Combined Endpoint Events Research Articles

Fondaparinux Sodium for Anticoagulant Therapy After Primary Percutaneous Coronary Intervention: A Single-Center Randomized Trial in China.

In this study, we investigated the safety and efficacy of fondaparinux sodium in postpercutaneous coronary intervention (PCI) anticoagulation therapy for patients with ST-segment elevation myocardial infarction. There are a total of 200 patients with ST segment elevation myocardial infarction underwent PCI and anticoagulation therapy. They were randomly split into experimental (n = 108) and control groups (n = 92). The experimental group received postoperative fondaparinux sodium (2.5 mg q.d), while the control group received enoxaparin (4000 IU q12 h). We did not use a loading dose for enoxaparin. Bleeding incidence and major adverse cardiovascular/cerebrovascular events were monitored during hospitalization, and at 1, 3, and 6 months postsurgery. The primary end points, including bleeding, mortality, and myocardial infarction during hospitalization, were not significantly different between the 2 groups. For secondary end points, the incidence of combined end point events at 1 month, 3 months, and 6 months after surgery in the experimental group was lower than in the control group (P < 0.05). According to Cox regression analysis, the risk of bleeding in the experimental group was significantly lower than that in the control group [hazard ratios: 0.506, 95% confidence interval (CI): 0.284-0.900] (P = 0.020). The risk of mortality in the experimental group was significantly lower than in the control group (hazard ratio: 0.188, 95% CI: 0.040-0.889) (P = 0.035). In summary, perioperative use of fondaparinux sodium during PCI in patients with STEMI in this study was associated with a lower risk of bleeding and death compared with enoxaparin use in the absence of loading dose.

Early β-blocker use and in-hospital outcomes in patients with chronic obstructive pulmonary disease hospitalized with acute coronary syndrome: findings from the CCC-ACS project.

Patients with chronic obstructive pulmonary disease (COPD) after acute coronary artery syndrome (ACS) are at an increased risk of heart failure and death. However, β-blockers have been underused in this population group due to concerns of adverse reactions. This study aims to investigate the β-blocker prescription at admission and its impact on the in-hospital outcomes in patients with COPD after ACS in a Chinese national cohort. Among 113,650 patients with ACS enrolled in the national registry of the Improving Care for Cardiovascular Disease in China between November 2014 and July 2019, a total of 1,084 ACS patients with COPD were included in this study. The primary endpoint was in-hospital mortality, and the secondary endpoint was the composite of in-hospital all-cause death and heart failure. Early oral β-blocker therapy was administered to 49.8% of patients. The Kaplan-Meier analysis showed that the early β-blocker treatment group had lower all-cause mortality (0.9% vs. 2.9%; P < 0.05) and lower combined endpoint event rate (8.2% vs. 12.0%; P < 0.05) compared to the those of the non-early β-blocker treatment group. The analysis of inverse probability of treatment weighting showed that the early β-blocker treatment group was associated with a significantly reduced incidence of all-cause death (risk ratio, 0.332, 0.119-0.923, P = 0.035), heart failure (risk ratio, 0.625, 95% CI 0.414-0.943, P = 0.025), and combined endpoint events (risk ratio: 0.616, 95% CI: 0.418-0.908, P = 0.014). In the subgroup of patients over 70 years of age, the corresponding hazard ratio was 0.268 (95% CI 0.077-0.938) for all-cause mortality and 0.504 (95% CI 0.316-0.805) for combined endpoint events. β-blockers have been underused in patients with COPD and ACS in China. Early β-blocker therapy is associated with an improvement in in-hospital outcomes in patients with COPD after ACS. ClinicalTrials.gov, identifier (NCT02306616).

Neutrophil extracellular traps as a promising marker of poor prognosis in operated patients with infective endocarditisarditis.

