; Anxiety; Chest Pain; Coronary Angiography; Coronary Occlusion; Drug Substitution; Drug-Eluting Stents; Drug-Related Side Effects and Adverse Reactions; Dyspnea; Electrocardiography; Humans; Inferior Wall Myocardial Infarction; Male; Percutaneous Coronary Intervention; Purinergic P2Y Receptor Antagonists; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome; Withholding Treatment

Topics: Dyspnea; Humans; Platelet Aggregation Inhibitors; Theophylline; Ticagrelor

This study aims to determine frequency and reasons for prematurely discontinuing or switching antiplatelet therapy in elderly patients admitted with non-ST-elevation acute coronary syndrome (NSTE-ACS).. Patients of 75 years or older admitted with suspected NSTE-ACS were included between 2013 and 2016. Information was extracted from the patients' medical files.. A total of 544 patients were included, 17.3% discontinued aspirin within one year, predominantly (57%) within 30 days. The most common reason was the start of a (non-vitamin-K) oral anticoagulant [(N)OAC], either combined with a P2Y12-inhibitor (43%) or as monotherapy (16%). The P2Y12-inhibitor was discontinued in 31.2% of patients within one year, of which 46% within 30 days. The most common reason was undergoing coronary artery bypass grafting (CABG; 22%). Switching of clopidogrel seldom occurred; however, ticagrelor was switched in 50/179 patients mainly due to dyspnoea (42%). Independent predictors for prematurely discontinuing antiplatelet therapy were undergoing CABG [odds ratio (OR) 3.257 (95% confidence interval [CI] 1.836-5.779)], need for (N)OAC [OR 2.167 (95% CI 1.423-3.300)] and type II ACS as final diagnosis [OR 3.793 (95% CI 1.721-8.361)]. Undergoing percutaneous coronary intervention [OR 0.393 (95% CI 0.243-0.634)] and use of clopidogrel [OR 0.441(95% CI 0.293-0.662)] were independent predictors of continuing antiplatelet therapy.. In elderly patients of at least 75 years with NSTE-ACS, antiplatelet therapy is frequently discontinued prematurely, most often within 30 days. Main reasons for discontinuing are need for (N)OAC, undergoing CABG or type II ACS as final diagnosis and suffering from dyspnoea while on ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Coronary Artery Bypass; Deprescriptions; Drug Substitution; Dual Anti-Platelet Therapy; Dyspnea; Factor Xa Inhibitors; Female; Humans; Male; Non-ST Elevated Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Ticagrelor

Guidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea.. To compare the risk of MACE with ticagrelor vs clopidogrel in patients with ACS treated with percutaneous coronary intervention (PCI), to compare major bleeding and dyspnea, and to evaluate the association between P2Y12 inhibitor adherence and MACE.. Population-based cohort study using data of patients discharged alive after PCI for ACS from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry from April 1, 2012, to March 31, 2016, with follow-up to 1 year. Analysis began April 2018.. Outpatient prescription for ticagrelor or clopidogrel within 31 days after PCI. Adherence was defined as a medication refill adherence value of 80% or higher.. Major adverse coronary events, a composite of all-cause death, hospitalization for ACS, unplanned coronary revascularization, or stent thrombosis within 365 days after index PCI. Secondary outcomes included hospitalization for major bleeding and emergency department visit for dyspnea.. Of 11 185 individuals who underwent PCI, the median (interquartile range) age was 61 (54-71) years, and 2760 (24.7%) were women. Ticagrelor users (4076 [36.4%]) were generally younger and had fewer cardiac and noncardiac comorbidities than clopidogrel users. Ticagrelor was not associated with lower risk of MACE (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (aHR, 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR, 1.98; 95% CI, 1.47-2.65). A total of 3328 ticagrelor users (81.6%) were adherent during the study vs 5256 of clopidogrel users (73.9%) (P < .001; χ2 = 86.4). In the full cohort, adherence was associated with a lower MACE risk (aHR, 0.79; 95% CI, 0.69-0.90 for adherence of ≥80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses.. In this population-based cohort study of patients with ACS who underwent PCI, outpatient use of ticagrelor was not associated with a statistically significant reduction in MACE vs clopidogrel; however, it was associated with more major bleeding and dyspnea.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Clopidogrel; Dyspnea; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Factors; Ticagrelor; Treatment Outcome

Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.. To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.. A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.. Ticagrelor vs clopidogrel.. The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.. After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.. Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Algorithms; Aspirin; Case-Control Studies; Cause of Death; Clopidogrel; Databases, Factual; Dyspnea; Female; Hemorrhage; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Network Meta-Analysis; Percutaneous Coronary Intervention; Propensity Score; Purinergic P2Y Receptor Antagonists; Recurrence; Republic of Korea; Retrospective Studies; Stroke; Ticagrelor; United States

Topics: Aspirin; Clopidogrel; Drug-Eluting Stents; Dyspnea; Humans; Ticagrelor

Topics: Aspirin; Clopidogrel; Drug-Eluting Stents; Dyspnea; Humans; Ticagrelor

Topics: Aged; Cheyne-Stokes Respiration; Clopidogrel; Dyspnea; Humans; Male; Myocardial Infarction; Polysomnography; Ticagrelor

The aim of the current study was to define the rate of emergency department visits for late-onset dyspnea in acute coronary syndrome patients treated with ticagrelor.. We conducted a population-based study on about 850 000 residents of Florence metropolitan area, by using data from healthcare records.. Between 2012 and 2014, 1073 subjects in Florence metropolitan area had at least one prescription of ticagrelor. Two-hundred and thirty-four patients were diagnosed with 'respiratory system or other chest symptoms' or 'other diseases of lung', and among them we identified 20 subjects with ticagrelor-related late-onset dyspnea. These, and the 979 nonevent subjects (receiving ticagrelor but not developing dyspnea), contributed to 413 person-years overall. The dyspnea rate was 4.84 per 100 person-years (95% confidence interval: 3.12-7.51).. Late-onset dyspnea rate is notably lower than early-onset one; nevertheless prescribing clinicians should be aware that about one in 20 outpatients with a stabilized ticagrelor treatment might develop a dyspnea leading to an emergency department visit, and they should consider ticagrelor replacement only in patients who cannot tolerate dyspnea.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Dyspnea; Emergency Service, Hospital; Female; Humans; Italy; Male; Middle Aged; Outpatients; Platelet Aggregation Inhibitors; Ticagrelor

Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated.. Premature ticagrelor cessation in routine clinical practice occurred in 1 of 6 patients and was primarily related to adverse effects among which bleeding and dyspnea were the most frequent. Although premature ticagrelor cessation was not associated with adverse cardiovascular outcomes, this finding requires careful interpretation in view of the modest sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Drug Administration Schedule; Drug Substitution; Dyspnea; Female; Hemorrhage; Humans; Male; Medication Adherence; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Registries; Switzerland; Tertiary Care Centers; Ticagrelor; Time Factors; Treatment Outcome

A 69-year-old male underwent elective percutaneous coronary intervention requiring placement of a drug-eluting stent to the first obtuse marginal artery. Four hours following the administration of a ticagrelor loading dose, he developed dyspnea and sinus pauses. Aminophylline was administered and resulted in immediate and sustained symptom resolution. Ticagrelor has been associated with dyspnea and bradyarrhythmias, both attributed to increased adenosine exposure. Ticagrelor inhibits reuptake of intracellular adenosine. Adenosine antagonists aminophylline and theophylline have been utilized to reverse the effects of adenosine and may relieve adenosine-mediated adverse effects induced by ticagrelor therapy. Aminophylline may be considered for reversal of dyspnea and bradyarrhythmia associated with ticagrelor therapy through alterations in adenosine exposure.

Topics: Adenosine; Aged; Aminophylline; Bradycardia; Dyspnea; Humans; Male; Purinergic P1 Receptor Antagonists; Purinergic P2Y Receptor Antagonists; Ticagrelor

