Low incidence of peripheral arterial disease in patients receiving dasatinib in clinical trials.
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ABSTRACT:
SUBMITTER: le Coutre PD
PROVIDER: S-EPMC4935977 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Peripheral arterial disease (PAD) describes the clinical manifestations of atherosclerosis affecting the circulation in the legs. The severity of PAD is classified according to symptom severity, time course, and anatomical distribution. The signs and symptoms of PAD reflect the degree of circulatory compromise and whether there has been a gradual reduction in the circulation or an abrupt, uncompensated decrease. Accurate clinical assessment underpins decisions on management strategy and should objectively assess the severity of the ischemia and need for revascularization. Clinical history should discriminate symptoms of PAD from other conditions presenting with leg pain, elucidate cardiovascular risk factors and the effect of symptoms on the patient's quality of life. Clinical examination includes signs of general cardiovascular disease and associated conditions before assessing the circulation and viability of the limb. Palpation of peripheral pulses must be augmented by determination of the ankle brachial pressure index using hand held Doppler. A whole patient approach to management is required and must include modification of cardiovascular risk status as well as dealing with the local circulatory manifestation of PAD.
| S-EPMC4232424 | biostudies-other
Project description:Matrix Gla protein is a vitamin K-dependent inhibitor of vascular calcification. Warfarin use is associated with increased breast arterial calcification, but whether this is reflective of other arteries or occurs in men is unclear. In this study, the prevalence of calcification in peripheral arteries was compared in patients with and without warfarin therapy.This retrospective matched cohort study assessed 430 patients with radiographs performed during or after warfarin therapy who were identified by a computerized search of medical records. Each patient was matched to a patient without warfarin exposure based on age, sex, and diabetes status. Patients with warfarin exposure <1 month, history of end-stage renal disease, or serum creatinine >2.0 mg/dl were excluded. Radiographs were reviewed visually for arterial calcification. The prevalence of arterial calcification was 44% greater in patients with versus without warfarin use (30.2% versus 20.9%, P=0.0023) but not on radiographs performed before warfarin therapy (26.4% versus 22.4%, n=156) or prior to 5 years of warfarin therapy. The increase was noted only in the ankle and foot, was limited to a medial pattern of calcification, and was similar in men and women.Warfarin use is associated with lower extremity arterial calcification in both men and women independent of age, sex, diabetes status, and other patient characteristics. This may have implications for the choice of therapies for long-term anticoagulation.
| S-EPMC4859382 | biostudies-other
Project description:An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.
| S-EPMC7921588 | biostudies-literature
Project description:BackgroundVedolizumab (ENTYVIO) is a humanized α4β7 integrin antagonist approved for the treatment of inflammatory bowel disease, which selectively blocks gut-specific lymphocyte trafficking. We evaluated the risk of opportunistic infections of interest in patients treated with vedolizumab.MethodsWe determined the frequency of opportunistic infections and tuberculosis in patients receiving vedolizumab in phase 3 clinical trials and post-marketing settings. We also evaluated adverse events reported in the post-marketing setting in patients with a history of or concurrent hepatitis B/C virus infection.ResultsThe incidence of opportunistic infections in patients receiving vedolizumab was 0.7 (GEMINI 1 and 2 clinical trials) and 1.0 (long-term safety study) per 100 patient-years, with 217 events reported in approximately 114,071 patient-years of exposure (post-marketing setting). Most opportunistic infections were nonserious and the majority of patients continued treatment with vedolizumab. Clostridium difficile was the most commonly reported infection, with an incidence rate of 0.5 per 100 patient-years (clinical trials). Tuberculosis was reported at 0.1 per 100 patient-years (clinical trials), with 7 events in the post-marketing setting. No tuberculosis-related deaths were reported in either setting. No cases of progressive multifocal leukoencephalopathy were reported. In 29 patients with a history of or concurrent hepatitis B/C infection in the post-marketing setting, no viral reactivation was observed.ConclusionsClinical trials and post-marketing data showed that the rate of serious opportunistic infections in patients receiving vedolizumab was low and most patients could continue vedolizumab treatment. The frequency of tuberculosis infection was also low and no hepatitis B/C viral reactivation was reported.
