Reply: An Incomplete Story Cleland, John G F; Flather, Marcus D; Altman, Douglas G ...
Journal of the American College of Cardiology,
01/2018, Letnik:
71, Številka:
1
Journal Article
Recenzirano
Beta-blockers reduced mortality in landmark, placebo-controlled trials of heart failure with a reduced left ventricular ejection fraction only for those in sinus rhythm rather than atrial ...fibrillation (AF), despite use of similar beta-blocker formulations and doses (84% of target) and similar heart rate reductions (1). 1 D. Kotecha, M.D. Flather, D.G. Altman, for the Beta-Blockers in Heart Failure Collaborative Group, Heart rate and rhythm and the benefit of beta-blockers in patients with heart failure, J Am Coll Cardiol, Vol. 69, 2017, 2885-2896 2 D. Cullington, K.M. Goode, J. Zhang, J.G. Cleland, A.L. Clark, J Am Coll Cardiol HF, Vol. 2, 2014, 213-220 3 O.J. Ziff, D.A. Lane, M. Samra, Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data, BMJ, Vol. 351, 2015, h4451 4 D. Kotecha, M. Calvert, J.J. Deeks, A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial, BMJ Open, Vol. 7, 2017, e015099
Abstract Background Angiographically-normal coronary arteries are reported in 10–20% of patients undergoing diagnostic coronary angiography despite screening with risk factors and functional tests. ...We sought to validate and determine the clinical value of radial artery pulse wave analysis (PWA), a simple, quick and non-invasive marker of central artery stiffness and define its ability to predict coronary artery disease in high-risk patients. Materials and methods 531 consecutive patients referred for elective coronary angiography, irrespective of previous co-morbidity, were assessed in a prospective, multicenter observational study the Alternative Risk Markers in Coronary Artery Disease (ARM-CAD) study. Results Mean age was 65 ± 11 years, 33% were women, 18% had impaired left-ventricular function and 22% a prior myocardial infarction. Angiography demonstrated normal coronary arteries in 20% of participants. The only independent associations with this outcome were younger age, female gender, absence of diabetes and PWA-derived central augmentation pressure < 24 mm Hg. The odds ratio for the latter after adjustment for medications and baseline risk factors (including blood pressure, high-sensitivity C-reactive protein and B-type natriuretic peptide) was 3.4 (95% CI 1.2 to 9.5; p = 0.021). The specificity for the multivariate model that included PWA was 95.7% with a receiver operator curve area of 0.876. Validation studies suggested that systolic variables from PWA were robust regardless of waveform quality and similar to measured aortic pressures (mean difference 2.7 mm Hg). Conclusions Assessment of radial artery waveforms is a useful non-invasive clinical test that can stratify the likelihood of coronary disease and assist in identifying patients who require diagnostic angiography.
The extent to which hospital and geographic characteristics influence the time course of uptake of evidence from key clinical trials and practice guidelines is unknown. The gap between evidence and ...practice is well recognized but the factors influencing this disjunction, and the extent to which such factors are modifiable, remain uncertain.
Using chronological data from the GRACE registry (n=12666, July 1999 to December 2001), we test the hypothesis that hospital and geographic characteristics influence the time course of uptake of evidence-based guideline recommendations for acute coronary syndromes (ACS) with and without ST elevation. Certain therapies were widely adopted in both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients (aspirin >94% of all patients; beta-blockers 85-95%) and changed only modestly over time. Significant increases in the use of low-molecular-weight heparins and glycoprotein IIb/IIIa inhibitors occurred in STEMI and NSTEMI patients in advance of published practice guidelines (September/November 2000) with marked geographical differences. The highest use of LMWH was in Europe in NSTEMI (86.8%) and the lowest in the USA (24.0%). Contrasting geographical variations were seen in the use of percutaneous coronary intervention (PCI) in NSTEMI: 39.5% USA, 34.6% Europe, 33.5% Argentina/Brazil, 25.0% Australia/New Zealand/Canada (July-December 2001). Theuse of PCI was more than five times greater in hospitals with an on-site catheterization laboratory compared to centres without these facilities, and geographic differences remained after correction for available facilities.
Hospital and geographical factors appear to have a marked influence on the uptake of evidence-based therapies in ACS management. The presentation and publication of major international guidelines was not associated with a measurable change in the temporal pattern of practice. In contrast, antithrombotic and interventional therapies changed markedly over time and were profoundly influenced by hospital and geographic characteristics.
