Showing papers by "Marc A. Pfeffer published in 2009"

Effect of clopidogrel added to aspirin in patients with atrial fibrillation.

Abstract: Background Vitamin K antagonists reduce the risk of stroke in patients with atrial fibrillation but are considered unsuitable in many patients, who usually receive aspirin instead. We investigated the hypothesis that the addition of clopidogrel to aspirin would reduce the risk of vascular events in patients with atrial fibrillation. Methods A total of 7554 patients with atrial fibrillation who had an increased risk of stroke and for whom vitamin K–antagonist therapy was unsuitable were randomly assigned to receive clopidogrel (75 mg) or placebo, once daily, in addition to aspirin. The primary outcome was the composite of stroke, myocardial infarction, non–central nervous system systemic embolism, or death from vascular causes. Results At a median of 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving clopidogrel (6.8% per year) and in 924 patients receiving placebo (7.6% per year) (relative risk with clopidogrel, 0.89; 95% confidence interval [CI], 0.81 to 0.98; P = 0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving clopidogrel (2.4% per year) and 408 patients receiving placebo (3.3% per year) (relative risk, 0.72; 95% CI, 0.62 to 0.83; P<0.001). Myocardial infarction occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 receiving placebo (0.9% per year) (relative risk, 0.78; 95% CI, 0.59 to 1.03; P = 0.08). Major bleeding occurred in 251 patients receiving clopidogrel (2.0% per year) and in 162 patients receiving placebo (1.3% per year) (relative risk, 1.57; 95% CI, 1.29 to 1.92; P<0.001). Conclusions In patients with atrial fibrillation for whom vitamin K–antagonist therapy was unsuitable, the addition of clopidogrel to aspirin reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage. (ClinicalTrials.gov number, NCT00249873.)

A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Abstract: Background Anemia is associated with an increased risk of cardiovascular and renal events among patients with type 2 diabetes and chronic kidney disease. Although darbepoetin alfa can effectively increase hemoglobin levels, its effect on clinical outcomes in these patients has not been adequately tested. Methods In this study involving 4038 patients with diabetes, chronic kidney disease, and anemia, we randomly assigned 2012 patients to darbepoetin alfa to achieve a hemoglobin level of approximately 13 g per deciliter and 2026 patients to placebo, with rescue darbepoetin alfa when the hemoglobin level was less than 9.0 g per deciliter. The primary end points were the composite outcomes of death or a cardiovascular event (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) and of death or end-stage renal disease. Results Death or a cardiovascular event occurred in 632 patients assigned to darbepoetin alfa and 602 patients assigned to placebo (hazard...

A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease

Abstract: Background In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. Methods We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. Results With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 μg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there w...

Red Blood Cell Distribution Width and Mortality Risk in a Community-Based Prospective Cohort

Abstract: Background:Red blood cell distribution width (RDW), an automated measure of red blood cell size heterogeneity(eg,anisocytosis)thatislargelyoverlooked,isanewly recognized risk marker in patients with established cardiovascular disease (CVD). It is unknown whether RDW is associated with mortality in the general population or whether this association is specific to CVD. Methods: We examined the association of RDW with all-cause mortality and with CVD, cancer, and chronic lower respiratory tract disease mortality in 15852 adult participants in the Third National Health and Nutrition ExaminationSurvey(1988-1994),anationallyrepresentative sample of the US population. Mortality status was obtained by matching to the National Death Index, with follow-up through December 31, 2000. Results:Estimated mortality rates increased 5-fold from the lowest to the highest quintile of RDW after accounting for age and 2-fold after multivariable adjustment (Ptrend.001foreach).A1–SDincrementinRDW(0.98%) was associated with a 23% greater risk of all-cause mortality (hazard ratio [HR], 1.23; 95% confidence interval [CI],1.18-1.28)aftermultivariableadjustment.TheRDW was also associated with risk of death due to CVD (HR, 1.22; 95% CI, 1.14-1.31), cancer (1.28; 1.21-1.36), and chronic lower respiratory tract disease (1.32; 1.171.49). Conclusions: Higher RDW is associated with increased mortality risk in this large, community-based sample, an association not specific to CVD. Study of anisocytosis may, therefore, yield novel pathophysiologic insights, and measurement of RDW may contribute to risk assessment.