| S-EPMC6185254 | biostudies-literature
Project description:Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia, both as first-line therapy and after imatinib intolerance or resistance. While generally well tolerated, dasatinib has been associated with a higher risk for pleural effusions. Frequency, risk factors, and outcomes associated with pleural effusion were assessed in two phase 3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11 trials that evaluated patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia treated with dasatinib (including DASISION and 034/Dose-optimization). In this largest assessment of patients across the dasatinib clinical trial program (N=2712), pleural effusion developed in 6-9% of patients at risk annually in DASISION, and in 5-15% of patients at risk annually in 034/Dose-optimization. With a minimum follow up of 5 and 7 years, drug-related pleural effusion occurred in 28% of patients in DASISION and in 33% of patients in 034/Dose-optimization, respectively. A significant risk factor identified for developing pleural effusion by a multivariate analysis was age. We found that overall responses to dasatinib, progression-free survival, and overall survival were similar in patients who developed pleural effusion and in patients who did not. clinicaltrials.gov identifier 00481247; 00123474.
| S-EPMC6312029 | biostudies-literature
Project description:The relationship between lifetime physical activity and the risk of developing peripheral arterial disease (PAD) is not known.We studied 1381 patients referred for elective coronary angiography in a point prevalence analysis. PAD was defined as ankle-brachial index (ABI) <0.9 at the time or a history of revascularization of the lower extremities regardless of ABI measure. We used a validated physical activity questionnaire to retrospectively measure each patient's lifetime recreational activity (LRA). Multivariate and logistic regression analyses were used to assess the independent association of LRA to ABI and the presence of PAD.PAD was present in 19% (n = 258) of all subjects. Subjects reporting no regular LRA had greater diastolic blood pressure and were more likely to be female. They had lower average ABI, and a higher proportion had PAD (25.6%). In a regression model, including traditional risk factors and LRA, multivariate analysis showed that age (P < .001), female gender (P < .001), systolic blood pressure (P = .014), fasting glucose (P < .001), serum triglycerides (P = .02), and cumulative pack years (P < .001) were independent negative predictors of ABI, and LRA was a positive predictor of ABI (P < .001). History of sedentary lifestyle independently increased the odds ratio for PAD (odds ratio, 0.46; 95% confidence interval, 1.01-2.10) when assessed by logistic regression. Intriguingly, there is a correlation between physical activity and gender, such that women with low LRA are at greatest risk.Recalled LRA is positively correlated to ABI and associated with PAD. Whereas the mechanism for this effect is not clear, LRA may be a useful clinical screening tool for PAD risk, and strategies to increase adult recreational activity may reduce the burden of PAD later in life.
| S-EPMC3152670 | biostudies-literature
Project description:BACKGROUND: We investigated the association of process of care measures with adverse limb and systemic events in patients with peripheral arterial disease (PAD). METHODS: We conducted a retrospective cohort study of patients with PAD, as defined by an ankle-brachial index (ABI) <0.9. The index date was defined as the date, during 1995 to 1998, when the patient was seen in the Michael E. DeBakey VA Medical Center noninvasive vascular laboratory and found to have PAD. We conducted a chart review for process of care variables starting 3 years before the index date and ending at the time of the first event or the final visit (December 31, 2001), whichever occurred first. We examined the association between PAD process of care measures, including risk factor control, and prescribing of medication, with time of the patient's first major limb event or death. RESULTS: Of the 796 patients (mean age, 65 +/- 9.9 years), 230 (28.9% experienced an adverse limb event (136 lower-extremity bypass, 94 lower-extremity amputation), and 354 (44.5%) died. Of the patients who died, 247 died without a preceding limb event. Glucose control was protective against death or a limb event with a hazard ratio (HR) of 0.74 (95% confidence limits [CL] 0.60, 0.91, P = 0.004). African Americans were at 2.8 (95% CL 1.7, 4.5) times the risk of Whites or Hispanics for an adverse limb event. However, this risk was no longer significant if their glucose was controlled. For process measures, the dispensing of PAD specific medication (HR 1.4, 95% CL 1.1, 1.7) was associated an increased risk for an adverse outcome. CONCLUSIONS: Our data suggest that glucose control is key to reducing the risk for adverse outcomes, particularly limb events in African Americans. Certain process of care measures, as markers of disease severity and disease management, are associated with poor outcomes in patients with PAD. Further work is needed to determine the role of early disease intervention to reduce poor outcomes in patients with PAD.