In 'real life' acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) and receiving contemporary antiplatelet treatment, data on dyspnea occurrence and impact on persistence with treatment are scarce. In a prospective, multicenter, cohort study, ACS patients undergoing PCI were recruited into the GReekAntiPlatElet (GRAPE) registry. During 1-year follow up, overall, 249/1989 (12.5%) patients reported dyspnea, more frequently at 1-month and decreasing thereafter. Multivariate analysis showed that ticagrelor administration (n = 738) at discharge was associated with the occurrence of dyspnea: Odds ratio 2.46 (95% confidence interval, CI, 1.87-3.25), p < 0.001. Older age, lower hematocrit, and prior bleeding event were also associated with dyspnea reports. Persistence, switching, and cessation rates were 68.3%, 20.9%, and 10.8% vs 76.7%, 12.5%, and 10.9% among patients reporting dyspnea compared with those who did not, p for trend = 0.002. In conclusion, in ACS patients undergoing PCI and treated with a P2Y

Topics: Acute Coronary Syndrome; Adenosine; Dyspnea; Female; Greece; Hematocrit; Hemorrhage; Humans; Male; Middle Aged; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Risk Factors; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Adenosine; Aged; Arrhythmias, Cardiac; Clinical Trials as Topic; Drug Therapy, Combination; Dyspnea; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Topics: Adenosine; Cheyne-Stokes Respiration; Dyspnea; Humans; Hypercapnia; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Respiratory Function Tests; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Aged; Dyspnea; Female; Humans; Incidence; Male; Middle Aged; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Ticagrelor

To compare healthcare resource utilization (HCRU) and healthcare costs in patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with prasugrel or ticagrelor.. Hospital charge master data were used to identify ACS-PCI patients aged ≥ 18 years with ≥ 1 in-hospital claim for prasugrel or ticagrelor between August 1, 2011-April 30, 2013. Treatment groups were propensity matched for baseline and index hospitalization characteristics. HCRU and costs were assessed through 90-days post-discharge. Costs were determined based on hospital-specific cost-to-charge ratios and adjusted to 2013 US dollars.. Before matching, ticagrelor patients were older, more-often female, and had increased cardiovascular (CV) and bleeding risks compared with prasugrel patients. Propensity-matched length of index hospital stay (4.7 vs 4.9 days, p = 0.23) and risk for all-cause [30-day: relative risk (RR) = 0.86; 95% CI = 0.73-1.0; 90-day: RR = 0.90; 95% CI = 0.80-1.0, and CV-related (30-day: RR = 0.77; 95% CI = 0.59-1.0; 90-day: RR = 0.89; 95% CI = 0.73-1.1) re-hospitalizations did not significantly differ between prasugrel and ticagrelor, respectively. Compared to ticagrelor, the propensity-matched risk of re-hospitalization for myocardial infarction (MI) (30-day: RR = 0.39; 95% CI = 0.21-0.75; 90-day: RR = 0.53; 95% CI = 0.34-0.81) and an outpatient medical encounter for dyspnea (30-day: RR = 0.49; 95% CI = 0.33-0.74; 90-day: RR = 0.60; 95% CI = 0.46-0.80) were significantly lower for prasugrel patients, with no significant differences in bleeding encounters between groups (30-day: RR =  0.87; 95% CI = 0.54-1.40; 90-day: RR = 1.0; 95% CI = 0.71-1.50). Matched total healthcare costs were not significantly different between groups during the index hospitalization ($36,011 vs $37,247, p = 0.21), 30-days post-discharge ($2007 vs $2522, p = 0.48), 90-days post-discharge ($4564 vs $5242, p = 0.49), and aggregate of the index hospitalization through 90-day follow-up ($40,576 vs $42,494, p = 0.09) timeframes.. Re-hospitalization for MI and outpatient encounters for dyspnea were lower in prasugrel treated than in ticagrelor treated ACS-PCI patients up to 90-days post-index hospitalization discharge, with no difference in bleeding encounters or healthcare costs between the two populations. This data supports the utility of prasugrel in routine clinical practice. These findings should be considered within limitations of observational research.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Dyspnea; Female; Health Services; Hemorrhage; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Ticagrelor

Topics: Adenosine; Aged; Aspirin; Cohort Studies; Dyspnea; Female; Hemorrhage; Humans; Male; Medication Adherence; Myocardial Infarction; Patient Satisfaction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Aged; Dyspnea; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Topics: Adenosine; Aged; Clopidogrel; Drug Substitution; Dyspnea; Humans; Male; Purinergic P2Y Receptor Antagonists; Stents; Thrombosis; Ticagrelor; Ticlopidine

