Valsartan In Acute Myocardial Infarction Research Articles

Combined Use of Sacubitril and Valsartan in Acute Myocardial Infarction

Combined Use of Sacubitril and Valsartan in Acute Myocardial Infarction

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Predicting Outcomes Over Time in Patients With Heart Failure, Left Ventricular Systolic Dysfunction, or Both Following Acute Myocardial Infarction.

BackgroundMost studies of risk assessment or stratification in patients with myocardial infarction (MI) have been static and fail to account for the evolving nature of clinical events and care processes. We sought to identify predictors of mortality, cardiovascular death or nonfatal MI, and cardiovascular death or nonfatal heart failure (HF) over time in patients with HF, left ventricular systolic dysfunction, or both post‐MI.Methods and ResultsUsing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial, we developed models to estimate the association between patient characteristics and the likelihood of experiencing an event from the time of a follow‐up visit until the next visit. The intervals are: hospital arrival to discharge or 14 days, whichever occurs first; hospital discharge to 30 days; 30 days to 6 months; and 6 months to 3 years. Models were also developed to predict the entire 3‐year follow‐up period using baseline information. Multivariable Cox proportional hazards modeling was used throughout with Wald chi‐squares as the comparator of strength for each predictor. For the baseline model of overall mortality, the 3 strongest predictors were age (adjusted hazard ratio [HR], 1.35; 95% CI, 1.28–1.42; P<0.0001), baseline heart rate (adjusted HR, 1.17; 95% CI, 1.14–1.21; P<0.0001), and creatinine clearance (≤100 mL/min; adjusted HR, 0.86; 95% CI, 0.84–0.89; P<0.0001). According to the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices, the updated model had significant improvement over the model with baseline covariates only in all follow‐up periods and with all outcomes.ConclusionsPatient information assessed closest to the time of the outcome was more valuable in predicting death when compared with information obtained at the time of the index hospitalization. Using updated patient information improves prognosis over using only the information available at the time of the index event.

Valsartan after myocardial infarction.

One of the important problems of the patients undergoing acute myocardial infarction (MI) is early development of heart failure. It has been revealed in various studies that renin-angiotensin-aldosterone system (RAAS) has a significant role in this process. The studies conducted with angiotensin converting enzyme (ACE) inhibitors have resulted in decreased mortality rate. Another RAAS blocker which was discovered about ten years later than other ACE inhibitors in historical process is angiotensin receptor blockers (ARB) inhibiting the efficiency of angiotensin 2 by binding to angiotensin 1 receptor. Valsartan is one of the molecules of this group, which has higher number of large-scale randomized clinical studies. In this review, following presentation of a general overview on heart failure after acute MI, the efficiency of ARBs in this patient group will be discussed. This discussion will mostly emphasize the construction, outcomes and clinical importance of VALIANT (VALsartan In Acute myocardial iNfarcTion), which is the study on valsartan after acute MI heart failure.

Impact of Cardiovascular Events on Change in Quality of Life and Utilities in Patients After Myocardial Infarction: A VALIANT Study (Valsartan In Acute Myocardial Infarction)

The objective of this study was to determine the impact of nonfatal cardiovascular (CV) events on changes in health-related quality of life (HRQL). There is limited understanding of the impact of nonfatal CV events on long-term changes in HRQL in survivors ofmyocardial infarction (MI). The VALIANT (Valsartan In Acute Myocardial Infarction) trial enrolled 14,703 patients post-MI complicated by Killip class II or higher (scale measuring heart failure severity post-MI ranging from class I to IV) and/or reduced ejection fraction. The HRQL substudy included 2,556 (17.4%) patients who completed the EQ-5D with 5 questions, with responses mapped to utility weight on a scale of 0 to 1 and a visual analog scale (VAS) ranging from 0 (worst) to 100 (best) imaginable health state. EQ-5D was administered at baseline and 6, 12, 20, and 24 months. The trajectory of EQ-5D scores was developed by using linear mixed effects regression models with calculation of deviation from this trajectory after nonfatal CV events. Patients who died before the next EQ-5D assessment were excluded. Over a 2-year period, 597 patients experienced a nonfatal CV event and survived to have another EQ-5D assessment. Their baseline EQ-5D scores were lower than patients without a subsequent nonfatal CV event (VAS 61.0 ± 19 vs 68.2 ± 18 [p< 0.001] and US-based utility score 0.76 ± 0.22 vs 0.83 ± 0.17 [p< 0.001]). These patients with CVevents experienced a trajectory-adjusted 6.6 point decrease (p< 0.001) in VAS scores and a 0.07 decrease (p<0.001) in utility score after the nonfatal CV event. MI survivors suffering a CV event experienced significantly worse HRQL than their previous trajectory, suggesting that generic instruments can be responsive to nonfatal events. Reduction in nonfatal CV events may affect longitudinal changes in HRQL.