Aim. To assess the prognostic value of the formation of neutrophil extracellular traps (NETs) in blood smears of operated patients with infective endocarditis (IE).Material and methods. We prospectively included 46 patients with verified IE and 50 patients with valvular heart disease without IE, hospitalized in a cardiac surgery hospital in 2021-2022 (Moscow), comparable by sex and age. In all patients, NETs were determined upon admission and 7 days after surgery using the MECOS-Ts2 automated microscope (Russia). Patients included in the study were prospectively followed during the in-hospital period (ME [IQR] 30,0 [21,0-41,0] days) for the primary composite endpoint (in-hospital all-cause mortality, embolic, intracardiac, infectious complications) and its individual components.Results. Patients with IE were predominantly male (n=37, 80,4%) with a median age of 55,5 [44,0-70,0] years. The primary combined endpoint was recorded in 76,1% (n=35) of those examined with IE. The NET level after 7 days was significantly higher in patients with IE who had primary combined endpoint events than in the group of operated patients with heart defects without IE (Me [IQR] 4,4 [0,6-26,6] vs 2,9 [1,1-4,3], respectively, p&lt;0,05). Patients with IE who died in the hospital had a significantly higher NET level compared with surviving patients with IE and the control group as at admission (9,2 [1,8-18,9] vs 4,2 [0,3-28 ,5] and 3,4 [1,76,9], respectively, p&lt;0,05), and in dynamics (18,2 [5,2-26,6] vs 4,0 [1, 0-26,6] and 2,9 [1,1-4,3], respectively, p&lt;0,001). The threshold value of dynamic NET ≥11,2% predicted in-hospital death with high accuracy (sensitivity 80,0%, specificity 90,0%, positive predictive value 66,7%, negative predictive value 100,0%, area under the curve 0,915, p=0,003) and the development of postoperative sepsis (sensitivity 75,0%, specificity 88,0%, positive predictive value 60,0%, negative predictive value 100,0%, area under the curve 0,884, p=0,01). The obtained cut-off values significantly predicted the death (OR 23,9 (95% CI 1,7-344,8, p=0,02)) and sepsis (OR 22,0 (95% CI 1,9-256,8, p=0,01)) in the hospital in operated patients with IE.Conclusion. The NET level in blood smears of operated patients with IE is a new promising marker for predicting the disease complicated course. NETs ≥11,2% in operated patients with IE increase the probability of hospital mortality by 24 times and postoperative sepsis by 22 times.

Association Between Early Oral β-Blocker Therapy and In-Hospital Outcomes in Patients With ST-Elevation Myocardial Infarction With Mild-Moderate Heart Failure: Findings From the CCC-ACS Project.

BackgroundThere are limited data available on the impact of early (within 24 h of admission) β-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral β-blocker therapy and in-hospital outcomes.MethodsInpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project (n = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed.ResultsEarly oral β-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, P < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early β-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486–0.844, P = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496–0.894, P = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453–0.884, P = 0.007) analyses. A dose-response trend between the first-day β-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses.ConclusionBased on nationwide Chinese data, early oral β-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.

Effect of Levosimendan on the short-term clinical efficacy of patients with acute decompensated heart failure

OBJECTIVE To observe the effect of levosimendan on the clinical efficacy of patients with acute decompensated heart failure (ADHF). METHODS Collected 124 patients with acute decompensated heart failure who were admitted to the cardiology department of our hospital from October 2019 to October 2020. According to the random number table method, they were divided into control group and levosimendan group. The control group was given traditional anti-heart failure treatment, and the levosimendan group was added with levosimendan injection on the basis of the control group. The clinical efficacy indicators, functional indicators, incidence of adverse reactions, mortality during hospitalization, rehospitalization rates and combined endpoint events within 3 months of follow-up were compared before and after treatment. RESULT The results of clinical efficacy comparison showed that the number of significant effective number in the controlgroup was less than that of the levosimendan group, and there was no difference in the number of effective, ineffective and total effective groups; the improvement of dyspnea after treatment in the levosimendan group was better than that of the control group; cardiac color Doppler ultrasound LVEF in control group is higher than Levosimendan group, LVEDV and LVESV are lower than control group; The BNP control group was higher than the levosimendan group. There was no significant difference in renal function between the two groups.The urine output of the control group was less than that of the levosimendan group.There was no statistically significant difference in adverse reactions, rehospitalization rates within 3 months, and mortality between the two groups of patients, and the combined endpoint event (death or rehospitalization) was significantly lower than that of the control group. CONCLUSION Levosimendan in the treatment of patients with acute decompensated heart failure can achieve significant clinical effects, and effectively improve the patient's hemodynamic indicators and increase renal perfusion.With the deepening of the aging of the population in China, the incidence of decompensated heart failure in the elderly population is higher, which seriously affects the normal life. Acute decompensated heart failure (ADHF), a kind of heart disease, is a clinical syndrome characterized by dyspnea with sudden onset and rapid peak based on abnormal heart function (11. It is typical of the late stage of heart disease, usually on the basis of chronic heart failure. The disease is complex and difficult to treat. In addition, the mortality rate of patients is high [2], which endangers the health of patients and threatens their life safety, and is the key disease of current clinical attention. At present, drug therapy is mainly adopted in the clinical treatment to stabilize the hemodynamic level of patients. Clinical practice shows that it is not significantthe to adopt conventional symptomatic treatment effect/which demands a new effective treatment scheme. Levosimendan .a new type of positive inotropic drug, -can increase myocardial contractility and has significant effects in improving heart failure which will reduce mortality, improve the incidence of arrhythmia and bring hope to patients [3]. This study took 124 cases admitted to our hospital as the research object, and analyzed the therapeutic effect of levosimendan. The report are as follows.

