Olaf Schouten

Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV).

Objective:This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate-risk patients undergoing noncardiovascular surgery. Summary Background Data:Beta-blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. Methods:In this randomized open-label 2 × 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. Results:Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17–0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35–1.10), but statistical significance was not reached (P = 0.17). Conclusion:Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome.

High-Dose β-Blockers and Tight Heart Rate Control Reduce Myocardial Ischemia and Troponin T Release in Vascular Surgery Patients

Background— Adverse perioperative cardiac events occur frequently despite the use of beta (&bgr;)-blockers. We examined whether higher doses of &bgr;-blockers and tight heart rate control were associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome. Methods and Results— In an observational cohort study, 272 vascular surgery patients were preoperatively screened for cardiac risk factors and &bgr;-blocker dose. Beta-blocker dose was converted to a percentage of maximum recommended therapeutic dose. Heart rate and ischemic episodes were recorded by continuous 12-lead electrocardiography, starting 1 day before to 2 days after surgery. Serial troponin T levels were measured after surgery. All-cause mortality was noted during follow-up. Myocardial ischemia was detected in 85 of 272 (31%) patients and troponin T release in 44 of 272 (16.2%). Long-term mortality occurred in 66 of 272 (24.2%) patients. In multivariate analysis, higher &bgr;-blocker doses (per 10% increase) were significantly associated with a lower incidence of myocardial ischemia (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.51 to 0.75), troponin T release (HR, 0.63; 95% CI, 0.49 to 0.80), and long-term mortality (HR, 0.86; 95% CI, 0.76 to 0.97). Higher heart rates during electrocardiographic monitoring (per 10-bpm increase) were significantly associated with an increased incidence of myocardial ischemia (HR, 2.49; 95% CI, 1.79 to 3.48), troponin T release (HR, 1.53; 95% CI, 1.16 to 2.03), and long-term mortality (HR, 1.42; 95% CI, 1.14 to 1.76). Conclusion— This study showed that higher doses of &bgr;-blockers and tight heart rate control are associated with reduced perioperative myocardial ischemia and troponin T release and improved long-term outcome in vascular surgery patients.

Long-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Postoperative Mortality in The Netherlands A Population-based Analysis of Surgery-specific Risk in Adults

Background:Few data are available that systematically describe rates and trends of postoperative mortality for fairly large, unselected patient populations. Methods:This population-based study uses a registry of 3.7 million surgical procedures in 102 hospitals in The Netherlands during 1991–2005. Patients older than 20 yr who underwent an elective, nonday case, open surgical procedure were enrolled. Patient data included main (discharge) diagnosis, secondary diagnoses, dates of admission and discharge, death during admission, operations, age, sex, and a limited number of comorbidities classified according to the International Classification of Diseases 9th revision Clinical Modification. The main outcome measure was postoperative all-cause mortality. Univariable and multivariable logistic regression analyses were applied to evaluate the relationship between type of surgery and the main outcome. Results:Postoperative all-cause death was observed in 67,879 patients (1.85%). In a model based on a classification into 11 main surgical categories, breast surgery was associated with lowest mortality (adjusted incidence, 0.07%), and vascular surgery was associated with highest mortality (adjusted incidence, 5.97%). In a model based on 36 surgical subcategories, the adjusted mortality ranged from 0.07% for hernia nuclei pulposus surgery to 18.5% for liver transplant. The c-index of the 36-category model was 0.88, which was significantly (P < 0.001) higher than the c-index that was associated with the simple surgical classification (low vs. high risk) in the commonly used Revised Cardiac Risk Index (c-index, 0.83). Conclusions:This population-based study provided a detailed and contemporary overview of postoperative mortality for the entire surgical spectrum, which may act as reference standard for surgical outcome in Western populations.