Background Registries have shown that quality of care for acute coronary syndromes (ACS) often falls below the standards recommended in professional guidelines. Quality improvement (QI) is a strategy ...to improve standards of clinical care for patients, but the efficacy of QI for ACS has not been tested in randomized trials. Methods We undertook a prospective, cluster-randomized, multicenter, multinational study to evaluate the efficacy of a QI program for ACS. Participating centers collected data on consecutive admissions for non–ST-elevation ACS for 4 months before the QI intervention and 3 months after. Thirty-eight hospitals in France, Italy, Poland, Spain, and the United Kingdom were randomized to receive the QI program or not, 19 in each group. We measured 8 in-hospital quality indicators (risk stratification, coronary angiography, anticoagulation, β-blockers, statins, angiotensin-converting enzyme inhibitors, and clopidogrel loading and maintenance) before and after the intervention and compared composite changes between the QI and non-QI groups. Results A total of 2604 patients were enrolled. The absolute overall change in use of quality indicators in the QI group was 8.5% compared with 0.8% in the non-QI group (odds ratio for achieving a quality indicator in QI versus non-QI 1.66, 95% CI 1.43-1.94; P < .001). The main changes were observed in the use of risk stratification and clopidogrel loading dose. Conclusions The QI strategy resulted in a significant improvement in the quality indicators measured. This type of QI intervention can lead to useful changes in health care practice for ACS in a wide range of settings.
Abstract Background Long term nationally representative mortality rates following acute coronary syndrome (ACS) admissions are lacking beyond 5 years. We report rates and causes of mortality at ...approximately 10 years from PRAIS-UK. Methods PRAIS-UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK hospitals between 1998 and 1999. 493 patients surviving to 6 months were consented to long term follow-up. We identified deaths and causes (ICD codes) via the UK central death register and examined the influence of baseline characteristics and early revascularisation procedures. A modified GRACE risk score was constructed to determine the association of baseline score with long term risk of death. Results The mean age was 66 years and 40% were women. After a median follow-up of 11.6 years (IQR 6.3–11.9), 46% (225) of patients had died with 55% being classified as cardiovascular. In a multivariate analysis, the following variables were associated with higher mortality (hazard ratio HR and 95% confidence intervals CI): age (10 years increase) 2.14 (1.87 to 2.45), ST depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67), and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for risk of death in patients who received a revascularisation procedure (versus those who did not) in the first 6 months was 0.41 (0.24 to 0.69). The mean adapted GRACE score was 99.3 ± 26.4, associated with approximately 50% mortality at 10 years. Conclusions Non-ST elevation ACS is associated with about 50% mortality over 10 years that may be improved by early revascularisation. Well designed long-term registries can provide key data to determine prognosis and burden of disease.
Background The SENIORS trial showed that nebivolol reduced the risk of death or cardiovascular (CV) hospitalization in elderly patients with heart failure (HF). We aimed to assess tolerability and ...dose-related effects of the β-blocker nebivolol in elderly patients from the SENIORS trial. Methods Patients assigned to nebivolol (n = 1031) were classified into 4 groups, according to the dose achieved at the end of titration phase (maintenance dose): 0 mg (n = 74), low dose (1.25 or 2.5 mg, n = 142), medium dose (5 mg, n = 127), and target dose (10 mg, n = 688) and compared with those allocated to placebo (n = 1030). Age, sex and ejection fraction were similar between the groups, but prior myocardial infarction, coronary revascularization, and serum creatinine levels were lower in patients who achieved higher maintenance doses of nebivolol. Results After adjustment, all-cause mortality or CV hospitalization was significantly reduced in the 10 mg dose group compared with placebo (hazard ratio HR 0.75, 95% CI 0.63-0.90) which was similar to the medium dose group (HR 0.73, 95% CI 0.52-1.02). The low dose group had an apparently lower benefit (HR 0.88, 95% CI 0.64-1.20), whereas patients unable to tolerate any dose of nebivolol had an increased risk of death or CV hospitalization (HR 1.95, 95% CI 1.38-2.75). Conclusions The benefits of nebivolol in elderly patients with HF appear to be related to the maintenance dose achieved. Patients unable to tolerate any dose have the worst prognosis.
Aims
Beneficial effects of beta‐blockade remain unclear in heart failure patients who have atrial fibrillation (AF), especially in the elderly. We evaluated the effect of nebivolol on cardiovascular ...outcomes in elderly patients with heart failure and AF.