Impact of Baseline Neutrophil-to-Lymphocyte Ratio on Long-Term Prognosis in Patients With Atrial Fibrillation.

We performed a retrospective analysis involving 1269 patients with atrial fibrillation (AF) to evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on long-term outcomes. The primary outcomes were all-cause mortality and combined end point events (CEEs). Cox proportional hazards regression analysis and net reclassification improvement (NRI) analysis were performed. During a median follow-up of 3.32 years, 285 deaths and 376 CEEs occurred. With the elevation of the NLR, the incidence of all-cause mortality (2.77, 4.14, 6.12, and 12.18/100 person-years) and CEEs (4.19, 7.40, 8.03, and 15.22/100 person-years) significantly increased. Multivariate Cox analysis indicated that the highest NLR quartile was independently associated with the incidence of all-cause mortality (hazard ratio [HR] = 1.77, 95% CI: 1.19-2.65) and CEEs (HR = 1.66, 95% CI: 1.18-2.33). When the NLR was analyzed as a continuous variable, a 1-unit increment in log NLR was related to 134% increased risk of all-cause mortality and 119% increased risk of CEEs. Net reclassification improvement analysis revealed that NLR significantly improved risk stratification for all-cause death and CEEs by 15.0% and 9.6%, respectively. Neutrophil-to-lymphocyte ratio could be an independent predictor of long-term outcomes in patients with AF.

Correlation between cardiac resynchronization response and pulmonary artery hemodynamic parameters.

To evaluate the response to cardiac resynchronization therapy (CRT) and the correlation between CRT and pulmonary artery hemodynamic parameters. The patients with chronic heart failure indicator for CRT were enrolled. The left ventricular end-systolic volume (LVESV) was measured by echocardiography and New York Heart Association (NYHA) classification was evaluated between one week before and six months after CRT. Mean pulmonary artery pressure (mPAP), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured by right heart catheterization. Left ventricular reverse remodeling (LVRR) is defined as a decrease of 15% or more in LVESV at the 6th month after CRT; Clinical response is defined as a decrease of NYHA classification at or above grade 1 at the 6th month after CRT. Pulmonary hypertension (PH) was defined as mPAP≥25 mmHg. According to the response, patients were divided into 3 groups: group A (LVRR+clinical response), group B (no LVRR+clinical response) and group C (no LVRR+no clinical response). The changes of NYHA classification, echocardiographic and pulmonary hemodynamic parameters were observed in the 3 groups. The Kaplan-Meier survival curve was used to analyze the differences in all-cause mortality, combined end-point events of death or re-hospitalization due to heart failure among different groups. A total of 45 patients with CRT implantation [aged (63.27±9.55) years, 36 males] were included. The average follow-up period was (33.76±11.50) months. Thirty-one patients (68.89%) were in group A, 9 of whom with PH. Eight patients (17.78%) were in group B, 7 of whom with PH. Six patients were in group C, all with PH. Cardiac function including NYHA classification, echocardiographic and pulmonary hemodynamic parameters had been significantly improved in group A after CRT implantation (P<0.05). In group B, NYHA classification and pulmonary hemodynamic parameters were decreased significantly (P<0.05), but echocardiographic parameters did not change obviously (P>0.05). There were no significant changes in NYHA classification, echocardiographic and pulmonary hemodynamic parameters in group C (P>0.05). Compared with group C, group A and group B had lower all-cause mortality (P=0.005) and lower incidence of composite endpoint events (P=0.001). Patients with LVRR and clinical response after CRT have a good prognosis. Patients with clinical response but without LVRR have a better prognosis than those without clinical response and LVRR, which may be related to the decrease of pulmonary hemodynamic parameters such as mPAP and TPG.

Association of VEGFR-2 Gene Polymorphisms With Clopidogrel Resistance in Patients With Coronary Heart Disease.

