Valsartan in acute myocardial infarction trial (VALIANT): rationale and design

BACKGROUND: Survivors of acute myocardial infarction (MI) complicated by heart failure and/or resulting in left ventricular dysfunction are at heightened risk for subsequent death and major nonfatal cardiovascular events. Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor has consistently been demonstrated to result in reductions in these risks by approximately 20%. The development of angiotensin II receptor blockers offers a new, more specific, and theoretically more complete pharmacologic mode to inhibit the adverse influence of angiotensin II. METHODS: Valsartan in Acute Myocardial Infarction (VALIANT) is a multicenter, double-blind, randomized, active controlled parallel group study comparing the efficacy and safety of long-term treatment with valsartan, captopril, and their combination in high-risk patients after MI. The trial is designed with 3 arms, giving equal statistical consideration to survival comparisons of captopril versus the angiotensin II receptor blocker valsartan, as well as the combination of captopril plus valsartan, compared with a proven effective dose of captopril. This 14,500-patient trial is designed with an 86% power to detect a 15% reduction in mortality rate with either use of valsartan compared with captopril. The trial encourages optimal individualization of other proven therapies in acute and chronic infarction, and the international patient body ensures good representation of multiple practice patterns. CONCLUSION: VALIANT is a large international investigative effort that will evaluate the role of valsartan in the management of patients with MI associated with heart failure and/or left ventricular dysfunction. The use of a proven dose of captopril and the comparator arms with valsartan alone or in combination with captopril provides a unique test of whether the angiotensin II receptor blocker can make an additional improvement in clinical outcomes beyond angiotensin-converting enzyme inhibitors.     

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.     

Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.

AIMS: We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.     

Association of duration of symptoms at presentation with angiographic and clinical outcomes after fibrinolytic therapy in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: We sought to determine if an underlying mechanism of the association between prolonged symptom-to-treatment times and adverse outcomes may be an association of symptom-to-treatment times with impaired Thrombolysis In Myocardial Infarction myocardial perfusion grades (TMPGs). BACKGROUND: Prolonged symptom duration among ST-segment elevation myocardial infarction (STEMI) patients undergoing fibrinolytic therapy is associated with adverse outcomes. METHODS: Angiography was performed 60 min after fibrinolytic administration in 3,845 Thrombolysis In Myocardial Infarction (TIMI) trial patients. RESULTS: The median time from symptom onset to treatment was longer among patients with impaired myocardial perfusion (3.0 h for TMPG 0/1 vs. 2.7 h for TMPG 2/3; p = 0.001). In a multivariate model, impaired tissue perfusion (TMPG 0/1) remained associated with increased time to treatment (odds ratio 1.14 per hour of delay; p = 0.007) even after adjusting for Thrombolysis In Myocardial Infarction flow grade (TFG) 3, left anterior descending infarct location, and baseline clinical characteristics. Impaired myocardial perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) was associated with longer median times to treatment (3.0 h for TMPG 2/3 vs. 2.7 h for TMPG 0/1; p = 0.017), as was abnormal epicardial flow after rescue/adjunctive PCI (3.3 h for TFG 0/1/2 vs. 2.8 h for TFG 3; p = 0.005). Thirty-day mortality was associated with longer time from onset of symptoms to treatment (6.6% mortality for time to treatment >4 h vs. 3.3%; p < 0.001), even among patients undergoing rescue PCI. CONCLUSIONS: A prolonged symptom to treatment time among STEMI patients is associated with impaired myocardial perfusion independent of epicardial flow both immediately after fibrinolytic administration and after rescue/adjunctive PCI. These data provide a pathophysiologic link between prolonged symptoms due to vessel occlusion, impaired myocardial perfusion, and poor clinical outcomes.     

Peripheral artery disease and outcomes after myocardial infarction: An individual-patient meta-analysis of 28,771 patients in CAPRICORN,EPEHESUS, OPTIMAAL and VALIANT

Objectives

To examine the prevalence of peripheral artery disease (PAD) and the relationship between PAD and cardiovascular (CV) outcomes in subjects with left ventricular systolic dysfunction, heart failure or both after acute myocardial infarction (MI).

Background

PAD is associated with poorer prognosis in patients with stable and unstable coronary heart disease but whether PAD is associated with worse outcomes following substantial acute MI is unknown.

