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.

Oral anticoagulation in atrial fibrillation: A pan-European patient survey.

BACKGROUND: Anticoagulation with vitamin K antagonists (VKAs) provides effective stroke prophylaxis in patients with atrial fibrillation (AF). Optimisation of such therapy requires frequent monitoring, dose adjustments and stringent lifestyle restrictions. We conducted a large multinational survey in patients with chronic AF to gain insights into their perceptions and understanding of VKA use. METHODS: Eligible patients were adults with AF who had been prescribed VKAs for at least 1 year. A total of 711 patient interviews were conducted in seven European countries during June and July 2004. RESULTS: The majority of patients (58% male; mean age 68 years) claimed to understand their treatment programme; despite this, only 7% knew that VKA use is aimed at preventing strokes and 24% stated that they would have liked more information. Patients attended an average of 14 monitoring sessions in the previous year; however, 21% missed appointments, especially younger patients (<65 years). The International Normalized Ratio (INR) was within the target range in most or all of the last five to ten visits in 64% of patients; nonetheless, 38% were not aware that an INR outside the target range is associated with health risks. On average, patients required dose adjustments every four sessions. VKA treatment impacted 67% of patients in terms of diet, socialising, career and independence, especially younger patients (74%). CONCLUSIONS: Monitoring, dose adjustments and lifestyle restrictions to optimise the intensity of anticoagulation with VKAs are problematic for patients with AF, and their knowledge of the consequences of such therapy is often poor.

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.

Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs.

BACKGROUND: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. AIM: To describe patient adherence to prophylactically prescribed PPIs and H2RAs in the clinical setting. METHODS: We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H2RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. RESULTS: The study cohort comprised 784 patients: 374 with H2RAs, 405 with PPIs, and 5 with both PPI and H2RA. Eighty-five percent of H2RA users and 7% of PPI users were prescribed these drugs at doses below the minimum recommended/effective dose for NSAID-associated gastroduodenal ulcer prophylaxis. Thirty-seven percent of patients were non-adherent. The lowest rate of non-adherence was associated with the first NSAID prescription (9%), increasing to 61% for patients with >/= 3 prescriptions. In a cohort of subjects who stopped their NSAID and were followed for up to 2 years (n = 711), there was significant persistent use of acid suppressive agents; 40% of patients had at least one additional prescription for the acid suppressive agent after stopping NSAIDs, and> 30% received enough drug to cover a period longer than 2 months after stopping their NSAID. CONCLUSIONS: The pattern of PPI and H2RA prescriptions, when prescribed as prophylactic strategy, does not correspond with the pattern of NSAID use. Physicians should consider the medical impact of non-adherence with dual therapies and the impact of prolonged use of GPAs on treatment cost.

Underutilization of preventive strategies in patients receiving NSAIDs.

BACKGROUND: Multiple treatment guidelines for non-steroidal anti-inflammatory drugs (NSAIDs) suggest that patients with one or more risk factors for NSAID-associated upper gastrointestinal (UGI) ulcer complications should be prescribed preventive strategies such as acid-suppressive drugs, misoprostol or cyclooxygenase (COX)-2-specific inhibitors to reduce their risk of serious ulcer complications. The purpose of the present study was to evaluate the extent to which new NSAID users receive recommended preventive strategies and to assess the association between risk factors and a prescription of acid suppressive drugs or misoprostol. METHOD: A retrospective observational cohort study was conducted using the Integrated Primary Care Information (IPCI) database, a longitudinal database of electronic general practitioner patient records in The Netherlands. The study population comprised all new NSAID users, defined as users of non-specific NSAIDs, COX-2-preferential NSAIDs and COX-2-specific inhibitors, during the period from January 1996 to April 2002. Subjects were excluded if they had an H2-receptor antagonist (H2RA), proton pump inhibitor (PPI) or misoprostol prescription in the 3 months prior to the first NSAID prescription. Preventive use of acid-suppressive drugs or misoprostol was identified by the coprescription for these drugs on the same day (+/-2 days) as the NSAID prescription. The drug use for each patient was validated as having a preventive indication by reviewing the physician-recorded symptoms and diagnoses. Risk factors for UGI ulcer events were defined as age >65 yr, UGI history (gastroduodenal ulcer, UGI bleeding, dyspepsia) and concomitant medications (anticoagulants, aspirin, oral corticosteroids). The study population comprised 69 648 new NSAID users. RESULTS: Overall, 7.9% of NSAID users received a preventive strategy (6.6% received a gastroprotective agent and an additional 1.3% received COX-2-specific inhibitors). Patients using preventive drugs had higher odds of having one or more UGI risk factors than patients without preventive drugs [adjusted odds ratio (OR) 1.78, 95% confidence interval 1.66-1.92]. Despite the greater rate of preventive drug prescriptions in patients who may have been at higher risk, 86.6% of patients with one risk factor and 81.2% with two or more risk factors received no preventive strategies. In contrast to non-specific NSAIDs, patients who received a prescription for a COX-2-specific inhibitor had significantly lower adjusted odds (OR = 0.22) of having H2RA/PPI or misoprostol coprescribed. CONCLUSIONS: Although patients who are treated with preventive strategies have higher odds of having gastrointestinal risk factors than those not prescribed preventive therapies, the majority (>80%) of patients with one or more gastrointestinal risk factors do not receive the recommended NSAID treatment regimen of a COX-2-specific inhibitor or NSAID + H2RA/PPI or misoprostol and are therefore undertreated.

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.