Showing papers by "Marc A. Pfeffer published in 2003"
TL;DR: There was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population, and the task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events.
Abstract: Chronic kidney disease1 (CKD) is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. The number of individuals with kidney failure treated by dialysis and transplantation exceeded 320 000 in 1998 and is expected to surpass 650 000 by 2010.1,2 There is an even higher prevalence of earlier stages of CKD (Table 1).1,3 Kidney failure requiring treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) is also frequently associated with CKD, which is important because individuals with CKD are more likely to die of CVD than to develop kidney failure,4 CVD in CKD is treatable and potentially preventable, and CKD appears to be a risk factor for CVD. In 1998, the National Kidney Foundation (NKF) Task Force on Cardiovascular Disease in Chronic Renal Disease issued a report emphasizing the high risk of CVD in CKD.5 This report showed that there was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population (Figure 1 and Table 2).6–18 The task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events and that treatment recommendations based on CVD risk stratification should take into account the highest-risk status of patients with CKD.
View this table:
TABLE 1. Stages of CKD
Figure 1. Cardiovascular mortality defined by death due to arrhythmias, cardiomyopathy, cardiac arrest, myocardial infarction, atherosclerotic heart disease, and pulmonary edema in general population (GP; National Center for Health Statistics [NCHS] multiple cause of mortality data files International Classification of Diseases, 9th Revision [ICD 9] codes 402, 404, 410 to 414, and …
4,037 citations
TL;DR: Cedesartan has a moderate impact in preventing admissions for CHF among patients who have heart failure and LVEF higher than 40%.
2,695 citations
TL;DR: The addition of candesartan to ACE inhibitor and other treatment leads to a further clinically important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction.
2,376 citations
TL;DR: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction and the combination of the two on mortality in this population of patients.
Abstract: background Angiotensin-converting–enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. methods Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. results During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartanand-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. conclusions Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.
2,305 citations
TL;DR: Codesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure and there was no significant heterogeneity for candesartan results across the component trials.
1,788 citations
TL;DR: There was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population, and the task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events.
Abstract: Chronic kidney disease1 (CKD) is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. The number of individuals with kidney failure treated by dialysis and transplantation exceeded 320 000 in 1998 and is expected to surpass 650 000 by 2010.1,2 There is an even higher prevalence of earlier stages of CKD (Table 1).1,3 Kidney failure requiring treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) is also frequently associated with CKD, which is important because individuals with CKD are more likely to die of CVD than to develop kidney failure,4 CVD in CKD is treatable and potentially preventable, and CKD appears to be a risk factor for CVD. In 1998, the National Kidney Foundation (NKF) Task Force on Cardiovascular Disease in Chronic Renal Disease issued a report emphasizing the high risk of CVD in CKD.5 This report showed that there was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population (Figure 1 and Table 2).6–18 The task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events and that treatment recommendations based on CVD risk stratification should take into account the highest-risk status of patients with CKD.
View this table:
TABLE 1. Stages of CKD
Figure 1. Cardiovascular mortality defined by death due to arrhythmias, cardiomyopathy, cardiac arrest, myocardial infarction, atherosclerotic heart disease, and pulmonary edema in general population (GP; National Center for Health Statistics [NCHS] multiple cause of mortality data files International Classification of Diseases, 9th Revision [ICD 9] codes 402, 404, 410 to 414, and …
1,537 citations
01 Jan 2003
TL;DR: In this article, the authors investigated the effect of addition of an angiotensin-receptor blocker to current treatments to prevent admissions for chronic heart failure (CHF) among patients who have heart failure and LVEF higher than 40%.
Abstract: BACKGROUND
Half of patients with chronic heart failure (CHF) have preserved left-ventricular ejection fraction (LVEF), but few treatments have specifically been assessed in such patients. In previous studies of patients with CHF and low LVEF or vascular disease and preserved LVEF, inhibition of the renin-angiotensin system is beneficial. We investigated the effect of addition of an angiotensin-receptor blocker to current treatments.
METHODS
Between March, 1999, and July, 2000, we randomly assigned 3023 patients candesartan (n=1514, target dose 32 mg once daily) or matching placebo (n=1509). Patients had New York Heart Association functional class II-IV CHF and LVEF higher than 40%. The primary outcome was cardiovascular death or admission to hospital for CHF. Analysis was done by intention to treat.
FINDINGS
Median follow-up was 36.6 months. 333 (22%) patients in the candesartan and 366 (24%) in the placebo group experienced the primary outcome (unadjusted hazard ratio 0.89 [95% CI 0.77-1.03], p=0.118; covariate adjusted 0.86 [0.74-1.0], p=0.051). Cardiovascular death did not differ between groups (170 vs 170), but fewer patients in the candesartan group than in the placebo group were admitted to hospital for CHF once (230 vs 279, p=0.017) or multiple times. Composite outcomes that included non-fatal myocardial infarction and non-fatal stroke showed similar results to the primary composite (388 vs 429; unadjusted 0.88 [0.77-1.01], p=0.078; covariate adjusted 0.86 [0.75-0.99], p=0.037).
