warfarin and Diabetic-Angiopathies

Direct oral anticoagulants (DOACs) include dabigatran, which inhibits thrombin, and apixaban, edoxaban, and rivaroxaban, which inhibit factor Xa. They have been extensively studied in large trials involving patients affected by the most common cardiovascular diseases. As the presence of diabetes leads to peculiar changes in primary and secondary hemostasis, in this review we highlight the current evidence regarding DOAC use in diabetic patients included in the majority of recently conducted studies. Overall, in trials involving patients with atrial fibrillation, data seem to confirm at least a similar efficacy and safety of DOACs compared to warfarin in patients with or without diabetes. Furthermore, in diabetic patients, treatment with DOACs is associated with a significant relative reduction in vascular death compared to warfarin. In trials enrolling patients undergoing percutaneous coronary intervention, results concerning bleeding events are consistent in patients with or without diabetes. With regards to the COMPASS study, in patients with diabetes (n = 10,241), addition of rivaroxaban 2.5 mg to aspirin resulted in a significantly lower incidence of major adverse cardiovascular events (HR 0.74, 95% CI 0.61-0.90; interaction p = 0.68) with higher rates of major bleeding expected (HR 1.70, 95% CI 1.25-2.31). The 3287 patients with peripheral artery disease and diabetes receiving rivaroxaban plus aspirin had a twofold higher absolute reduction in the composite endpoint (cardiovascular death, myocardial infarction, and stroke) than patients without diabetes. Finally, we report the involvement of cytochromes or P-glycoprotein on the metabolism of the most commonly prescribed glucose-lowering drugs. No clinically relevant interactions are expected during the concomitant use of DOACs and anti-diabetic agents.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Diabetes Mellitus; Diabetic Angiopathies; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Stroke; Treatment Outcome; Warfarin

The decline in stroke incidence and mortality in the U.S. over the past 20 years is reaching a plateau, and the number of strokes may actually start to increase as the population ages. However, recent clinical trials have demonstrated that there are numerous opportunities to improve stroke prevention strategies and also opportunities to effectively intervene in and treat acute strokes. For patients with diabetes and for those with prior strokes or transient ischemic attacks, it has become evident that aggressive low-density lipoprotein lowering with statin medications will decrease the risk for total and fatal strokes. Optimal anticoagulation and antiplatelet therapy for primary and secondary stroke prevention in atrial fibrillation is being carefully defined. With numerous novel factor Xa and direct thrombin inhibitor drugs completing phase III clinical trials, it is likely that additional oral anticoagulant drugs will be clinically available for stroke prevention soon. Additionally, a major clinical trial is nearing completion that may resolve the role of carotid stenting and carotid endarterectomy in primary and secondary stroke prevention. There are recent notable advances in the acute treatment of stroke. It is likely that the time window for thrombolysis for appropriate patients with strokes will be increased from 3 to 4.5 h, permitting the inclusion of more patients in this treatment approach. There is ongoing investigation of intra-arterial thrombolysis and of acute intra-arterial thrombus extraction for treatment of selected patients with strokes. Unlike the progress in treatment of ischemic strokes, treatment of hemorrhagic stroke is progressing more slowly.

Topics: Anticoagulants; Atrial Fibrillation; Brain Ischemia; Cholesterol, LDL; Diabetic Angiopathies; Endarterectomy, Carotid; Foramen Ovale, Patent; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; International Normalized Ratio; Intracranial Hemorrhages; Stents; Stroke; Thrombectomy; Thrombolytic Therapy; Thrombosis; United States; Warfarin

