ABSTRACT: Randomized clinical trials have suggested that treatment of anaemia with erythropoiesis-stimulating agents (ESAs) in patients with cancer or chronic kidney disease may increase cardiovascular risk. We therefore examined the effect of treating anaemia with an ESA in patients with heart failure in a meta-analysis of randomized clinical trials, including the recently reported TREAT study.
We performed a systematic review and meta-analysis of all prospective, randomized, controlled studies of ESAs enrolling patients with heart failure and reporting data on mortality or non-fatal heart failure events. Of 10 trials initially identified by our search strategy, we pooled data from 9 placebo-controlled studies enrolling a total of 2039 patients, of whom 1023 (50.2%) were allocated to ESA treatment. The pooled risk ratio for ESA treatment relative to placebo was 1.03 [95% confidence interval (CI): 0.89-1.21, P = 0.68] for overall mortality and 0.95 (95% CI: 0.82-1.10, P = 0.46) for worsening heart failure.
The use of ESAs to manage anaemia in patients with heart failure was associated with a neutral effect on both mortality and non-fatal heart failure events. Definitive assessment of the balance of risk and benefit in this population awaits the completion of a randomized clinical trial adequately powered to assess clinical outcomes.
European Journal of Heart Failure 09/2010; 12(9):936-42. · 4.90 Impact Factor
Journal of the American College of Cardiology 05/2006; 47(8):1612-4. · 14.16 Impact Factor
ABSTRACT: To evaluate the effect of the angiotensin receptor blocker candesartan on patients' perception of symptoms, using the McMaster Overall treatment evaluation (OTE), in a broad spectrum of patients with chronic heart failure (CHF).
Patients with symptomatic CHF, randomised in the CHARM Programme in North America (n=2498), were studied. OTE was assessed at baseline, at 6, 14 and 26 months and the patient's final or closing visit. Patient's status was classified as "improved (score +1 to +7)", "unchanged (score 0)" or "deteriorated (score -1 to -7)" at the end of the study compared to baseline. Both a simple "last visit carried forward" (LVCF) analysis and "worst rank carried forward" (WRCF) analysis (where patients who died were allocated the worst OTE score) were used. In the LVCF analysis, compared to placebo, more candesartan patients improved (37.7% versus 33.5%) and fewer worsened (10.8% versus 12.0%) in OTE (p=0.017). The WRCF analysis also showed better overall OTE scores with candesartan compared to placebo (p=0.029). There was no heterogeneity in the response to candesartan between the CHARM component trials or across four exploratory sub-groups (age, sex, NYHA class and beta-blocker).
Candesartan was shown to be better than placebo, when using the McMaster OTE to measure patient perception of treatment. More patients treated with candesartan reported improvement and fewer reported deterioration. This benefit was obtained when candesartan was added to extensive background therapy and is consistent with the benefits of candesartan on NYHA class, hospital admission for worsening heart failure and mortality.
European Journal of Heart Failure 07/2005; 7(4):650-6. · 4.90 Impact Factor
ABSTRACT: This study examined the hypothesis that patients who develop angiotensin-converting enzyme inhibitor intolerance attributable to circulatory-renal limitations (CRLimit) have more severe underlying disease and worse outcome.
Although the renin-angiotensin system contributes to the progression of heart failure (HF), it also supports the failing circulation. Patients with the most severe disease may not tolerate inhibition of this system.
Consecutive inpatient admissions to the cardiomyopathy service of the Brigham and Women's Hospital between 2000 and 2002 were reviewed retrospectively for initial profiles, discharge medications, and documented reasons for discontinuation of angiotensin-converting enzyme inhibitors. Outcomes of death and transplantation were determined.
Of the 259 patients, 86 were not on an angiotensin-converting enzyme inhibitor at discharge. Circulatory-renal limitations of symptomatic hypotension, progressive renal dysfunction, or hyperkalemia were documented in 60 patients (23%); other adverse effects, including cough, in 24 patients; and absent reasons in 2 patients. Compared with patients on angiotensin-converting enzyme inhibitors, patients with CRLimit were older (60 vs. 55 years; p = 0.006), with longer history of HF (5 vs. 2 years; p = 0.009), lower systolic blood pressure (104 vs. 110 mm Hg; p = 0.05), lower sodium (135 vs. 138 mEql/l; p = 0.002), and higher initial creatinine (2.5 vs. 1.2 mg/dl; p = 0.0001). Mortality was 57% in patients with CRLimit and 22% in the patients on angiotensin-converting enzyme inhibitors during a median 8.5-month follow-up (p = 0.0001).
Development of CRLimit to angiotensin-converting enzyme inhibitor intolerance identifies patients with severe disease who are likely to die during the next year. New treatment strategies should be targeted to this population.
Journal of the American College of Cardiology 07/2003; 41(11):2029-35. · 14.16 Impact Factor
ABSTRACT: Advanced heart failure, defined as persistence of limiting symptoms despite therapy with agents of proven efficacy, accounts for the majority of morbidity and mortality in heart failure.
To review current medical therapy for advanced heart failure.
We searched MEDLINE for all articles containing the term advanced heart failure that were published between 1980 and 2001; EMBASE was searched from 1987-1999, Best Evidence from 1991-1998, and Evidence-Based Medicine from 1995-1999. The Cochrane Library also was searched for critical reviews and meta-analyses of congestive heart failure.
Randomized controlled trials of therapy for 150 patients or more were included if advanced heart failure was represented. Other common clinical situations were addressed from smaller trials as available, trials of milder heart failure, consensus guidelines, and both published and personal clinical experience.
Data quality was determined by publication in peer-reviewed literature or inclusion in professional society guidelines.
A primary focus for care of advanced heart failure is ongoing identification and treatment of the elevated filling pressures that cause disabling symptoms. While angiotensin-converting enzyme inhibitors and beta-adrenergic agents can slow disease progression and prolong survival, titration and tolerability often present challenges. Most patients are not eligible for surgical intervention but do benefit from a medical regimen tailored to individual clinical and hemodynamic profiles and from heart failure management programs that reduce rehospitalization. Survival ranges from 80% at 2 years for patients rendered free of congestion to less than 50% at 6 months for patients with refractory symptoms, in whom end-of-life options may include hospice care and inactivation of implantable defibrillators.
Current management of advanced heart failure is based more on consensus than on randomized trials. Systematic investigation should address not only new therapies but also strategies for selecting and optimizing therapies already available.
JAMA The Journal of the American Medical Association 03/2002; 287(5):628-40. · 30.03 Impact Factor