INTERPRETATION
Candesartan has a moderate impact in preventing admissions for CHF among patients who have heart failure and LVEF higher than 40%.
539 citations
TL;DR: The analysis of the cardiovascular end points that were monitored as secondary end points in the Irbesartan Diabetic Nephropathy Trial (IDNT) was reported to assess whether an angiotensin II receptor blocker or a calcium-channel blocker alters the risk for cardiovascular events beyond those observed by blood pressure reduction alone without such agents.
Abstract: Treatment with irbesartan, amlodipine, or placebo led to the same composite cardiovascular event rate (cardiovascular death, myocardial infarction, congestive heart failure, strokes, and coronary r...
379 citations
TL;DR: Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.
Abstract: ContextSeveral lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis.ObjectiveTo determine the effect of 12 weeks of antibiotic therapy on coronary
heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure.Design, Setting, and ParticipantsRandomized, placebo-controlled trial of 7747 adults with previous myocardial
infarction that had occurred at least 6 weeks previously (median, 2.6 years)
and a C pneumoniae IgG titer of 1:16 or more. Patients
were recruited from 271 clinical practices in North America, Europe, Argentina,
and India, from October 10, 1997, to July 22, 2001.InterventionThe patients received either azithromycin (600 mg/d for 3 days during
week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868).Main Outcome MeasuresThe primary event was the first occurrence of death from any cause,
nonfatal reinfarction, coronary revascularization, or hospitalization for
angina. Patients were followed up until 1038 events accrued.ResultsAfter a median of 14 months of follow-up, there was no significant risk
reduction in the likelihood of a primary event with azithromycin vs placebo
(7% [95% confidence interval, −5% to 17%], P =
.23). Analysis of hazard ratios suggested early benefits of azithromycin on
the primary event and on death or reinfarction, but these decreased over time.
There were no significant risk reductions for any of the components of the
primary end point including death (8%), recurrent myocardial infarction (7%),
revascularization procedures (5%), or hospitalizations for angina (−1%).
Adverse events related to study drug were reported by 13.2% of those randomized
to receive azithromycin, predominantly a result of diarrhea, compared with
4.6% randomized to receive placebo, and resulted in discontinuation of drug
in 1.6% of those taking azithromycin and 0.4% taking placebo.ConclusionAmong stable patients with previous myocardial infarction and with evidence
of C pneumoniae exposure, a 3-month course of azithromycin
did not significantly reduce the clinical sequelae of coronary heart disease.
326 citations
TL;DR: The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained‐release (SR) moxonidine, an imidazoline receptor agonist.
Abstract: Background:
The association between sympathetic activation and mortality in chronic heart failure and the favorable effect of beta blocking drugs has raised the possibility of therapeutic efficacy for central sympathetic inhibition with sustained-release (SR) moxonidine, an imidazoline receptor agonist.
Methods:
A randomized double-blind, placebo-controlled trial was initiated in 425 centers in 17 countries with a plan to enter 4533 patients with New York Heart Association class II–IV heart failure and a reduced ejection fraction. Moxonidine SR or matching placebo was titrated to a target dose of 1.5 mg BID. The trial was powered to detect a 20% reduction in mortality, which required a total of 724 deaths.
Findings:
An early increase in death rate and adverse events in the moxonidine SR group led to premature termination of the trial because of safety concerns after 1934 patients were entered. Final analysis revealed 54 deaths (5.5%) in the moxonidine SR group and 32 deaths (3.4%) in the placebo group during the active treatment phase. Survival curves revealed a significantly (P=0.012) worse outcome in the moxonidine SR group. Hospitalization for heart failure, acute myocardial infarction and adverse events were also more frequent in the moxonidine SR group. Plasma norepinephrine was significantly decreased by moxonidine SR (−18.8% from baseline) vs. placebo (+6.9%).
Interpretation:
Early termination of the trial limited conclusions regarding the long-term effects of central sympathetic inhibition. Nonetheless, the excess early mortality and morbidity suggest the likelihood of an adverse effect of moxonidine SR and raise concerns regarding the efficacy of generalized sympathetic inhibition in heart failure.
322 citations
TL;DR: Elevated PP in systolic hypertension was independent of MAP and was attributable primarily to elevated Zc and reduced effective diameter of the proximal aorta, suggesting that aortic function may play an active role in the pathophysiology of syStolic hypertension.
Abstract: Background— Elevated pulse pressure (PP) is associated with increased cardiovascular risk and is thought to be secondary to elastin fragmentation with secondary collagen deposition and stiffening of the aortic wall, leading to a dilated, noncompliant vasculature. Methods and Results— By use of calibrated tonometry and pulsed Doppler, arterial stiffness and pulsatile hemodynamics were assessed in 128 subjects with uncomplicated systolic hypertension (supine systolic pressure ≥140 mm Hg off medication) and 30 normotensive control subjects of comparable age and gender. Pulse-wave velocity was assessed from tonometry and body surface measurements. Characteristic impedance (Zc) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Effective aortic diameter was assessed by use of the water hammer equation. Hypertensives were heavier (P<0.001) and had higher PP (P<0.001), which was attributable primarily to higher Zc (P<0.001), especially in women. Pulse-wave velocity was ...