Methods

Univariate and multivariate Cox proportional hazards modelling was used to compare clinical outcomes in an individual-patient meta-analysis of 4 trials (CAPRICORN, EPHESUS, OPTIMAAL and VALIANT).

Results

Of the 28,771 patients randomized, 2357 (8.2%) had PAD. These patients were older and had more co-morbidity and were less likely to be prescribed aspirin or a beta-blocker compared to patients without PAD. Over a mean follow-up of 2.7 years, 5121 (17.8%) patients died and 15,055 (52.3%) experienced CV death or hospitalization. PAD was an independent predictor of all individual and composite CV outcomes examined (including heart failure), with the exception of stroke. In patients with PAD (compared to those without PAD), the adjusted hazard ratio (HR) for all-cause mortality was 1.25 (95% CI 1.15–1.37; p < 0.001) and the HR for CV death, non-fatal MI, non-fatal stroke or heart failure hospitalization was 1.24 (1.16–1.33; p < 0.001).

Conclusions

PAD is common and is an independent predictor of worse outcomes in patients already at high risk after MI because of left ventricular systolic dysfunction, heart failure or both. These patients represent an important group for intensive application of secondary preventive therapies.     

心电图QRS时限与老年急性心肌梗死患者预后的关系

目的研究老年急性心肌梗死(AMI)患者心电图QRS时限与预后的相关性。方法选取老年AMI患者204例,按心电图QRS时限是否>110 ms,分为QRS时限正常组87例(QRS时限≤110 ms),QRS时限延长组117例(QRS时限>110 ms)。检测N末端脑钠肽前体(NT -proBNP)浓度,LVEF,观察Killip分级、主要不良心血管事件(MACE)的发生率、住院心源性死亡发生率。结果 2组的NT-proBNP、LVEF、KillipⅡ～Ⅳ级、MACE发生率及心源性死亡发生率比较有显著差异(P<0.05,P<0.01)。结论老年AMI患者心电图QRS时限延长的预后差,心力衰竭、MACE和心源性病死率发生率高。     

Long-term outcomes of left bundle branch block in high-risk survivors of acute myocardial infarction: The VALIANT experience

BACKGROUND: In survivors of myocardial infarction (MI), new left bundle branch block (LBBB) is associated with adverse outcomes, but its impact is not well described in post-MI patients with left ventricular (LV) systolic dysfunction and/or heart failure (HF). OBJECTIVES: The aim of this study was to determine if new LBBB is an independent predictor of long-term fatal and nonfatal outcomes in high-risk survivors of MI by reviewing data from the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. METHODS: In VALIANT, 14,703 patients with LV systolic dysfunction and/or HF were randomized to valsartan, captopril, or both a mean of 5 days after MI. Baseline ECG data were available from 14,259 patients. We assessed the predictive value of new LBBB for death and major cardiovascular outcomes after 3 years, adjusting for multiple baseline covariates including LV ejection fraction. RESULTS: At follow-up, patients with new LBBB (608 [4.2%]) compared with patients without new LBBB had more comorbidities and increased adjusted risk of death (hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.2-1.6), cardiovascular death (HR 1.4, 95% CI 1.2-1.7), HF (HR 1.3, 95% CI 1.1-1.6), MI (HR 1.5, 95% CI 1.2-1.9), and the composite of death, HF, or MI (HR 1.4, 95% CI 1.2-1.6). CONCLUSION: In post-MI survivors with LV systolic dysfunction and/or HF, new LBBB was an independent predictor of all major adverse cardiovascular outcomes during long-term follow-up. This readily available ECG marker should be considered a major risk factor for long-term cardiovascular complications in high-risk patients after MI.     

Relationship of admission QRS duration and changes in QRS duration with myocardial reperfusion in patients with acute ST segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy.

