Risk Chart for Future Mortality and Ischaemic Events Following Peripheral Bypass Surgery.

OBJECTIVES: A prediction model to identify determinants and quantify the risk of future ischaemic events in patients with peripheral arterial disease (PAD) provides a personal risk profile to offer individualized patient care. A risk chart was derived and validated in patients who received infrainguinal bypass surgery. METHODS: The Bypass Oral anticoagulants or Aspirin Risk Chart (BOA-RC2) was based on a pre-defined subgroup of the Dutch BOA trial (N = 482), the derivation cohort. The primary outcome event for BOA-RC2 was the composite of all cause death, non-fatal myocardial infarction, or non-fatal ischaemic stroke during a 10 year follow up. Determinants and long-term risk were identified with multivariate Cox regression analyses. Validation of the BOA-RC2 was performed in the remaining patients of the complete BOA trial cohort (N = 2,650 - 482 = 2,168), the validation cohort. RESULTS: The primary outcome event occurred in 67% (321/454) of the derivation cohort and in 66% (1,371/2,083) of the validation cohort during a median follow up of 6.6 years. The BOA-RC2 included the following determinants: age, critical limb ischaemia, diabetes, and a prior vascular intervention. The performance of the BOA-RC2 was good with a Brier score of 0.19, an area under the curve of 0.73, and a Hosmer-Lemeshow statistic of p = .9. CONCLUSIONS: The BOA-RC2 proves to be fit for the prediction of mortality and major ischaemic events in patients after peripheral bypass surgery. The BOA-RC2 can be used to adequately inform the patient about his/her risk of future events in an illustrative manner and stress the necessity of preventative measures, such as lifestyle adjustments, screening for risk factors, and drug treatments. In the future, the BOA-RC2 may be of interest to identify patients at high risk of mortality and ischaemic events for clinical research on new therapeutic options.

Medical treatment after peripheral bypass surgery over the past decade.

OBJECTIVE: The Dutch Bypass and Oral anticoagulants or Aspirin (BOA) Study demonstrated that in patients with peripheral arterial disease after bypass surgery oral anticoagulants were more effective in preventing venous graft occlusions than aspirin, while aspirin was more effective in non-venous grafts. We evaluated if this finding was implemented in the clinical practice of former BOA participants by reconstructing a 10-year overview of their applied various drug treatments including anti-hypertensive and lipid-lowering drugs. METHODS: In 482 patients from six centers that contributed most patients anti-thrombotic, anti-hypertensive, and lipid-lowering drug use was recorded at baseline (n = 478), retrospectively up to two years after BOA (n = 388), and prospectively for patients still alive between 2005 and 2009 (n = 209). RESULTS: At baseline, 54% of patients received anti-thrombotics which increased to 96% at follow-up. At baseline 15% of patients were treated with lipid-lowering drugs and 49% with anti-hypertensives. This increased over time to 65% and 76%, respectively. CONCLUSION: After the BOA Study its recommendations were applied marginally. Despite improvements over time, current lipid-lowering and anti-hypertensive drug use remained suboptimal. Our trend analyses, however, should be interpreted with caution, because drug use and compliance in survivors might be better than average.

Outcome after occlusion of infrainguinal bypasses in the Dutch BOA Study: comparison of amputation rate in venous and prosthetic grafts.