Papillary Muscle Infarction, Mitral Regurgitation, and Long-Term Prognosis

In patients with acute myocardial infarction, the presence of mitral regurgitation (MR) is clinically important. The reported prevalence of MR after myocardial infarction varies. Bursi et al1 have pointed out that the prevalence varies between 1.6% and 19% in angiographic studies, but may be higher in echocardiographic studies. Indeed, among 773 patients undergoing echocardiography <30 days after infarction, MR was present in 50% of patients, of which MR was mild in 38% patients and moderate to severe in 12%.2 Thus, the variability in the reported prevalence of MR seems to be related to the technique used to assess its presence and to quantify its severity. It may also be related to the timing of MR assessment after infarction. In a recent report from the Valsartan in Acute Myocardial Infarction (VALIANT) study, the prevalence of MR was quantitatively assessed at baseline, 1 month, and 20 months in 341 patients after infarction.3 In this study, MR worsened by 1 degree in 78 patients (23%) and by 2 degrees in 10 patients (3%) after 20 months of follow-up. Conversely, 47 patients (14%) improved in MR by ≥1 degree, whereas in the remaining 206 patients (60%), the severity of MR remained unchanged. In particular, at 20 months follow-up, 15% of patients had moderate to severe MR. Article see p 890 It has been reported in various studies that patients with MR after infarction have a worse prognosis. In 1190 patients with acute infarction, the hazard ratios for development of heart failure, as compared with patients without MR, were 2.8 for patients with mild MR and 3.6 for patients with moderate to severe MR.4 In the same population, the hazard ratios for death were 1.2% (mild MR) and 2.0% (moderate to severe regurgitation). Similarly, Bursi et al2 reported a relative …

Management of Acute Coronary Syndromes

Management of Acute Coronary Syndromes

Controversy surrounding the best time for ICD implantation after myocardial infarction

Controversy surrounding the best time for ICD implantation after myocardial infarction

Predicting the Future

It's tough to make predictions, especially about the future. —Yogi Berra Risk stratification for any disease is, in many ways, medicine's attempt to predict the future. The challenges in risk stratification for sudden death, however, may be unparalleled in medicine. Although the many types of sudden death all present with similar phenotypes, risk stratification efforts generally center on the prediction of death resulting from either ischemic or arrhythmic events. The focus of this article is on current and future approaches to risk stratification for sudden death caused by ventricular tachyarrhythmias in patients with left ventricular dysfunction (referred to here as sudden cardiac death [SCD]). Recent advances that limit the myocardial injury and remodeling that leads to left ventricular dysfunction continue to favorably affect SCD rates. However, the prevalence of SCD and the low survival rate once it occurs remain major public health concerns and underscore the importance of risk stratification and preemptive intervention. For many other disease processes for which risk factors are established or sought, investigators have successfully relied on objective criteria to define the end point of interest such as myocardial infarction (MI). For SCD, we have often depended on clinical trials that assessed arrhythmic death or surrogate markers such as appropriate implantable cardioverter-defibrillator (ICD) therapy or total mortality. Many of these end points, however, may not accurately assess the occurrence of fatal ventricular tachyarrhythmias that are otherwise amenable to defibrillation. Our ability to correctly distinguish cause of death on clinical grounds is marginal at best, with data suggesting that at least in patients with ischemic heart disease, we may be wrong nearly half the time. For example, in a substudy of the Valsartan in Acute Myocardial Infarction (VALIANT) trial, autopsies were performed on post-MI patients whose deaths were considered sudden on clinical grounds. Of these, 49% were …

Incremental value of echocardiographic assessment beyond clinical evaluation for prediction of death and development of heart failure after high-risk myocardial infarction

Echocardiographic measurements of left ventricular (LV) function, predominantly LV ejection fraction (LVEF), have been used to define risk in patients after myocardial infarction. However, the extent to which measures of LV structure and function provide incremental prognostic value over clinical variables in survivors of high-risk myocardial infarction has not been well defined. Predictors of death and development of heart failure were assessed in 603 patients from the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiographic substudy. We used multivariable proportional hazards models to assess the individual predictive value of echocardiographic measures including left ventricular mass index, LVEF, LV volumes, left atrial volume index, right ventricular fractional area change, mitral regurgitation, and deceleration time. We adjusted for the 11 clinical variables found previously to be most associated with all-cause mortality in this cohort. Receiver operating characteristic curves obtained via binary response regression were used to assess the incremental predictive value of echocardiographic measures in predicting outcomes of death and hospital stay for heart failure. Each echocardiographic measure was independently associated with outcome of death or development of heart failure (all P < .002). Left ventricular ejection fraction alone added minimal prognostic value to the clinical assessment, yet adding additional echocardiographic assessments to a multivariable model improved in predicting 17-month survival free of heart failure significantly, increasing the c-statistic from 0.74 to 0.84 (P < .001). Echocardiographic measures of cardiac structure and function beyond LVEF provide important prognostic information beyond the clinical assessment.