Liver function abnormalities and outcome in patients with chronic heart failure: data from the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program

Abstract: Aims The prevalence and importance of liver function test (LFT) abnormalities in a large contemporary cohort of heart failure patients have not been systematically evaluated. Methods and results We characterized the LFTs of 2679 patients with symptomatic chronic heart failure from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity program (CHARM). We used multivariable modelling to assess the relationships between baseline LFT values and long-term outcomes. Liver function test abnormalities were common in patients with chronic heart failure, ranging from alanine aminotransferase elevation in 3.1% of patients to low albumin in 18.3% of patients; total bilirubin was elevated in 13.0% of patients. In multivariable analysis, elevated total bilirubin was the strongest LFT predictor of adverse outcome for both the composite outcome of cardiovascular death or heart failure hospitalization (HR 1.21 per 1 SD increase, P < 0.0001) and all-cause mortality (HR 1.19 per 1 SD increase, P < 0.0001). Even after adjustment for other variables, elevated total bilirubin was one of the strongest independent predictors of poor prognosis (by global chi-square). Conclusion Bilirubin is independently associated with morbidity and mortality. Changes in total bilirubin may offer insight into the underlying pathophysiology of chronic heart failure.

Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design

Abstract: Background. Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-convertingenzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin Iand angiotensin IIlevels, may thereby provide greater benefit compared to ACEi or ARB alone. Methods. The primary objective of the ALTITUDE trial is to determine whether aliskiren 300 mg once daily, reduces cardiovascular and renal morbidity and mortality compared withplacebowhenaddedtoconventionaltreatment(including ACEi or ARB). ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged ≥35 years): those with either urinary albumin/creatinine ratio (UACR) ≥200 mg/g; microalbuminuria(UACR) ≥20 <200mg/gandeGFR ≥30 <60 mL/min/1.73 m 2 ; and thirdly, those with a history of cardiovascular disease and eGFR ≥30 <60 mL/min/1.73 m 2 with or without microalbuminuria. ALTITUDE is an event driven trial that aims to randomize 8600 patients with a planned follow-up time of 48 months. The primary outcome measure is time to first event for the composite endpoint of cardiovascular death, resuscitated death, myocardial infarction, stroke, unplanned hospitalization for heart failure,onsetofend-stagerenaldiseaseordoublingofbaseline serum creatinine concentration. Secondary endpoints include a composite CV endpoint and a composite renal endpoint.

Relation Between Alkaline Phosphatase, Serum Phosphate, and All-Cause or Cardiovascular Mortality

Abstract: Background— Higher levels of serum alkaline phosphatase (AlkP) are associated with excess mortality in dialysis patients, but whether AlkP is associated with adverse outcomes among people without kidney failure is unknown. Methods and Results— We first analyzed the association between AlkP and cardiovascular outcomes among 4115 participants with a previous myocardial infarction (the Cholesterol And Recurrent Events [CARE] study). Results were validated by analyzing the association between AlkP and mortality in an independent sample of 14 716 adults from the general US population (the Third National Health and Nutrition Examination Survey). A graded, independent association was noted between baseline tertile of AlkP and the adjusted hazard ratio of all-cause mortality in CARE participants (Ptrend=0.02). After adjustment for serum phosphate, hepatic enzymes, and other potential confounders, participants with AlkP in the highest tertile had an adjusted hazard ratio of 1.43 (95% confidence interval 1.08 to 1....

Design of the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF): a Phase III, anaemia correction, morbidity-mortality trial

Abstract: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. The Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF; Clinical Trials.gov NCT 003 58215) was designed to evaluate the effect of the long-acting erythropoietin-stimulating agent darbepoetin alfa on mortality and morbidity (and quality of life) in patients with HF and anaemia. Approximately 2600 patients with New York Heart Association class II-IV, an ejection fraction = 9.0 g/dL will be enrolled. Patients are randomized 1:1 to double-blind subcutaneous administration of darbepoetin alfa or placebo. Investigators are also blinded to Hb measurements and darbepoetin alfa is dosed to achieve an Hb concentration of 13.0 g/dL (but not exceeding 14.5 g/dL) with sham adjustments of the dose of placebo. The primary endpoint is the time to death from any cause or first hospital admission for worsening HF, whichever occurs first. The study will complete when similar to 1150 subjects experience a primary endpoint.

Adherence to medication according to sex and age in the CHARM programme.

