hirudin and Diabetes-Mellitus

The efficacy and safety of bivalirudin (Biva) versus heparin in patients with diabetes mellitus (DM) who undergo percutaneous coronary intervention (PCI) remain controversial. Our meta-analysis was undertaken to evaluate the efficacy and safety of Biva compared with those of heparin in patients with diabetes undergoing PCI.. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials.gov databases for randomized controlled trials (RCTs). The primary efficacy endpoint was the incidence of major adverse cardiovascular events (MACE), and the primary safety endpoint was the incidence of major bleeding. Secondary efficacy endpoints were incidence of net adverse clinical events (NACE), myocardial infarction (MI), and death. The pooled risk ratio (RR) with the corresponding 95% confidence intervals (CIs) were used to assess the efficacy and safety of Biva versus heparin.. Eleven RCTs met the inclusion criteria, and 8428 patients were included. No significant difference was observed in the subgroup and overall risk of MACE (RR 0.87; 95% CI 0.74-1.02; P = .08; I = 39%) and NACE (RR 0.81; 95% CI 0.61-1.07; P = .14; I = 71%). Biva had an effect similar to that of heparin on the endpoint of death (RR 0.75; 95% CI 0.56-1.02; P = .07; I = 0) and MI (RR 0.92; 95% CI 0.67-1.26; P = .59; I = 0) but decreased the risk of major bleeding (RR 0.63; 95% CI 0.52-0.75; P < .00001; I = 0%).. The use of Biva and heparin is associated with a similar risk of MACE, NACE, death, and MI. Biva decreases the risk of major bleeding more significantly than heparin.

Topics: Anticoagulants; Diabetes Mellitus; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Recombinant Proteins

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

A history of diabetes mellitus (DM) is an independent predictor for adverse events in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Outcomes of patients with STEMI and newly diagnosed DM (NDM) are less well described. We used the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial database to identify the outcomes at 30 days and 3 years according to no, known, and NDM in patients with STEMI. In HORIZONS-AMI, 3,602 patients with STEMI were randomized to bivalirudin versus heparin and a glycoprotein IIb/IIIa inhibitor, and eligible patients were randomized again to a paclitaxel-eluting stent or a bare-metal stent. DM was defined as a history of hyperglycemia managed by insulin, oral hypoglycemic agents, or diet. NDM was defined as the absence of previous diagnosis or treatment for DM at baseline and its addition at discharge. DM was present in 593/3,599 patients (16.5%), and NDM was diagnosed in 130 cases (3.6%). Compared with nondiabetics, those with DM and NDM had higher 3-year rates of death (11.4% and 12.0% vs 5.6%, respectively, p <0.0001) and major adverse cardiac events (29.6% and 30.2% vs 19.9%, respectively, p <0.0001). There were no significant differences in adverse events between new and known diabetic patients. DM and NDM were independent predictors of 3-year mortality and 3-year major adverse cardiac events. In conclusion, patients with NDM have a similarly poor prognosis after primary percutaneous coronary intervention in STEMI as those with previously established DM.

Topics: Aged; Cause of Death; Diabetes Mellitus; Drug-Eluting Stents; Electrocardiography; Female; Follow-Up Studies; Heparin; Hirudins; Humans; Hypoglycemic Agents; Incidence; Male; Middle Aged; Paclitaxel; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Glycoprotein GPIIb-IIIa Complex; Postoperative Period; Prognosis; Recombinant Proteins; ST Elevation Myocardial Infarction; Survival Rate; Time Factors; Treatment Outcome; United States

We sought to evaluate the safety and efficacy of bivalirudin compared with glycoprotein IIb/IIIa inhibitors (GPI) in diabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).. Prior studies have demonstrated that GPI are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI.. In the multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI were randomized to bivalirudin or unfractionated heparin plus a GPI. Clinical outcomes were analyzed at 30 days and 1 year in patients with diabetes.. Diabetes mellitus was present in 593 patients (16.5%). The rates of cardiac death were significantly lower in diabetic patients treated with bivalirudin compared with heparin plus GPI (30 days: 2.1% vs. 5.5%, p = 0.04; 1 year: 2.5% vs. 7.1%, p = 0.01), and bivalirudin resulted in lower 30-day rates of stroke (0% vs. 2%, p = 0.02). There were no significant differences among diabetic patients randomized to bivalirudin versus heparin plus GPI in the 1-year rates of major adverse cardiac events (14.2% vs. 16.2%, p = 0.44), major bleeding (8.7% vs. 10.7%, p = 0.42), or stent thrombosis (4.2% vs. 3.8%, p = 0.85). By interaction testing, the relative effects of bivalirudin compared with heparin plus GPI were not significantly different in patients with and without diabetes.. In patients with diabetes mellitus presenting with STEMI undergoing primary PCI, anticoagulant therapy with bivalirudin compared with heparin plus GPI is safe and effective and might reduce cardiac mortality at 30 days and 1 year. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Topics: Aged; Angioplasty, Balloon, Coronary; Antithrombins; Coronary Angiography; Diabetes Mellitus; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Hirudins; Humans; Hypoglycemic Agents; Male; Middle Aged; Myocardial Infarction; Peptide Fragments; Prospective Studies; Recombinant Proteins; Stents; Survival Rate; Time Factors; Treatment Outcome

