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Biomedical subjects

Marc A Pfeffer

Publications and source records attributed to Marc A Pfeffer.

At least 55 records · Page 3Linked to original sources
PubMed2005

Pulsatile hemodynamic effects of candesartan in patients with chronic heart failure: the CHARM Program.

BACKGROUND: Abnormal large artery function and increased pulsatile load are exacerbated by excess angiotensin-II acting through the AT1 receptor and contribute to the pathogenesis and progression of chronic heart failure (CHF). AIMS: To evaluate effects of the AT1 receptor blocker candesartan (N = 30) or placebo (N = 34) on pulsatile hemodynamics in participants with CHF in the CHARM program. METHODS AND RESULTS: Noninvasive hemodynamics were assessed following 6 and 14 months of treatment and averaged. Using calibrated tonometry and aortic outflow Doppler, characteristic impedance was calculated as the ratio of the change in carotid pressure and aortic flow in early systole. Total arterial compliance was calculated by the diastolic area method. Brachial blood pressure, cardiac output and peripheral resistance did not differ between groups. Lower central pulse pressure in the candesartan group (57+/-20 vs. 67+/-17 mmHg, P = 0.043) was accompanied by lower characteristic impedance (200+/-78 vs. 240+/-74 dyne s/cm5, P = 0.039) and higher total arterial compliance (1.87+/-0.70 vs. 1.47+/-0.48 ml/mmHg, P = 0.008). Similar favorable differences were seen when analyses were stratified for ejection fraction (< or = 0.40 vs. >0.40) and baseline angiotensin converting enzyme inhibitor use. CONCLUSIONS: Candesartan has a favorable effect on large artery function in patients with chronic heart failure.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Effect of angiotensin-converting enzyme inhibition on functional class in patients with left ventricular systolic dysfunction--a meta-analysis.

BACKGROUND: The effect of angiotensin converting enzyme (ACE) inhibitors on symptoms in patients with left ventricular systolic dysfunction (LVSD) is controversial. AIMS: To perform a meta-analysis of studies evaluating effect of ACE inhibitors on New York Heart Association (NYHA) class in patients with LVSD. METHODS: Individual data from 10389 patients in NYHA classes I-IV from four large long-term studies (2-4-year follow-up) and summary data from 2302 patients in NYHA classes II-IV from 16 short-term studies (3 months follow-up) were meta-analysed to assess changes in NYHA class. RESULTS: The large long-term studies showed a significant improvement in the worst NYHA classes (classes II-IV compared to class I) in the ACE inhibitor arm versus placebo, odds ratio (OR) = 0.875 (0.811-0.943) p = 0.0005. This effect was only present in studies which included patients with chronic heart failure and was particularly pronounced on deterioration to the worst NYHA class IV, OR = 0.66 (0.52-0.84) p = 0.001. There was no effect in the studies which included patients after myocardial infarction. The short-term chronic heart failure studies showed a significant improvement in NYHA class; OR for improvement of at least one NYHA class was 2.11 (1.48-2.98, 95% CI) p < 0.0001. CONCLUSION: ACE inhibition significantly improves symptomatic status measured as NYHA classification in patients with chronic heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease.

