Biomedical subjects

Marc A Pfeffer

Publications and source records attributed to Marc A Pfeffer.

At least 37 records · Page 2Linked to original sources

PubMed2006

Controversies in ventricular remodelling.

Ventricular remodelling describes structural changes in the left ventricle in response to chronic alterations in loading conditions, with three major patterns: concentric remodelling, when a pressure load leads to growth in cardiomyocyte thickness; eccentric hypertrophy, when a volume load produces myocyte lengthening; and myocardial infarction, an amalgam of patterns in which stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas. Whether left-ventricular hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns of signalling pathways, transgenic models, and clinical findings in aortic stenosis. The transition from apparently compensated hypertrophy to the failing heart indicates a changing balance between metalloproteinases and their inhibitors, effects of reactive oxygen species, and death-promoting and profibrotic neurohumoral responses. These processes are evasive therapeutic targets. Here, we discuss potential novel therapies for these disorders, including: sildenafil, an unexpected option for anti-transition therapy; surgery for increased sphericity caused by chronic volume overload of mitral regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of transforming growth factor beta; mechanical intervention in advanced heart failure; and stem-cell therapy.

Animals↗

PubMed2006

The association of the heart failure score with mortality and heart failure hospitalizations in elderly patients: insights from the Mode Selection Trial (MOST).

BACKGROUND: Patient and physician preferences as well as cost favor an increasingly higher threshold for hospital admission for heart failure (HF) treatment. This trend risks masking the severity and prevalence of HF as hospitalization for HF may decrease. METHODS: Heart Failure Score (HFS) has 4 ordinal subscales assessing (1) HF symptoms, physical signs of left (2) and (3) right HF, and (4) therapy changes for HF. Heart Failure Score was calculated for 1257 of 2010 (63%) patients enrolled in the MOST trial in sinus node dysfunction, who survived and had complete first-year HFS data at 4 postpacemaker implant visits (1, 3, 6, and 12 months). Heart Failure Score was summed and ranged from 0 to 14, with lower scores representing less HF. RESULTS: There were 1257 patients (median age 74 years [interquartile range 68-79], 47% were women, 61% had hypertension, 20%, diabetes mellitus, and 23%, prior myocardial infarction). The median HFS accumulated during 1 year was 4 (interquartile range 1-8). Of patients with a benign first year, those with a higher HFS were more likely to die during subsequent follow-up compared with patients with lower HFS (hazard ratio 1.07, 95% CI 1.04-1.10 for each 1-point increase, P < .001). CONCLUSIONS: Increasing HFS is associated with an increased risk of mortality in mostly elderly patients without pre-existing HF. Heart Failure Score may be a useful surrogate HF end point for clinical trials.

Aged↗

PubMed2006

Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used. RESULTS: 6446 patients (84.8%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.08%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.

Aged↗

PubMed2006

Metabolic syndrome, C-reactive protein, and prognosis in patients with established coronary artery disease.

BACKGROUND: The prognosis associated with metabolic syndrome and high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease has not been well established. METHODS: The WIZARD study was to determine the effects of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known Chlamydia pneumoniae exposure. Baseline metabolic risk factors were available for 3319 patients enrolled from 1997 to 1998. The primary outcome was the first occurrence of death, recurrent myocardial infarction, coronary revascularization procedure, or hospitalization for angina. RESULTS: Of the 3319 subjects, 825 patients experienced the primary outcome during the mean follow-up of 37 months. For the composite outcome, there was an increased hazard ratio (HR) for metabolic syndrome (HR 1.40, 95% CI 1.22-1.61) (unadjusted) and for hs-CRP (HR 1.60, 95% CI 1.38-1.85) (unadjusted). Both the metabolic syndrome and hs-CRP indicated, in a multivariable model including age and sex, an increased HR for the primary outcome (metabolic syndrome: HR 1.33, 95% CI 1.15-1.53; hs-CRP: HR 1.52, 95% CI 1.30-1.76). CONCLUSIONS: Although related, the presence of the metabolic syndrome and increased levels of hs-CRP were associated with increased risk of adverse cardiovascular outcomes.

Aged↗

PubMed2006

Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. METHODS: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. RESULTS: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. CONCLUSIONS: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Aged↗

PubMed2006

Relationship of dose of background angiotensin-converting enzyme inhibitor to the benefits of candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)-Added trial.

