prasugrel-hydrochloride and Diabetes-Mellitus

Cardiovascular complications remain the main cause of mortality and morbidity in diabetes. This is related to advanced vascular pathology in this population, together with an enhanced thrombotic environment. The increased risk in thrombosis is secondary to platelet hyper-reactivity and increased levels and/or altered activity of coagulation factors. The current review is focused on the role of antiplatelet agents in modulating the thrombotic milieu in diabetes and improving vascular outcome in this high-risk population. We review the latest evidence for the use of aspirin in primary vascular prevention together with long-term treatment with this agent for secondary prevention. We also discuss the effects of the various P2Y

Topics: Aspirin; Cardiovascular Diseases; Clopidogrel; Diabetes Mellitus; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Primary Prevention; Secondary Prevention; Thrombosis; Ticagrelor

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics.

Topics: Administration, Oral; Angioplasty, Balloon, Coronary; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus; Drug Resistance; Drug Therapy, Combination; Humans; Myocardial Infarction; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke; Thiophenes; Thrombosis; Time Factors; Treatment Outcome

Acute coronary syndromes (ACS) are the leading cause of mortality in Western countries. Until a few years ago, the antiplatelet drug to be administered in association with aspirin was indisputably clopidogrel. Recent data from randomized trials conducted in ACS patients have shown that the new oral antiplatelet regimens, prasugrel and ticagrelor, are associated with a significant reduction in cardiovascular events, as compared to clopidogrel. Moreover ticagrelor reduced both all-cause and cardiovascular mortality as compared to clopidogrel in the PLATO trial. However, there are intrinsic differences between the trials design and among the enrolled ACS populations, that make complex the generalization of the mortality results in the whole spectrum of ACS patients. We aimed to provide further insights into the unresolved mortality issues raised in the PLATO and TRITON-TIMI 38 trials, by analysing the effects of ticagrelor and prasugrel in the ACS populations included in the respective trials.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Angiography; Diabetes Mellitus; Female; Humans; Hypertension; Male; Middle Aged; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2 Receptor Antagonists; Randomized Controlled Trials as Topic; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Atherothrombosis--defined as atherosclerotic lesion disruption with superimposed thrombus formation--is a leading cause of death in patients with diabetes mellitus. Platelets play a pivotal role in atherothrombosis and platelets of diabetic patients are hyperreactive. Numerous studies have investigated the usefulness of antiplatelet therapy for primary and secondary prevention of atherothrombotic events in diabetic patients. However, there are limited evidences that aspirin may be effective in the reduction of atherothrombotic complication in this population. Additionally, dual antiplatelet therapy with aspirin and clopidogrel has been suggested to be harmful. In contrast, the role of antiplatelet therapy in secondary prevention after ischemic cardiac events is well established in diabetes. Glycoprotein IIb/IIIa receptor antagonists can reduce mortality in diabetic patients committed to undergo percutaneous coronary intervention (PCI). Upregulation of P2Y(12) signalling occurs in hyperglycemia, and the relevance of platelet P2Y(12) receptor inhibition with prasugrel in reducing adverse events following PCI has been recently suggested. Besides platelet activation, several other mechanisms may be involved in the pathophysiology of diabetic atherothrombosis. Tissue factor (TF)-bearing procoagulant microparticles (MPs) are a heterogeneous population of membrane-coated vesicles released by several cell lines upon activation or apoptosis. There is converging evidence that MPs and MP-associated TF activity are upregulated in patients with diabetes mellitus and can participate actively in promoting atherothrombotic complications. In this context, drugs that may reduce the release of microparticles and/or their thrombogenic capacity has the potential to improve upon current antiplatelet therapy, possibly resulting in lower adverse events rates in diabetic individuals.

Topics: Acute Coronary Syndrome; Apoptosis; Aspirin; Blood Platelets; Clopidogrel; Diabetes Complications; Diabetes Mellitus; Glycoproteins; Humans; Models, Biological; Piperazines; Platelet Activation; Prasugrel Hydrochloride; Receptors, Purinergic P2Y12; Thiophenes; Thromboplastin; Thrombosis; Ticlopidine

Diabetic patients who present with an acute coronary syndrome (ACS) have a particularly adverse prognosis, largely contributed by increased platelet reactivity and higher burden of disease severity. Diabetic patients with ACS derive a greater benefit from established therapies, particularly platelet-inhibiting therapies, including clopidogrel pretreatment, and glycoprotein IIb/IIIa inhibitor use. Recent data show intense ADP-P2Y12 platelet receptor inhibition with prasugrel is of particular clinical value in the diabetic patient with ACS, without excessive bleeding. Diabetic patients with ACS also benefit more from aggressive revascularization strategies. Recent data show the benefit of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in decreasing target vessel revascularization up to 2 years, particularly in patients at highest risk for restenosis with bare metal stents (likely diabetic patients). This review summarizes the data supporting the key pharmacologic and revascularization management strategies to guide the clinician in taking care of diabetic patients who present with an ACS event.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Anticoagulants; Clopidogrel; Diabetes Mellitus; Drug-Eluting Stents; Humans; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Risk Factors; Thiophenes; Ticlopidine