Impact of Cardioselective β-Blockers on Mortality in Patients with Chronic Obstructive Pulmonary Disease and Atherosclerosis

RATIONALE beta-Blocker use is associated with improved health outcomes in patients with cardiovascular disease. There is a general reluctance to prescribe beta-blockers in patients with chronic obstructive pulmonary disease (COPD) because they may worsen symptoms. OBJECTIVES We investigated the relationship between cardioselective beta-blockers and mortality in patients with COPD undergoing major vascular surgery. METHODS We evaluated 3,371 consecutive patients who underwent major vascular surgery at one academic institution between 1990 and 2006. The patients were divided into those with and without COPD on the basis of symptoms and spirometry. The major endpoints were 30-day and long-term mortality after vascular surgery. Patients were defined as receiving low-dose therapy if the dosage was less than 25% of the maximum recommended therapeutic dose; dosages higher than this were defined as intensified dose. MEASUREMENTS AND MAIN RESULTS There were 1,205 (39%) patients with COPD of whom 462 (37%) received cardioselective beta-blocking agents. beta-Blocker use was associated independently with lower 30-day (odds ratio, 0.37; 95% confidence interval, 0.19-0.72) and long-term mortality in patients with COPD (hazards ratio, 0.73; 95% confidence interval, 0.60-0.88). Intensified dose was associated with both reduced 30-day and long-term mortality in patients with COPD, whereas low dose was not. CONCLUSIONS Cardioselective beta-blockers were associated with reduced mortality in patients with COPD undergoing vascular surgery. In carefully selected patients with COPD, the use of cardioselective beta-blockers appears to be safe and associated with reduced mortality.

Timing of Noncardiac Surgery After Coronary Artery Stenting With Bare Metal or Drug-Eluting Stents

The current guidelines have recommended postponing noncardiac surgery (NCS) for > or =6 weeks after bare metal stent (BMS) placement and for > or =1 year after drug-eluting stent (DES) placement. However, much debate has ensued about these intervals. The aim of the present study was to assess the influence of different intervals between stenting and NCS and the use of dual antiplatelet therapy on the occurrence of perioperative major adverse cardiac events (MACEs). We identified 550 patients (376 with a DES and 174 with a BMS) by cross-matching the Erasmus Medical Center percutaneous coronary intervention (PCI) database with the NCS database. The following intervals between PCI-BMS (<30 days, <3 months, and >3 months) or PCI-DES (<30 days, <3 months, 3 to 6 months, 6 to 12 months, and >12 months) and NCS were studied. MACEs included death, myocardial infarction, and repeated revascularization. In the PCI-BMS group, the rate of MACEs during the intervals of <30 days, 30 days to 3 months, and >3 months was 50%, 14%, and 4%, respectively (overall p <0.001). In the PCI-DES group, the rate of MACE changed significantly with the interval after PCI (35%, 13%, 15%, 6%, and 9% for patients undergoing NCS <30 days, 30 days to 3 months, 3 to 6 months, 6 to 12 months, and >12 months, respectively, overall p <0.001). Of the patients who experienced a MACE, 45% and 55% were receiving single and dual antiplatelet therapy at NCS, respectively (p = 0.92). The risk of severe bleeding in patients with single and dual therapy at NCS was 4% and 21%, respectively (p <0.001). In conclusion, we found an inverse relation between the interval from PCI to NCS and perioperative MACEs. Continuation of dual antiplatelet therapy until NCS did not provide complete protection against MACEs.

Clinical ResearchPeripheral Vascular DiseaseLong-Term Prognosis of Patients With Peripheral Arterial Disease: A Comparison in Patients With Coronary Artery Disease

OBJECTIVES This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. BACKGROUND The PAD is considered to be a risk factor for adverse late outcome. METHODS A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. RESULTS The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. CONCLUSIONS Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death.

Prognostic implications of asymptomatic left ventricular dysfunction in patients undergoing vascular surgery.

