Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE) Follow-up.

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however, longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardial infarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore, we describe the longer-term outcomes, procedures, and medication use in Global Registry of Acute Coronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performance of the discharge GRACE risk score in predicting 2-year mortality. METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome were enrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronary syndrome diagnosis in 57 sites. RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge, 14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery, and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), beta-blocker (80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heart failure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE risk score was highly predictive of all-cause mortality at 2 years (c-statistic 0.80). CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were important later adverse consequences, including frequent morbidity and mortality. These findings were seen in the context of additional coronary procedures and despite continued use of evidence-based therapies in a high proportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors for predicting longer-term mortality was maintained.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE)Follow-up

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however,longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardialinfarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore,we describe the longer-term outcomes, procedures, and medication use in Global Registry of AcuteCoronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performanceof the discharge GRACE risk score in predicting 2-year mortality.METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome wereenrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronarysyndrome diagnosis in 57 sites.RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge,14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery,and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), betablocker(80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heartfailure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE riskscore was highly predictive of all-cause mortality at 2 years (c-statistic 0.80).CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were importantlater adverse consequences, including frequent morbidity and mortality. These findings were seen in thecontext of additional coronary procedures and despite continued use of evidence-based therapies in a highproportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors forpredicting longer-term mortality was maintained.

Late Consequences of Acute Coronary Syndromes: Global Registry of Acute Coronary Events (GRACE)Follow-up

PURPOSE: Short-term outcomes have been well characterized in acute coronary syndromes; however,longer-term follow-up for the entire spectrum of these patients, including ST-segment-elevation myocardialinfarction, non-ST-segment-elevation myocardial infarction, and unstable angina, is more limited. Therefore,we describe the longer-term outcomes, procedures, and medication use in Global Registry of AcuteCoronary Events (GRACE) hospital survivors undergoing 6-month and 2-year follow-up, and the performanceof the discharge GRACE risk score in predicting 2-year mortality.METHODS: Between 1999 and 2007, 70,395 patients with a suspected acute coronary syndrome wereenrolled. In 2004, 2-year prospective follow-up was undertaken in those with a discharge acute coronarysyndrome diagnosis in 57 sites.RESULTS: From 2004 to 2007, 19,122 (87.2%) patients underwent follow-up; by 2 years postdischarge,14.3% underwent angiography, 8.7% percutaneous coronary intervention, 2.0% coronary bypass surgery,and 24.2% were re-hospitalized. In patients with 2-year follow-up, acetylsalicylic acid (88.7%), betablocker(80.4%), renin-angiotensin system inhibitor (69.8%), and statin (80.2%) therapy was used. Heartfailure occurred in 6.3%, (re)infarction in 4.4%, and death in 7.1%. Discharge-to-6-month GRACE riskscore was highly predictive of all-cause mortality at 2 years (c-statistic 0.80).CONCLUSION: In this large multinational cohort of acute coronary syndrome patients, there were importantlater adverse consequences, including frequent morbidity and mortality. These findings were seen in thecontext of additional coronary procedures and despite continued use of evidence-based therapies in a highproportion of patients. The discriminative accuracy of the GRACE risk score in hospital survivors forpredicting longer-term mortality was maintained.

Prevalence and management of hypertension in acute coronary syndrome patients varies by sex: observations from the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) randomized clinical trials.

BACKGROUND: Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). METHODS: We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. RESULTS: In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. CONCLUSION: Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.

Medication performance measures and mortality following acute coronary syndromes.

PURPOSE: To identify patient and health care factors which are related to the use of medical treatments that comprise quality measures and to assess the relation of these measures with mortality. METHODS: The study sample consisted of 20 140 patients with acute coronary syndromes from the international GRACE registry. Multivariable logistic regression modeling was used to determine predictors of quality performance. Quality indicators were use of aspirin and beta-blockers within 24 hours and at hospital discharge, use of angiotensin-converting enzyme (ACE) inhibitors at discharge, and in-hospital mortality. RESULTS: Use of medications in eligible patients at discharge ranged from 73% for ACE inhibitors to 93% for aspirin. High-risk features (eg, heart failure, older age) were related to failure to use aspirin and beta-blockers. Being at a teaching hospital and care by a cardiologist were associated with better use of aspirin and beta-blockers. Coronary artery bypass surgery was associated with failure to use ACE inhibitors and aspirin. When hospitals were divided into quartiles of quality performance, adjusted in-hospital mortality was 4.1% in the top versus 5.6% in the bottom quartile, representing a 27% (95% confidence interval: 11% to 42%) lower relative mortality. CONCLUSION: Identification of factors associated with failure to use proven treatments, including high-risk groups that would derive particular benefit from effective therapies, provides an opportunity to focus quality improvement interventions. The association of lower hospital mortality with better use of selected medical treatments supports their measurement to improve quality of care.