Diabetic patients with acute coronary syndromes (ACSs) are at a high risk for subsequent cardiovascular events but derive, at the same time, greater benefit from evidence-based therapy than non-diabetic individuals. State-of-the-art anti-thrombotic therapy includes a triple anti-platelet combination - aspirin, clopidogrel and glycoprotein (GP) IIb/IIIa receptor inhibitors - and unfractionated heparin or enoxaparin. For low- or medium-risk individuals, a treatment based on aspirin, clopidogrel and bivalirudin is a valuable alternative. Prasugrel, a new and more potent inhibitor of the platelet P2Y(12) receptor, has to be regarded as the most promising anti-thrombotic agent for diabetic patients with ACS. This agent may replace clopidogrel - and possibly GP IIb/IIIa inhibitors - in the future. In addition to aggressive anti-thrombotic therapy, diabetic patients should undergo systematic early invasive angiography if presenting with non-ST-segment elevation ACS, and immediate percutaneous coronary intervention if presenting with ST-segment elevation myocardial infarction. Indeed, the benefit derived from these strategies appears to be more pronounced in the diabetic population than in non-diabetic individuals. Despite the benefit, multiple surveys have demonstrated that, in the setting of ACS, diabetic patients receive evidence-based therapy less frequently than non-diabetic counterparts.

Topics: Acute Coronary Syndrome; Anticoagulants; Aspirin; Blood Glucose; Clopidogrel; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enoxaparin; Hirudins; Humans; Hypoglycemic Agents; Peptide Fragments; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Recombinant Proteins; Thiophenes; Thrombosis; Ticlopidine

The aim of this study was to evaluate the efficacy and safety of prasugrel dose de-escalation therapy in patients with diabetes mellitus (DM)-acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).. This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and Bleeding Academic Research Consortium (BARC) class ≥2 bleeding events. The secondary ischaemic outcome was major adverse cardiovascular and cerebrovascular events, defined as the composite of cardiac death, non-fatal MI, ST, or ischaemic stroke. Of 2338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM [hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.43-0.99; P = 0.049]. Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischaemic events (HR 1.03; 95% CI 0.56-1.88; P = 0.927) but decreased BARC class ≥2 bleeding in patients with DM (HR 0.44; 95% CI 0.23-0.84; P = 0.012).. Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischaemic events in patients with DM. Trial Registration: HOST-REDUCE-POLYTECH-ACS, NCT02193971, https://clinicaltrials.gov/ct2/show/NCT02193971.

Topics: Acute Coronary Syndrome; Brain Ischemia; Clopidogrel; Diabetes Mellitus; Hemorrhage; Humans; Ischemia; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke

The role of percutaneous coronary interventions (PCI) in patients with diabetes mellitus and multi-vessel disease has been questioned by the results of the FREEDOM trial, which showed superiority of coronary artery bypass graft(CABG) over first generation drug-eluting stents (DES) including a reduction in mortality. In the light of safer and more efficacious stents and significantly better medical management, those results that date back to 2012 need to be revisited. TUXEDO-2 is a study designed to compare two contemporary stents in Indian diabetic patients with multi-vessel disease.. The primary objective of the TUXEDO-2 study is to compare the clinical outcomes of PCI with ultra-thin Supraflex Cruz vs Xience when combined with contemporary optimal medical therapy (OMT) in diabetic patients with multi-vessel disease. The secondary objective is to compare clinical outcomes between a pooled cohort from both arms of the study (Supraflex Cruz + Xience; PCI arm) vs CABG based on a performance goal derived from the CABG arm of the FREEDOM trial (historical cohort). The tertiary objective is a randomized comparison of ticagrelor vs prasugrel in addition to aspirin for the composite of ischemic and bleeding events.. In this prospective, open-label, multi-centre, 2 × 2 factorial, randomized, controlled study, 1,800 patients with diabetes mellitus and multi-vessel disease (inclusion criteria similar to FREEDOM trial) with indication for coronary revascularization will be randomly assigned to Supraflex Cruz or Xience stents and also to ticagrelor- or prasugrel- based antiplatelet strategies. All patients will receive guideline directed OMT and optimal PCI including image- and physiology-guided complete revascularization where feasible. The patients will be followed through five years to assess their clinical status and major clinical events. The primary endpoint is a non-inferiority comparison of target lesion failure at one-year for Supraflex Cruz vs Xience (primary objective) with an expected event rate of 11% and a non-inferiority margin of 4.5%. For PCI vs CABG (secondary objective), the primary endpoint is major adverse cardiac events (MACE), defined as a composite of all cause death, nonfatal myocardial infarction, or stroke at one-year and yearly up to five years, with a performance goal of 21.6%. For ticagrelor vs prasugrel (tertiary objective), the primary endpoint is composite of death, myocardial infarction, stroke, and major bleeding as per the Bleeding Academic Research Consortium (BARC) at one-year with expected event rate of 15% and a non-inferiority margin of 5%.. The TUXEDO-2 study is a contemporary study involving state-of-the-art PCI combined with guideline directed OMT in a complex subset of patients with diabetes mellitus and multi-vessel disease. The trial will answer the question as to whether a biodegradable polymer coated ultra-thin Supraflex Cruz stent is an attractive option for PCI in diabetic patients with multi-vessel disease. It will also help address the question whether the results of FREEDOM trial would have been different in the current era of safer and more efficacious stents and modern medical therapy. In addition, the comparative efficacy and safety of ticagrelor vs prasugrel in addition to aspirin will be evaluated. (CTRI/2019/11/022088).