BACKGROUND: Limited data suggest that HMG-CoA reductase inhibitors (statins) reduce rates of kidney function loss. We performed this analysis to determine whether pravastatin reduced the rate of kidney function loss over approximately 5 years in people with or at high risk for coronary disease. METHODS AND RESULTS: This was a post hoc subgroup analysis of data from 3 randomized double-blind controlled trials comparing pravastatin 40 mg/d and placebo in subjects with a previous acute coronary syndrome or who were at high cardiovascular risk. The primary outcome was the rate of change in estimated glomerular filtration rate (GFR; in mL/min per 1.73 m2/y). The Modified Diet and Renal Disease Study (MDRD) and Cockcroft-Gault equations were used to estimate GFR. We studied 18,569 participants, 3402 (18.3%) of whom had moderate chronic kidney disease as defined by an estimated GFR of 30 to 59.9 mL/min per 1.73 m2 body surface area. In subjects with moderate chronic kidney disease at baseline, pravastatin reduced the adjusted rate of kidney function loss by approximately 34%, although the absolute reduction in the rate of loss was small (0.22 mL/min per 1.73 m2/y by MDRD-GFR; 95% CI, 0.07 to 0.37). Pravastatin did not reduce the frequency of > or =25% decreases in kidney function in this group when MDRD-GFR was used to estimate GFR (relative risk [RR], 0.84; 95% CI, 0.66 to 1.06). When all 18,569 subjects were considered, pravastatin reduced the adjusted rate of kidney function loss by 8% (0.08 mL/min per 1.73 m2/y by MDRD-GFR; 95% CI, 0.01 to 0.15) and the risk of acute renal failure (RR, 0.60; 95% CI, 0.41 to 0.86) but did not significantly reduce the frequency of a > or =25% decline in kidney function by MDRD-GFR (RR, 0.94; 95% CI, 0.88 to 1.01). CONCLUSIONS: Pravastatin modestly reduced the rate of kidney function loss in people with or at risk for cardiovascular disease. However, the primary indication for the use of statins in people with or at risk for coronary events remains the reduction in mortality that results from their use.

Aged↗
PubMed2005

Effects of candesartan on the development of a new diagnosis of diabetes mellitus in patients with heart failure.

BACKGROUND: Diabetes is a risk factor for heart failure, and both conditions are increasing. Identifying treatments that prevent both conditions will be clinically important. We previously reported that candesartan (an angiotensin receptor blocker) reduces cardiovascular mortality and heart failure hospitalizations in heart failure patients (CHARM: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity Program). METHODS AND RESULTS: We assessed the impact of candesartan versus placebo on the development of diabetes, a predefined secondary outcome in a randomized, controlled, double-blind study involving 5436 of the 7601 patients with heart failure, irrespective of ejection fraction, who did not have a diagnosis of diabetes at entry into the trial. Patients received candesartan (target of 32 mg once daily) or matching placebo for 2 to 4 years. One hundred sixty-three (6.0%) individuals in the candesartan group developed diabetes, as compared with 202 (7.4%) in the placebo group (hazard ratio [HR], 0.78 with a 95% confidence interval [CI] of 0.64 to 0.96; P=0.020). The composite end point of death or diabetes occurred in 692 (25.2%) and 779 (28.6%), respectively, in the candesartan and placebo groups (HR, 0.86; 95% CI, 0.78 to 0.95; P=0.004). The results were not statistically heterogeneous in the various subgroups examined, although the apparent magnitude of benefit appeared to be smaller among those treated concomitantly with angiotensin-converting enzyme inhibitors at trial entry (HR, 0.88; 95% CI, 0.65 to 1.20) compared with those not receiving these drugs (HR, 0.71; 95% CI, 0.53 to 0.93; P for heterogeneity, 0.28). CONCLUSIONS: The angiotensin receptor blocker candesartan appears to prevent diabetes in heart failure patients, suggesting that the renin-angiotensin axis is implicated in glucose regulation.

Adult↗
PubMed2005

Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both.

BACKGROUND: The risk of sudden death from cardiac causes is increased among survivors of acute myocardial infarction with reduced left ventricular systolic function. We assessed the risk and time course of sudden death in high-risk patients after myocardial infarction. METHODS: We studied 14,609 patients with left ventricular dysfunction, heart failure, or both after myocardial infarction to assess the incidence and timing of sudden unexpected death or cardiac arrest with resuscitation in relation to the left ventricular ejection fraction. RESULTS: Of 14,609 patients, 1067 (7 percent) had an event a median of 180 days after myocardial infarction: 903 died suddenly, and 164 were resuscitated after cardiac arrest. The risk was highest in the first 30 days after myocardial infarction--1.4 percent per month (95 percent confidence interval, 1.2 to 1.6 percent)--and decreased to 0.14 percent per month (95 percent confidence interval, 0.11 to 0.18 percent) after 2 years. Patients with a left ventricular ejection fraction of 30 percent or less were at highest risk in this early period (rate, 2.3 percent per month; 95 percent confidence interval, 1.8 to 2.8 percent). Nineteen percent of all sudden deaths or episodes of cardiac arrest with resuscitation occurred within the first 30 days after myocardial infarction, and 83 percent of all patients who died suddenly did so in the first 30 days after hospital discharge. Each decrease of 5 percentage points in the left ventricular ejection fraction was associated with a 21 percent adjusted increase in the risk of sudden death or cardiac arrest with resuscitation in the first 30 days. CONCLUSIONS: The risk of sudden death is highest in the first 30 days after myocardial infarction among patients with left ventricular dysfunction, heart failure, or both. Thus, earlier implementation of strategies for preventing sudden death may be warranted in selected patients.