Abstract: Aims Although many patients with heart failure have incomplete adherence to prescribed medications, predisposing factors remain unclear. This analysis investigates factors associated with adherence, with particular emphasis on age and sex. Methods and results A multivariable regression analysis of 7599 heart failure patients from the CHARM trial was done to evaluate factors associated with adherence. Adherence was measured as the proportion of time patients took more than 80% of study medication. The mean age was 66 years (SD 11) and 31.5% (n = 2400) were women. Women were slightly less adherent than men (87.3 vs. 89.8%, P = 0.002), even in adjusted, multivariable models (treatment, P = 0.006; placebo P = 0.004; and overall P < 0.001). However, all-cause mortality was lower in women (21.5%) than in men (25.3%) (adjusted hazard ratio, 0.77; 95% CI, 0.69–0.86; P < 0.001), but patients with a low adherence regardless of sex had a higher mortality. Age, severity of heart failure, number of medications, and smoking status were not associated with adherence. Conclusion Women, particularly those <75 years of age, were less likely to be adherent in this large sample of patients with symptomatic heart failure. Understanding factors associated with adherence may provide opportunities for intervention.

Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT).

Abstract: Aims Chronic obstructive pulmonary disease is an independent predictor of mortality in patients with myocardial infarction (MI). However, the impact on mode of death and risk of atherosclerotic events is unknown. Methods and results We assessed the risk of death and major cardiovascular (CV) events associated with chronic obstructive pulmonary disease in 14 703 patients with acute MI enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) trial. Cox proportional hazards models were used to evaluate the relationship between chronic obstructive pulmonary disease and CV outcomes. A total of 1258 (8.6%) patients had chronic obstructive pulmonary disease. Over a median follow-up period of 24.7 months, all-cause mortality was 30% in patients with chronic obstructive pulmonary disease, compared with 19% in those without. The adjusted hazard ratio (HR) for mortality was 1.14 (95% confidence interval 1.02–1.28). This reflected increased incidence of both non-CV death [HR 1.86 (1.43–2.42)] and sudden death [HR 1.26 (1.03–1.53)]. The unadjusted risk of all pre-specified CV outcomes was increased. However, after multivariate adjustment, chronic obstructive pulmonary disease was not an independent predictor of atherosclerotic events [MI or stroke: HR 0.98 (0.77–1.23)]. Mortality was significantly lower in patients receiving beta-blockers, irrespective of airway disease. Conclusion In high-risk patients with acute MI, chronic obstructive pulmonary disease is associated with increased mortality and non-fatal clinical events (both CV and non-CV). However, patients with chronic obstructive pulmonary disease did not experience a higher rate of atherosclerotic events.

Exact and efficient inference procedure for meta-analysis and its application to the analysis of independent 2 × 2 tables with all available data but without artificial continuity correction

Abstract: Recently, meta-analysis has been widely utilized to combine information across comparative clinical studies for evaluating drug efficacy or safety profile. When dealing with rather rare events, a substantial proportion of studies may not have any events of interest. Conventional methods either exclude such studies or add an arbitrary positive value to each cell of the corresponding 2×2 tables in the analysis. In this article, we present a simple, effective procedure to make valid inferences about the parameter of interest with all available data without artificial continuity corrections. We then use the procedure to analyze the data from 48 comparative trials involving rosiglitazone with respect to its possible cardiovascular toxicity.

Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial

Abstract: Aims The risk of gastrointestinal (GI) bleeding limits the use of antiplatelet and anticoagulant drugs. Risk factors for GI bleeding in post- myocardial infarction (MI) patients have not been well defined. We sought to identify risk factors for GI bleeding in patients following MI. Methods and results The VALsartan In Acute myocardial iNfarcTion trial (VALIANT) enrolled 14 703 post-MI patients with left ventricular dysfunction and/or heart failure and followed them for a median of 24.7 months. In the present secondary analysis, times from baseline to first GI bleeding were identified from the VALIANT serious adverse event database. Potential risk factors were explored from medical history, demographics, clinical profile, and medications, both at baseline and during follow-up. We also explored the relationship between the occurrence of GI bleeding and subsequent mortality. During follow-up, 98 (0.7%) patients had a serious GI bleeding event. These patients were older, had more comorbidities, were more likely to be taking additional antiplatelet drugs, and had worse left ventricular systolic and renal function. The Kaplan–Meier estimated rate of GI bleeding at 6 months was 0.37% (95% CI 0.27–0.47). In a multivariable Cox model, dual antiplatelet therapy was the most powerful predictor of GI bleeding, with an adjusted hazard ratio of 3.18 (95% CI 1.91–5.29). Other predictors were non-white race, history of alcohol abuse, increasing age, worse New York Heart Association class, anticoagulant therapy, diabetes, lower estimated glomerular filtration rate, and male sex. Gastrointestinal bleeding was associated with increased risk of death [adjusted hazard ratio 2.54 (95% CI 1.66–3.89)]. Conclusion Following MI, clinical characteristics can identify patients with increased risk of GI bleeding. The use of dual antiplatelet agents appears to be the most profound risk factor. Whether these patients would benefit from GI prophylaxis therapy remains unknown.