Topics: Aspirin; Coronary Artery Disease; Diabetes Mellitus; Everolimus; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prospective Studies; Stroke; Ticagrelor; Treatment Outcome

Switching P2Y

Topics: Adenosine; Adenosine Diphosphate; Aspirin; Blood Platelets; Clopidogrel; Coronary Artery Disease; Diabetes Mellitus; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Ticagrelor

A guided de-escalation of P2Y12 inhibitor treatment is considered an alternative treatment strategy in ACS patients undergoing PCI. However, the safety and efficacy of this strategy may differ in diabetic vs non-diabetic patients. The aim of this study was to compare the outcomes of platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) in ACS patients with and without diabetes mellitus.. The TROPICAL-ACS trial randomised 2,610 biomarker-positive ACS patients 1:1 to either standard treatment with prasugrel for 12 months (control group) or PFT-guided DAPT de-escalation. The association and interaction of diabetes on clinical endpoints across treatment groups and on platelet reactivity was investigated. In diabetic patients (n=527, 20.2%), the overall event rates were high and the one-year incidence of the primary endpoint (cardiovascular death, myocardial infarction, stroke or bleeding ≥grade 2) did not differ between guided de-escalation and control group patients (12.5% vs 10.8%; HR 1.17, 95% CI: 0.71-1.93, p=0.55). In non-diabetic patients (n=2,083, 79.8%), the one-year incidence of the primary endpoint was lower in the guided de-escalation vs control group (6.1% vs 8.5%; HR 0.71, 95% CI: 0.52-0.99, p=0.04, pint=0.10). Diabetic patients showed higher platelet reactivity levels in both control (=on prasugrel, p=0.01) and guided de-escalation group (=on clopidogrel, p=0.005) patients.. Although diabetic status did not significantly interfere with the treatment effects of guided DAPT de-escalation, our results suggest that this approach might be safe and effective in non-diabetic patients. Further investigation is definitely warranted in diabetic patients.

Topics: Acute Coronary Syndrome; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Treatment Outcome

Patients with diabetes mellitus (DM) presenting with acute coronary syndrome (ACS) and undergoing percutaneous coronary intervention (PCI) derived enhanced benefit with dual antiplatelet therapy (DAPT) with prasugrel vs. clopidogrel. The risk profile and treatment response to DAPT for medically managed ACS patients with DM remains uncertain.. The TRILOGY ACS trial compared aspirin + prasugrel vs. aspirin + clopidogrel for up to 30months in non-ST-segment elevation (NSTE) ACS patients managed medically without revascularization. We compared treatment-related outcomes among 3539 patients with DM vs. 5767 patients without DM. The primary endpoint was a composite of cardiovascular death, myocardial infarction, or stroke.. Among NSTE ACS patients managed medically without revascularization, patients with DM had a higher risk of ischemic events that was amplified among those treated with insulin. There was no differential treatment effect with a more potent DAPT regimen of aspirin + prasugrel vs. aspirin + clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Aspirin; Clopidogrel; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Myocardial Revascularization; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticlopidine; Time Factors; Treatment Outcome

Topics: Administration, Oral; Blood Platelets; Diabetes Mellitus; Drug Resistance; Humans; Hypoglycemic Agents; Insulin; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Factors; ST Elevation Myocardial Infarction; Ticagrelor; Treatment Outcome

Optimal P2Y12 receptor blockade is critical to prevent ischaemic recurrence in patients undergoing percutaneous coronary intervention (PCI). We aimed to compare the level of platelet reactivity (PR) inhibition achieved by prasugrel and ticagrelor loading dose (LD) in diabetic acute coronary syndrome (ACS) patients undergoing PCI. We performed a single-center prospective open-label randomised trial. Patients with diabetes mellitus undergoing PCI for an ACS were randomised to receive prasugrel 60 mg or ticagrelor 180 mg. The primary endpoint of the study was the level of platelet reactivity (PR) assessed between 6 and 18 hours post-LD using the VASP index. We randomised 100 diabetic patients undergoing PCI for an ACS. No difference was observed in baseline characteristics between the two groups. In particular, the rate of patient receiving insulin therapy was identical (25 vs 28.6%; p =0.7). Ticagrelor achieved a significantly lower PR compared to prasugrel loading dose (17.3 ± 14.2 vs 27.7 ± 23.3%; p=0.009). In addition the rate of high on-treatment platelet reactivity, defined by a VASP ≥50%, tend to be lower in the ticagrelor group although the difference did not reach statistical significance (6 vs 16%; p=0.2). The rate of low on treatment PR was identical (60 vs 54%; p=0.8). The present study demonstrates that ticagrelor LD is superior to prasugrel LD to reduce PR in ACS patients with diabetes mellitus. Whether the higher potency of ticagrelor could translate into a clinical benefit should be investigated.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Biomarkers; Blood Platelets; Cell Adhesion Molecules; Diabetes Mellitus; Female; France; Humans; Hypoglycemic Agents; Insulin; Male; Microfilament Proteins; Middle Aged; Percutaneous Coronary Intervention; Phosphoproteins; Pilot Projects; Piperazines; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies; Receptors, Purinergic P2Y12; Thiophenes; Ticagrelor; Time Factors; Treatment Outcome

Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel.. This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ＞30 kg/m. The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor.. Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Diabetes Mellitus; Humans; Ischemia; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Treatment Outcome

High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated.. Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model.. In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001).. The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.