Continuous haemodynamic monitoring during exercise in patients with pulmonary hypertension.

BACKGROUND: Right heart haemodynamic parameters can be recorded continuously with the help of an implanted haemodynamic monitor. Aim of the study was to assess the haemodynamic response with and without inhalation of iloprost during cardiopulmonary exercise testing (CPET) in patients with pulmonary hypertension. MATERIALS AND METHODS: Five female patients with documented pulmonary hypertension (mean +/- S.D. age 47 +/- 16 years, 4 arterial, 1 venous) previously implanted with a haemodynamic monitor underwent an incremental exercise test on 2 separate days. The tests were performed before and immediately after inhalation of a single dose of iloprost (17 microg). Parameters recorded by the device were right ventricular (RV)-afterload (RV systolic pressure, RVSP), RV-preload (RV diastolic pressure, RVDP), estimated pulmonary artery diastolic pressure (ePAD), heart rate (HR) and maximum positive rate of RV pressure development (RVdP/dt) (reflecting the dynamic and inotropic state of the RV). RESULTS: After inhalation of iloprost, RV systolic pressure was always reduced at rest. It was followed by an increase with higher workloads without any difference at VO(2peak). The time course of RV systolic pressure was not linear with a flattening at higher workload during the test. This behaviour was found irrespective of iloprost treatment. The remaining determinants of RV performance showed no relevant differences and a linear behaviour during the exercise test. CONCLUSIONS: Inhalation of aerosolised iloprost resulted in a reduction in right ventricular pressure at rest but not at maximal workload. The implantable haemodynamic monitor (IHM) may be useful for the evaluation of RV haemodynamics during exercise and in assessing treatment efficacy.

Hemodynamic observations in two pulmonary hypertensive patients changing treatment from inhaled iloprost to the oral endothelin-antagonist bosentan.

Two female patients with pulmonary arterial hypertension and a permanently implanted hemodynamic monitor changed treatment from inhaled iloprost to oral bosentan. The hemodynamic changes were seen very early after the first dose of bosentan and there was no need to re-establish inhaled iloprost.

Evaluation of the Coroflex Theca-Stent for reduction of restenosis (ECORI).

BACKGROUND: Various stent coatings have been shown to significantly reduce restenosis rates in comparison to non-coated devices. Therefore, the short- and mid-term performance of the new polyphosphazene-coated Coroflex Theca-Stent was investigated. METHODS: 103 patients [63.9 +/- 11 yrs, 5/103 (4.9%) lesion type A, 52/103 (50.5%) type B1, and 46 of 103 (44.6%) type B2] were enrolled for elective single stent deployment into de-novo coronary lesions (stenoses: greater than or equal to 70%, < 100%; reference diameter greater than or equal to 2.75 mm, less than or equal to 4 mm; lesion length: < 16 mm). RESULTS: Deployment and procedural success were 100%, in 57/103 (55.3%) patients without pre-dilatation. 3/103 (2.9%) patients were lost to follow-up. During the 7.1 +/- 2.3 months clinical follow-up, 3 of 100 (3.0%) patients underwent premature target lesion revascularizations, 4 /100 (4%) had non-target lesion-related deaths, and 1 of 100 (1%) suffered myocardial infarction. Among the 77 of 100 (77.0%) patients who underwent angiographic follow-up, the initial stenosis declined from 87.3 +/- 5.7% to 14.2 +/- 8.3% after stenting, and increased to 32.8 +/- 22.7% after 6.4 +/- 1.3 months. The late loss and late loss index were 0.6 +/- 0.7 mm and 0.2 +/- 0.4, respectively; the recurrence rate was 12 of 77 (15.6%), with reintervention required in 11 of 77 (14.3%) of these patients. CONCLUSION: The Coroflex Theca-Stent provides excellent procedural results and a low restenosis rate. Further development of this polymer as the final coating and as the basis for drug-eluting stents seems justified.

