Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes.

AIMS: To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. RESULTS: We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95). CONCLUSIONS: Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Direct Oral Anticoagulants as the First Choice of Anticoagulation for Patients with Peripheral Artery Disease to Prevent Adverse Vascular Events: A Systematic Review and Meta-Analysis.

The best method of anticoagulation for patients with peripheral artery disease (PAD) is still a topic of interest for physicians. We conducted a meta-analysis to compare the effects of direct oral anticoagulants (DOACs) with those of vitamin-K-antagonist (VKA) anticoagulants in patients with peripheral artery disease. Five databases (Medline (via PubMed), EMBASE, Scopus, Web of Science, and CENTRAL) were searched systematically for studies comparing the effects of the two types of anticoagulants in patients with PAD, with an emphasis on lower-limb outcomes, cardiovascular events, and mortality. In PAD patients with concomitant non-valvular atrial fibrillation (NVAF), the use of DOACs significantly reduced the risk of major adverse limb events (HR = 0.58, 95% CI, 0.39-0.86, p < 0.01), stroke/systemic embolism (HR 0.76; 95% CI 0.61-0.95; p < 0.01), and all-cause mortality (HR 0.78; 95% CI 0.66-0.92; p < 0.01) compared with warfarin, but showed similar risks of MI (HR = 0.81, 95% CI, 0.59-1.11, p = 0.2) and cardiovascular mortality (HR = 0.77, 95% CI, 0.58-1.02, p = 0.07). Rivaroxaban at higher doses significantly increased the risk of major bleeding (HR = 1.16, 95% CI, 1.07-1.25, p < 0.01). We found no significant difference in terms of revascularization (OR = 1.49, 95% CI, 0.79-2.79, p = 0.14) in PAD patients in whom a poor distal runoff was the reason for the anticoagulation. DOACs have lower rates of major limb events, stroke, and mortality than VKAs in PAD patients with atrial fibrillation. Rivaroxaban at higher doses increased the risk of major bleeding compared with other DOAC drugs. More high-quality studies are needed to determine the most appropriate anticoagulation regimen for patients with lower-limb atherosclerosis.

Association of Sodium-Glucose Cotransporter 2 Inhibitors with Osteomyelitis and Other Lower Limb Safety Outcomes in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Our aim was to evaluate osteomyelitis and other major lower limb safety outcomes (i.e., peripheral artery disease or PAD, ulcers, atraumatic fractures, amputations, symmetric polyneuropathy, and infections) in patients affected by type 2 diabetes mellitus (T2DM) and treated with sodium-glucose cotransporter 2 inhibitors (SGLT2-is). We thus performed a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing SGLT2-is at approved doses for T2DM with a placebo or standard of care. MEDLINE, Embase, and Cochrane CENTRAL were searched through August 2022. Separate intention-to-treat analyses were implemented for each molecule to calculate Mantel-Haenszel risk ratios (RRMH) with 95% confidence intervals (CIs) through a random-effects model. We processed data from 42 RCTs for a total of 29,491 and 23,052 patients, respectively assigned to SGLT2-i and comparator groups. SGLT2-is showed a pooled neutral effect on osteomyelitis, PAD, fractures, and symmetric polyneuropathy, whereas slightly deleterious sway on ulcers (RRMH 1.39 [1.01-1.91]), amputations (RRMH 1.27 [1.04-1.55]), and infections (RRMH 1.20 [1.02-1.40]). In conclusion, SGLT2-is appear to not significantly interfere with the onset of osteomyelitis, PAD, lower limb fractures, or symmetric polyneuropathy, even though the number of these events proved consistently higher in the investigational groups; otherwise, local ulcers, amputations, and overall infections may be favoured by their employment. This study is registered with the Open Science Framework (OSF).

Diabetic foot ulcers: Classification, risk factors and management.