BACKGROUND: Whether an angiotensin receptor blocker is of benefit when added to a full dose of angiotensin-converting enzyme (ACE) inhibitor in heart failure (HF) is uncertain. METHODS: The effect of candesartan, compared with placebo, in 2548 patients randomized in the CHARM-Added trial was analyzed according to (i) ACE inhibitor dose at baseline, (ii) ACE inhibitor dose during follow-up, and (iii) combination treatment with ACE inhibitor and beta-blocker at baseline. The main outcome was the composite of cardiovascular death or HF hospitalization. RESULTS: The benefit of candesartan was not modified by the dose of ACE inhibitor. In all patients (n = 2548), the candesartan/placebo hazard ratio (HR) for the primary outcome was 0.85 (95% CI 0.75-0.96). In patients taking a guideline recommended dose of ACE inhibitor at baseline (n = 1291), this HR was 0.79 (95% CI 0.67-0.95; interaction P value .26). In patients taking a Food and Drug Administration-designated maximum dose of ACE inhibitor (n = 529), this HR was 0.75 (95% CI 0.57-0.98; interaction P value .29). The benefit of candesartan was preserved in patients taking beta-blockers in addition to a higher dose of ACE inhibitor and in patients maintaining a high dose of ACE inhibitor throughout follow-up. CONCLUSIONS: These clinical findings support the pharmacologic evidence that ACE inhibitors and angiotensin receptor blockers have distinct mechanisms of action and show that their combined use improves outcomes in patients with HF more than an evidence-based dose of ACE inhibitor alone.

Aged↗

PubMed2006

Rationale and design of the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial.

BACKGROUND: Patients with chronic kidney disease, including kidney transplant recipients, are at high risk for cardiovascular disease (CVD). In addition to the constellation of traditional CVD risk factors in chronic kidney disease, elevated total homocysteine (tHcy) is notably more prevalent among the general population. The Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) trial is designed to evaluate whether lowering tHcy using vitamin supplementation reduces CVD events in renal transplant recipients. METHODS: FAVORIT is a multicenter double-blind randomized controlled clinical trial. Participants are clinically stable renal transplant recipients who are 6 months or longer posttransplant with elevated tHcy. Patients are randomized to a multivitamin that includes either a high-dose or low-dose of folic acid (5 or 0 mg), vitamin B6 (50 or 1.4 mg), and vitamin B12 (1000 or 2 microg). The primary end point is a composite of incident or recurrent CVD outcomes, that is, coronary heart, cerebrovascular, or abdominal aortic/lower extremity arterial events. A sample size of 4000 is estimated to provide 87% power to detect a 20% treatment effect. Recruitment is expected to continue until July 2006, with follow-up through June 2010. RESULTS: From August 2002 through December 2004, 2234 of the target 4000 patients were enrolled. In accordance with trial design, mean (SD) screening tHcy was elevated (17.4 +/- 6.2 micromol/L), and mean (SD) estimated creatinine clearance was consistent with stable renal function (58.0 +/- 18.6 mL/min). Evaluating baseline results to date, 42% of the randomized participants had a history of diabetes mellitus, and 21% had prevalent CVD. CONCLUSIONS: The FAVORIT trial is designed with sufficient power and follow-up time to detect a clinically relevant change in CVD risk between renal transplant recipients receiving a high or low tHcy-lowering folic acid multivitamin. Preliminary screening and baseline data support the trial's objectives.

Adult↗

PubMed2006

Risk assessment in patients with depressed left ventricular function after myocardial infarction using the myocardial performance index--Survival and Ventricular Enlargement (SAVE) experience.

BACKGROUND: Myocardial performance index (MPI) is a noninvasive, quantitative Doppler measure of global cardiac function, integrating systolic and diastolic functions. The prognostic significance of MPI is less clear for cardiovascular (CV) events after myocardial infarction (MI) among individuals at high risk with depressed left ventricular (LV) systolic function. METHODS: We analyzed echocardiograms from 512 patients with depressed LV function after MI enrolled in the Survival and Ventricular Enlargement (SAVE) echocardiographic substudy. Baseline MPI measures were obtainable in 226 patients. The cohort was separated by median MPI (0.50). MPI was related to baseline clinical and echocardiographic characteristics, ventricular remodeling, and subsequent CV events, including recurrent MI, heart failure, CV death, and a composite of all CV end points. RESULTS: An MPI of 0.5 or more was associated with larger infarct size and reduced LV systolic function at baseline; other baseline characteristics between the groups were similar. A total of 64 (28.3%) patients experienced CV events. Baseline MPI did not influence ventricular remodeling and did not modify the relationship between ventricular dilatation and CV events. After covariate adjustment, an MPI of 0.50 or higher remained an independent predictor for adverse CV events (hazard ratio [HR], 2.00, 95% confidence interval 1.17-3.43). CONCLUSIONS: An MPI of 0.50 or greater is an independent predictor for CV events after MI in patients with known LV dysfunction.