Predictors of heart failure in patients with stable coronary artery disease: a PEACE study.

Abstract: Background— Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. Methods and Results— In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64�8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfat...

Predictors of Development of Diabetes in Patients With Chronic Heart Failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) Program

Abstract: OBJECTIVE The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program. RESEARCH DESIGN AND METHODS A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses. RESULTS Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P P P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes. CONCLUSIONS In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.

Patients with prior coronary artery bypass grafting have a poor outcome after myocardial infarction: an analysis of the VALsartan in acute myocardial iNfarcTion trial (VALIANT).

Abstract: Aims The number of patients presenting with an acute myocardial infarction (MI) and prior coronary artery bypass grafting (CABG) is increasing. We compared the baseline characteristics, treatment, and clinical outcomes of patients with and without prior CABG in the VALIANT trial. Methods and results Of the 14 703 patients with heart failure (HF), left ventricular systolic dysfunction, or both enrolled in VALIANT, 1026 (7%) had prior CABG. Prior CABG patients were older [mean age (SD): 67 (10) vs. 65 (12) years; P < 0.0001], had more comorbidity, and more frequent non-Q wave MI (66 vs. 30%; P < 0.0001). At hospital presentation, prior CABG patients received less aspirin (82 vs. 90%; P < 0.0001) and thrombolysis (21 vs. 36%; P < 0.0001), but had a similar rate of primary percutaneous coronary intervention (14 vs. 15%; P = 0.2). Prior CABG patients were more likely to experience the composite outcome of cardiovascular death, MI, HF, resuscitated cardiac arrest, or stroke; 3 year Kaplan–Meier rate, 64 vs. 39% (adjusted hazard ratio 1.29, 95% confidence interval 1.17–1.43; P < 0.0001). Conclusion Patients with prior CABG had a worse clinical profile and experienced more fatal and non-fatal outcomes. Greater recognition is necessary for these high-risk patients including optimization of evidence-based secondary preventive therapy.

Transplantation Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial

Abstract: Background:Hyperhomocysteinemia may be a modifiable risk factor for the prevention of arteriosclerotic outcomes in patients with chronic kidney disease (CKD). Few clinical trials of homocysteine lowering have been conducted in persons with CKD before reaching end-stage renal disease. Kidney transplant recipients are considered individuals with CKD. Objectives: To describe the baseline characteristics of renal transplant recipients enrolled in a clinical trialofhomocysteineloweringwithastandardmultivitamincontaininghighdosesoffolicacidandvitaminsB6 and B12 aimed at reducing arteriosclerotic outcomes. Factors considered were level of kidney function, total homocysteine concentration, and prevalence of diabetes and previous cardiovascular disease (CVD). Study Design: Cross-sectional survey within a randomized controlled trial cohort. Setting & Participants: Participants were recruited from kidney transplant clinics in the United States, Canada, and Brazil. Eligible participants had increased levels of homocysteine (12.0 mol/L in men and 11.0 mol/L in women) and kidney function measured by means of Cockroft-Gault estimated creatinine clearance of 30 mL/min or greater. Results: Of 4,110 randomly assigned participants, 38.9% had diabetes and 19.5% had previous CVD. Mean total homocysteine concentration was 17.1 6.3 (SD) mol/L, whereas mean creatinine clearance was 66.4 23.2 mL/min. Approximately 90% of the trial cohort had an estimated glomerular filtration rate consistent with stages 2 to 3 CKD (ie, 30 to 89 mL/min). Limitations: Analysis is based on cross-sectional data from a randomized controlled trial, self-report of comorbid illnesses, and level of kidney function was estimated. Conclusions: A large population of stable renal transplant recipients who are at high risk of the development of CVD (both de novo and recurrent) has been recruited into the Folic Acid for Vascular Outcome Reduction in Transplantation Trial and are likely to experience a sufficient number of events to address the primary hypothesis of the trial. Am J Kidney Dis 53:121-128. ©2008 by the National Kidney Foundation, Inc.