Aged↗
PubMed2005

Heart failure on admission and the risk of stroke following acute myocardial infarction: the VALIANT registry.

AIMS: We sought to assess the relative contribution of heart failure (HF) on admission for an acute myocardial infarction (MI) to the subsequent in-hospital stroke risk. METHODS AND RESULTS: The VALsartan In Acute myocardial iNfarcTion (VALIANT) registry enrolled 5573 consecutive MI patients at 84 international sites from 1999 to 2001. We calculated odds ratios (ORs) for stroke and adjusted for baseline characteristics, Killip Class, and risk factors for stroke, such as diabetes and prior HF. In-hospital stroke occurred in 81 (1.5%) patients. HF was present on admission in 38% of patients who developed a stroke and in 24% who did not (P=0.001). Older age (OR 1.03 increase/year, 95% confidence interval (CI) 1.01-1.04), Killip Class III (OR 1.66, CI 0.86-3.19) or IV (OR 4.85, CI 1.69-13.93), history of hypertension (OR 1.73, CI 1.06-2.82), and history of stroke (OR 1.89, CI 1.06-3.37) were more common in patients who had in-hospital stroke. In-hospital mortality in patients with and without stroke was 27.2 and 6.5%, respectively (P<0.001). CONCLUSION: Patients with stroke after MI have a dismal prognosis. The presence of HF on admission for an acute MI increases in-hospital stroke risk. HF treatments may modify the risk of stroke.

Aged↗
PubMed2005

Changes in ventricular size and function in patients treated with valsartan, captopril, or both after myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been shown to attenuate left ventricular (LV) enlargement in association with reducing mortality after myocardial infarction (MI). Preclinical data suggest that angiotensin receptor blockers (ARBs) may have similar structural and functional effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo study was designed to test the hypothesis that the ARB valsartan, either alone or in combination with captopril, could attenuate progressive LV enlargement or improve LV ejection fraction to a greater extent than captopril alone. METHODS AND RESULTS: Six hundred ten patients enrolled in the main VALIANT study who experienced MI and evidence of LV dysfunction, heart failure, or both were enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan 160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril 50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had echocardiograms of sufficient quality for quantitative analysis. Echocardiograms were digitized, and endocardial borders were traced manually from 2 short-axis and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and infarct segment length were measured, and changes in echocardiographic measures from baseline to 20 months were compared between treatment groups. Baseline clinical and echocardiographic characteristics were similar in the 3 treatment arms. The changes from baseline to 20 months in all echocardiographic parameters were similar in all 3 treatment arms. Baseline echocardiographic measures of ejection fraction, end-diastolic volume, and infarct segment length were highly predictive of outcomes including total mortality, death or hospitalization for heart failure, or death or any cardiovascular event (heart failure, MI, stroke, resuscitated sudden death), even after adjustment for known covariates. CONCLUSIONS: Treatment with the ACE inhibitor captopril, valsartan, or the combination of captopril plus valsartan resulted in similar changes in cardiac volume, ejection fraction, and infarct segment length between baseline and 20 months after MI. Baseline echocardiographic measures were powerfully and independently predictive of all major outcomes.

Aged↗
PubMed2005

Impact of achieved blood pressure on cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial.

Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP <85 mmHg was associated with a trend to increase in all-cause mortality, significant increase in MI, but decreased risk for strokes. Increased pulse pressure predicted increased all-cause mortality, CV mortality, MI, and CHF. It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients. BP < or =120/85 may be associated with an increase in CV events.

Antihypertensive Agents↗
PubMed2005

Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.

BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. METHODS: We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. RESULTS: For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.

Adenomatous Polyps↗
PubMed2005

C-reactive protein levels and outcomes after statin therapy.

BACKGROUND: Statins lower the levels of low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP). Whether this latter property affects clinical outcomes is unknown. METHODS: We evaluated relationships between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3745 patients with acute coronary syndromes. RESULTS: Patients in whom statin therapy resulted in LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter) had lower event rates than those with higher levels (2.7 vs. 4.0 events per 100 person-years, P=0.008). However, a virtually identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels (2.8 vs. 3.9 events per 100 person-years, P=0.006), an effect present at all levels of LDL cholesterol achieved. For patients with post-treatment LDL cholesterol levels of more than 70 mg per deciliter, the rates of recurrent events were 4.6 per 100 person-years among those with CRP levels of more than 2 mg per liter and 3.2 events per 100 person-years among those with CRP levels of less than 2 mg per liter; the respective rates among those with LDL cholesterol levels of less than 70 mg per deciliter were 3.1 and 2.4 events per 100 person-years (P<0.001). Although atorvastatin was more likely than pravastatin to result in low levels of LDL cholesterol and CRP, meeting these targets was more important in determining the outcomes than was the specific choice of therapy. Patients who had LDL cholesterol levels of less than 70 mg per deciliter and CRP levels of less than 1 mg per liter after statin therapy had the lowest rate of recurrent events (1.9 per 100 person-years). CONCLUSIONS: Patients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.

Anticholesteremic Agents↗
PubMed2005

Resource use, costs, and quality of life among patients in the multinational Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: In a multinational clinical trial, valsartan was statistically not inferior to captopril in reducing mortality and cardiovascular morbidity after myocardial infarction (MI) in patients with signs of heart failure and/or left ventricular dysfunction. We conducted a prospective economic evaluation to compare within-trial resource use, costs, and quality of life in patients receiving valsartan, captopril, or both after MI. METHODS: We assigned country-specific unit costs to resource use data for 14703 patients and measured health-related quality of life in a subset of 4524 patients. We used the nonparametric bootstrap method to compare rates of resource use and costs, and a piecewise linear mixed-effects regression analysis to compare longitudinal measures of quality of life. RESULTS: There were no significant differences in rates of resource use between the valsartan and captopril groups. During an average follow-up of 2 years, total costs for patients receiving valsartan were significantly higher than for patients receiving captopril (USD 14103 vs USD 13038; 95% CI USD 369-USD 1875). The cost differential was caused primarily by the cost of the study medications (USD 1056 for valsartan vs USD 165 for captopril; 95% CI USD 867 to USD 912). Quality of life did not differ significantly between groups. CONCLUSIONS: For most patients at high risk after MI, the availability of generic captopril confers a cost advantage over valsartan because of lower medication costs. The difference will be smaller or nonexistent in settings where brand-name ACE inhibitors are prescribed.

Ambulatory Care↗
PubMed2005

Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular disease in patients with CKD, but these data remain unsubstantiated by any randomized controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia management in patients with CKD are based on limited data. The need for new RCTs to address critical knowledge deficits, particularly with regard to the impact of anemia therapy on cardiovascular disease and survival, is recognized within the guidelines and independent comprehensive reviews of the existing published trial data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient, multicenter, double-blind RCT, designed to determine the impact of anemia therapy with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1 manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a composite primary end point comprising time to mortality and nonfatal cardiovascular events, including myocardial infarction, myocardial ischemia, stroke, and heart failure. TREAT will provide data that are critical to evolution of the management of cardiovascular risk in this high-risk population.