Ticagrelor is a new antiplatelet agent that was pitted against clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Because ticagrelor is the first oral, reversible, twice-daily agent, sufficient information on drug interactions is not available. Our objective was to ascertain the safety of ticagrelor with other common medications. The US Food and Drug Administration Complete Response Review indicates that renal adverse events (AEs) and renal function AEs were higher in ticagrelor-treated patients who were concomitantly treated with angiotensin receptor blockers (ARBs) >50% of study days compared to ticagrelor-treated patients who did not receive ARBs >50% of study days. Clopidogrel-treated patients showed a trend for an increase in adverse renal events with ARB use. However, this was not as pronounced as that observed with ticagrelor. Dyspnea was also significantly increased in patients on concomitant ticagrelor-ARB compared to ticagrelor without concomitant ARB and clopidogrel (21.4% vs 14.6% vs 9.9%, respectively) as well as angioedema (0.15% vs 0.09%). Furthermore, in patients with a baseline estimated glomerular filtration rate (eGFR) <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel. In patients on ticagrelor, ARBs significantly increased the frequency of renal related AEs, renal function AEs, and dyspnea. Moreover, in patients with a baseline eGFR <30 mL/min, the risk of major bleeding, death, and renal failure was increased in patients on ticagrelor compared to patients on clopidogrel.

Topics: Adenosine; Angiotensin II Type 1 Receptor Blockers; Clopidogrel; Drug Interactions; Dyspnea; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Kidney Diseases; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticagrelor; Ticlopidine; United States; United States Food and Drug Administration

There may be a universal mechanism explaining dyspnea after ticagrelor and elinogrel, namely, transfusion-related acute lung injury (TRALI). Indeed, recent clinical trials with ticagrelor (DISPERSE, DISPERSE-II, and PLATO), and elinogrel (INNOVATE PCI) revealed double-digit rates of dyspnea after novel reversible antiplatelet agents. In contrast, dyspnea is not associated with conventional non-reversible agents such as aspirin, or thienopyridines (ticlopidine, clopidogrel, or prasugrel) suggesting distinct mechanism of shortness of breath after ticagrelor and elinogrel. The adenosine hypothesis has been offered to explain such adverse association. However, despite obvious similarity between ticagrelor and adenosine molecules, the chemical structure of elinogrel is entirely different. In fact, ticagrelor is a cyclopentyl-triazolo-pyrimidine, while elinogrel is a quinazolinedione. Since both agents cause dyspnea, the adenosine hypothesis is no longer valid. In contrast, the reversible nature of platelet inhibition attributable to both ticagrelor and elinogrel causing premature cell ageing, apoptosis, impaired turnover due to sequestration of overloaded, exhausted platelets in the pulmonary circulation are among potential autoimmune mechanism(s) resulting in the development of a TRALI-like reaction, and frequent dyspnea. Despite expected benefit for better bleeding control, further development of reversible antithrombins is severely limited due to the existence of a potentially universal serious adverse event, such as TRALI-syndrome with dyspnea as a predominant clinical manifestation. Since TRALI is an established number one contributor to mortality after blood transfusions, ticagrelor death "benefit" in PLATO is challenged further.

Topics: Acute Lung Injury; Adenosine; Blood Platelets; Dyspnea; Humans; Models, Biological; Platelet Aggregation Inhibitors; Quinazolinones; Sulfonamides; Syndrome; Ticagrelor; Transfusion Reaction

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y₁₂ receptor inhibitors. While clopidogrel remains the "workhorse" P2Y₁₂ receptor inhibitor for many patients with ACS and prasugrel has an established role in select situations, clinicians must now assimilate the evolving role of ticagrelor. Although ticagrelor offers important advances in the management of ACS (eg, reversibility), there are also notable clinical considerations (eg, unique adverse effects such as dyspnea). Based on the current evidence, we propose an algorithm to aid clinicians in the selection of a P2Y₁₂ receptor inhibitor for patients with ACS in various clinical situations.

Topics: Acute Coronary Syndrome; Adenosine; Algorithms; Dyspnea; Humans; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Dyspnea; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Ticagrelor; Ticlopidine

Topics: Adenosine; Dyspnea; Humans; Purinergic P2 Receptor Antagonists; Ticagrelor

Topics: Adenosine; Clinical Trials, Phase II as Topic; Dyspnea; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Ticagrelor