Cohort Studies↗

PubMed2006

Comparison of regional versus global assessment of left ventricular function in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction: the valsartan in acute myocardial infarction echocardiographic study.

BACKGROUND: Left ventricular (LV) ejection fraction (EF) and wall-motion index (WMI) have both been shown to be independent predictors of outcome after myocardial infarction (MI). OBJECTIVES: We sought to determine whether these two measurements of LV systolic function provide similar or complementary information about prognosis after MI. METHODS: Echocardiography was performed in 610 patients with LV dysfunction, heart failure, or both after MI enrolled in the Valsartan in Acute MI trial. LVEF was estimated by biplane Simpson's rule, and WMI was assessed using a 16-segment model in 502 patients with echocardiograms of sufficient quality for wall-motion assessment. RESULTS: Both LVEF and WMI were independent predictors of adverse outcome after MI. LVEF conferred no additional prognostic information in multivariable analysis including WMI (P = .39) or number of affected segments (P = .53), whereas WMI (P = .02) and total number of affected segments (P = .006) remained significant even when adjusting for LVEF. CONCLUSIONS: Assessment of regional dysfunction by WMI or the number of affected segments has slightly more prognostic value than LVEF in patients with LV dysfunction, heart failure, or both after MI. Regional assessment might be a more sensitive predictor of outcome than global assessment in patients with acute MI.

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PubMed2006

Resource utilization and costs in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: More treatments are needed to improve clinical outcomes in chronic heart failure (HF). It is, however, important that treatments for a condition as common as HF are affordable. We have carried out a prospective economic analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. METHODS AND RESULTS: Patients with NYHA class II-IV HF and LVEF < or =0.40 were randomized to CHARM-Alternative if intolerant of an ACE-inhibitor or to CHARM-Added if taking an ACE-inhibitor. Patients with a LVEF >0.40 were randomized in CHARM-Preserved. Each trial compared the effect of candesartan to placebo on the primary outcome of cardiovascular death or HF hospitalization. Detailed information was prospectively collected on hospital admissions, procedures/operations and drugs. A cost-consequence analysis was performed for France, Germany and the UK for CHARM-Overall and a cost-effectiveness analysis for the low LVEF trials. The cost of candesartan was substantially offset by a reduction in hospital admissions, especially for HF. In the cost-consequence analysis, candesartan was cost-saving in most scenarios for CHARM-Alternative and Added but the marginal annual net cost per patient was upto 372 euros per year in CHARM-Preserved, in which candesartan did not reduce the primary outcome significantly. In the cost-effectiveness analysis of patients with a LVEF < or = 0.40, candesartan was cost-saving in some scenarios and in the others the maximum cost per life year gained was 3881 euros. CONCLUSION: Candesartan improves functional class, reduces the risk of hospital admission, and increases survival in patients with a HF and a LVEF < or =0.40 at an acceptable cost.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population. METHODS: 7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used. RESULTS: 6379 patients (83.9%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.15%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57). CONCLUSIONS: Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.

Aged↗

PubMed2005

Adherence to candesartan and placebo and outcomes in chronic heart failure in the CHARM programme: double-blind, randomised, controlled clinical trial.

BACKGROUND: Chronic heart failure (CHF) is an important cause of hospital admission and death. Poor adherence to medication is common in some chronic illnesses and might reduce the population effectiveness of proven treatments. Because little is known about adherence in patients with CHF and about the consequences of non-adherence, we assessed the association between adherence and clinical outcome in the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme. METHODS: CHARM was a double-blind, randomised, controlled clinical trial, comparing the effects of the angiotensin receptor blocker candesartan with placebo in 7599 patients with CHF. Median follow-up was 38 months. The proportion of time patients took more than 80% of their study medication was defined as good adherence and 80% or less as poor adherence. We used a Cox proportional hazards regression model, with adherence as a time-dependent covariate in the model, to examine the association between adherence and mortality in the candesartan and placebo groups. FINDINGS: We excluded 187 patients because of missing information on adherence. In the time-dependent Cox regression model, after adjustment for predictive factors (demographics, physiological and severity-of-illness variables, smoking history, and number of concomitant medications), good adherence was associated with lower all-cause mortality in all patients (hazard ratio [HR] 0.65, 95% CI 0.57-0.75, p<0.0001). The adjusted HR for good adherence was similar in the candesartan (0.66, 0.55-0.81, p<0.0001) and placebo (0.64, 0.53-0.78, p<0.0001) groups. INTERPRETATION: Good adherence to medication is associated with a lower risk of death than poor adherence in patients with CHF, irrespective of assigned treatment. This finding suggests that adherence is a marker for adherence to effective treatments other than study medications, or to other adherence behaviours that affect outcome. Understanding these factors could provide an opportunity for new interventions, including those aimed at improving adherence.