OBJECTIVE: To compare the consequences of occlusion of infrainguinal venous and prosthetic grafts. METHODS: In total, 2690 patients were included in the Dutch BOA study, a multicenter randomised trial that compared the effectiveness of oral anticoagulants with aspirin in the prevention of infrainguinal bypass graft occlusion. Two thousand four hundred and four patients received a femoropopliteal or femorodistal bypass with a venous (64%) or prosthetic (36%) graft. The incidence of occlusion and amputation was calculated according to graft material and the incidence of amputation after occlusion was compared with Cox regression to adjust for differences in prognostic factors. RESULTS: The indication for operation was claudication in 51%, rest pain in 20% and tissue loss in 28% of patients. The mean follow up was 21 months. After venous bypass grafting 171 (15%) femoropopliteal and 96 (24%) femorodistal grafts occluded. After prosthetic bypass grafting 234 (30%) femoropopliteal and 25 (38%) femorodistal grafts occluded. Patients with occlusions in the venous group had more severe ischemia, less runoff vessels and were older than the patients with prosthetic grafts. In the venous occlusion group 54 (20%) amputations were performed compared to 42 (16%) in the prosthetic occlusion group; crude hazard ratio 1.17 (95% CI 0.78-1.75). After adjustment for above mentioned differences in patient characteristics the hazard ratio was 0.86 (95% CI 0.56-1.32). CONCLUSION: The need for amputation after occlusion is not influenced by graft material in infrainguinal bypass surgery.

Risk of major haemorrhage in patients after infrainguinal venous bypass surgery: therapeutic consequences? The Dutch BOA (Bypass Oral Anticoagulants or Aspirin) Study.

OBJECTIVES: The beneficial effect of oral anticoagulants after infrainguinal venous bypass surgery is compromised by bleeding complications. We developed a model to identify patients, treated with anticoagulation, at risk of major haemorrhage and estimated whether this complication could have been prevented if patients had received aspirin. DESIGN: Randomised clinical trial. METHODS: Data of patients who participated in the Dutch Bypass Oral Anticoagulation or Aspirin Study were reanalysed using Cox regression. After infrainguinal bypass surgery these patients were randomised to oral anticoagulants (n = 1326) or aspirin (n = 1324). RESULTS: Predictors of major haemorrhage for patients on oral anticoagulants were increased systolic blood pressure (> or = 140 mmHg, hazard ratio [HR] 1.62), age > or = 75 years (HR 2.77) and diabetes mellitus (HR 1.60). If the 345 patients in the highest risk quartile had received aspirin, major haemorrhages would have been reduced from 46 to 22, with no major changes in ischemic events and graft occlusions. In the subgroup with venous bypasses major haemorrhages would have been reduced from 27 to 13, at the cost of seven more ischemic events (mostly fatal) and 17 more graft occlusions. CONCLUSIONS: Treating patients at highest risk of major haemorrhage with aspirin instead of oral anticoagulants would have resulted in a reduction of non-fatal haemorrhages, but for venous bypasses this reduction was outweighed by an increase in ischemic events and graft occlusions. We still recommend treatment with oral anticoagulants after peripheral venous bypass surgery.

The influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery in the Dutch BOA Study.

OBJECTIVE: Hyperhomocysteinemia has been identified as a risk factor for (cardio)vascular disease. Whether hyperhomocysteinemia contributes to graft failure after peripheral bypass surgery remains unclear. The present study evaluated the influence of hyperhomocysteinemia on graft patency after infrainguinal bypass surgery. DESIGN: The present study was designed as a nested case-control study. METHOD: In this study (nested in the Dutch Bypass Oral anticoagulants or Aspirin Study), 150 patients with graft occlusion were each matched with two randomly selected controls with patent grafts (N = 299) from the same trial. Venous blood samples were drawn from cases and controls, and total plasma homocysteine (tHcy) was determined. Mean serum homocysteine levels and the presence of hyperhomocysteinemia (>95th percentile in healthy individuals) were compared between cases and controls. RESULTS: No significant differences were found between serum levels of homocysteine in patients with and without graft occlusion. The mean plasma homocysteine levels were 14.4 micromol/L and 14.9 micromol/L in the case and control groups, respectively. The resulting mean difference was -0.4 (95% confidence interval [CI], -1.8-0.9). The odds ratio of hyperhomocysteinemia was 0.81 (95% CI, 0.49-1.33). Adjustment for risk factors of graft occlusion did not change these results. CONCLUSIONS: Postoperative raised serum levels of homocysteine proved not to be a risk factor for graft occlusion after infrainguinal bypass grafting.