Combined Endpoint Of Mortality Research Articles

Clinical and Quality of Life Comparison of Accelerometer, Piezoelectric Crystal, and Blended Sensors in DDDR‐Paced Patients with Sinus Node Dysfunction in the Mode Selection Trial (MOST)

Permanent pacemakers are capable of increasing heart rate in response to physical activity by a variety of sensors including accelerometers, piezoelectric crystals, or blended sensors. The impact of these different physiologic sensors on cardiovascular events and quality of life is not known. Of 2,010 patients randomized in the Mode Selection Trial, 1,245 patients were selected with the most commonly used pacemakers with these three sensors. Clinical characteristics and quality of life were compared between groups at baseline, 3 months, and then yearly. There were 449 patients with an accelerometer sensor device, 682 with a piezoelectric sensor, and 114 with a blended sensor. The groups were similar in terms of age (mean 74 years), gender, and cardiac risk factors but differences existed in weight, heart rate, mitral regurgitation, revascularization history, and drug therapy. The median ventricular pacing frequency was 80% (25th, 75th percentiles 42, 97). After a median follow-up of 33.1 months, the risk of death, heart failure hospitalization, atrial fibrillation, and the combined endpoint of mortality and stroke was not significantly different between the sensor types, after adjustment for baseline differences. Quality of life analyses demonstrated that patients with blended sensors had significantly worse (P < 0.01) physical function than did patients with the other two sensor systems. Moreover, patients receiving blended sensors had the poorest absolute scores, without reaching statistical significance, on 9 of 13 quality of life measures after adjusting for differences in the groups. We found no significant differences among the three most utilized sensors in clinical endpoints. Those patients who received blended sensors had worse physical function quality of life scores. However, clinical selection of the most sophisticated sensor for the most ill patients cannot be excluded as an explanation of these results.

Rate Control Is Preferable to Rhythm Control in the Majority of Patients With Atrial Fibrillation

“…but to his surprise — the more he looked — the more Piglet wasn’t there.” — A.A. Milne, The House at Pooh Corner The management of patients with atrial fibrillation has been the subjects of intense investigation over the past 2 decades. In the 1980s and early 1990s, large clinical trials of anticoagulant therapy for stroke prevention were performed. These consistently demonstrated that atrial fibrillation confers a significant and ongoing stroke risk and that anticoagulant therapy significantly reduces this risk.1–10 Warfarin subsequently became a standard of therapy for patients with atrial fibrillation, whether paroxysmal, persistent, or permanent. If patients with atrial fibrillation had a high stroke risk compared with those in sinus rhythm, then logic appeared to dictate that restoration and maintenance of sinus rhythm should reduce the likelihood of thromboembolism and hence obviate the need for long-term warfarin anticoagulation. Perhaps driven in part by this belief, new atrial antiarrhythmic drugs were introduced during this period, and there was an increasing use of such drugs among patients with atrial fibrillation.11 A decade after the trials of anticoagulation in atrial fibrillation, several international trials were implemented to determine whether heart rate control would result in a similar outcome to the outcome after a strategy of restoration and maintenance of sinus rhythm.12–15 Analysis of these trials demonstrated no benefit either in mortality or in a combined end point of mortality and morbidity. These results are generally interpreted as showing that either rate control or rhythm control is a suitable strategy in a patient with atrial fibrillation, and there has therefore been a rethinking of the appropriate way in which to treat a patient with atrial fibrillation when the options include control of either rate or rhythm. In the treatment of atrial fibrillation, as with most things in medicine, one …

Complexity of program and clinical outcomes of heart failure disease management incorporating specialist nurse-led heart failure clinics. A meta-regression analysis