Aged↗

PubMed2005

Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients.

BACKGROUND: Left ventricular function is a principal determinant of cardiovascular risk in patients with heart failure. The growing number of patients with preserved systolic function heart failure underscores the importance of understanding the relationship between ejection fraction and risk. METHODS AND RESULTS: We studied 7599 patients with a broad spectrum of symptomatic heart failure enrolled in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Program. All patients were randomized to candesartan at a target dose of 32 mg once daily or matching placebo and followed up for a median of 38 months. We related left ventricular ejection fraction (LVEF), measured before randomization at the sites, to cardiovascular outcomes and causes of death. Mean LVEF in patients enrolled in CHARM was 38.8+/-14.9% (median LVEF 36%). Patients with lower LVEF tended to have higher baseline New York Heart Association class. The hazard ratio for all-cause mortality increased by 39% for every 10% reduction in ejection fraction below 45% (hazard ratio 1.39, 95% CI 1.32 to 1.46), with adjustment for baseline covariates. All-cause mortality, cardiovascular death, and all components of cardiovascular death declined with increasing ejection fraction until an ejection fraction of 45%, after which the risk of these outcomes remained relatively stable with increasing LVEF. The absolute change in rate per 100 patient-years for each 10% reduction in LVEF was greatest for sudden death and heart failure-related death. The effect of candesartan in reducing cardiovascular outcomes was consistent across LVEF categories. CONCLUSIONS: LVEF is a powerful predictor of cardiovascular outcome in heart failure patients across a broad spectrum of ventricular function. Nevertheless, once elevated to a range above 45%, ejection fraction does not further contribute to assessment of cardiovascular risk in heart failure patients.

Aged↗

PubMed2005

Mortality and morbidity remain high despite captopril and/or Valsartan therapy in elderly patients with left ventricular systolic dysfunction, heart failure, or both after acute myocardial infarction: results from the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

BACKGROUND: The elderly constitute an increasing proportion of acute myocardial infarction patients and have disproportionately high mortality and morbidity. Those with heart failure or impaired left ventricular left ventricular function after acute myocardial infarction have high complication and mortality rates. Little is known about outcomes with contemporary therapies in these patients. METHODS AND RESULTS: The Valsartan in Acute Myocardial Infarction Trial (VALIANT) randomized 14,703 patients with heart failure and/or left ventricular ejection fraction <40% to receive captopril, valsartan, or both. Mortality and a composite end point, including cardiovascular mortality, readmission for heart failure, reinfarction, stroke, and resuscitated cardiac arrest, were compared for the age groups of <65 (n=6988), 65 to 74 (n=4555), 75 to 84 (n=2777), and > or =85 (n=383) years. With increasing age, 3-year mortality almost quadrupled (13.4%, 26.3%, 36.0%, and 52.1%, respectively), composite end-point events more than doubled (25.2%, 41.0%, 52.3%, and 66.8%), and hospital admissions for heart failure almost tripled (12.0%, 23.1%, 31.3%, and 35.4%). Outcomes did not differ between the 3 study treatments in any age group. Adverse events associated with captopril and valsartan were more common in the elderly and in patients receiving combination therapy. With increasing age, use of aspirin, beta-blockers, and statins declined, and use of digoxin, calcium-channel blockers, and non-potassium-sparing diuretics increased. On 3-year multivariable analysis, each 10-year age increase was associated with a hazard ratio of 1.49 (95% CI, 1.426 to 1.557; P<0.0001) for mortality and an odds ratio of 1.38 (95% CI, 1.31 to 1.46; P<0.0001) for readmission with heart failure. CONCLUSIONS: Outcomes remained poor in elderly patients with heart failure and/or impaired left ventricular systolic function after acute myocardial infarction, although most received beta-blockers and all received an ACE inhibitor and/or an angiotensin receptor blocker. Better therapies and increased use of aspirin, beta-blockers, and statins are needed in this important and increasing patient group.