Acute Decline in Renal Function, Inflammation, and Cardiovascular Risk after an Acute Coronary Syndrome

Abstract: Background and objectives: Chronic kidney disease is associated with a higher risk of cardiovascular outcomes. The prognostic significance of worsening renal function has also been shown in various cohorts of cardiac disease; however, the predictors of worsening renal function and the contribution of inflammation remains to be established. Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants. Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3). Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease.

Usefulness of beta blockers in high-risk patients after myocardial infarction in conjunction with captopril and/or valsartan (from the VALsartan In Acute Myocardial Infarction [VALIANT] trial).

Abstract: Concern has been raised about combining β blockers with angiotensin-receptor blockers in patients with heart failure. The VALsartan In Acute myocardial infarction (VALIANT) trial enrolled 14,703 patients with myocardial infarction complicated by heart failure or documented left ventricular systolic dysfunction. These patients were randomly allocated to treatment with valsartan, captopril, or both. Physicians were also encouraged to prescribe β blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking β blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with β blockers were at lower risk than those not treated at any period. Those treated with β blockers at both intervals had a lower 3-year mortality rate (17.7%) than those treated only at randomization (30.7%) or only at discharge (25.9%). The greatest mortality (35.1%) occurred in patients not treated at either point. No statistically significant interaction with prognosis was observed between β-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a β blocker had a significant survival advantage after adjustment for differences in baseline characteristics and intervening complications (hazard ratio 0.89, 95% confidence interval 0.81 to 0.98, p = 0.02). This association was most pronounced in patients prescribed consistent β blockers at randomization and discharge and was present in both patients with impaired and those with preserved systolic left ventricular function. These results have further confirmed that β blockers reduce the risk of death and nonfatal cardiovascular events in patients with heart failure or systolic left ventricular dysfunction after myocardial infarction. In conclusion, no evidence was found of adverse interactions between the angiotensin-receptor blocker valsartan and β blockers or of a negative effect of the combination of valsartan, captopril, and β blockers.

Infarct haemorrhage detected by cardiac magnetic resonance imaging: are we seeing the latest culprit in adverse left ventricular remodelling?

Abstract: > The force of the heart decreases … as the greater number of its parts become tendinous instead of fleshy. De sedibus et causus morborum > > G. B. Morgagni, 1761 All myocardial infarctions are not equal, and those that produce more extensive left ventricular topographical alterations are much more likely to result in premature morbidity and mortality. The advent of non-invasive cardiac imaging, particularly echocardiography, provided a temporal window to evaluate the dynamics of the structural alterations produced by a myocardial infarction. In the late 1970s, infarct expansion was defined as an acute dilatation and thinning of the infarcted region leading to an elongation of that segment which was not accounted for by further necrosis.1 This early change in ventricular contour often leading to an aneurysm identified patients at higher risk for early mortality and other infarct complications. In animal models, it became apparent that the early distortion of ventricular architecture in response to an extensive loss of myocytes was part of a more insidious progressive process of ventricular enlargement which involved the viable segment as well as the infarcted region. This architectural-modifying process termed ‘ventricular remodelling after myocardial infarction’ results in a larger ventricular chamber.2 Although the early enlargement may provide some compensation by restoring stroke volume despite a reduced ejection fraction, the alterations in left ventricular architecture create a chronic imbalance in loading conditions that leads to further topographic changes which augment risks for adverse events. Larger infarct size is the major factor promoting adverse left ventricular remodelling, and myocardial reperfusion performed during the myocyte salvage period remains the most definitive therapeutic modality to reduce adverse ventricular remodelling. Early studies also indicated that re-establishing coronary perfusion just outside of the window of salvage could still favourably attenuate some of the adverse structural changes by promoting prompter healing in the infarcted region.3 The complementary … *Corresponding author. Tel: +1 617 732 5500, Fax: +1 617 732 5291, E-mail: mapfeffer{at}bics.bwh.harvard.edu or mpfeffer{at}rics.bwh.harvard.edu

Inhibiting the Renin Angiotensin Aldosterone System in Patients with Heart Failure and Myocardial Infarction

Abstract: Pharmacologic inhibitors of the renin angiotensin aldosterone system (RAAS) have played an important role in treating and preventing a variety of cardiovascular diseases. Although mainly developed as antihypertensive agents, the life-saving benefits of inhibiting the RAAS at several steps along its neurohumoral cascade in patients with chronic heart failure and high-risk myocardial infarction have earned these compounds a central role in the pharmacologic armamentarium. This chapter will highlight proven accomplishments of various inhibitors of the RAAS and discuss optimal clinical use of these compounds individually and in combinations in both of these conditions.