To determine whether a hierarchy of effectiveness exists with respect to complexity of published protocols of heart failure (HF) disease management (DM) incorporating specialist nurse-led HF clinics. We searched MEDLINE (1966-November 2004), the Cochrane Library, article bibliographies, and contacted experts. Inclusion criteria were random allocation of at least 100 patients, specialist HF nurses, HF clinics, and readmission as an outcome measure. Paired reviewers conducted quality assessment, deconstructed and categorized protocols by complexity, and extracted results for readmission, mortality, the combined endpoint of mortality and hospitalization, HF readmission, and hospital days utilized. Six trials were selected (N=949, mean age 73 years [range 62-79], men 58%, LVEF 34% [27-41], and average follow-up of 8.5 months [3-12]). Compared with usual care, the overall relative risk [95% confidence interval] for readmission with this strategy was 0.91 [0.72, 1.16], mortality was 0.80 [0.57, 1.06], and the combined endpoint of mortality and hospitalization was 0.88 [0.74, 1.04]. We observed better outcomes for programs with versus programs without hospital discharge planning and immediate post-discharge follow-up; readmission 0.30 [0.04, 2.60] vs. 1.00 [0.86, 1.17], mortality 0.96 [0.63, 1.47] vs. 0.75 [0.55, 1.03], the combined endpoint of mortality and hospitalization 0.61 [0.18, 2.02] vs. 0.91 [0.80, 1.03], HF readmission 0.09 [0.10, 0.65] vs. 0.65 [0.43, 1.00], and hospitalized days utilized per patient -0.26 [-0.49,-0.02] vs. 0.09 [-1.17, 1.34]. HF DM with specialist nurse-led HF clinics is a promising strategy or effective alternative whose benefit may be optimized by programs with a homogeneous structure and components that are delivered with consistency.

Picotamide, a combined inhibitor of thromboxane A 2 synthase and receptor, reduces 2-year mortality in diabetics with peripheral arterial disease: The DAVID study

Aims Patients with diabetes are at excessive risk of mortality and cardiovascular morbidity. Previous studies suggest that aspirin may be less effective in diabetic patients. In this multi-centre, randomized, double blind trial picotamide, a dual inhibitor of thromboxane A2 synthase and receptor, was compared with aspirin for the prevention of mortality and major cardiovascular events in diabetics with peripheral arterial disease (PAD). Methods and results A total of 1209 adults aged 40–75 years with type 2 diabetes and PAD were randomized to receive picotamide (600 mg bid) or aspirin (320 mg od) for 24 months. The cumulative incidence of the 2 years overall mortality was significantly lower amongst patients who received picotamide (3.0%) than in those who received aspirin (5.5%) with a relative risk ratio for picotamide versus aspirin of 0.55 (95% CI: 0.31–0.98%). Events were reported in 43 patients (7.1%) on picotamide and 53 (8.7%) on aspirin. The combined endpoint of mortality and morbidity had a slightly lower incidence in the picotamide group but this difference did not reach statistical significance. Conclusion Picotamide is significantly more effective than aspirin in reducing overall mortality in type 2 diabetic patients with associated PAD.

Prognostic utility of comparative methods for assessment of ST-segment resolution after primary angioplasty for acute myocardial infarctionThe controlled abciximab and device investigation to lower late angioplasty complications (CADILLAC) trial

This study was done to assess and compare the prognostic significance of multiple methods for measuringST-segment elevation resolution (STR) following primary percutaneous coronary intervention (PCI). Resolution of ST-segment elevation (STE) is a powerful predictor of both infarct-related artery patency and mortality in acute myocardial infarction (AMI). Recent thrombolytic studies have suggested that simple measures of STR may be as powerful as more complex algorithms. The optimal method of assessing STR following primary PCI has not been studied. We analyzed 700 patients with technically adequate baseline and post-PCI electrocardiograms from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Five methods were used to assess STR: 1) summed %STR across multiple leads (ΣSTR); 2) %STR in the single lead with maximum baseline STE (MaxSTR); 3) absolute maximum STE before the procedure; 4) absolute maximum STE after intervention (MaxSTPost); and 5) a categorical variable based upon MaxSTPost (High Risk). At 30 days, ΣSTR, MaxSTR, and MaxSTPost all correlated strongly with mortality (p = 0.004, p = 0.005, and p < 0.0001, respectively) and the combined end point of mortality or reinfarction (p = 0.001, p = 0.001, and p < 0.0001). At one year, ΣSTR and MaxSTPost correlated with mortality (p = 0.04, p = 0.0001), reinfarction (p = 0.02, p = 0.0015), and the combined end point (p = 0.02, p < 0.0001). By multivariate analysis, only the simpler measures of MaxSTPost and High Risk categorization independently predicted all outcomes at both time points. The STR following primary PCI in AMI correlates strongly with mortality and reinfarction, independent of target vessel patency. The simple measure of the maximal residual degree of STE after primary PCI is a strong independent predictor of both survival and freedom from reinfarction at 30 days and 1 year.