Vascular endothelial growth factor receptor 2 (VEGFR-2) plays a central role in atherogenesis. We investigated the correlation between VEGFR-2 polymorphisms and the risk of clopidogrel resistance (CR) in patients with coronary heart disease (CHD). The study involved 275 patients with CHD undergoing percutaneous coronary intervention and on antiplatelet clopidogrel therapy. The participants were divided into CR group (n = 59) and non-CR group (NCR, n = 216) based on maximum platelet aggregation measurements. VEGFR-2 gene polymorphisms, +1192C>T (rs2305948), +1416T>A (rs1870377), and -271A>G (rs7667298), were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Enzyme-linked immunosorbent assay was used to measure serum transforming growth factor, beta receptor 2 levels. CR was found in 59 patients (20.45%). A significantly higher proportion of patients in the CR group had a history of diabetes mellitus compared with the NCR group (P < 0.05). Genotype and allele frequency of VEGFR-2 +1192C>T (rs2305948) was significantly higher in the CR group than in the NCR group (all P < 0.01). In the VEGFR-2 +1192C>T (rs2305948), the angina pectoris, recurrent myocardial infarction, and combined end point events were significantly more prevalent in the TT carriers than in the CC + CT carriers. In VEGFR-2 -271A>G (rs7667298), the GG carriers had a lower proportion of target lesion revascularization and angina pectoris in contrast to the AA + AG carriers (all P < 0.05). Based on our results, VEGFR-2 +1192C>T (rs2305948) polymorphism is strongly associated with increased CR and main adverse cardiovascular event incidence in patients with CHD undergoing percutaneous coronary intervention. Additionally, patients with CHD with diabetes mellitus history were more likely to develop CR. The associations of +1416T>A (rs1870377) and -271A>G (rs7667298) polymorphisms with CR were inconclusive and will need to be examined further.

Clinical characteristics and impact of diabetes mellitus on outcomes in patients with nonvalvular atrial fibrillation.

PurposeStudies have shown that diabetes mellitus (DM) is a risk factor for cardiovascular disease, including atrial fibrillation (AF); however, the clinical characteristics and prognostic impact of DM in patients with nonvalvular AF have not been well understood in China.Materials and MethodsIncluded were 1644 consecutive patients with nonvalvular AF. Endpoints included all-cause mortality, cardiovascular mortality, stroke, major bleeding, and combined endpoint events (CEE) during a 1-year follow-up.ResultsThe prevalence of DM was 16.8% in nonvalvular AF patients. Compared with non-diabetic AF patients, diabetic AF patients were older and tended to coexist with other cardiovascular diseases. Most patients with DM (93.5%) were eligible for anticoagulation, as determined by CHADS2 scores. However, only 11.2% of patients received anticoagulation. During a 1-year follow-up, the all-cause mortality and CEE rate in the DM group were significantly higher than those of the non-DM group, while the incidence of stroke was comparable. After multivariate adjustments, DM was still an independent risk factor for 1-year all-cause mortality [hazard ratio (HR)=1.558; 95% confidence interval (CI) 1.126-2.156; p=0.007], cardiovascular mortality (HR=1.615; 95% CI 1.052-2.479; p=0.028), and CEE (HR=1.523; 95% CI 1.098-2.112; p=0.012), yet not for stroke (HR=1.119; 95% CI 0.724-1.728; p=0.614).ConclusionDM is a common morbidity coexisting with nonvalvular AF and is associated with an increased risk of 1-year all-cause mortality, cardiovascular mortality, and CEE. However, no increased risk of stroke was found during a 1-year follow-up in patients with AF and DM.

Efficacy of levosimendan vs.milrinone in decompensated heart failure patients

Objective To evaluate the short-term clinical efficacy and safety of administration of levosimendan or milrinone added to conventional therapy in patients with decompensated heart failure.Methods A total of 180 patients admitted due to heart failure [NYHA (New York Heart Association) class Ⅲ or Ⅳ] were randomly (random number) divided into control group,milrinone group and levosimendan group (n =60,each group).A continuous infusion of milrinone added to conventional therapy was administered for 72 hours in milrinone group,while administration of levosimendan for 24 hours in levosimendan group.The changes in left ventricular ejection fraction (LVEF),left ventricle end-diastolic diameter (LVDD) and B-type natriuretic peptide (BNP) plasma level were compared between before and after treatment,respectively,and comparisons of improvement in cardiac function (NYHA class) and hospital mortality were carried out among three groups.Patients were further followed up at 3 months after treatment.Results The LVEF in levosimendan group after treatment had significantly more increased than that in control group [(32.0±6.3)％ vs.(30.6 ±5.5)％,P =0.007].Compared BNP before treatment,the sums of BNP deducted were 444.0 (-74.0,1068.0) pg/mL,469.0 (141.5,1151.5) pg/mL and 936.5 (437.8,1566.8) pg/mL in control group,milrinone group and levosimendan group,respectively after treatment (all P ＜ 0.01).Moreover,the deduction in BNP was more dramatic in levosimendan group compared with control or milrinone group (t =3.256 or 2.665,P =0.004 or 0.026).After treatment for 5 days,the probability at least of achieving more effectively better improvement in NYHA class (cardiac function) in levosimendan group was 2.036 times that of control group (95％ CI:1.030-4.028,P =0.041).The incidence of combined end point events (death or readmission) in levosimendan group was significantly lower than that in milrinone group (50％ vs.70％,HR =0.573,95％ CI:0.358-0.917,P=0.020),while in hospital mortality,readmission or 3-month mortality incidence was similar among 3 groups (P ＞ 0.05).Conclusions The short-term clinical efficacy of levosimendan is superior to that of milrinone or conventional therapy in patients with decompensated heart failure. Key words: Heart failure; Levosimendan; Milrinone ; Treatment; Prognosis