Topics: Blood Platelets; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Diabetes Mellitus; Humans; Hypertension; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Prospective Studies

To prevent thrombotic events after angioplasty, current guidelines recommend dual antiplatelet therapy with aspirin and thienopyridine. Clopidogrel is the only thienopyridine currently available in the Brazilian National Health System. The purpose of this study was to determine the cost-effectiveness of prasugrel, an alternative thienopyridine, compared with clopidogrel in patients with acute coronary syndrome and diabetes mellitus who underwent angioplasty.. A state-transition Markov model was created to simulate the progression of diabetic patients after angioplasty. The model had a lifetime horizon and discounted outcomes at a 5% annual rate. The risks of myocardial infarction and death were calculated using data from the diabetes subgroup, and the risks of bleeding were calculated using data from the overall group from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel Thrombolysis in Myocardial Infarction 38 trial. Direct costs were estimated using official Brazilian open data. Quality of life values were obtained through literature search. Univariate and multivariate sensitivity analyses were performed.. Prasugrel was associated with more quality-adjusted life-years (QALYs) (5.03 vs 4.94) and higher costs (US$975.11 vs US$575.97), resulting in an incremental cost-utility ratio (ICUR) of US$4303.86/QALY. In one-way sensitivity analysis, the costs of prasugrel had the greatest impact on ICUR, followed by the initial age entering the cohort. In the probabilistic sensitivity analysis, all ICUR values simulations were less than one Brazilian gross domestic product per capita/QALY (US $5802.86).. Given the appealing economic profile, the clinical debate between reducing the risk of myocardial infarction and increasing the risk of bleeding may overcome economic concerns in the Brazilian National Health System.

Topics: Clopidogrel; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Quality of Life; 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

Topics: Acute Coronary Syndrome; Bayes Theorem; Diabetes Mellitus; Humans; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel in patients with diabetes mellitus (DM) presenting with acute coronary syndromes (ACS) in whom invasive therapy was planned.. The efficacy and safety of ticagrelor versus prasugrel in patients with ACS with DM undergoing invasive treatment remain unknown.. This pre-specified analysis of the ISAR-REACT (Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment) 5 trial included 892 patients with ACS with DM and 3,124 patients with ACS without DM randomized to prasugrel or ticagrelor. The primary endpoint was a composite of death, myocardial infarction, or stroke; the safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding (both assessed 12 months after randomization).. DM seems to affect the efficacy of ticagrelor and prasugrel in patients with ACS. In patients with DM, the efficacy of ticagrelor was comparable with that of prasugrel. (Prospective, Randomized Trial of Ticagrelor Versus Prasugrel in Patients With Acute Coronary Syndrome [ISAR-REACT 5]; NCT01944800).

Topics: Acute Coronary Syndrome; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Diabetes Mellitus; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Ticagrelor; Treatment Outcome

Background Peripheral artery disease (PAD) is a known risk factor for adverse outcomes in patients undergoing percutaneous coronary intervention. However, in some studies PAD is not an independent risk factor. We sought to examine the independent impact of PAD on a large prospective percutaneous coronary intervention registry. Methods and Results From our single-center prospective percutaneous coronary intervention registry, we have retrospectively analyzed 25 690 patients (years 2004-2018). We examined the influence of PAD on short- and long-term outcomes using both regression and propensity-matched analyses. Patients with documented PAD (n=1610, 6.3% of total) were older (66.7±10.8 versus 65.4±12.1,

Topics: Aged; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus; Female; Humans; Hypertension; Male; Middle Aged; Percutaneous Coronary Intervention; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Renal Insufficiency; Retrospective Studies; Risk Factors; Ticagrelor; Treatment Outcome

Topics: Acute Coronary Syndrome; Blood Platelets; Diabetes Mellitus; Drug Monitoring; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticlopidine; Treatment Outcome

The safety and efficacy of prasugrel and ticagrelor in patients with diabetes mellitus presenting with acute coronary syndrome and treated with percutaneous coronary intervention remain to be assessed.. All diabetes patients admitted for acute coronary syndrome and enrolled in the REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) were compared before and after propensity score matching. Net adverse cardiovascular events (composite of death, stroke, myocardial infarction and BARC 3-5 bleedings) and major adverse cardiovascular events (composite of death, stroke and myocardial infarction) were the co-primary endpoints. Single components of primary endpoints were secondary endpoints.. Among 4424 patients enrolled in RENAMI, 462 and 862 diabetes patients treated with prasugrel and ticagrelor, respectively, were considered. After propensity score matching, 386 patients from each group were selected. At 19±5 months, major adverse cardiovascular events and net adverse cardiovascular events were similar in the prasugrel and ticagrelor groups (5.4% vs. 3.4%,. Diabetes patients admitted for acute coronary syndrome seem to benefit equally in terms of major adverse cardiovascular events from ticagrelor or prasugrel use. Ticagrelor was associated with a significant reduction in all-cause death and bleedings, without differences in recurrent ischaemic events, which should be confirmed in dedicated randomised controlled trials.