Prognostic utility of comparative methods for assessment of ST-segment resolution after primary angioplasty for acute myocardial infarction: The controlled abciximab and device investigation to lower late angioplasty complications (CADILLAC) trial

This study was done to assess and compare the prognostic significance of multiple methods for measuring ST-segment elevation resolution (STR) following primary percutaneous coronary intervention (PCI). Resolution of ST-segment elevation (STE) is a powerful predictor of both infarct-related artery patency and mortality in acute myocardial infarction (AMI). Recent thrombolytic studies have suggested that simple measures of STR may be as powerful as more complex algorithms. The optimal method of assessing STR following primary PCI has not been studied. We analyzed 700 patients with technically adequate baseline and post-PCI electrocardiograms from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Five methods were used to assess STR: 1) summed %STR across multiple leads (SigmaSTR); 2) %STR in the single lead with maximum baseline STE (MaxSTR); 3) absolute maximum STE before the procedure; 4) absolute maximum STE after intervention (MaxSTPost); and 5) a categorical variable based upon MaxSTPost (High Risk). At 30 days, SigmaSTR, MaxSTR, and MaxSTPost all correlated strongly with mortality (p = 0.004, p = 0.005, and p < 0.0001, respectively) and the combined end point of mortality or reinfarction (p = 0.001, p = 0.001, and p < 0.0001). At one year, SigmaSTR and MaxSTPost correlated with mortality (p = 0.04, p = 0.0001), reinfarction (p = 0.02, p = 0.0015), and the combined end point (p = 0.02, p < 0.0001). By multivariate analysis, only the simpler measures of MaxSTPost and High Risk categorization independently predicted all outcomes at both time points. The STR following primary PCI in AMI correlates strongly with mortality and reinfarction, independent of target vessel patency. The simple measure of the maximal residual degree of STE after primary PCI is a strong independent predictor of both survival and freedom from reinfarction at 30 days and 1 year.

Meta-analyses of mortality and morbidity effects of an angiotensin receptor blocker in patients with chronic heart failure already receiving an ACE inhibitor (alone or with a β-blocker)

Background: While treatment with either angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) is clearly superior to placebo in the treatment of heart failure patients, controversy still surrounds the effects of ARBs in patients already receiving an ACEi. Even more controversial is the wisdom of administering ARBs in patients already on an ACEi and β-blocker. Methods: We present meta-analyses of the available randomised controlled trials to date (October 2003) of angiotensin II receptor antagonists versus placebo in patients with symptomatic chronic heart failure in which both groups received ACEi. The two largest eligible trials were CHARM-Added and Val-HeFT. We examined two endpoints: mortality and a combined endpoint of mortality and morbidity. Results: In the first meta-analysis, covering all patients regardless of β-blocker use, we found a significant reduction in the combined endpoint (odds ratio [OR]=0.89; 95% confidence interval [CI] 0.81–0.98), but no significant reduction in mortality itself (OR=0.97; CI: 0.87–1.08). In the second meta-analysis, covering patients concomitantly on β-blockers, we found no significant effect on mortality (OR=1.08; CI: 0.90–1.29) or on the combined endpoint (OR=0.94; CI: 0.82–1.10). In the third meta-analysis, covering patients not on concomitant β-blockers, there is clear evidence of a reduction in the combined endpoint (OR=0.83; CI: 0.73–0.94), but not on mortality (OR=0.93; CI: 0.81–1.06). Conclusion: There is now good evidence for the use of ARBs to prevent events in patients with heart failure on ACEi who are not suitable for β-blockers.