| S-EPMC2219734 | biostudies-other
Project description:Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12 to 15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed. The presence of PAD predicts a 50% to 1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking approximately five times per week, at a significant intensity that requires frequent rest periods, are most significant. Preclinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, and mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. A synthesis is provided as to how these adaptations can develop in the context of our current state of knowledge and events known to be orchestrated by exercise. The benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a lifestyle pattern that includes enhanced physical activity prior to the advance of PAD limitations is the most desirable and beneficial.
| S-EPMC3767482 | biostudies-other
Project description:Peripheral arterial disease (PAD) is a clinical manifestation of extracoronary atherosclerosis. Despite sharing the same risk factors, only 20% to 30% of patients with coronary artery disease (CAD) develop PAD. Decline in the number of bone marrow-derived circulating progenitor cells (PCs) is thought to contribute to the pathogenesis of atherosclerosis. Whether specific changes in PCs differentiate patients with both PAD and CAD from those with CAD alone is unknown.Determine whether differences exist in PCs counts of CAD patients with and without known PAD.1497 patients (mean age: 65 years; 62% men) with known CAD were identified in the Emory Cardiovascular Biobank. Presence of PAD (n=308) was determined by history, review of medical records, or imaging and was classified as carotid (53%), lower extremity (41%), upper extremity (3%), and aortic disease (33%). Circulating PCs were enumerated by flow cytometry. Patients with CAD and PAD had significantly lower PC counts compared with those with only CAD. In multivariable analysis, a 50% decrease in cluster of differentiation 34 (CD34+) or CD34+/vascular endothelial growth factor receptor-2 (VEGFR2+) counts was associated with a 31% (P=0.032) and 183% (P=0.002) increase in the odds of having PAD, respectively. CD34+ and CD34+/VEGFR2+ counts significantly improved risk prediction metrics for prevalent PAD. Low CD34+/VEGFR2+ counts were associated with a 1.40-fold (95% confidence interval, 1.03-1.91) and a 1.64-fold (95% confidence interval, 1.07-2.50) increases in the risk of mortality and PAD-related events, respectively.PAD is associated with low CD34+ and CD34+/VEGFR2+ PC counts. Whether low PC counts are useful in screening for PAD needs to be investigated.
| S-EPMC4975640 | biostudies-literature
Project description:Peripheral arterial disease (PAD) is characterized by myofiber degeneration and loss of function in muscles of the lower limbs. Human enterovirus (HEV) infection has been implicated in the pathogenesis of a number of muscle diseases. However, its association with PAD has not been studied. In this study, we tested the hypothesis that infectious HEV is present in skeletal muscle of patients with PAD and is associated with severity of disease.Gastrocnemius biopsies from 37 patients with PAD and 14 controls were examined for the presence of HEV RNA, viral capsid protein, viral RNA copy number, and viral infectivity. HEV RNA was detected in 54% of the biopsies from patients with PAD but was not detected in muscle biopsies from control patients. This difference in prevalence among PAD and control patients was significant at P<0.001. Viral RNA copy numbers were increased significantly at the later stages of disease; Fontaine Stage IV (10(5.50) copies/mg muscle wet weight, at P<0.005) and Stage III (10(4.87) copies/mg, at P<0.010) compared to Stage II (10(2.50) copies/mg). Viral replication was confirmed by the presence of the negative-strand of viral RNA in all specimens positive for HEV RNA. Cultures of HeLa and human skeletal muscle cells treated with muscle homogenates showed HEV replication and the presence of HEV capsid protein.Our data identified infectious HEV in the gastrocnemius of PAD patients but not in controls. Viral copy number and prevalence of infection were higher in the later stages of disease. Our data point to the need for further studies to determine the contribution of HEV infection to the pathophysiology of PAD.
| S-EPMC3828788 | biostudies-literature