Anemia↗
PubMed2005

Effect of angiotensin-converting enzyme or vasopeptidase inhibition on ventricular size and function in patients with heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) echocardiographic study.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibition attenuates ventricular remodeling and improves ventricular function in heart failure patients. Vasopeptidase inhibition has shown similar effects in experimental models. OBJECTIVES: The OVERTURE echocardiographic study was designed to test the hypothesis that the vasopeptidase inhibitor omapatrilat would attenuate ventricular remodeling and improve ventricular function to a greater extent than an ACE inhibitor. METHODS: Three hundred twenty-one patients with heart failure (New York Heart Association class > or = 2) were included in the OVERTURE echocardiographic substudy and were randomized to receive enalapril (10 mg twice a day) or omapatrilat (40 mg every day). Echocardiograms were performed at baseline and at 1 year (n = 214). Left ventricular size was estimated by summation of ventricular areas in apical and short-axis views and by calculation of ventricular volumes. Ejection fraction was calculated from ventricular volumes. RESULTS: Combined diastolic and systolic areas and volumes decreased significantly (mean diastolic area change -8.36 cm2, 95% CI -9.4 to -7.3 cm2; mean systolic change -8.4 cm2, 95% CI -9.5 to -7.3 cm2), and ejection fractions increased significantly (3.6%, 95% CI 2.6% to 4.6%) in both treatment groups from baseline to 1 year. There were no differences in the magnitude of improvement in ventricular size or function based on treatment assignment. Patients who died or were hospitalized for heart failure subsequent to the final assessment demonstrated the least degree of reverse remodeling. CONCLUSION: Ventricular size and function improved similarly after 1 year with ACE or vasopeptidase inhibition in patients with heart failure. Reverse remodeling was associated with improved outcome.

Aged↗
PubMed2005

Prognostic use of echocardiography 1 year after a myocardial infarction.

BACKGROUND: Left ventricular (LV) and right ventricular (RV) function are known predictors of morbidity and mortality after an acute myocardial infarction (MI). However, the prognostic use of a late evaluation of cardiac function after an MI remains unclear. METHODS: We analyzed echocardiograms obtained 1 year after MI in patients with LV dysfunction at baseline (ejection fraction [EF] < or = 40%) from 291 patients enrolled in the SAVE echocardiographic substudy who did not develop heart failure (HF) or a recurrent MI during this first year. Left ventricular EF and RV fractional area change were assessed. RESULTS: After a median follow-up of 22 months after the 1-year echocardiogram, a low LVEF (< 30%) at 1 year was associated with an increased risk of death and/or HF (hazards ratio [HR] 2.7, 95% CI 1.3-5.3). Presence of RV dysfunction was also associated with an increased risk of death (HR 8.9, 95% CI 3.5-22.1), development of HF (HR 7.1, 95% CI 3.4-15.0), and the composite end point of death or HF (HR 7.6, 95% CI 4.1-14.2). In multivariate analyses, both low LVEF and RV dysfunction remained independently predictive of the composite end point of death or HF. Patients with biventricular dysfunction were at the greatest risk of death and/or HF (HR 19.4, 95% CI 8.2-46.0) in follow-up. CONCLUSIONS: In a stable population of survivors of MI, impaired LV and RV function at 1 year after MI are independently and additively predictive of increased risk of HF or death.

Female↗
PubMed2005

Patient perception of the effect of treatment with candesartan in heart failure. Results of the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme.

AIMS: 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). METHODS AND RESULTS: 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). CONCLUSIONS: 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.

Aged↗
PubMed2005

Uncertainty in the treatment of anemia in chronic kidney disease.

The practice of medicine requires that the assimilation of today's best available data be directed toward individual patient-care decisions. In the absence of definitive data, surrogate measures are adopted to anticipate how therapeutic strategies would influence clinical outcomes and prognosis. Unfortunately, randomized controlled clinical trials (RCTs) have not always found these estimates of outcome to be reliable. Anemia is a clear marker of adverse prognosis, which can be modified by erythropoietic stimulating proteins (ESP). At present, there is sufficient uncertainty regarding the risks and benefits of ESP treatment in patients with chronic kidney disease and anemia to warrant major RCTs. This article reviews the rationale and design features for these trials.

Anemia↗