Valsartan for the treatment of heart failure

Heart failure (HF) still has a discouraging prognosis. Therapeutic strategies aim to reduce mortality as well as slow the progression of the disease, improve symptoms and reduce the frequency of hospital admission. Activation of the renin-angiotensin-aldosterone system (RAAS) is a hallmark of several cardiocirculatory diseases, including HF. Drugs for evidence-based therapy of HF are angiotensin-coverting enzyme inhibitors (ACEIs), β-blockers and aldosterone antagonists. A promising alternative is a more complete action on the RAAS through selective blockade of the angiotensin type 1 (AT1) receptors, taking into account not only physiopathological issues but also pharmacological, experimental and clinical data. The effect of valsartan, an orally-active, selective antagonist of AT1 receptors, on the outcome in patients with chronic and symptomatic HF was evaluated in a large-scale, international, placebo-controlled clinical study, the Valsartan in Heart Failure Trial (Val-HeFT). In this study, overall mortality was similar in the valsartan and placebo groups (19.7 and 19.4%, respectively). However, valsartan, in addition to recommended therapy of HF including an ACEI, significantly reduced the combined end point of mortality and morbidity, with a significant reduction in the risk of hospitalisation, paralleled by improvements in New York Heart Association (NYHA) functional class, signs and symptoms and quality of life. Valsartan also improved left ventricular anatomy and function and significantly reduced neurohormonal activation. These results were confirmed and extended by the CHARM trial, where the benefits of candesartan were proved not only in all 7599 patients with HF, but also in the 2548 given an ACEI, the 2028 not given an ACEI and in the 3023 patients with an ejection fraction of > 40%. In conclusion, the first choice for HF remains an ACEI with a β-blocker, but two new options are emerging. In patients intolerant to ACEI, the combination of valsartan or candesartan with a β-blocker is proposed, whereas an ACEI with either valsartan or candesartan can be considered in patients intolerant to or with contraindications to β-blockers.

Determinants of failure to prescribe target doses of angiotensin-converting enzyme inhibitors for heart failure.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, frequency of hospitalisation for heart failure and slow the progression of left ventricular systolic dysfunction w1,2x. These benefits are independent of baseline use of diuretics, aspirin and beta-blockers and of the type of ACE inhibitor prescribed. Since the original descriptions of outcome benefit from ACE inhibitors, attention has been focussed on examining the dose–response relationship. The ATLAS study demonstrated reduction in the combined endpoint of mortality and hospitalisation (hazard ratio 0.85, 95% CI 0.78–0.93) with lisinopril 32.5–35 mg daily vs. 2.5–5 mg daily but there is no significant benefit in all-cause mortality and cardiovascular mortality w3x. The NETWORK trial, conducted by general practitioners and hospital physicians in the UK, compared low dose enalapril (5 mg) with intermediate dose (10 mg) and high dose (20 mg) in patients aged 18–85 years with NYHA class II–IV w4x. The study did not demonstrate a relationship between dose of enalapril and clinical outcome (hospitalisation for heart failure, worsening heart failure, death). However, this study had limited power since it treated patients for only 6 months and reported few deaths and hospitalisations. An American study of elderly patients discharged from hospital on ACE inhibitors showed significantly lower mortality at 1 year in patients treated with high dose ACE inhibitors (enalapril 20 mg a day, lisinopril 20 mg a day and captopril 150 mg a day) w5x. The results of the ongoing ACHIEVE trial comparing quinapril 10 vs. 40 mg are

The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial

Introduction: The devices used to prove the benefit of ICD therapy had only VVI pacing but most current ICD devices provide dual chamber pacing therapy. The DAVID trial sought to measure the impact of dual chamber pacing at 70 bpm (DDDR‐70) vs. ventricular backup pacing at 40 bpm (VVI‐40) in patients with standard indications for ICD implantation but without indications for bradycardia pacing. Methods: This single‐blind, multicenter, parallel‐group, randomized clinical trial enrolled 506 patients with indications for ICD therapy between 10/2000 and 9/2002. All patients had an LVEF ≤0.40, no indication for pacemaker therapy and no persistent atrial arrhythmias. ICDs with dual chamber, rate‐responsive pacing capability were implanted and programmed to VVI‐40 or DDDR‐70. Results: The combined endpoint of mortality or hospitalization for congestive heart failure (CHF) at one year was 16.1% (VVI‐40) vs. 26.7% (DDDR‐70), (p ∼ 0.03), mortality 6.5% vs. 10.1% (p ∼ 0.15) and CHF hospitalization 13.3% vs. 22.5% (p ∼ 0.07). Conclusion: For ICD patients, DDDR‐70 pacing exhibits no clinical advantage over VVI‐40 pacing and may increase CHF and mortality.