BACKGROUND: Although ischemia induced QRS complex changes have been described previously, their relationship with impaired reperfusion, which is known to be associated with poor clinical outcomes, is not clear. METHODS AND RESULTS: To investigate the relationship of QRS duration changes with myocardial reperfusion, we studied 165 acute myocardial infarction (MI) patients who were administered fibrinolytic therapy for reperfusion. For each patient, 12-lead electrocardiogram (ECG) with a paper speed of 50 mm/s was recorded on admission and repeated at the 60(th) and 90(th) min following fibrinolytic therapy. Based on the myocardial blush grades obtained from a control coronary angiography, patients were divided into reperfusion (grades 2, 3) and impaired reperfusion (grades 0, 1) groups. We detected impaired reperfusion in 74 patients. The patients in the impaired reperfusion group were older, more often diabetic, and had longer pain-to-needle intervals. They also had significantly longer QRS durations at admission compared to reperfusion group patients (91+/-11 vs 79+/-11 ms, p<0.001). Reperfusion group patients showed significantly greater resolution in QRS duration at the 90(th) min post fibrinolysis ECG (18+/-5 vs 5+/-4 ms, p<0.001). In regression analysis, the pain-to-needle time (odds ratio (OR): 0.55, 95% confidence interval (CI) 0.35-0.88, p=0.012), QRS duration on admission (OR: 0.80, 95% CI 0.67-0.97, p=0.021), and change in QRS duration at the post fibrinolysis 90(th) min ECG (OR: 2.43, 95% CI, 1.29-4.60, p=0.006) were determined as independent predictors of adequate reperfusion. CONCLUSION: The present study, for the first time, has shown that admission QRS duration and post fibrinolysis 90(th) min QRS duration changes are related to tissue reperfusion in fibrinolytic administered acute MI patients.     

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

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

Improving outcomes after myocardial infarction: a randomized controlled trial evaluating effects of a telephone follow-up intervention.

BACKGROUND: Providing information is an important part of standard care and treatment for acute myocardial infarction inpatients. Evidence exists indicating that acute myocardial infarction patients experience an information gap in the period immediately after discharge from the hospital. The aim of this study was to assess the short-term effects of a nurse-led telephone follow-up intervention to provide information and support to patients with acute myocardial infarction after their discharge from hospital. DESIGN AND METHOD: A prospective randomized, controlled trial with a 6-month follow-up was conducted. A total of 288 patients were allocated to either an intervention group (n=156) or a control group (n=132). The latter received routine post-discharge care. The primary endpoint measured at 3 and 6 months after discharge was the health-related quality of life using the 36-item Short Form Health Survey. Secondary endpoints included smoking and exercise habits. RESULTS: In both groups, health-related quality of life improved significantly over time on most subscales. A statistically significant difference in favour of the intervention group was found on the 36-item Short Form Health Survey Physical Health Component Summary Scale (P=0.034) after 6 months. No difference was found between the groups on the Mental Health Component Summary Scale. We found a significant difference with respect to frequency of physical activity in favour of the intervention group after 6 months (P=0.004). More participants in the intervention group than the control group had ceased smoking at the 6-month follow-up (P=0.055). CONCLUSION: A nurse-led systematic telephone follow-up intervention significantly improved the physical dimension of health-related quality of life in patients in the intervention group compared with usual care patients. Participation in this intervention also seemed to promote health behaviour change in patients after acute myocardial infarction.     

The relationship between renal function and cardiac structure, function, and prognosis after myocardial infarction: the VALIANT Echo Study.

OBJECTIVES: The purpose of this study was to determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment after myocardial infarction (MI). BACKGROUND: Renal impairment is associated with adverse cardiovascular outcomes after MI. METHODS: Echocardiography was performed on 603 patients with left ventricular (LV) dysfunction, heart failure (HF), or both after MI. Patients were grouped according to their estimated glomerular filtration rate (eGFR), and measures of cardiac structure and function were related to baseline eGFR. The relationship between eGFR and cardiac structure and function and clinical outcomes of death or HF was assessed with multivariable Cox regression. RESULTS: Ejection fraction, infarct segment length, right ventricular function, and mitral deceleration time were not influenced by renal function. Patients with reduced eGFR had smaller LV and larger left atrial (LA) volumes and higher left ventricular mass index (LVMI) and LV mass/LV volume ratio. A greater proportion of the patients with reduced eGFR had LV hypertrophy. The relationship between eGFR and the outcome of death or HF was attenuated by including baseline differences in LVMI, and both LVMI and LA volume conferred additional prognostic information in a multivariable model. CONCLUSIONS: Renal impairment was associated with smaller LV and larger LA volumes and increased LVMI. Systolic function was similar when compared with patients with normal renal function. Thus, reduced systolic function cannot account for worse outcomes in patients with renal impairment after MI. Indirect measures of diastolic function suggest that diastolic dysfunction might be an important mediator of increased risk in this population.