Topics: Acute Coronary Syndrome; Aged; Case-Control Studies; Coronary Angiography; Diabetes Complications; Diabetes Mellitus; Hemorrhage; Hospitalization; Humans; Middle Aged; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Recurrence; Registries; Safety; Stents; Thrombosis; Ticagrelor; Treatment Outcome

Clinical trial data studies suggest superiority of prasugrel over clopidogrel in patients with diabetes. However, the use, safety and efficacy profile of prasugrel in unselected diabetic patients presenting with acute coronary syndromes (ACS) remain unclear.. PROMETHEUS was a prospective multicenter observational study of 19,919 ACS PCI patients enrolled between 2010 and 2013. The primary endpoint was 90-day major adverse cardiovascular events (MACE), comprising all-cause death, myocardial infarction, stroke or unplanned revascularization. The safety endpoint was bleeding requiring hospitalization.. We identified 7580 (38%) subjects with and 12,329 (62%) without diabetes. Diabetic patients were older and had significantly higher rates of cardiovascular risk factors. However, they were less likely to receive prasugrel (18.2% vs. 21.7%). Use of prasugrel did not increase with the severity of clinical presentation in diabetics, whereas, among non-diabetics, prescription of prasugrel was higher in NSTEMI and STEMI compared to unstable angina. The 90-day and 1-year adjusted risk of MACE was greater in diabetics (at 1 year: 22.7% vs. 16.5%; HR 1.22 [1.14-1.33], p < 0.001). At 1 year, the risk of bleeding was also higher in diabetics (4.9% vs. 4.1%, HR 1.19 [1.01-1.39], p = 0.035). After multivariable adjustment, use of prasugrel was associated with a lower risk of death in diabetic patients both at 90 days and 1 year.. Use of prasugrel in diabetic patients with PCI-treated ACS was lower than in non-diabetics despite their high-risk profile and the severity of their clinical presentation. In diabetics, prasugrel was associated with a lower adjusted risk of 90-day death compared with clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Cause of Death; Clopidogrel; Comorbidity; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Prognosis; Prospective Studies; Purinergic P2Y Receptor Antagonists; Risk Factors; Survival Rate; United States

Although the new oral P2Y12 inhibitors, prasugrel/ticagrelor have shown greater efficacy than clopidogrel in patients with the acute coronary syndrome, but they have not shown better efficacy in Korean patients. So we evaluated the efficacy of the prasugrel/ticagrelor in patients with myocardial infarction (MI) and diabetes, a more high-risk patients group.From the Korea Acute Myocardial Infarction Registry-National Institute of Health, 3985 patients with MI and diabetes who underwent PCI were enrolled between November 2011 and December 2015. The patients were divided into 2 groups: clopidogrel (n = 2985) and prasugrel/ticagrelor (n = 1000).After propensity score matching, prasugrel/ticagrelor group showed a no significant difference in risk of the composite of cardiac death (CD), recurrent MI or stroke (hazard ratio [HR], 0.705; 95% confidence interval [CI], 0.474-1.048; P = .084). However, the risk of major bleeding was significantly higher in the prasugrel/ticagrelor group. (HR; 2.114, 95% CI; [1.027-4.353], P = .042). In subgroup analysis, major bleeding was significantly increased in the subgroup of creatinine clearance <60 ml/min/1.73 m, hypertension, underwent a trans-femoral approach and diagnosed as NSTEMI among the prasugrel/ticagrelor group.The use of prasugrel/ticagrelor did not improve the composite of CD, recurrent MI or stroke, however, significantly increased major bleeding events in Korean patients with MI and diabetes undergoing PCI.

Topics: Aged; Clopidogrel; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Myocardial Infarction; Outcome and Process Assessment, Health Care; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Period; Prasugrel Hydrochloride; Republic of Korea; Thromboembolism; Ticagrelor