Survival and hospitalization in heart failure patients with or without diabetes treated with β-blockers

Background: Physicians are still concerned about prescribing β-blockers in diabetic patients with heart failure. Methods: In the outcome research study (the Beta-Blockers in Patients With Congestive Heart Failure: Guided Use in Clinical Practice [BRING-UP] study), the responsible clinicians could decide whether to start β-blocker treatment and which agent to use. A total of 3091 patients were enrolled by 202 cardiologic centers: 25% of the recruited patients were already on β-blockers, 28% started treatment at the enrollment visit, and 47% were not started on β-blockers. Results: The 1-year mortality, hospitalization rate, and the combined end point of mortality or hospitalization were higher in diabetic patients (15.8% versus 10.9%; relative risk [RR] = 1.44; 95% confidence intervals [CI] 1.16-1.78, P =.001) (31.0% versus 24.0%; RR = 1.28; 95% CI 1.11-1.49; P =.0009) (40.5% versus 30.1%; RR = 1.35; 95% CI 1.19-1.51; P =.0001). The event-free analysis of the 4 groups (diabetic patients not treated with β-blockers, diabetic patients treated with β-blockers, nondiabetic patients not treated with β-blockers, nondiabetic patients treated with β-blockers) showed that patients treated with β-blockers had a higher event-free probability than patients not treated with β-blockers regardless the presence of diabetes (P <.0001). Conclusions: On the basis of post hoc analysis, diabetic patients with chronic heart failure benefit from β-blockers even if at a lower degree. Thus, there are no justifications to avoid β-blockers in heart failure patients in the presence of diabetes.

Serum levels of carbohydrate antigen 125 in patients with chronic heart failure: Relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities, and short-term prognosis

ObjectivesThe aim of this study was to evaluate the serum levels of carbohydrate antigen 125 (CA125) in patients with congestive heart failure (CHF). BackgroundCA125 is a glycoprotein produced by serosal epithelium, found to be increased in ovarian cancer. MethodsSerum levels of CA125 were obtained in 286 patients (122 males and 164 females; age 69 ± 13 years) with CHF (left ventricular ejection fraction 30 ± 11%). A non-invasive evaluation was obtained by Doppler echocardiography; right heart catheterization was performed in 88 patients. An attempt to adjust medical therapy to maximally tolerated doses was done, and CA125 was repeated after 18 days (range 7 to 40) in 80 patients. The mean follow-up duration was 6 ± 3 months in 240 patients. ResultsThe mean value of CA125 was 68 ± 83 U/ml (range 3 to 537): 71 ± 85 in men and 56 ± 64 U/ml in women (p = NS). CA125 above the normal value (<35 U/ml) was found in 152 (53%) of 286 patients; it was higher in patients with advanced New York Heart Association (NYHA) functional class (n = 140 in class I/II: 15 ± 9 U/ml; n = 63 in class III: 57 ± 18 U/ml; n = 83 in class IV: 167 ± 94 U/ml; p < 0.005). CA125 was related to the deceleration time of early filling on transmitral Doppler (r = −0.63, p < 0.05) and to pulmonary artery wedge pressure (r = 0.66, p < 0.05) and right atrial pressure (r = 0.69, p < 0.05). During 6 ± 3 months of follow-up, a combined end point of mortality and CHF hospitalization was observed in 16 of 127 patients with CA125 <35 U/ml, compared with 70 of 113 patients with CA125 >35 U/ml (p < 0.01). After medical treatment optimization, NYHA class decreased by more than one grade in 56 of 80 patients and was unchanged or increased in 24 patients: CA125 decreased from 125 ± 98 to 53 ± 61 U/ml (p < 0.001) in the former and changed from 130 ± 81 to 153 ± 61 U/ml (p = NS) in the latter. ConclusionsOur data suggest that CA125 is related to CHF severity and short-term prognosis. Furthermore, fluctuations of CA125 serum levels over time may reflect changes induced by therapy. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of CHF patients.