Background:The prognostic value of heart failure symptoms on postoperative outcome is well acknowledged in perioperative guidelines. The prognostic value of asymptomatic left ventricular (LV) dysfunction remains unknown. This study evaluated the prognostic implications of asymptomatic LV dysfunction in vascular surgery patients assessed with routine echocardiography. Methods:Echocardiography was performed preoperatively in 1,005 consecutive vascular surgery patients. Systolic LV dysfunction was defined as LV ejection fraction less than 50%. Ratio of mitral-peak velocity during early and late filling, pulmonary vein flow, and deceleration time was used to diagnose diastolic LV dysfunction. Troponin-T measurements and electrocardiograms were performed routinely perioperatively. Multivariate regression analyses evaluated the relation between LV function and the study endpoints, 30-day cardiovascular events, and long-term cardiovascular mortality. Results:Left ventricular dysfunction was diagnosed in 506 (50%) patients of which 80% were asymptomatic. In open vascular surgery (n = 649), both asymptomatic systolic and isolated diastolic LV dysfunctions were associated with 30-day cardiovascular events (odds ratios 2.3, 95% confidence interval [CI] 1.4–3.6 and 1.8, 95% CI 1.1–2.9, respectively) and long-term cardiovascular mortality (hazard ratios 4.6, 95% CI 2.4–8.5 and 3.0, 95% CI 1.5–6.0, respectively). In endovascular surgery (n = 356), only symptomatic heart failure was associated with 30-day cardiovascular events (odds ratio 1.8, 95% CI 1.1–2.9) and long-term cardiovascular mortality (hazard ratio 10.3, 95% CI 5.4–19.3). Conclusions:This study demonstrated that asymptomatic LV dysfunction is predictive for 30-day and long-term cardiovascular outcome in open vascular surgery patients. These data suggest that preoperative risk stratification should include not only solely heart failure symptoms but also routine preoperative echocardiography to risk stratify open vascular surgery patients.

Plasma N-terminal pro-B-type natriuretic peptide as long-term prognostic marker after major vascular surgery

Objective: To assess the long-term prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) after major vascular surgery. Design: A single-centre prospective cohort study. Patients: 335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery. Interventions: Prior to surgery, baseline NT-proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress-induced myocardial ischaemia. Main outcome measures: The prognostic value of NT-proBNP was evaluated for the endpoints all-cause mortality and major adverse cardiac events (MACE) during long-term follow-up. Results: In this patient cohort (mean age: 62 years, 76% male), median NT-proBNP level was 186 ng/l (interquartile range: 65–444 ng/l). During a mean follow-up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6-month mortality and MACE, NT-proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT-proBNP level of 319 ng/l was identified as the optimal cut-off value to predict 6-month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT-proBNP ⩾319 ng/l was associated with a hazard ratio of 4.0 for all-cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9). Conclusion: Preoperative NT-proBNP level is a strong predictor of long-term mortality and major adverse cardiac events after major non-cardiac vascular surgery.

Effect of Statin Therapy on Mortality in Patients With Peripheral Arterial Disease and Comparison of Those With Versus Without Associated Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD) are both inflammatory conditions. Statins are commonly used in patients with PAD and have anti-inflammatory properties, which may have beneficial effects in patients with COPD. The relation between statin use and mortality was investigated in patients with PAD with and without COPD. From 1990 to 2006, we studied 3,371 vascular surgery patients. Statin use was noted at baseline and, if prescribed, converted to <25% (low dose) and > or =25% (intensified dose) of the maximum recommended therapeutic dose. The diagnosis of COPD was based on the Global Initiative for Chronic Obstructive Lung Disease guidelines using pulmonary function test. End points were short- (30-day) and long-term (10-year) mortality. A total of 330 patients with COPD (25%) used statins, and 480 patients (23%) without COPD. Statin use was independently associated with improved short- and long-term survival in patients with COPD (odds ratio 0.48, 95% confidence interval [CI] 0.23 to 1.00; hazard ratio 0.67, 95% CI 0.52 to 0.86, respectively). In patients without COPD, statins were also associated with improved short- and long-term survival (odds ratio 0.42, 95% CI 0.20 to 0.87; hazard ratio 0.76, 95% CI 0.60 to 0.95, respectively). In patients with COPD, only an intensified dose of statins was associated with improved short-term survival. However, for the long term, both low-dose and intensive statin therapy were beneficial. In conclusion, statin use was associated with improved short- and long-term survival in patients with PAD with and without COPD. Patients with COPD should be treated with an intensified dose of statins to achieve an optimal effect on both the short and long term.