Hypovitaminosis D represents an emerging cardiovascular risk factor, and especially among higher-risk subsets of patients, such as in those with diabetes mellitus. The anti-inflammatory and anti-thrombotic properties of vitamin D, in fact, could be even more beneficial among diabetics, where platelet hyperreactivity and suboptimal response to antiplatelet drugs has been associated with poorer outcomes. However, no study has so far evaluated the impact of vitamin D levels on platelet reactivity and high-on treatment platelet reactivity (HRPR) among diabetic patients receiving dial antiplatelet therapy (DAPT).. Our population is represented by a consecutive cohort ofdiabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients).. We included 440 patients, that were divided according to quartiles values of vitamin D (< 9.4; 9.4-15.59; 15.6-21.64; ≥ 21.65 ng/ml). Among them, 31 were excluded as chronically treated with vitamin D supplementation. Lower vitamin D quartiles were associated with more advanced age (p = 0.01), female gender (p = 0.04), renal failure (p = 0.005), history of previous MI (p = 0.01), CABG and use of diuretics (p = 0.003), severe coronary disease (p = 0.002), but lower ejection fraction (p = 0.001), treatment with statins (p = 0.04) and new ADP-antagonists (p = 0.002). Vitamin D levels related with higher HbA1c (p = 0.001), cholesterol (p = 0.02) and creatinine (p = 0.004) and lower hemoglobin (p = 0.004). The prevalence of HRPR with ASA was low and not related to vitamin D quartiles (3.4% vs 2.7% vs 1.8% vs 2.1%, p = 0.44; adjusted OR[95%CI] = 1.16[0.60-2.26], p = 0.67). The prevalence of HRPR for ADP antagonists was associated to hypovitaminosis D (40.2% vs 29.1% vs 29.4% vs 25.5%, p = 0.03; (adjusted OR[95%CI] = 1.76[1.04-2.98], p = 0.036for I vs II-IV quartile). The impact of vitamin D quartiles, was significant only in patients on new ADP antagonists (n = 225, of whom 81 on prasugrel 5 mg; p = 0.03; adjusted OR[95%CI] = 3.12[1.34-7.49], p = 0.009) but not with clopidogrel (p = 0.85, adjusted OR[95%CI] = 1.05[0.49-2.24], p = 0.89).. Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, severe vitamin D deficiency is associated with a higher ADP-mediated platelet reactivity and rate of HRPR, and especially for new ADP-antagonists over clopidogrel.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Aspirin; Biomarkers; Clopidogrel; Diabetes Mellitus; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome; Vitamin D; Vitamin D Deficiency

We compared the clinical outcome of diabetic versus nondiabetic patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the GReek AntiPlatElet (GRAPE) registry.. GRAPE is a prospective observational study, focusing on contemporary antiplatelet use in moderate-risk to high-risk ACS patients receiving PCI. Major adverse cardiovascular events (MACE), (composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and bleeding events (Bleeding Academic Research Consortium definition) at 1 year of follow-up were analyzed using propensity score adjustment. A subanalysis according to diabetes mellitus (DM) status was performed.. Out of 2047 registered patients, 469 (22.9%) were diabetic. Complete 1-year follow-up was available in 95.1% of patients. MACE occurred in 12.2 and 7.2% of those patients with and without DM, respectively [adjusted hazard ratio (HR), 95% confidence interval (CI)=1.27 (0.89-1.79), P=0.2]. Observed BARC type ≥3 bleeding risk was not higher in diabetic patients: adjusted HR (95% CI)=1.20 (0.79-1.84). In the subgroup of clopidogrel-treated patients (N=238), MACE rate was significantly higher in diabetic compared with nondiabetic cohort [13.4 vs. 9%, adjusted HR (95% CI)=1.68 (1.07-2.64), P=0.03]. In the subgroup of ticagrelor-treated or prasugrel-treated patients (N=228), MACE rate did not differ significantly between diabetic and nondiabetic patients: 9.6 versus 5%, adjusted HR (95% CI)=1.35 (0.77-2.37), P=0.38.. In 'real-life' ACS undergoing PCI, diabetic patients have higher - although not significantly - MACE rate and no difference in bleeding events. This difference in MACE was significant among clopidogrel-treated patients, whereas when newer antiplatelet agents were used the negative impact of DM on ischemic events was eliminated.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Case-Control Studies; Clopidogrel; Cohort Studies; Comorbidity; Diabetes Mellitus; Female; Greece; Hemorrhage; Humans; Male; Middle Aged; Mortality; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Propensity Score; Proportional Hazards Models; Prospective Studies; Stroke; Ticagrelor; Ticlopidine

Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel.. The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals.. A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization.. At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription.. In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher thrombotic risk, did not influence this choice; however, bleeding risk was taken into account.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Aged, 80 and over; Anticoagulants; Clopidogrel; Diabetes Complications; Diabetes Mellitus; Humans; Middle Aged; Multivariate Analysis; Platelet Aggregation Inhibitors; Practice Patterns, Physicians'; Prasugrel Hydrochloride; Prospective Studies; Registries; Ticagrelor

Topics: Adverse Drug Reaction Reporting Systems; Aged; Cardiovascular Diseases; Comorbidity; Data Accuracy; Diabetes Mellitus; Female; Humans; Male; Prasugrel Hydrochloride; Research Design; Risk Assessment; Risk Factors; Ticagrelor; Treatment Outcome; United States; United States Food and Drug Administration