Noninvasive Assessment of Cardiac Pumping Capacity During Exercise Predicts Prognosis in Patients with Congestive Heart Failure

Prognostic parameters in patients with congestive heart failure (CHF) are important for guiding therapeutic options. Maximal oxygen uptake (O(2)max) is a widely used parameter for prognostic assessment in patients with CHF and correlates with exercise cardiac output; however, afterload is not taken into account. The concept of a noninvasive surrogate of cardiac power output combines exercise systolic BP (SBP), as an estimate of afterload, with O(2)max, as an estimate of exercise cardiac output neglecting preload. Thus, a variable termed exercise cardiac power (ECP) is defined as the product of O(2)max (expressed as a percent predicted value) and SBP (ECP, expressed as %mm Hg, is the product of O(2)max, expressed as percentage of predicted maximum, times systolic pressure. The prognostic value of ECP obtained during routine treadmill ergospirometry was assessed in patients referred to our heart failure clinic. Patients undergoing heart transplantation were censored at the time of transplantation. One hundred fifty-four patients were followed prospectively for a mean (+/- SE) duration of 625 +/- 32 days. Thirty-two patients (21%) died. ECP was the most powerful predictor of mortality, was the combined end point of mortality or hospitalization for worsening heart failure (all p < 0.001), and was an independent predictor in multivariate analysis. An ECP of < 5,000 %mm Hg indicated a poor prognosis with a 1-year mortality rate of 37%, whereas only 2% of the patients having an ECP of > 9,000 %mm Hg died during the first year. The integration of afterload and O(2)max improves the prognostic value of each indicator, and provides an easily available and independent predictor of mortality and morbidity in CHF patients. This integrative concept of cardiac hydraulic performance is superior to O(2)max and can be used in routine ergospirometry.

Effect of statin (HMG-Co-A-Reductase Inhibitor) use on 1-year mortality and hospitalization rates in older patients with cardiovascular disease living in nursing homes.

To quantify the effect of statins on 1-year mortality, hospitalizations, and decline in physical function among patients with cardiovascular disease (CVD) aged 65 and older living in nursing homes. Retrospective cohort study. All Medicare/Medicaid certified nursing homes (N = 1,492) in Maine, New York, Mississippi, and South Dakota. We identified 51,559 older patients with CVD from a population database that merged sociodemographic data and functional, clinical, and drug treatments from more than 300,000 newly admitted nursing home residents from 1992 to 1997. Statin users (n = 1,313) were matched with nonusers (n = 1,313) in the same facilities. All-cause mortality, hospitalization, combined endpoint of mortality or hospitalization, and decline in physical function were determined at 1 year, and survival analysis was performed. Prevalence of statin use in this frail older cohort with CVD was 2.6%. Statin use varied by age, gender, comorbid condition, medication use, and cognitive and physical function. One-year mortality was 229/1,000 person-years in the statin group and 404/1,000 person-years in the nonusers, with an adjusted hazard rate ratio (HRR) of 0.69, 95% confidence interval (CI) = 0.58-0.81. The estimated number needed to treat was seven (95% CI = 5-13). This association with improved all-cause mortality was evident for women and men and for age groups 75 to 84, and 85 and older. Statin therapy is associated with improved clinical outcomes, including reduction in 1-year all-cause mortality, and the combined endpoint of death or hospitalization in a frail older population with CVD. Some caution should be taken in interpreting these results because potential bias from residual confounding could affect these results.

A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure

Background Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure. Methods A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours. Results Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a low...

Valsartan: in chronic heart failure.

Valsartan, an orally active nonpeptide angiotensin II (AII) receptor antagonist with selectivity for the AII type I (AT(1)) receptor subtype, has recently been approved by the US Food and Drug Administration for the treatment of patients with heart failure (New York Health Association class II-IV) who are intolerant of ACE-inhibitor therapy. Results from the Valsartan Heart Failure Trial (Val-HeFT) showed that in patients with chronic heart failure (CHF) [n = 5010], valsartan 160 mg twice daily, when used in combination with conventional therapy for heart failure, reduced the risk of the combined endpoint of mortality and morbidity by 13.2% compared with placebo. However, there was no significant difference in overall mortality between the valsartan and placebo groups. Morbidity was defined as cardiac arrest with resuscitation, hospitalization for heart failure, or administration of intravenous inotropic or vasodilator drugs for > or =4 hours without hospitalization. Among patients not receiving an ACE inhibitor, irrespective of concomitant beta-blocker use, valsartan reduced the risk of mortality and the combined endpoint by 33.1% and 44% compared with placebo; total hospitalizations for heart failure were also significantly lower in the valsartan group (27.6 vs 64.6%). In the subgroup of patients who were taking an ACE inhibitor and a beta-blocker at baseline (n = 1610), mortality was significantly higher in the valsartan group than in the placebo group. The most common adverse events in the valsartan and placebo groups which led to discontinuation of treatment were dizziness, renal impairment (both of which occurred in significantly more valsartan recipients) and hypotension.

