Ven, L.L.M. van de

Influence of order and type of drug (bisoprolol vs. enalapril) on outcome and adverse events in patients with chronic heart failure: A post hoc analysis of the CIBIS-III trial (Article)

2011-07-01T00:00:00Z

AimsAngiotensin-converting enzyme inhibitors (ACE-Is) and beta-blockers are associated with improved outcome in patients with chronic heart failure (CHF). In this post hoc analysis of the CIBIS III trial, we examined the influence of the order of drug administration on clinical events and achieved dose. We also assessed the relations between dose levels and baseline variables or adverse events.Methods and resultsIn the CIBIS III trial, 1010 patients (mean age: 72.4 years; mean ejection fraction: 28.8; male: 68.2) with stable CHF were randomized to up-titration of monotherapy with either bisoprolol (target dose 10 mg o.d.) or enalapril (target dose 10 mg b.i.d.) for 6 months, followed by their combination for 624 months. Endpoints were mortality or all-cause hospitalization, mortality alone and mortality or cardiovascular hospitalization.The study drug (ACE-I or beta-blocker) was last prescribed at <50 of target dose to significantly more patients for the first initiated drug in both treatment groups (both P< 0.001). Sixty per cent of endpoints were reached during the monotherapy phase and randomized treatment during monotherapy was not a predictor of the three assessed outcomes. Monotherapy phase was the strongest independent predictor of outcome (P< 0.0001 for all endpoints). Older age, NYHA class III, impaired renal function, lower body weight and blood pressure at baseline, and hypotension, bradycardia and heart failure during treatment were associated with the inability to reach high dose of both study drugs.ConclusionThe order of drug administration plays an important role in whether CHF patients reach target doses of bisoprolol and enalapril. For both study drugs, the dose level reached was associated with baseline characteristics and adverse events. In CHF patients not treated with an ACE-I or a beta-blocker, the duration of monotherapy with either type of drug should be shorter than 6 months.

Prevalence and pharmacological treatment of left-ventricular dysfunction in patients undergoing vascular surgery (Article)

2010-03-01T00:00:00Z

AimsThis study evaluated the prevalence of left-ventricular (LV) dysfunction in vascular surgery patients and pharmacological treatment, according ESC guidelines.Methods and resultsEchocardiography was performed pre-operatively in 1005 consecutive patients. Left ventricular ejection fraction (LVEF) ≤50 defined systolic LV dysfunction. Diastolic LV dysfunction was diagnosed based on E/A-ratio, pulmonary vein flow, and deceleration time. Optimal pharmacological treatment to improve LV function was considered as: (i) angiotensin-blocking agent (ACE-I/ARB) in patients with LVEF ≤40; (ii) ACE-I/ARB and-blocker in patients with LVEF ≤40 + heart failure symptoms or previous myocardial infarction; and (iii) a diuretic in patients with symptomatic heart failure, regardless of LVEF. Left-ventricular dysfunction was present in 506 patients (50), of whom 209 (41) had asymptomatic diastolic LV dysfunction, 194 (39) had asymptomatic systolic LV dysfunction, and 103 (20) had symptomatic heart failure. Treatment with ACE-I/ARB and/or-blocker could be initiated/improved in 67 (34) of the 199 patients with (a)symptomatic LVEF ≤40. A diuretic could be initiated in 32 patients (31) with symptomatic heart failure (regardless of LVEF).ConclusionsThis study demonstrates a high prevalence of LV dysfunction in vascular surgery patients and under-utilization of ESC recommended pharmacological treatment. Standard pre-operative evaluation of LV function could be argued based on our results to reduce this observed care gap.

Impact of Prophylactic β-Blocker Therapy to Prevent Stroke After Noncardiac Surgery (Article)

2010-01-01T00:00:00Z

β Blockers are widely used to improve the postoperative cardiac outcome in patients with coronary artery disease scheduled for noncardiac surgery. However, recently serious concerns regarding the safety of perioperative β blockers have emerged. To assess the incidence, risk factors, and β-blocker use associated with postoperative stroke in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) trials, we evaluated all 3,884 patients of the DECREASE trials for postoperative stroke. All cardiac risk factors and medication use were assessed. The incidence of stroke within 30 days after surgery was recorded. The incidence of postoperative stroke in the DECREASE trials was 0.46% (18 of 3,884). For the β-blocker users, the incidence was 0.5%. All the strokes had an ischemic origin. A history of stroke was associated with a greater incidence of postoperative stroke (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.2 to 11.6). Statins and anticoagulants were not associated with postoperative stroke (OR 0.85, 95% CI 0.3 to 2.4; and OR 1.27, 95% CI 0.4 to 4.6, respectively). No association with bisoprolol therapy was found (OR 1.16, 95% CI 0.4 to 3.4). In conclusion, with a low-dose bisoprolol regimen started ≥30 days before surgery, no association was observed between β-blocker use and postoperative stroke.