The aim of this article was to describe (i) the epidemiology and outcomes of stroke relating to diabetes; (ii) the pathophysiology of diabetes as a risk factor for stroke; (iii) the management of acute stroke in patients with diabetes; (iv) the evidence of primary and secondary prevention of stroke in patients with diabetes; and (v) the risk of new-onset diabetes using older antihypertensive agents. The combination of diabetes and stroke disease is a major cause of morbidity and mortality worldwide. Evidence from large clinical trials performed in patients with diabetes supports the need for aggressive and early intervention to target patients' cardiovascular (CV) risks in order to prevent the onset, recurrence and progression of acute stroke. Identification of at-risk patients with diabetes and metabolic syndrome has also allowed the delivery of early and effective intervention to reduce stroke risks, while active treatment during the acute phase of stroke will reduce long-term neurological and functional deficits. While the ongoing debate on the risk benefits of different antihypertensive, lipid-lowering and antiplatelet agents should not detract clinicians from pursuing aggressive CV risk reduction, the application of evidence-based medicine specifically in patients with diabetes will facilitate the use of appropriate agents to improve clinical outcomes. The overall management of patients with diabetes and acute stroke or at risk of secondary stroke should also include multifactorial intervention that not only targets patient's CV risk but also includes behavioural, lifestyle and, where appropriate, surgical intervention.

Topics: Anticoagulants; Carotid Stenosis; Diabetic Angiopathies; Dyslipidemias; Endarterectomy, Carotid; Humans; Hyperglycemia; Hypertension; Platelet Aggregation Inhibitors; Risk Factors; Smoking Cessation; Stroke; Warfarin

To assess the effectiveness and safety of rivaroxaban vs warfarin in people with non-valvular atrial fibrillation and diabetes treated in routine practice.. Using US MarketScan claims data for the period November 2011 to December 2016, we identified oral anticoagulation-naïve people with non-valvular atrial fibrillation and diabetes (Type 1 or Type 2) and ≥12 months of continuous insurance coverage prior to the qualifying oral anticoagulation dispensing time. Rivaroxaban users were 1:1 propensity score-matched to warfarin users. Participants were followed until an event, oral anticoagulation switch/discontinuation, insurance disenrolment or end of follow-up. Rates (events/100 person-years) of the composite of stroke or systemic embolism and major bleeding were compared using Cox regression and reported as hazard ratios and 95% CIs.. We assessed 5517 rivaroxaban users (20% received the reduced dose) and 5517 warfarin users with non-valvular atrial fibrillation and diabetes (~97% with Type 2 diabetes) with a median (interquartile range) available follow-up of 1.5 (0.7, 2.7) years. Rivaroxaban was associated with nonsignificant reductions in stroke or systemic embolism (0.87 vs 1.35/100 person-years; hazard ratio 0.68, 95% CI 0.44-1.05) and ischaemic stroke (0.69 vs 0.93/100 person-years; hazard ratio 0.78, 95% CI 0.48-1.30) compared with warfarin. No differences in major bleeding (2.7 vs 3.0/100 person-years; hazard ratio 0.96, 95% CI 0.74-1.25) were observed. Similar results were seen when analysis was limited to standard-dose rivaroxaban. Reduced-dose rivaroxaban was associated with a significantly decreased hazard of stroke or systemic embolism and ischaemic stroke, without an increase in major bleeding risk.. Rivaroxaban has effectiveness and safety at least as good as those of warfarin in people with diabetes and non-valvular atrial fibrillation treated in routine clinical practice.

Topics: Administrative Claims, Healthcare; Aged; Atrial Fibrillation; Databases, Factual; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Retrospective Studies; Rivaroxaban; Treatment Outcome; Warfarin

Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally.. Male Wistar rats received a high fat diet during 2 months followed by a low dose of streptozotocin to induce diabetes (D). Elastocalcinosis was facilitated by 3 weeks of treatment with warfarin and vitamin K (WVK). We started WVK treatment 1 week (D4WVK) and 4 weeks (D7WVK) after the injection of streptozotocin and in age-matched healthy rats. Measurements of hemodynamic and metabolic parameters, aortic and femoral calcium content, and immunohistochemistry for alkaline phosphatase, osteopontin, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-TGF-beta were performed.. Three weeks of WVK treatment alone did not increase the calcium content in the aorta and femoral arteries. However, in the D7WVK group, femoral calcification, but not aortic calcium content, increased significantly as compared to the WVK group. This response was not observed in the D4WVK group. In femoral arteries, strong immunostaining for alkaline phosphatase and osteopontin was observed in the D7WVK group. TNF-alpha and TGF-beta expressions were mainly localized in the adventitia of arteries from diabetic rats.. We have established a model of accelerated elastocalcinosis in diabetes related to its duration and localized in distal arteries. The modification of local protein expression is also in accordance with clinical data, suggesting that this model could be useful to investigate mechanisms related to this important clinical macrovascular complication of diabetes.

Topics: Alkaline Phosphatase; Animals; Aorta; Arteriosclerosis; Calcinosis; Calcium; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Femoral Artery; Immunohistochemistry; Male; Models, Animal; Osteopontin; Rats; Rats, Wistar; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Vitamin K; Warfarin

Observations by pharmacists monitoring anticoagulated patients suggested that patients with diabetes often require more frequent international normalized ratio (INR) monitoring than patients without diabetes. The purpose of this investigation was to examine the association between glycemic control and therapeutic anticoagulation control.. Patients with diabetes who were receiving warfarin therapy monitored by the Kaiser Permanente of Colorado Clinical Pharmacy Anticoagulation Service were eligible for inclusion. Patients were included if they had a diagnosis of diabetes mellitus type 1 or 2, aged > or =18 years, and had initiated anticoagulant therapy > or =120 days before their most recent hemoglobin A1C measurement. The primary outcome was the correlation between hemoglobin A1C value and percent of time in the patient-specific INR range. Multivariate analysis was undertaken to regress percent of time in INR range on an A1C value > or =8.0 while adjusting for other possible explanatory variables.. A total of 911 patients with diabetes were included in the study. Subjects with an A1C value > or =8.0 had similar characteristics as those subjects with an A1C value < 8.0. Correlation analysis revealed no relationship between percent of time spent in INR range and A1C value (Spearman Correlation Coefficient = 0.012, p = 0.805). Multivariate analysis revealed no relationship between percent of time spent in INR range and A1C value > or =8.0 (Odds Ratio = 1.00; 95% Confidence Interval = 0.99, 1.01) when adjusting for possible explanatory variables.. For patients with diabetes on warfarin anticoagulation therapy, there is no association between glycemic control and therapeutic anticoagulation control. However, anticoagulation therapy providers should manage these patients with the same diligence and care as patients without diabetes.

Topics: Aged; Aged, 80 and over; Anticoagulants; Cross-Sectional Studies; Diabetes Mellitus; Diabetic Angiopathies; Drug Interactions; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; International Normalized Ratio; Male; Middle Aged; Retrospective Studies; Treatment Outcome; Warfarin

To evaluate in a group of seriously diseased patients with nonreconstructable chronic critical leg ischemia (CLI), treated by a combination of i.v. hydroxyethylrutosides (HR)* and oral anticoagulation (AC) by warfarin, the short-term effects on the cutaneous microvascular blood perfusion of the soles of feet and especially the long-term clinical outcome in terms of amputation and death.. A retrospective comparison between two groups of patients, HR + AC and a comparable reference group, fulfilling the same inclusion and exclusion criteria corresponding to the definition of CLI according to the Second European Consensus Document (1991). Clinical follow-up in both groups was made after 1, 3, 6, 12, and 24 months.. Patients were examined at university departments of clinical physiology with special interest in peripheral vascular disease, in cooperation with colleagues at university departments of surgery, internal medicine and dermatology of Karolinska Hospital, Södersjukhuset and Huddinge Hospital.. A total of seventy patients with CLI according to the definition of the Second European Consensus Document, 1991, ie, besides severe rest pain or ischemic lesions also a toe blood pressure < 30 mg Hg. Group with HR + anticoagulation (AC): 42 patients (19 diabetics, 23 nondiabetics). Reference group: 28 patients (18 diabetics, 10 nondiabetics). For distribution of age and toe blood pressure at baseline, see Table I.. Therapy group: besides ordinary standard therapy, daily HR infusions for a mean period of 3.6 weeks + oral anticoagulation continued to the end of the study at 24 months. A comparable reference group on the same basic therapy but without the combination HR + AC. PARAMETERS IN EVALUATION: Short-term parameters: clinical data, skin temperature, and fluorescein imaging. Long-term outcome: amputation or death.. Short-term and long-term results with HR + AC indicated that patients with severe CLI and very poor prognosis benefited in terms of survival and limb salvage from initial therapy with HR infusion combined with long-term oral anticoagulation. Results of this combined treatment seem at least comparable with those with i.v. prostacyclin analogies.