Comparative outcomes of treatment with antiplatelet drugs in patients with acute coronary syndrome (ACS) and co-morbid diabetes mellitus (DM) are not well studied.. We performed a cohort study using US commercial claims data (2009-2015) and conducted the following pairwise comparisons in ACS patients with DM: prasugrel vs clopidogrel, ticagrelor vs clopidogrel, and prasugrel vs ticagrelor. Outcomes of interest included (1) a composite effectiveness endpoint including myocardial infarction, ischemic stroke, or inpatient mortality; (2) a composite safety endpoint including major bleeding events requiring hospitalization; and (3) pneumonia hospitalizations as a negative control endpoint. We used calendar time-specific propensity score matching to account for confounding and applied Cox proportional hazard models to calculate hazard ratios (HR) with 95% confidence intervals (CI).. Comparative risk of the effectiveness endpoint was lower among prasugrel initiators compared to clopidogrel initiators (HR 0.82, 95% CI 0.68-0.99, N = 7011 matched pairs), but no different between ticagrelor and clopidogrel (HR 1.02, 95% CI 0.76-1.37, N = 3013 pairs) or prasugrel and ticagrelor (HR 0.83, 95% CI 0.58-1.18, N = 2207 pairs). Bleeding risk was higher among prasugrel initiators when compared to clopidogrel initiators within the first month of treatment (HR 1.85, 95% CI 1.03-3.35); no other comparison indicated any difference. No differences in the negative control outcomes were noted after PS matching for all comparisons, indicating adequate confounding control.. Prasugrel was associated with superior cardiovascular outcomes and a higher risk of short-term bleeding compared to clopidogrel in patients with ACS and DM. Comparative outcomes were similar between ticagrelor and clopidogrel or prasugrel and ticagrelor.

Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Cohort Studies; Comorbidity; Comparative Effectiveness Research; Diabetes Mellitus; Female; Hemorrhage; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Stroke; Ticagrelor; Treatment Outcome; United States

Topics: Aspirin; Belgium; Clopidogrel; Diabetes Mellitus; Drug Therapy, Combination; Humans; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome

Patients with diabetes mellitus and acute coronary syndrome (ACS) present an increased risk of adverse cardiovascular events. An Italian Consensus Document indicated 'three specific must' to obtain in this subgroup of patients: optimal oral antiplatelet therapy, early invasive approach and a tailored strategy of revascularization for unstable angina/non-ST-elevation-myocardial infarction (UA/NSTEMI); furthermore, glycemia at admission should be managed with dedicated protocols.. To investigate if previous recommendations are followed, the present multicenter prospective observational registry was carried out in Lombardia during a 9-week period between March and May 2015.. A total of 559 consecutive ACS patients (mean age 68.7 ± 11.3 years, 35% ≥75 years, 50% STEMI), with 'known DM' (56%) or 'hyperglycemia', this last defined as blood glucose value ≥ 126 mg/dl at admission, were included in the registry at 29 hospitals with an on-site 24/7 catheterization laboratory. Patients with known diabetes mellitus received clopidogrel in 51% of the cases, whereas most patients with hyperglycemia (72%) received a new P2Y12 inhibitor: according to clinical presentation in case STEMI prasugrel/ticagrelor were more prescribed than clopidogrel (70 vs. 30%, P < 0.001); on the contrary, no significant difference was found in case of UA/NSTEMI (48 vs. 52%, P = 0.57).Overall, 96% of the patients underwent coronary angiography and 85% received a myocardial revascularization (with percutaneous coronary intervention in 92% of cases) that was however performed in fewer patients with known diabetes mellitus compared with hyperglycemia (79 vs. 90%, P = 0.001).Among UA/NSTEMI, 85% of patients received an initial invasive approach, less than 72 h in 80% of the cases (51% <24 h); no difference was reported comparing known diabetes mellitus to hyperglycemia. Despite similar SYNTAX score, patients with known diabetes mellitus had a higher rate of Heart Team discussion (29 vs. 12%, P = 0.03) and received a surgical revascularization in numerically more cases.Most investigators (85%) followed a local protocol for glycemia management at admission, but insulin was used in fewer than half of the cases; diabetes consulting was performed in 25% of the patients and mainly in case of known diabetes mellitus.. Based on data of the present real world prospective registry, patients with ACS and known diabetes mellitus are treated with an early invasive approach in case of UA/NSTEMI and with a tailored revascularization strategy, but with clopidogrel in more cases; glycemia management is taken into account at admission.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Aged, 80 and over; Clopidogrel; Coronary Angiography; Diabetes Mellitus; Disease Management; Female; Hospitalization; Humans; Hyperglycemia; Italy; Male; Middle Aged; Myocardial Revascularization; Percutaneous Coronary Intervention; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Registries; Ticagrelor; Ticlopidine

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; Adenosine; Cross-Over Studies; Diabetes Mellitus; Endothelial Progenitor Cells; Humans; Inflammation; Prasugrel Hydrochloride; Prospective Studies; Purinergic P2Y Receptor Antagonists; Ticagrelor

Topics: Acute Coronary Syndrome; Adenosine; Blood Platelets; Diabetes Mellitus; Humans; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Treatment Outcome