Clinical applications of cardiovascular magnetic resonance.

The clinical role of magnetic resonance in diseases of the heart and great vessels is rapidly evolving. Cardiovascular magnetic resonance (CMR) has become an established non-invasive imaging modality for the assessment of various cardiac disorders, such as congenital heart disease, cardiac masses, cardiomyopathies, aortic and pericardial diseases. Moreover, due to its accuracy and reproducibility, CMR is currently considered the gold standard for quantification of ventricular volumes, function, and mass. Thus, this technique is ideally suited to assess the efficacy of therapeutic interventions on ventricular hypertrophy and remodelling, which may allow a reduction in sample size to show clinically relevant effects. Comprehensive functional assessment is possible by CMR due to its capability to measure flow velocity and flow volume, which is a basic requirement to quantify lesion severity in valvular heart disease. Within the past years, major technical advances have considerably improved acquisition speed and image quality making CMR a useful tool for the evaluation of patients with ischaemic heart disease. Although the clinical robustness of coronary magnetic resonance angiography still needs improvement, CMR currently provides valuable information to detect reversible ischemia, myocardial infarction, and residual viability. In this review we will present in detail the well-established indications of CMR accompanied by an outlook on new applications that are likely to enter the clinical arena in the near future.

Austrian survey of treating heart failure--AUSTRIA.

BACKGROUND: Treatment of chronic heart failure is based on the results of large clinical trials, which form the basis of treatment guidelines, such as those from the European Society of Cardiology (ESC). The aim of this study was to record treatment-modalities and the implementation of guidelines of chronic heart failure in clinical practice in Austria. METHODS: Overall 96 general physicians, specialists for internal medicine in private practice or in hospital outpatient departments participated in the survey. Physicians were asked to prospectively document 30 consecutive patients with chronic heart failure. RESULTS: 1880 patients were documented. The majority of patients were treated by general physicians (57%). Coronary artery disease was the most frequent aetiology for heart failure (47%). The most frequently used drugs were blockers of the renin-angiotensin-system (RAS-blocker including ACE-inhibitors and angiotensin-receptor-blockers, 78%), diuretics (76%) and beta-blockers (49%). Other drugs like digitalis and spironolactone were used infrequently. Average doses of ACE-inhibitors were approximately 90% of those recommended by the ESC, average doses of beta-blockers were approximately 50% of those recommended. Treatment among the three classes of physicians differed with respect to RAS-blockers and beta-blockers, which were used infrequently by general practitioners. Both groups of drugs were given more frequently to younger patients (<70 years) while digitalis was given more often to elderly patients. CONCLUSIONS: Results from this survey suggest that Austrian physicians treating patients with heart failure use the appropriate drugs in dosages that are suggested by recently published guidelines (ACE-inhibitors and beta-blockers). However, dosages of spironolactone clearly differed from current recommendations.

Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events.

BACKGROUND: There are limited data describing the presenting characteristics, management, and outcomes of diabetic and nondiabetic patients with an acute coronary syndrome (ACS). OBJECTIVE: To examine differences in these factors, patients with ST-segment elevation acute myocardial infarction, non-ST-segment elevation acute myocardial infarction, and unstable angina were enrolled in a large multinational coronary disease registry. METHODS: The Global Registry of Acute Coronary Events is a prospective observational study of patients hospitalized with an ACS at 94 hospitals in 14 countries. The study sample consisted of 5403 patients with ST-segment elevation acute myocardial infarction, 4725 with non-ST-segment elevation acute myocardial infarction, and 5988 with unstable angina. RESULTS: Approximately 1 in 4 patients presented to participating hospitals with a history of diabetes. Patients with diabetes were older, more often women, with a greater prevalence of comorbidities, and they were less likely to be treated with effective cardiac therapies than nondiabetic patients. Patients with diabetes who developed an ACS were at increased risk for each hospital outcome examined including heart failure, renal failure, cardiogenic shock, and death. These differences remained after adjustment for potentially confounding prognostic factors. CONCLUSIONS: A considerable proportion of patients with an ACS has diabetes and is at increased risk for adverse outcomes compared with patients without diabetes. There are certain proven therapeutic strategies that remain underused in the diabetic population. A more widespread awareness of this increased risk and a more diligent use of proven cardiac treatment approaches are indicated for patients with diabetes who develop an ACS.