Prognostic implications of TIMI flow grade in the infarct related artery compared with continuous 12-lead ST-segment resolution analysis: Reexamining the “gold standard” for myocardial reperfusion assessment

OBJECTIVETo compare the prognostic significance of reperfusion assessment by Thrombolysis in Myocardial Infarction (TIMI) flow grade in the infarct related artery and ST-segment resolution analysis, by correlating with clinical outcomes in patients with acute myocardial infarction (AMI).BACKGROUNDAngiographic assessment, based on epicardial coronary anatomy, has been considered the “gold standard” for reperfusion. The electrocardiogram (ECG) monitoring provides a noninvasive, real-time physiologic marker of cellular reperfusion and may better predict clinical outcomes.METHODSTwo hundred fifty-eight AMI patients from the Thrombolytics and Myocardia Infarction phase 7 and Global Utilization of Streptokinase tPA for Occluded coronary arteries phase 1 trials were stratified based on blinded, simultaneous reperfusion assessment on the acute angiogram (divided into TIMI grades 0 & 1, TIMI grade 2 and TIMI grade 3) and ST-segment resolution analysis (divided into: <50% ST-segment elevation resolution or reelevation and ≥50% ST-segment elevation resolution). In-hospital mortality, congestive heart failure (CHF) and combined mortality or CHF were compared to determine the prognostic significance of reperfusion assessment by each modality using chi-square and Fisher’s Exact tests for univariable correlation and logistic regression analysis for univariable and multivariable prediction models.RESULTSBy logistic regression analysis, ST-segment resolution patterns were an independent predictor of the combined outcome of mortality or CHF (p = 0.024), whereas TIMI flow grade was not (p = 0.693). Among the patients determined to have failed reperfusion by TIMI flow grade assessment (TIMI flow grade 0 & 1), the ST-segment resolution of ≥50% identified a subgroup with relatively benign outcomes with the incidence of the combined end point of mortality or CHF 17.2% versus 37.2% in those without ST-segment resolution (p = 0.06).CONCLUSIONContinuous 12-lead ECG monitoring can be an inexpensive and reliable modality for monitoring nutritive reperfusion status and to obtain prognostic information in patients with AMI.

Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks atter acute myocardial infarction: The GISSI-3 trial

Objectives. This 6-month follow-up analysis sought to assess whether the early reduction of mortality obtained with a 6-week treatment course of lisinopril or glyceryl trinitrate, or both, in unselected patients with acute myocardial infarction outlasts therapy and is still present after 6 months. The primary outcome of the 6-month follow-up was the combined end point of mortality and severe left ventricular dysfunction.Background. The assumption was that the early benefit on remodeling processes may be maintained over a longer period of time, even in the absence of treatment.Methods. A total of 19,394 patients with acute myocardial infarction were randomized within 24 h of onset of symptoms to a 6-week treatment course of oral lisinopril or open control and, according to a 2 × 2 factorial design, to glyceryl trinitrate or open control. Randomized treatments were stopped after 6 weeks in the absence of specific indications, and the patients were followed up for 6 months.Results. At 6 months, among patients randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was found between patients with and without glyceryl trinitrate therapy (ISA% vs. 18.9%, 2p = 039).Conclusions. Although the systematic administration of glyceryl trinitrate started early and continued for 6 weeks after acute myocardial infarction does not yield evidence of benefit, early treatment with lisinopril appears to improve prognosis. This effect seems to carry over the first 6 months from randomization, even after treatment withdrawal.