prasugrel-hydrochloride and Renal-Insufficiency--Chronic

 The clinical benefit of anti-platelet agents in patients with chronic kidney disease (CKD) is uncertain. In addition, the risk-benefit ratio of potent oral P2Y12-adenosine diphosphate (ADP) receptor antagonists (PPAs), namely, prasugrel and ticagrelor, compared with clopidogrel in CKD patients suffering from acute coronary syndrome (ACS) remains unknown..  We performed a meta-analysis of all studies comparing the clinical outcomes of PPA and clopidogrel therapy in CKD patients suffering from ACS..  We searched PubMed, the Cochrane library, Google Scholar, Clinical trial.org and the abstracts of international cardiology congresses from April 2000 to October 2017. Clinical studies comparing PPA with clopidogrel in ACS patients with CKD were selected. Our literature research identified five studies which were included in the meta-analysis. The primary endpoint was a composite of major adverse cardiovascular events (MACEs) at the latest follow-up available. Secondary endpoint included bleedings..  Compared with clopidogrel, PPAs were associated with a reduced rate of MACE without increased bleedings in CKD patients with ACS. Among invasively managed patients, this benefit from PPA included a reduction in mortality.

Topics: Acute Coronary Syndrome; Administration, Oral; Clopidogrel; Drug-Related Side Effects and Adverse Reactions; France; Hemorrhage; Humans; Odds Ratio; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Survival Analysis; Ticagrelor; Treatment Outcome

Patients with chronic kidney disease are particularly prone to cardiovascular disorders because of a tendency to thrombosis, but also have an enhanced hemorrhagic risk. The use of antiplatelet agents in this subset of patients is not yet well defined and caution should be given on which AAP is prescribed to them.

Topics: Adenosine; Blood Platelet Disorders; Clopidogrel; Evidence-Based Practice; Humans; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Renal Insufficiency, Chronic; Thiophenes; Thrombosis; Ticagrelor; Ticlopidine

We aimed to study the relationship of chronic kidney disease stages with long-term ischemic and bleeding outcomes in medically managed acute coronary syndrome patients and the influence of more potent antiplatelet therapies on platelet reactivity by chronic kidney disease stage.. We estimated creatinine clearance for 8953 medically managed acute coronary syndrome patients enrolled in the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial. Patients were classified by chronic kidney disease stage: normal renal function/mild (creatinine clearance >60 mL/min); moderate (creatinine clearance 30-60 mL/min); severe (creatinine clearance <30 mL/min). Kaplan-Meier event rates through 30 months were evaluated for ischemic (cardiovascular death, myocardial infarction or stroke; primary end point) and bleeding (Global Use of Strategies to Open Occluded Coronary Arteries and Thrombolysis In Myocardial Infarction bleeding) outcomes by chronic kidney disease stage and treatment allocation (prasugrel vs. clopidogrel) within each stage. Adjusted hazard ratios (95% confidence intervals) for moderate and for severe chronic kidney disease vs. normal/mild chronic kidney disease were estimated. Platelet reactivity at 30 days was assessed in a subset of patients (n = 1947). The majority of patients were in the normal/mild chronic kidney disease group (67%), followed by moderate chronic kidney disease (29%) and severe chronic kidney disease (4%). The incidence of ischemic and bleeding outcomes increased sharply across chronic kidney disease stages and no significant treatment interactions were observed. The adjusted risk of the primary end point increased across chronic kidney disease stages (moderate vs. normal/mild: hazard ratio 1.26; 95% confidence interval 1.09-1.46; severe vs. normal/mild: hazard ratio 1.60; 95% confidence interval 1.25-2.04). Platelet reactivity was lower in patients treated with prasugrel compared with clopidogrel, across all three chronic kidney disease stages.. Among medically managed acute coronary syndrome patients, the long-term risks of ischemic and bleeding outcomes increased markedly with worse chronic kidney disease stages. Despite lower platelet reactivity of prasugrel compared with clopidogrel, no treatment interactions for ischemic and bleeding outcomes were observed.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Creatinine; Female; Hemorrhage; Humans; Kaplan-Meier Estimate; Male; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Renal Insufficiency, Chronic; Stroke; Ticlopidine; Treatment Outcome