The influence of diabetes mellitus (DM) on platelet reactivity (PR) in prasugrel or ticagrelor treated patients is not well studied.. In an observational study involving 777 patients with acute coronary syndrome undergoing percutaneous coronary intervention treated by either prasugrel 10 mg od (n = 315) or ticagrelor 90 mg bid (n = 462), platelet function was assessed using the VerifyNow P2Y12 function assay (in PRU) at one month post intrvention.. In the overall population, ticagrelor and insulin-treated DM affected PR, with a decrease in log by 0.88 (corresponding to a 58 % decrease in PR) compared to prasugrel-treated patients (p < 0.001), and an increase in log by 0.26 (corresponding to a 30 % increase in PR) compared to non-diabetic patients (p = 0.01), respectively. PR in prasugrel-treated patients differed significantly by DM status: 70.0 (36.3-113.0) in non-diabetic vs 69.0 (44.5-115.3) in non insulin-treated diabetic vs 122.0 (69.0-161.0) in insulin-treated diabetic patients, p for trend = 0.01. No differences were observed in ticagrelor-treated patients. By multivariate analysis, in prasugrel-treated patients insulin-treated DM was the only factor predicting PR, with log of PR increased by 0.42 (corresponding to a 52 % increase in PR) compared to non-diabetic patients (p = 0.001). No factor was found to affect PR in ticagrelor-treated patients.. Patients with insulin-treated DM treated with prasugrel post PCI have higher PR, than patients without DM or non insulin-treated diabetic patients treated with this drug. Ticagrelor treated patients have overall lower PR than patients on prasugrel, independent of DM status or insulin treatment.. Clinical Trials Gov. NCT01774955.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Ticagrelor; Treatment Outcome

Diabetes has been identified as a risk factor for impaired clopidogrel response, and these patients might have greater benefit with new P2Y12 blockers such as prasugrel. The present study was designed to assess response to thienopyridine in diabetic patients undergoing PCI for ACS.. 107 diabetic patients undergoing PCI for ACS were included and treated by clopidogrel 600 mg loading dose and switched to prasugrel 10mg daily after PCI. Platelet reactivity was assessed by PRI VASP. High-on-treatment platelet reactivity (HTPR) was defined by PRI VASP>50% and Low-on-treatment platelet reactivity (LTPR) as PRI VASP below the 75th percentile (PRI VASP<20%). After clopidogrel, mean PRI VASP was 47 ± 21% and 54 patients (50%) were non responders. At one month, mean PRI VASP on prasugrel 10mg daily was 31 ± 13%, 9 patients (8%) had HTPR and 23 patients (22%) had LTPR. In multivariate analysis, factors associated with platelet reactivity were waist circumference for HTPR on clopidogrel and body weight for HTPR and LTPR on prasugrel. 10 patients (9%) suffered from BARC bleeding complications. Patients with bleeding complications had significantly lower PRI VASP values: 22 ± 9 vs. 32 ± 13, p=0.02 and ROC curves identified a cut-off value of VASP=28% to predict bleeding complications.. The present study confirmed that many diabetic patients treated with clopidogrel for ACS have inadequate platelet inhibition. Switch to prasugrel is effective with acceptable safety in this specific population. We observed a significant relationship between on-treatment platelet reactivity and bleeding complications.

Topics: Acute Coronary Syndrome; Aged; Blood Platelets; Clopidogrel; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Piperazines; Platelet Activation; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Thiophenes; Ticlopidine; Treatment Outcome

The prevalence of prasugrel contraindications and specific conditions requiring precaution for its use in a real world acute coronary syndrome (ACS) population is not known. We performed a prospective descriptive study in 1016 consecutive moderate to high risk ACS patients. In 646 patients (63.6%) subjected to percutaneous coronary intervention, analysis of absolute contraindications (history of stroke/transient ischemic attack or active bleeding), relative contraindications and specific conditions (age ≥ 75 years and/or weight < 60 kg) for prasugrel theoretical administration was performed. In 242 (37.5%) patients there was at least one absolute or relative contraindication or specific condition requiring attention for its use. Overall, 23.1% of patients in our cohort had a prior stroke/transient ischemic attack and/or specific condition to be considered for prasugrel administration. Specifically, the prevalence of stroke/TIA was 3.6%, the prevalence of patients ≥75 years 20% and the prevalence of patients weighing <60 kg 2.2%. Among patients ≥75 years old, 63 (9.8%) had diabetes mellitus or previous myocardial infarction, consisting a high risk subgroup that might benefit from prasugrel administration. In a real world ACS population a relatively high proportion of patients have a potential contraindication for prasugrel administration or necessitate special attention for its use.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Aged, 80 and over; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Piperazines; Prasugrel Hydrochloride; Prevalence; Prospective Studies; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Thiophenes

Contrary to the decline in the prevalence of several risk factors such as hypertension, hypercholesterolemia and smoking, diabetes is an expanding health burden in the western world. Because of the proatherosclerotic, proinflammatory, and prothrombotic states associated with diabetes, diabetic patients with acute coronary syndromes (ACS) are at high risk of subsequent cardiovascular events. However, they derive greater benefit from aggressive platelet inhibition and an early invasive strategy than non-diabetic individuals. Despite the documented efficacy, diabetic patients with ACS receive evidence-based treatments less frequently than non-diabetic individuals.

Topics: Acute Coronary Syndrome; Algorithms; Angioplasty; Anti-Inflammatory Agents, Non-Steroidal; Clopidogrel; Diabetes Complications; Diabetes Mellitus; Drug Therapy, Combination; Enoxaparin; Evidence-Based Medicine; Fibrinolytic Agents; Heparin; Humans; Hypoglycemic Agents; Piperazines; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk Factors; Secondary Prevention; Stents; Thiophenes; Ticlopidine; Treatment Outcome