Bivalirudin demonstrated similar efficacy but resulted in a lower rate of bleeding compared to unfractionated heparin (UFH) plus platelet glycoprotein IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention. It has not been clearly evaluated whether this can also be applied to patients with diabetes mellitus. A total of 335 consecutive patients with diabetes mellitus referred for elective percutaneous coronary intervention were randomized in the Novel Approaches for Preventing or Limiting EventS (NAPLES) trial to receive bivalirudin monotherapy or UFH plus routine tirofiban. The primary composite end point (30-day composite incidence of death, urgent repeat revascularization, myocardial infarction, and all bleeding) was lower in the bivalirudin group than in the UFH plus tirofiban group (18.0% vs 31.5%, odds ratio 0.47, 95% confidence interval 0.28 to 0.79, p = 0.004). No death, urgent revascularization, or Q-wave myocardial infarction occurred. The rate of non-Q-wave myocardial infarction was similar in the 2 groups (10.2% in the bivalirudin group vs 12.5% in the UFH plus tirofiban group, p = 0.606). In contrast, fewer patients in the bivalirudin group experienced bleeding (8.4% vs 20.8%, odds ratio 0.34, 95% confidence interval 0.18 to 0.67, p = 0.002). This difference was mainly ascribed to the lower rate of minor bleeding (7.8% in the bivalirudin group vs 18.5% in the UFH plus tirofiban group, odds ratio 0.37, 95% confidence interval 0.19 to 0.74, p = 0.005), although the rate of major bleeding in the 2 groups was comparable (0.6% vs 2.4%, respectively; p = 0.371). In conclusion, in patients with diabetes mellitus undergoing elective percutaneous coronary intervention, the strategy of bivalirudin monotherapy compared to UFH plus routine tirofiban is safe and feasible and associated with a significant reduction of in-hospital bleeding.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Coronary Artery Disease; Diabetes Mellitus; Drug Therapy, Combination; Female; Hemorrhage; Heparin; Hirudins; Humans; Male; Myocardial Infarction; Peptide Fragments; Platelet Aggregation Inhibitors; Prospective Studies; Recombinant Proteins; Retreatment; Thrombocytopenia; Tirofiban; Tyrosine

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Endothelial Cells; Hirudins; Kidney; Mice; Pyroptosis; Rats

To explore the mechanism of hirudin in the treatment of diabetic kidney disease (DKD).. Cytoscape software was used to analyze the network between hirudin targets and active components in the treatment of DKD. The biological function and mechanism of effective targets of hirudin for DKD treatment were analyzed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Molecular docking technology was used to simulate the docking of key targets, and the DKD rat model was used to verify the first 4 key targets with high "Hydrogen number" among the top 10 targets verified by molecular docking.. Total of 12334 DKD targets were screened in GeneCards, OMIM and other databases, Hirudin and DKD had 247 common target genes, and the protein interaction network got 2115 edges. The DAVID database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, confirming that hirudin in treatment of DKD involves multiple signaling pathways such as the forkhead box O signaling pathway, the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, the vascular endothelial-derived growth factor signaling pathway and other signaling pathways. The top ten key targets of hirudin in treatment of DKD were verified by molecular docking. Animal experiments showed that hirudin could decrease the expression of caspase-3 in renal tissue of DKD rats, and increase the expression of RAC-alpha serine/threonine-protein kinase, Catalase, and Heat shock protein HSP 90-alpha in renal tissue of DKD rats.. This study preliminarily reveals that hirudin treats DKD through multiple targets and pathways, and molecular docking and animal experiments indicates the feasibility of this study. Hirudin may be directly or indirectly involved in the regulation of cell metabolism, oxidative stress and other mechanisms in the treatment of DKD, which will lay the foundation for future molecular biological experiments of hirudin in the treatment of DKD.

Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Drugs, Chinese Herbal; Hirudins; Medicine, Chinese Traditional; Molecular Docking Simulation; Network Pharmacology; Protein Interaction Maps; Rats

Optimal anticoagulants for patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are unclear. This retrospective observational study is aimed at evaluating efficacy and safety of bivalirudin versus unfractionated heparin (UFH) monotherapy in patients with DM undergoing PCI.. A total of 3890 diabetic patients receiving PCI in the General Hospital of Northern Theater Command were divided into the bivalirudin group (. After propensity score matching, the bivalirudin group was associated with a lower incidence of NACEs (3.0% vs. 6.0%,. In diabetic patients undergoing PCI, bivalirudin was significantly associated with reduced risks of 30-day NACE and MACCE, mainly driven by the lower rates of bleeding and mortality, compared with heparin monotherapy.

Topics: Anticoagulants; Antithrombins; Diabetes Mellitus; Fibrinolytic Agents; Hemorrhage; Heparin; Hirudins; Humans; Peptide Fragments; Percutaneous Coronary Intervention; Recombinant Proteins; Treatment Outcome

The in vivo inhibitory effect of r-hirudin variant III (rHV3) on streptozotocin (STZ)-induced diabetic cataracts in rats was investigated. SD-rats were firstly made diabetic by a single intraperitoneal injection of 2% (W/V) STZ (65 mg/kg). Two weeks later, cataract formation was examined by slit lamp microscope, and the cataracted animals were randomly grouped. The animals in the treated groups received rHV3 drops administration to the eyes with various doses. After 4 weeks treatment, the animals were sacrificed to evaluate the biochemical changes of aldose reductase (AR), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in the eye lens. Meanwhile, the cataract progression was monitored by slit lamp microscope. As a result, rHV3 drops treatment significantly increased the activities of SOD and GSH-Px in the lens in a dose-dependent manner, whereas AR activity and MDA level in the lens were dramatically decreased. Also, the morphological observation further confirmed the inhibition of the development of STZ-induced diabetic cataracts by the rHV3 drops treatment. Thus, our data suggest that rHV3 drops are pharmacologically effective for the protection against STZ-induced diabetic cataracts in rats.

Topics: Animals; Cataract; Diabetes Mellitus; Diabetes Mellitus, Experimental; Hirudin Therapy; Hirudins; Humans; Male; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Streptozocin; Treatment Outcome