Perioperative strokes and β-blockade (Article)

2009-11-01T00:00:00Z

Bisoprolol reduces cardiac death and myocardial infarction in high-risk patients as long as 2 years after successful major vascular surgery. (Article)

2001-08-22T00:00:00Z

AIM: To assess the long-term cardioprotective effect of bisoprolol in a randomized high-risk population after successful major vascular surgery. High-risk patients were defined by the presence of one or more cardiac risk factor(s) and a dobutamine echocardiography test positive for ischaemia. METHODS: 1351 patients were screened prior to surgery, 846 patients had one or more risk factor(s), and 173 of these patients also had ischaemia during dobutamine echocardiography. One hundred and twelve patients could be randomized for additional bisoprolol therapy or standard care. Eleven patients died in the peri-operative period (up to 1 month after surgery). Randomized patients continued bisoprolol or standard care after surgery. During follow-up of 101 survivors (median 22 months, range 11-30) cardiac death or myocardial infarction was noted. No patient was lost during follow-up.Results The incidence of cardiac events during follow-up in the bisoprolol group was 12% vs 32% in the standard care group (P=0.025). Cardiac death occurred in 15 patients, nine patients in the standard care and in six in the bisoprolol group; myocardial infarction occurred in six patients, five in the standard care and one in the bisoprolol group. The odds ratio for cardiac death or myocardial infarction after surgery in high-risk patients with additional bisoprolol therapy was 0.30 (0.11-0.83). CONCLUSIONS: Bisoprolol significantly reduced long-term cardiac death and myocardial infarction in high-risk patients after successful major cardiac vascular surgery.

Predictors of cardiac events after major vascular surgery: Role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy (Article)

2001-01-01T00:00:00Z

CONTEXT: Patients who undergo major vascular surgery are at increased risk of perioperative cardiac complications. High-risk patients can be identified by clinical factors and noninvasive cardiac testing, such as dobutamine stress echocardiography (DSE); however, such noninvasive imaging techniques carry significant disadvantages. A recent study found that perioperative beta-blocker therapy reduces complication rates in high-risk individuals. OBJECTIVE: To examine the relationship of clinical characteristics, DSE results, beta-blocker therapy, and cardiac events in patients undergoing major vascular surgery. DESIGN AND SETTING: Cohort study conducted in 1996-1999 in the following 8 centers: Erasmus Medical Centre and Sint Clara Ziekenhuis, Rotterdam, Twee Steden Ziekenhuis, Tilburg, Academisch Ziekenhuis Utrecht, Utrecht, and Medisch Centrum Alkmaar, Alkmaar, the Netherlands; Ziekenhuis Middelheim, Antwerp, Belgium; and San Gerardo Hospital, Monza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy. PATIENTS: A total of 1351 consecutive patients scheduled for major vascular surgery; DSE was performed in 1097 patients (81%), and 360 (27%) received beta-blocker therapy. MAIN OUTCOME MEASURE: Cardiac death or nonfatal myocardial infarction within 30 days after surgery, compared by clinical characteristics, DSE results, and beta-blocker use. RESULTS: Forty-five patients (3.3%) had perioperative cardiac death or nonfatal myocardial infarction. In multivariable analysis, important clinical determinants of adverse outcome were age 70 years or older; current or prior angina pectoris; and prior myocardial infarction, heart failure, or cerebrovascular accident. Eighty-three percent of patients had less than 3 clinical risk factors. Among this subgroup, patients receiving beta-blockers had a lower risk of cardiac complications (0.8% [2/263]) than those not receiving beta-blockers (2.3% [20/855]), and DSE had minimal additional prognostic value. In patients with 3 or more risk factors (17%), DSE provided additional prognostic information, for patients without stress-induced ischemia had much lower risk of events than those with stress-induced ischemia (among those receiving beta-blockers, 2.0% [1/50] vs 10.6% [5/47]). Moreover, patients with limited stress-induced ischemia (1-4 segments) experienced fewer cardiac events (2.8% [1/36]) than those with more extensive ischemia (>/=5 segments, 36% [4/11]). CONCLUSION: The additional predictive value of DSE is limited in clinically low-risk patients receiving beta-blockers. In clinical practice, DSE may be avoided in a large number of patients who can proceed safely for surgery without delay. In clinically intermediate- and high-risk patients receiving beta-blockers, DSE may help identify those in whom surgery can still be performed and those in whom cardiac revascularization should be considered.

The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography Study Group (Article)

1999-01-01T00:00:00Z

BACKGROUND: Cardiovascular complications are the most important causes of perioperative morbidity and mortality among patients undergoing major vascular surgery. METHODS: We performed a randomized, multicenter trial to assess the effect of perioperative blockade of beta-adrenergic receptors on the incidence of death from cardiac causes and nonfatal myocardial infarction within 30 days after major vascular surgery in patients at high risk for these events. High-risk patients were identified by the presence of both clinical risk factors and positive results on dobutamine echocardiography. Eligible patients were randomly assigned to receive standard perioperative care or standard care plus perioperative beta-blockade with bisoprolol. RESULTS: A total of 1351 patients were screened, and 846 were found to have one or more cardiac risk factors. Of these 846 patients, 173 had positive results on dobutamine echocardiography. Fifty-nine patients were randomly assigned to receive bisoprolol, and 53 to receive standard care. Fifty-three patients were excluded from randomization because they were already taking a beta-blocker, and eight were excluded because they had extensive wall-motion abnormalities either at rest or during stress testing. Two patients in the bisoprolol group died of cardiac causes (3.4 percent), as compared with nine patients in the standard-care group (17 percent, P=0.02). Nonfatal myocardial infarction occurred in nine patients given standard care only (17 percent) and in none of those given standard care plus bisoprolol (P<0.001). Thus, the primary study end point of death from cardiac causes or nonfatal myocardial infarction occurred in 2 patients in the bisoprolol group (3.4 percent) and 18 patients in the standard-care group (34 percent, P<0.001). CONCLUSIONS: Bisoprolol reduces the perioperative incidence of death from cardiac causes and nonfatal myocardial infarction in high-risk patients who are undergoing major vascular surgery.