TL;DR: Age and left ventricular ejection fraction were the most important predictors of HF, and diabetes, history of hypertension, previous MI, and baseline heart rate were independently associated with a 30% lower risk of HF.
TL;DR: Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias and changes in these measurements over time predict ventricularArrhythmias after infarction.
Abstract: Background— The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction. Methods and Results— Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 ye...
TL;DR: The clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure randomised in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartans, are described.
Abstract: Aims:
To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan.
Methods and results:
CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients.
Conclusions:
The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.
TL;DR: The VALsartan In Acute myocardial iNfarcTion trial compared outcomes with angiotensin‐converting enzyme inhibition with the reference agent captopril, or with valsartan both in patients with heart failure and/or left ventricular systolic dysfunction after myocardIAL infarction.
Abstract: Background:
The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin-converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin-receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) after myocardial infarction (MI).
Aims:
A goal of this active-control trial was to simulate conditions that would lead current practitioners to use ACEIs. Thus, we compared characteristics of VALIANT patients with those of patients in placebo-controlled trials that established ACEIs as standard treatment.
Methods and Results:
We collected demographic, clinical, medication and imaging information from 14703 patients in 24 countries. This high-risk population was a median 65.8 years old, and 31.1% were female. Most (51.8%) showed imaging evidence of LVSD at enrollment. Most (72%) had Killip class≥II HF. Patients received evidence-based therapies at rates similar to those of contemporary MI trials and at an improved rate compared with prior placebo-controlled ACEI trials.
Conclusion:
VALIANT represents the largest globally representative cohort enrolled with HF and/or LVSD after MI. Patients were similar to those in placebo-controlled ACEI trials while reflecting improvements in evidence-based care. With enrollment complete, VALIANT is poised to define the optimal strategy for renin–angiotensin system blockade after MI to improve cardiovascular outcomes.
01 Jan 2003
TL;DR: Prelischarge ECG may be a useful tool for early identification of patients at risk of ventricular enlargement and persistent dysfunction following myocardial infarction, and the sum of ST- and maximum ST-segment elevation and the number of leads with ST-Segment elevation > or =1 mm in the predischarge ECGs were independent predictors of vent cardiac enlargement.
TL;DR: The renin-angiotensin-aldosterone system is believed to have evolved to maintain blood volume and perfusion pressure in conditions of hemorrhage or hypovolemia.
Patent•
16 May 2003TL;DR: In this article, the authors proposed a method of treating cardiovascular disease in patients following myocardial infarction comprising administering an effective amount of an ARB, especially valsartan, in combination with a beta-blocker to such patients.
Abstract: The invention relates to a method of treating cardiovascular disease in patients following myocardial infarction comprising administering an effective amount of an ARB, especially valsartan, in combination within an effective amount of a beta-blocker to such patients.
TL;DR: The Valsartan in Acute Myocardial Infarction Trial (VALIANT) study is in its final phases of completion and is testing whether the use of the ARB valsartans either alone or in combination with captopril can improve survival over and above what is already achievable with the ARBs.
Abstract: There is a tremendous spectrum of disease severity within the diagnosis of myocardial infarction. The risk of major cardiovascular outcomes is highly related to age and concomitant medical conditions, as well as factors that characterize the extent of the myocardial infarction. Patients that develop pulmonary congestion with transient signs of heart failure and/or left ventricular dysfunction as measured by a reduced ejection fraction are generally at the high end of risk stratification. Prior studies have demonstrated that these patients derive particular benefit with the use of angiotensin-converting enzyme (ACE) inhibitors. The development of angiotensin-receptor blockers (ARBs) raises the question of whether this mode of inhibiting the renin—angiotensin system will be as good as or potentially even better than the ACE inhibitors. Unfortunately, the first major test of this concept in the Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) study did not show a favourable trend for the ARB. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) study is in its final phases of completion and is testing whether the use of the ARB valsartan either alone or in combination with captopril can improve survival over and above what is already achievable with the ARB. Since this patient population is at particularly high risk, even small relative improvements in clinical outcomes will have major public health implications. © 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved
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TL;DR: Los pacientes fueron aleatorizados para recibir candesartan y el objetivo primario principal fue the mortalidad of causa cardiovascular u hospitalizacion por IC.
TL;DR: I had the pleasure working with Drs Jonathan Abrams, Howard A. Cohen, Sudhir S. Kushwaha, and Eric S. Williams to develop the specific contributions in the broad field of cardiac function and heart failure to be presented as original work at these Scientific Sessions.