Age Factors↗

PubMed2005

Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy.

OBJECTIVES: This study sought to evaluate the safety and efficacy of achieving very low calculated low-density lipoprotein (LDL) levels with intensive statin therapy. BACKGROUND: Intensive statin therapy reduces clinical events occurring after acute coronary syndrome (ACS) and may result in LDL levels markedly lower than guideline levels. Prior epidemiologic and preclinical studies raise concerns about the safety of very low cholesterol levels. METHODS: The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study compared intensive therapy (atorvastatin, 80 mg) and moderate therapy (pravastatin, 40 mg) in patients after ACS. Patients treated with atorvastatin were divided by four-month LDL values into groups: >100, >80 to 100 (reference-range-meeting guidelines), >60 to 80, >40 to 60, and <40 mg/dl. Baseline, clinical, and safety data were compared among groups achieving guideline recommendation levels or lower. RESULTS: Among 1,825 patients with four-month LDL, 91% were at goal (<100 mg/dl). The distribution was >80 to 100 mg/dl (14%), >60 to 80 mg/dl (31%), >40 to 60 mg/dl (34%), and <40 mg/dl (11%). Those with lower LDL levels were more often male, older, and diabetic, and had lower baseline LDL levels. They had prior statin therapy and fewer prior myocardial infarctions (MI). There were no significant differences in safety parameters, including muscle, liver, or retinal abnormalities, intracranial hemorrhage, or death, in the very low LDL groups. The <40 mg/dl and 40 to 60 mg/dl groups had fewer major cardiac events (death, MI, stroke, recurrent ischemia, revascularization). CONCLUSIONS: Compared with patients treated with an accepted LDL goal (80 to 100 mg/dl), there was no adverse effect on safety with lower achieved LDL levels, and apparent improved clinical efficacy. These data identify no intrinsic safety concern of achieving low LDL and, therefore, a strategy of intensive treatment need not be altered in patients achieving very low LDL levels.

Acute Disease↗

PubMed2005

Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure.

CONTEXT: Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect. OBJECTIVE: To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure. DESIGN, SETTING, AND PARTICIPANTS: The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic. MAIN OUTCOME MEASURE: The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo. RESULTS: During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan. CONCLUSION: In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.

Aged↗

PubMed2005

Predictors of mortality and morbidity in patients with chronic heart failure.

AIMS: We aimed to develop prognostic models for patients with chronic heart failure (CHF). METHODS AND RESULTS: We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality (n=1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization (n=2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. CONCLUSION: In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.

Adult↗

PubMed2005

Left ventricular assessment in myocardial infarction: the VALIANT registry.

BACKGROUND: How often echocardiography and cardiac catheterization are used to evaluate left ventricular (LV) function in patients with myocardial infarction (MI) and how they are associated with quality of care is unknown. METHODS: Patients with MI in the Valsartan in Acute Myocardial Infarction (VALIANT) registry were divided into those with (n = 1423) and without (n = 3968) heart failure (HF), and the use of either echocardiography or cardiac catheterization for LV assessment in each group was compared along with associated baseline characteristics. We evaluated the association between LV assessment and discharge medications. Using a multivariable model with a propensity analysis, we evaluated the association of LV assessment with in-hospital outcomes. RESULTS: Of the patients with HF, 322 (22.6%) had no LV assessment. Patients with HF with LV assessment were discharged more frequently under treatment with aspirin (81.3% vs 70.0%; P<.001), beta-blockers (65.6% vs 56.4%; P = .008), clopidogrel (30.4% vs 14.0%; P<.001), and statins (45.9% vs 34.2%; P<.001). Patients without HF who underwent LV assessment were discharged more frequently under treatment with an angiotensin-converting enzyme inhibitor (53.8% vs 41.5%; P<.001). After adjustment for regional use, other covariates, and revascularization, LV assessment was associated with lower in-hospital mortality in patients with HF (adjusted odds ratio [OR], 0.45; P<.001) and in patients without HF (adjusted OR, 0.30; P<.001). After excluding deaths during the first 2 days, LV assessment remained associated with lower mortality in patients with HF (adjusted OR, 0.59; P = .03) and in patients without HF (adjusted OR, 0.41; P<.001). CONCLUSION: Left ventricular assessment was frequently not performed during the in-hospital stay of patients with acute MI, including those with clinical HF, and its use was associated with better quality of care.

Aged↗