Topics: Administration, Oral; Aged; Amputation, Surgical; Anticoagulants; Arteriosclerosis; Blood Pressure; Cardiovascular Agents; Contrast Media; Diabetic Angiopathies; Drug Therapy, Combination; Fluorescein; Follow-Up Studies; Foot; Humans; Hydroxyethylrutoside; Infusions, Intravenous; Ischemia; Leg; Longitudinal Studies; Microcirculation; Prognosis; Retrospective Studies; Skin Temperature; Survival Rate; Treatment Outcome; Warfarin

Topics: Anticoagulants; Aortic Arch Syndromes; Cerebrovascular Disorders; Diabetes Complications; Diabetic Angiopathies; Female; Hemiplegia; Humans; Ischemia; Leg; Middle Aged; Postoperative Complications; Warfarin

In cases of ischemic extremities and diabetes mellitus, the trauma on finger and toe is very intractable. For such injuries amputation of extremity is indicated very often because of severe necrosis. The number of such cases has been increasing recently because many cases of these patients have arteriosclerotic arterial occlusion and diabetes mellitus, and these are correlated with the changes of aging. The number of cases of Buerger's disease has been also increasing and it is another etiology of intractable trauma in ischemic extremity. The repeated hyperbaric oxygenation, sympathetic block, warfarin therapy and insulin bath with bubbling of hyperbaric oxygen, were applied to has been of such necrosis. By these procedures, the rate of amputation of extremity decreasing. It was concluded that the surgical reconstruction of artery for ischemic extremity has never any meaning as the therapy of such intractable injuries, if blood flow in the peripheral tissue is not kept physiologically, before vascular reconstruction. In order to increase peripheral tissue circulation, the hyperbaric oxygenation, sympathetic block and warfarin therapy wer performed in many cases and these methods were very effective for intractable injuries with severe necrosis.

Topics: Adult; Aged; Arteriosclerosis Obliterans; Diabetic Angiopathies; Female; Finger Injuries; Humans; Hyperbaric Oxygenation; Ischemia; Male; Middle Aged; Necrosis; Raynaud Disease; Thromboangiitis Obliterans; Toes; Warfarin

Topics: Aged; Animals; Cattle; Diabetic Angiopathies; Female; Femoral Artery; Humans; Intermittent Claudication; Knee; Leg Ulcer; Male; Middle Aged; Pain; Popliteal Artery; Postoperative Complications; Radiography; Rest; Thrombosis; Transplantation, Heterologous; Warfarin

Topics: Adult; Aged; Amputation, Surgical; Arteriosclerosis; Diabetic Angiopathies; Female; Femoral Artery; Follow-Up Studies; Heparin; Humans; Male; Methods; Middle Aged; Postoperative Care; Transplantation, Autologous; Veins; Warfarin

Topics: Angina Pectoris; Anticoagulants; Carotid Artery Thrombosis; Diabetic Angiopathies; Fibrinolysis; Gangrene; Heart Failure; Humans; Myocardial Infarction; Raynaud Disease; Thromboangiitis Obliterans; Thromboembolism; Warfarin