There are very few clinical data concerning the safety of switching from clopidogrel to prasugrel in patients undergoing coronary stenting. However, in the daily activity, clinicians face the decision of switching patients at high-risk of thrombotic events from clopidogrel to prasugrel. Thus, we sought to evaluate clinical events in patients undergoing coronary stent implantation and prasugrel therapy with (SWITCH group) or without (NAÏVE group) prior clopidogrel therapy. A total of 454 patients with stable or unstable coronary artery disease, aged 70 ± 10 years, underwent non-emergent stent implantation and received prasugrel therapy. Of these, 315 (69 %) patients received clopidogrel before switching to prasugrel therapy. In 239 patients with high residual platelet reactivity (HRPR) on clopidogrel, prasugrel decreased platelet aggregation from 72 ± 11 to 43 ± 16 % (p < 0.001). There was no difference in in-hospital major or minor TIMI bleeding (2.8 vs. 4.3 %; p = 0.411) between the SWITCH and NAÏVE groups as well as in mortality, acute stent thrombosis, reinfarction and stroke rates. At multivariable analysis, independent predictors of bleeding were female gender (OR 5.56 [1.41-19.88] p = 0.014) and chronic renal failure (OR 6.27 [1.59-21.65] p = 0.009), but switching therapy did not. This result was confirmed after switching propensity score adjustment (c-statistic 0.81; Hosmer-Lemeshow test p = 860). Switching from clopidogrel to prasugrel in patients undergoing non-emergent coronary stent implantation seems to be tolerated with no overt signs of increased bleeding.

Topics: Aged; Aged, 80 and over; Clopidogrel; Coronary Artery Disease; Drug Substitution; Female; Hemorrhage; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Piperazines; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Sex Factors; Stents; Thiophenes; Thrombosis; Ticlopidine

High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear.. Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR.. A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles.. Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Topics: Blood Platelets; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Renal Insufficiency, Chronic; Ticlopidine

The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction.. All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985).. In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Glomerular Filtration Rate; Hemorrhage; Humans; Kidney; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Recurrence; Registries; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Prasugrel was approved at a lower dose in 2014 in Japan than in the West because East Asian patients are considered more susceptible to bleeding than Western patients. However, real-world outcomes with low-dose prasugrel treatment remain unclear.. To investigate the association of low-dose prasugrel vs standard-dose clopidogrel administration with short-term outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI).. This study used data from the Japan Cardiovascular Database-Keio Interhospital Cardiovascular Studies registry, a large, ongoing, multicenter, retrospective cohort of consecutive patients who underwent PCI. The present cohort study evaluated 2770 patients with acute coronary syndrome who underwent PCI and received either low-dose prasugrel (loading dose, 20 mg; maintenance dose, 3.75 mg) or clopidogrel (loading dose, 300 mg; maintenance dose, 75 mg) in combination with aspirin between 2014 and 2018. Propensity score-matching analysis was conducted to balance the baseline characteristics of patients receiving low-dose prasugrel and those receiving clopidogrel. Data analysis was conducted in June 2019.. Prescription of either low-dose prasugrel or standard-dose clopidogrel prior to PCI.. Primary ischemic events (in-hospital death, recurrent myocardial infarction, and ischemic stroke) and primary bleeding events, defined as bleeding complications within 72 hours after PCI consistent with the National Cardiovascular Data Registry CathPCI Registry definition.. Of 2559 patients included in the study, the mean (SD) age was 67.8 (12.7) years, and 78.2% were male. In total, 1297 patients (50.7%) received low-dose prasugrel, and 1262 patients (49.3%) received clopidogrel. After propensity score matching, primary ischemic events among patients receiving low-dose prasugrel and those receiving clopidogrel were comparable (odds ratio [OR], 1.42; 95% CI, 0.90-2.23), but primary bleeding events were significantly higher among patients receiving prasugrel (OR, 2.91; 95% CI, 1.63-5.18). This increase in bleeding events was associated with the presence of a profile of high-bleeding risk (≥75 years of age, body weight <60 kg, or history of stroke or transient ischemic attack) (OR, 4.08; 95% CI, 1.86-8.97), being female (OR, 3.84; 95% CI, 1.05-14.0), or the presence of ST-segment elevation myocardial infarction (OR, 2.07; 95% CI, 1.05-4.09) or chronic kidney disease (OR, 4.78; 95% CI, 1.95-11.7).. Since its approval, low-dose prasugrel has been used by nearly 80% of patients who undergo PCI. Despite the modified dose, bleeding events were higher among patients receiving low-dose prasugrel than among patients receiving clopidogrel, with no difference in ischemic events between the 2 groups. These results suggest the importance of a risk assessment of bleeding prior to selecting a P2Y12 inhibitor, even for the use of a lower approved dose, when treating patients of East Asian descent.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Case-Control Studies; Clopidogrel; Death; Drug Therapy, Combination; Female; Hemorrhage; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Registries; Renal Insufficiency, Chronic; Retrospective Studies; Risk Assessment; Stroke

Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors.. We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%.. Patients with CKD [estimate glomerular filtration rate (eGFR) < 60 ml/min/1.73 m, n = 28] were prevalent older, diabetic, had previous coronary revascularization. In these patients, platelet aggregation was significantly higher than in those with eGFR ≥ 60 ml/min/1.73 m (ADP 10 μmol/l: 28.46 ± 26.19 vs. 16.64 ± 12.79, P < 0.001; ADP 20 μmol/l: 30.07 ± 25.89 vs. 17.46 ± 12.82, P < 0.001). HRPR was observed in 4.4% of patients, with higher prevalence in those with eGFR less than 60 ml/min/1.73 m [21.4 vs. 1.7%, P < 0.001, odds ratio (OR) [95% confidence interval (CI)] = 15.91 (3.71-68.17), P < 0.001]. At multivariate analysis, after correction for baseline confounders, eGFR [adjusted OR (95% CI) = 0.95 (0.91-0.98), P = 0.007], together with the use of clopidogrel [adjusted OR (95% CI) = 23.59 (4.01-138.82), P < 0.001], emerged as determinants of HRPR.. In patients with ACS receiving dual antiplatelet therapy, CKD is associated with an increasing ADP-induced platelet aggregation and higher prevalence of HRPR, which is mainly correlated to clopidogrel use.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Drug Resistance; Dual Anti-Platelet Therapy; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Severity of Illness Index; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Clopidogrel; Evidence-Based Medicine; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Renal Insufficiency, Chronic

Topics: Acute Coronary Syndrome; Clopidogrel; Humans; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic

This study sought to compare clinical outcomes in a contemporary acute coronary syndrome (ACS) percutaneous coronary intervention (PCI) cohort stratified by chronic kidney disease (CKD) status.. Patients with CKD exhibit high risks for both thrombotic and bleeding events, thus complicating decision making regarding antiplatelet therapy in the setting of ACS.. The PROMETHEUS study was a multicenter observational study comparing outcomes with prasugrel versus clopidogrel in ACS PCI patients. Major adverse cardiac events (MACE) at 90 days and at 1 year were defined as a composite of death, myocardial infarction, stroke, or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Cox regression multivariable analysis was performed for adjusted associations between CKD status and clinical outcomes. Hazard ratios for prasugrel versus clopidogrel treatment were generated using propensity score stratification.. The total cohort included 19,832 patients, 28.3% with and 71.7% without CKD. CKD patients were older with greater comorbidities including diabetes and multivessel disease. Prasugrel was less often prescribed to CKD versus non-CKD patients (11.0% vs. 24.0%, respectively; p < 0.001). At 1 year, CKD was associated with higher adjusted risk of MACE (1.27; 95% confidence interval: 1.18 to 1.37) and bleeding (1.46; 95% confidence interval: 1.24 to 1.73). Although unadjusted rates of 1-year MACE were lower with prasugrel versus clopidogrel in both CKD (18.3% vs. 26.5%; p < 0.001) and non-CKD (10.9% vs. 17.9%; p < 0.001) patients, associations were attenuated after propensity stratification. Similarly, unadjusted differences in 1-year bleeding with prasugrel versus clopidogrel (6.0% vs. 7.4%; p = 0.18 in CKD patients; 2.6% vs. 3.5%; p = 0.008 in non-CKD patients) were not significant after propensity score adjustment.. Although risks for 1-year MACE were significantly higher in ACS PCI patients with versus without CKD, prasugrel use was 50% lower in patients with renal impairment. Irrespective of CKD status, outcomes associated with prasugrel use were not significant after propensity adjustment. These data highlight the need for randomized studies evaluating the optimal antiplatelet therapy in CKD patients with ACS.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Chi-Square Distribution; Clopidogrel; Coronary Thrombosis; Databases, Factual; Hemorrhage; Humans; Kaplan-Meier Estimate; Kidney; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Renal Insufficiency, Chronic; Risk Factors; Stroke; Ticlopidine; Time Factors; Treatment Outcome; United States

To describe contemporary trends of P2Y12 inhibitor use in patients with acute coronary syndrome (ACS) and comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD) who have a higher risk of recurring ACS and may benefit from treatment with higher efficacy third-generation agents (prasugrel and ticagrelor).. Observational cohort study.. A large U.S. commercial insurance program (2009-2015).. P2Y12 inhibitor initiated within 2 weeks after an ACS event.. We identified 98,649 P2Y12 inhibitor initiators, of whom 24.5% had comorbid DM (no CKD), 10.5% had CKD (no DM), and 12.6% had DM and CKD. Overall, 85.2% of patients initiated clopidogrel, followed by prasugrel (11.6%) and ticagrelor (3.2%). Prasugrel use decreased over time irrespective of preexisting DM and/or CKD; ticagrelor use increased. In logistic regression models accounting for patient demographics and clinical covariates, preexisting DM alone was not associated with prasugrel or ticagrelor versus clopidogrel treatment initiation; however, having CKD with or without DM significantly reduced the likelihood of receiving prasugrel versus clopidogrel (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.74-0.88 for CKD alone; OR 0.91, 95% CI 0.83-0.98 for DM and CKD). Comorbid DM and CKD reduced the odds of initiating ticagrelor versus clopidogrel (OR 0.80, 95% CI 0.70-0.92).. We observed lower or similar use of prasugrel and ticagrelor compared with clopidogrel in patients with ACS and comorbid DM and/or CKD. Given the potential for worse clinical outcomes with clopidogrel in these patients, our findings highlight the need to investigate the implications of these trends on recurrent ACS and bleeding events.

Topics: Acute Coronary Syndrome; Adenosine; Clopidogrel; Cohort Studies; Diabetes Mellitus; Drug Utilization Review; Humans; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Ticagrelor; Ticlopidine

Topics: Acute Coronary Syndrome; Clopidogrel; Humans; Kidney Failure, Chronic; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Renal Insufficiency, Chronic

Topics: Acute Coronary Syndrome; Adenosine; Aged; Drug Monitoring; Female; Humans; Kidney Function Tests; Male; Middle Aged; Platelet Aggregation; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Renal Insufficiency, Chronic; Statistics as Topic; Ticagrelor; Treatment Outcome