Different effects of exercise on plasma concentrations of nebivolol, bisoprolol and carvedilol.

BACKGROUND: In-vitro studies have shown that beta-blockers are taken up into and released from adrenergic cells together with epinephrine and norepinephrine. Consequently, studies in humans revealed an increase in plasma concentrations of propranolol and atenolol, whereas those of carvedilol were not affected by physical exercise. However, nebivolol and bisoprolol never were investigated on this issue. METHODS: Ten healthy males received oral doses of 5 mg nebivolol, 5 mg bisoprolol, and 50 mg carvedilol daily for one week in a cross-over fashion. Exercise was performed at 3 hours following oral intake of the respective last drugs on the eighth day. Blood samples were taken at rest, during the last minute of exercise, and after 15 min of recovery. RESULTS: At rest and during exercise, heart rates were as follows: Nebivolol, 57 +/- 7 and 137 +/- 11 beats/min; bisoprolol, 55 +/- 5 and 139 +/- 14 beats/min; carvedilol, 56 +/- 5 and 135 +/- 13 beats/min, with no significant differences between the drugs. Plasma concentrations were as follows: Nebivolol-rest 0.273 +/- 0.029 ng/ml, exercise 0.274 +/- 0.035 ng/ml, recovery 0.272 +/- 0.035 ng/ml (n.s.). Bisoprolol-rest 4.99 +/- 2.73 ng/ml, exercise 6.49 +/- 5.58 ng/ml, recovery 4.90 +/- 3.06 ng/ml ( p < 0.01). Carvedilol-rest 10.3 +/- 9.3 ng/ml, exercise 9.7 +/- 8.2 ng/ml, recovery 6.5 +/- 5.6 ng/ml ( p < 0.05). DISCUSSION: Plasma concentrations of bisoprolol increased during exercise and returned to baseline during recovery, a behaviour which would have been predicted according to present knowledge. However, exercise had no effect on plasma concentrations of nebivolol and carvedilol, a finding that is in contrast to previous results with other beta-blockers such as propranolol and atenolol. We conclude that both nebivolol and carvedilol are not taken up into and released from adrenergic nerves during exercise, a feature that clearly distinguishes these drugs from other beta-blockers so far investigated.

Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.

BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.

Determinants and prognostic impact of heart failure complicating acute coronary syndromes: observations from the Global Registry of Acute Coronary Events (GRACE).

BACKGROUND: Few data are available on the impact of heart failure (HF) across all types of acute coronary syndromes (ACS). METHODS AND RESULTS: The Global Registry of Acute Coronary Events (GRACE) is a prospective study of patients hospitalized with ACS. Data from 16 166 patients were analyzed: 13 707 patients without prior HF or cardiogenic shock at presentation were identified. Of these, 1778 (13%) had an admission diagnosis of HF (Killip class II or III). HF on admission was associated with a marked increase in mortality rates during hospitalization (12.0% versus 2.9% [with versus without HF], P<0.0001) and at 6 months after discharge (8.5% versus 2.8%, P<0.0001). Of note, HF increased mortality rates in patients with unstable angina (defined as ACS with normal biochemical markers of necrosis; mortality rates: 6.7% with versus 1.6% without HF at admission, P<0.0001). By logistic regression analysis, admission HF was an independent predictor of hospital death (odds ratio, 2.2; P<0.0001). Admission HF was associated with longer hospital stay and higher readmission rates. Patients with HF had lower rates of catheterization and percutaneous cardiac intervention, and fewer received beta-blockers and statins. Hospital development of HF (versus HF on presentation) was associated with an even higher in-hospital mortality rate (17.8% versus 12.0%, P<0.0001). In patients with HF, in-hospital revascularization was associated with lower 6-month death rates (14.0% versus 23.7%, P<0.0001; adjusted hazard ratio, 0.5; 95% CI, 0.37 to 0.68, P<0.0001). CONCLUSIONS: In this observational registry, heart failure was associated with reduced hospital and 6-month survival across all ACS subsets, including patients with normal markers of necrosis. More aggressive treatment of these patients may be warranted to improve prognosis.