Diabetic foot ulceration is a devastating complication of diabetes that is associated with infection, amputation, and death, and is affecting increasing numbers of patients with diabetes mellitus. The pathogenesis of foot ulcers is complex, and different factors play major roles in different stages. The refractory nature of foot ulcer is reflected in that even after healing there is still a high recurrence rate and amputation rate, which means that management and nursing plans need to be considered carefully. The importance of establishment of measures for prevention and management of DFU has been emphasized. Therefore, a validated and appropriate DFU classification matching the progression is necessary for clinical diagnosis and management. In the first part of this review, we list several commonly used classification systems and describe their application conditions, scope, strengths, and limitations; in the second part, we briefly introduce the common risk factors for DFU, such as neuropathy, peripheral artery disease, foot deformities, diabetes complications, and obesity. Focusing on the relationship between the risk factors and DFU progression may facilitate prevention and timely management; in the last part, we emphasize the importance of preventive education, characterize several of the most frequently used management approaches, including glycemic control, exercise, offloading, and infection control, and call for taking into account and weighing the quality of life during the formulation of treatment plans. Multidisciplinary intervention and management of diabetic foot ulcers (DFUs) based on the effective and systematic combination of these three components will contribute to the prevention and treatment of DFUs, and improve their prognosis.

Diabetes and peripheral artery disease: A review.

Peripheral arterial disease (PAD) refers to partial or complete occlusion of the peripheral vessels of the upper and lower limbs. It usually occurs as part of systemic atherosclerosis in the coronary and cerebral arteries. The prevalence of PAD is expected to continue to increase in the foreseeable future owing to the rise in the occurrence of its major risk factors. Nonhealing ulcers, limb amputation and physical disability are some of its major complications. Diabetes mellitus (DM) remains a major risk for PAD, with DM patients having more than two-fold increased prevalence of PAD compared with the general population. The clinical presentation in people with DM also differs slightly from that in the general population. In addition, PAD in DM may lead to diabetic foot ulcers (DFUs), which precipitate hyperglycaemic emergencies and result in increased hospital admissions, reduced quality of life, and mortality. Despite the epidemiological and clinical importance of PAD, it remains largely under diagnosed and hence undertreated, possibly because it is largely asymptomatic. Emphasis has been placed on neuropathy as a cause of DFUs, however PAD is equally important. This review examines the epidemiology, pathophysiology and diagnosis of lower limb PAD in people with diabetes and relates these to the general population. It also highlights recent innovations in the management of PAD.

Pedobarography as a clinical tool in the management of diabetic feet in New Zealand: a feasibility study.

BACKGROUND: The peripheral complications of diabetes mellitus remain a significant risk to lower-limb morbidity. In New Zealand, risk of diabetes, comorbidity and lower-limb amputation are highly-differential between demographic groups, particularly ethnicity. There is growing and convincing evidence that the use of pedobarography - or plantar pressure measurement - can usefully inform diabetic foot care, particularly with respect to the prevention of re-ulceration among high-risk patients. METHODS: For the current feasibility study, we embedded pedobarographic measurements into three unique diabetic foot clinic settings in the New Zealand context, and collected pedobarographic data from n = 38 patients with diabetes using a platform-based (Novel Emed) and/or in-shoe-based system (Novel Pedar). Our aim was to assess the feasibility of incorporating pedobarographic testing into the clinical care of diabetic feet in New Zealand. RESULTS AND CONCLUSIONS: We observed a high response rate and positive self-reported experience from participants. As part of our engagement with participants, we observed a high degree of lower-limb morbidity, including current ulceration and chronic foot deformities. The median time for pedobarographic testing (including study introduction and consenting) was 25 min. Despite working with a high-risk population, there were no adverse events in this study. In terms of application of pedobarography as a clinical tool in the New Zealand context, the current feasibility study leads us to believe that there are two avenues that deserve further investigation: a) the use of pedobarography to inform the design and effectiveness of offloading devices among high-risk diabetic patients; and b) the use of pedobarography as a means to increase offloading footwear and/or orthoses compliance among high-risk diabetic patients. Both of these objectives deserve further examination in New Zealand via clinical trial.