Atrial fibrillation management strategies and early mortality after myocardial infarction: results from the Valsartan in Acute Myocardial Infarction (VALIANT) Trial

Atrial fibrillation management strategies and early mortality after myocardial infarction: results from the Valsartan in Acute Myocardial Infarction (VALIANT) Trial

Diabetes mellitus in patients with myocardial infarction complicated by heart failure: a ‘low ejection fraction’ equivalent?

Diabetes mellitus in patients with myocardial infarction complicated by heart failure: a ‘low ejection fraction’ equivalent?

Departures from the protocol during conduct of a clinical trial: a pattern from the data record consistent with a learning curve

ObjectiveRecognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinised. The VALsartan In Acute myocardial iNfarcTion,...

Atrial fibrillation management strategies and early mortality after myocardial infarction: results from the Valsartan in Acute Myocardial Infarction (VALIANT) Trial

ObjectiveThe management of patients with atrial fibrillation (AF) following a myocardial infarction (MI) remains uncertain. This study compared a rate control strategy to an anti-arrhythmic-based rhythm control strategy for the...

Mechanical Dyssynchrony After Myocardial Infarction in Patients With Left Ventricular Dysfunction, Heart Failure, or Both

Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined. We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure. Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis.

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)

Concern has been raised about combining beta 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 beta blockers because of previous evidence of benefit. The baseline characteristics, treatments, and outcomes were compared among 4 groups: patients taking beta blockers at admission only, at discharge only, at both admission and discharge, and neither. Patients treated with beta blockers were at lower risk than those not treated at any period. Those treated with beta 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 beta-blocker use and treatment with valsartan or valsartan plus captopril. Patients discharged with a beta 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 beta 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 beta 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 beta blockers or of a negative effect of the combination of valsartan, captopril, and beta blockers.

An Economic Evaluation of Valsartan for Post-MI Patients in the UK Who Are Not Suitable for Treatment with ACE Inhibitors

ObjectivesThe overall objective of this study was to estimate the costs and outcomes associated with treatment with valsartan for post-myocardial infarction (post-MI) patients with left ventricular systolic dysfunction, heart failure, or both, who are not suitable for treatment with angiotensin-converting enzyme (ACE) inhibitors, compared to placebo. MethodsA Markov model, using data drawn from the Valsartan in Acute Myocardial Infarction (VALIANT) trial and other trials, was developed to predict the future health pathways, resource use, and costs for patients who have recently experienced an MI. Patients received either valsartan (mean dose 247 mg) or placebo. Cost data were drawn from national databases and published literature, although health outcome utility weights were derived from existing studies. Patient outcomes were modeled for 10 years, and incremental cost-effective ratios were calculated for valsartan compared with placebo. ResultsOver a period of 10 years, a cohort of 1000 patients treated with valsartan experienced 147 fewer cardiovascular deaths, 37 fewer nonfatal MIs, and 95 fewer cases of heart failure than a cohort who received placebo. The incremental cost of valsartan, compared with placebo, was £2680 per patient, although the incremental effectiveness of valsartan was 0.5021 quality-adjusted life-years (QALYs) gained per patient. Therefore, the incremental cost per QALY for treatment with valsartan was £5338. When analysis was undertaken using life-years rather than QALYs, the cost per life-year gained was £4672. ConclusionsFor patients who are not suitable for treatment with ACE inhibitors, valsartan is a viable and cost-effective treatment for their management after an MI.