Elevated leukocyte count and adverse hospital events in patients with acute coronary syndromes: findings from the Global Registry of Acute Coronary Events (GRACE).

OBJECTIVE: To examine the association between elevated leukocyte count and hospital mortality and heart failure in patients enrolled in the multinational, observational Global Registry of Acute Coronary Events (GRACE). BACKGROUND: Elevated leukocyte count is associated with adverse hospital outcomes in patients presenting with acute myocardial infarction (AMI). The association of this prognostic factor with hospital mortality and heart failure in patients with other acute coronary syndromes (ACS) is unclear. METHODS: We examined the association between admission leukocyte count and hospital mortality and heart failure in 8269 patients presenting with an ACS. This association was examined separately in patients with ST-segment elevation AMI, non-ST-segment elevation AMI, and unstable angina. Leukocyte count was divided into 4 mutually exclusive groups (Q): Q1 <6000, Q2 = 6000-9999, Q3 = 10,000-11,999, Q4 >12,000. Multiple logistic regression analysis was performed to examine the association between elevated leukocyte count and hospital events while accounting for the simultaneous effect of several potentially confounding variables. RESULTS: Increasing leukocyte count was significantly associated with hospital death (adjusted odds ratio [OR] 2.8, 95% CI 2.1-3.6 for Q4 compared to Q2 [normal range]) and heart failure (OR 2.7, 95% CI 2.2-3.4) for patients presenting with ACS. This association was seen in patients with ST-segment elevation AMI (OR for hospital death 3.2, 95% CI 2.1-4.7; OR for heart failure 2.4, 95% CI 1.8-3.3), non-ST-segment elevation AMI (OR for hospital death 1.9, 95% CI 1.2-3.0; OR for heart failure 1.7, 95% CI 1.1-2.5), or unstable angina (OR for hospital death 2.8, 95% CI 1.4-5.5; OR for heart failure 2.0, 95% CI 0.9-4.4). CONCLUSION: In men and women of all ages with the spectrum of ACS, initial leukocyte count is an independent predictor of hospital death and the development of heart failure.

Influence of beta-blocker use on percentage of target heart rate exercise prescription.

BACKGROUND: Exercise is recommended for cardiac patients irrespective of beta-blockers. Percentages of maximal heart rate (%HRmax) and heart rate reserve (%HRR) are widely used to determine training intensities. The purpose of this study was to investigate the influence of chronic cardioselective beta blockade on the %HRmax and %HRR model. METHODS: Ten healthy male subjects randomly received oral placebo or beta-blocker bisoprolol (5 mg/day) for 2 weeks using a double-blind, crossover design. In the second week, the subjects performed a cardiopulmonary exercise test until exhaustion to determine the aerobic (AeT) and anaerobic (AnT) threshold. RESULTS: No significant differences were found for absolute and relative values of oxygen consumption, power output and ratings of perceived exertion at AeT, AnT and maximum workload. Mean HR was significantly (P<0.05) lower at rest (-15 +/- 5 bpm), AeT (-19 +/- 8 bpm), AnT (-22 +/- 10 bpm) and maximal workload (-19 +/- 11 bpm) with bisoprolol compared to placebo. Percentage of maximal heart rate (%HRmax) was significantly (P<0.05) reduced at rest (43 versus 39%), AeT (64 versus 60%) and AnT (86 versus 82%), a trend for a reduction was found for %HRR at AnT (75 versus 71%, P=0.07). CONCLUSIONS: Exercise prescription using %HRmax or %HRR methods are of limited accuracy for patients taking beta-blockers. Although %HRmax and %HRR are easy to determine and therefore attractive, we suggest that the most precise exercise prescription would depend on AeT and AnT. Percentages of maximal oxygen consumption or maximal workload or ratings of perceived exertion may be suggested as a substitute. Alternatively, upper limits for %HRmax and %HRR should be lower for patients taking beta-blockers.