Methods and results
The SENIORS trial showed an overall benefit of nebivolol compared with placebo in 2128 heart failure patients >70 years of age. At baseline, AF was present in 738 (34.7%) patients. The primary outcome was all‐cause mortality or cardiovascular hospitalizations. After 21 months, the cumulative incidence of the primary outcome was significantly more common in patients with AF compared with those with sinus rhythm (38.5% vs. 30.4%, respectively, P < 0.001). In patients with AF, nebivolol had no beneficial effect on the primary outcome nebivolol vs. placebo, 37.1% vs. 39.8%, hazard ratio (HR) 0.92, 95% confidence interval (CI), 0.73–1.17, P = 0.46, in contrast to patients with sinus rhythm (28.1% vs. 32.9%, in the nebivolol vs. placebo group, respectively, HR 0.82, 95% CI 0.67–0.99, P = 0.049). In patients with AF, the primary outcome was similar in the impaired and preserved left ventricular ejection fraction (LVEF) groups (39.0% with LVEF ≤35% vs. 37.3% in patients with LVEF > 35%). There was also no evidence of benefit of nebivolol in AF patients stratified by LVEF.
Conclusion
Nebivolol failed to improve outcomes in elderly patients with stable heart failure and co‐existing AF, irrespective of LVEF. Furthermore, in patients with AF, outcome was comparable between patients with preserved and impaired LVEF.
We aimed to provide a quantitative analysis of the 1-year clinical outcomes of patients with multisystem coronary artery disease who were included in recent randomized trials of percutaneous coronary ...intervention with multiple stenting versus coronary artery bypass graft surgery.
An individual patient database was composed of 4 trials (Arterial Revascularization Therapies Study, Stent or Surgery Trial, Argentine Randomized Trial of Percutaneous Transluminal Coronary Angioplasty Versus Coronary Artery Bypass Surgery in Multivessel Disease 2, and Medicine, Angioplasty, or Surgery Study 2) that compared percutaneous coronary intervention with multiple stenting (N = 1518) versus coronary artery bypass graft surgery (N = 1533). The primary clinical end point of this study was the combined incidence of death, myocardial infarction, and stroke at 1 year after randomization. Secondary combined end points included the incidence of repeat revascularization at 1 year. All analyses were based on the intention-to-treat principle.
After 1 year of follow-up, 8.7% of patients randomized to percutaneous coronary intervention with multiple stenting versus 9.1% of patients randomized to coronary artery bypass graft surgery reached the primary clinical end point (hazard ratio 0.95 and 95% confidence interval 0.74’1.2). Repeat revascularization procedures occurred more frequently in patients allocated to percutaneous coronary intervention with multiple stenting compared with coronary artery bypass graft surgery (18% vs 4.4%; hazard ratio 4.4 and 95% confidence interval 3.3’5.9). The percentage of patients who were free from angina was slightly lower after percutaneous coronary intervention with multiple stenting than after coronary artery bypass graft surgery (77% vs 82%;
P = .002).
One year after the initial procedure, percutaneous coronary intervention with multiple stenting and coronary artery bypass graft surgery provided a similar degree of protection against death, myocardial infarction, or stroke for patients with multisystem disease. Repeat revascularization procedures remain high after percutaneous coronary intervention, but the difference with coronary artery bypass graft surgery has narrowed in the era of stenting.
The beneficial effects of β blockers in younger patients with heart failure (HF) due to systolic dysfunction are well established. However, data from patients ≥70 years old with diabetes mellitus and ...HF are lacking. The Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors with heart failure SENIORS tested the efficacy of the vasodilator β blocker nebivolol in patients ≥70 years old with HF and impaired or preserved left ventricular ejection fraction. In the present analysis, we evaluated the association between diabetes mellitus and baseline glucose levels on the primary outcome (all-cause mortality and cardiovascular hospitalization) and secondary end points, including all-cause mortality, cardiovascular hospitalizations, and cardiovascular mortality. Of 2,128 patients, 555 (26.1%) had diabetes mellitus. Of the 555 patients with diabetes mellitus, 223 (40.2%) experienced the primary end point compared to 484 (30.8%) of the 1,573 nondiabetic patients (p <0.001). For the nondiabetic patients, the rate of the primary outcome for placebo compared to nebivolol was 33.7% for the placebo group and 27.8% for the nebivolol group (hazard ratio 0.78, 95% confidence interval 0.65 to 0.93; p = 0.006). In the diabetic subset, the rate was 40.3% for the placebo group and 40.1% for the nebivolol group (hazard ratio 1.04, 95% confidence interval 0.80 to 1.35, p = 0.773). The subgroup interaction p value was 0.073. The baseline glucose levels in the nondiabetic patients did not significantly affect the outcomes. The effect of diabetes mellitus on outcome was independent of the left ventricular ejection fraction and was most pronounced in those with HF due to a nonischemic etiology. In conclusion, in patients ≥70 years old with HF, diabetes mellitus was associated with a worse prognosis. Nebivolol was less effective in the patients with diabetes and HF than in those with HF but without diabetes who were ≥70 years old.
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