Prognostic Implications of Left Ventricular Mass and Geometry Following Myocardial Infarction: The VALIANT (VALsartan In Acute myocardial iNfarcTion) Echocardiographic Study

This study sought to understand prognostic implications of increased baseline left ventricular (LV) mass and geometric patterns in a high risk acute myocardial infarction. The LV hypertrophy and alterations in LV geometry are associated with an increased risk of adverse cardiovascular events. Quantitative echocardiographic analyses were performed at baseline in 603 patients from the VALIANT (VALsartan In Acute myocardial iNfarcTion) echocardiographic study. The left ventricular mass index (LVMi) and relative wall thickness (RWT) were calculated. Patients were classified into 4 mutually exclusive groups based on RWT and LVMi as follows: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), and concentric hypertrophy (increased LVMi and increased RWT). Cox proportional hazards models were used to evaluate the relationships among LVMi, RWT, LV geometry, and clinical outcomes. Mean LVMi and RWT were 98.8 +/- 28.4 g/m(2) and 0.38 +/- 0.08. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, heart failure, stroke, or resuscitation after cardiac arrest was lowest for patients with normal geometry, and increased with concentric remodeling (hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.9 to 4.9), eccentric hypertrophy (HR: 3.1; 95% CI: 1.9 to 4.8), and concentric hypertrophy (HR: 5.4; 95% CI: 3.4 to 8.5), after adjusting for baseline covariates. Also, baseline LVMi and RWT were associated with increased mortality and nonfatal cardiovascular outcomes (HR: 1.22 per 10 g/m(2) increase in LVMi; 95% CI: 1.20 to 1.30; p < 0.001) (HR: 1.60 per 0.1-U increase in RWT; 95% CI: 1.30 to 1.90; p < 0.001). Increased risk associated with RWT was independent of LVMi. Increased baseline LV mass and abnormal LV geometry portend an increased risk for morbidity and mortality following high-risk myocardial infarction. Concentric LV hypertrophy carries the greatest risk of adverse cardiovascular events including death. Higher RWT was associated with an increased risk of cardiovascular complications after high-risk myocardial infarction.

Racial Analysis of Patients With Myocardial Infarction Complicated by Heart Failure and/or Left Ventricular Dysfunction Treated With Valsartan, Captopril, or Both

African Americans have a high incidence of heart failure (HF). Limited retrospective observational subgroup analyses of patients with left ventricular systolic dysfunction (LVSD) suggest marginal benefit of angiotensin-converting enzyme inhibitors in the prevention of HF hospitalizations or total mortality in African Americans. Very few data exist concerning the effectiveness of angiotensin receptor blockers in this population. Baseline characteristics, treatments, and outcomes of patients from the U.S. (3,390 white and 340 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were compared. This trial included patients with an acute myocardial infarction (MI) after initial stabilization and documented LVSD and/or HF. Patients were randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up continued for up to 3 years (median 24.7 months). African Americans had more coronary risk factors, more markers of poor outcome after MI, and were less likely to be revascularized when compared with white patients. After adjusting for treatment assignment, baseline characteristics, and post-infarction parameters, no difference was found in the 3-year rate of all-cause mortality, cardiovascular mortality, rehospitalization for HF, recurrent MI, or stroke between the 2 groups. African Americans sustaining an acute MI with LVSD and/or HF had similar clinical outcomes compared with white Americans. Valsartan, captopril, or the combination had comparable effects on cardiovascular morbidity and mortality in African Americans and white Americans.

High-risk myocardial infarction in the young: The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial

Advanced age is a well-established prognostic risk factor after acute myocardial infarction (AMI), yet approximately 10% of MIs occur in patients <45 years. We examined characteristics, cardiovascular outcomes, and the influence of risk factors on outcomes in young survivors of AMI. Fourteen thousand seven hundred three patients enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial were divided into 3 age groups: 18 to < 45 (n = 803), 45 to < 65 (n = 6185), > or = 65 years (n = 7715). Multivariate Cox regression was used to compare cardiovascular event rates and assess the impact of risk factors on outcomes. The youngest patients had less diabetes, hypertension, and history of MI and were more likely to be male (18 to < 45 years, 88%; > or = 65 years, 59.1%), nonwhite (18 to < 45 years, 9.6%; > or = 65 years, 5%), current smokers (18 to < 45 years, 73.7%; > or = 65 years, 15.9%), obese (18 to < 45 years, 37.9%; > or = 65 years, 25.1%), and dyslipidemic at randomization (18 to < 45 years, 43.1%; > or = 65 years, 32.7%). Adjusted relative risks of smoking (18 to < 45 years, hazard ratio [HR] 1.6 [95% confidence interval {CI} 1.1-2.5]; > or = 45 years, HR 0.9 [95% CI 0.9-1.1]; P =.014) and hypertension (18 to < 45 years, HR 1.8 [95% CI 1.3-2.6]; > or = 45 years, HR 1.2 [95% CI 1.1-1.3]; P = .044) were higher in the young, with significant interactions observed between age and these risk factors. After AMI, risk factors and outcomes of the young differ substantively from their older counterparts. The influence of hypertension and smoking is more profound in the young, underscoring the need for aggressive risk factor modification post-AMI.