prasugrel-hydrochloride and Dyspnea

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

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

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

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

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

Current clinical practice guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel or prasugrel for patients with acute coronary syndrome (ACS). Ticagrelor, an experimental antiplatelet therapy, has been shown to be associated with significantly higher rates of dyspnea than clopidogrel in clinical trials. Patients with ACS presenting with dyspnea require additional medical attention to rule out possible heart failure or other serious diagnoses. This study used real-world data to quantify the direct medical costs of dyspnea among patients with a history of ACS.. To determine the clinical and economic impact of a dyspnea episode for patients with a history of ACS using commercial and Medicare supplemental claims data.. Patients with an emergency room (ER) visit with a primary diagnosis of dyspnea (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] diagnosis code, 786.0x) in 2008 or 2009 were identified using Thomson Reuters MarketScan(®) Research Databases. Patients were required to have 6 months of continuous medical enrollment prior to an ER visit and a history of ACS (ie, ≥ 1 inpatient claim, ≥ 1 ER visit, or ≥ 2 outpatient claims, with an ICD-9-CM diagnosis code for ACS [410.xx or 411.1x] in any position on the outpatient claim during either the baseline period or on the index date). An episode of dyspnea was defined as all ER and outpatient services on the day of an ER claim with a primary diagnosis of dyspnea, and any inpatient admissions occurring on the day of or day following the ER visit. Procedure utilization and expenditures were evaluated for the ER visit and associated outpatient services, as well as the proportion of ER visits that led to an inpatient stay. Costs were allowed charges (ie, provider payment plus member cost-share) adjusted to 2009 US constant dollars.. A total of 8433 ER visits for dyspnea were identified during 2008 to 2009 from these databases of approximately 74 million beneficiaries. The average cost per dyspnea episode was $6958, of which $1621 were outpatient costs associated with the ER visit (standard deviation, $3269). Along with physician services, assessment of dyspnea often included electrocardiogram (71.3%), chest radiograph (75.9%), and, occasionally, a B-type natriuretic peptide test (14.9%) or chest computed axial tomography scan (12.2%). More than one-fourth (25.8%) of dyspnea ER visits preceded an inpatient stay, with an average cost of $20 693 per patient.. Dyspnea is a significant event associated with high medical resource utilization and hospital costs. Ticagrelor, an experimental antiplatelet agent not yet available on the market, has been shown to be associated with significantly higher rates of dyspnea than clopidogrel in clinical trials. Considering that the increased risk of dyspnea for ticagrelor is well documented, these costs may be important to health plan decision-makers when evaluating costs associated with each antiplatelet therapy.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Aspirin; Clopidogrel; Costs and Cost Analysis; Diagnostic Techniques and Procedures; Drug Therapy, Combination; Dyspnea; Emergency Service, Hospital; Female; Humans; Insurance Claim Review; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Thiophenes; Ticlopidine