Association of Body Mass Index With Cardiac Reverse Remodeling and Long-Term Outcome in Advanced Heart Failure Patients With Cardiac Resynchronization Therapy

The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT. METHODS AND RESULTS: A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24-28 kg/m(2), ≥28 kg/m(2), respectively) were inclined to have better clinical and echocardiographic improvements (P<0.05) as well as higher response rate (P<0.001) than underweight and normal weight patients (BMI, <18.5 kg/m(2), 18.5-24 kg/m(2), respectively). During long-term follow-up, overweight and obese patients had lower all-cause mortality (P=0.015) and combined endpoint of death or HF hospitalizations (P=0.001) than underweight and normal weight patients. Compared with normal weight patients, underweight patients had a 2.29-fold increase in risk of combined endpoint events whereas overweight and obese patients had a reduction in the risk of death (66% and 58%, respectively) and combined endpoint events (52% and 38%, respectively). Patients with obesity and overweight derived more benefit from CRT. Higher BMI was independently associated with better clinical outcome in CRT patients.

Safety and tolerability of a high-potency zoster vaccine in adults ≥50 years of age

Background Herpes zoster (HZ) incidence rises with age, especially after 50 years of age, probably due to waning varicella-zoster virus (VZV)-specific immunity. The Shingles Prevention Study [Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults, N Engl J Med 2005;352:2271–84], enrolled people ≥60 years of age and showed that zoster vaccine prevents HZ and postherpetic neuralgia (PHN), presumably through boosting VZV-specific immunity. This study of people ≥50 years of age compared the safety and tolerability of two zoster vaccine potencies. Methods Adults ≥50 years old enrolled in a randomized, double-blind, multicenter study to compare the safety and tolerability of one dose of two zoster vaccine potencies, ∼58,000 and ∼207,000 plaque-forming units/dose. Adverse experiences (AEs) were recorded on a standardized Vaccination Report Card for 42 days postvaccination. For assessment of injection-site AEs, clinically acceptable tolerability was predefined based on experience with PNEUMOVAX™ 23, a licensed vaccine recommended for use in older people. Results Six hundred and ninety-eight subjects (age 50–90 years, median 64 years) were enrolled. No serious vaccine-related AEs were reported. Similar AE rates were observed in the higher and lower potency groups (overall systemic AEs: 37.5 and 39.3%, vaccine-related systemic AEs: 10.9 and 13.2%, injection-site AEs: 63.0 and 59.8%). Rates for a combined endpoint of moderate or severe injection-site pain/tenderness/soreness and swelling were 17.2% (95% CI 13.9, 21.0) and 9.0% (95% CI 5.6, 13.4), respectively. Most combined endpoint events were reported as moderate in intensity. Conclusions Both vaccine potencies were generally well tolerated in this study of people ≥50 years of age. Although rates of some moderate or severe injection-site AEs were greater in the higher potency group, all rates met the prespecified criteria for clinically acceptable tolerability.

Clinical Judgment and Treatment Options in Stable Multivessel Coronary Artery Disease: Results From the One-Year Follow-Up of the MASS II (Medicine, Angioplasty, or Surgery Study II)

This study examined the predictive power of clinical judgment in the incidence of cardiovascular end points in a group of individuals with multivessel coronary artery disease (CAD) followed up in the MASS II (Medicine, Angioplasty, or Surgery Study II). There is still no consensus on the best treatment for patients with stable multivessel CAD and preserved left ventricular function. Preferred treatment allocation was recorded for each of the 611 randomized patients in the MASS II trial before randomization. We have divided our sample according to physician-guided decision and randomization result into two categories: concordant or discordant. The incidence of the points of cardiac death, myocardial infarction, and refractory angina was compared between concordant and discordant patients. The number of concordant individuals was 292 (48.2%), and this number was not different between the three studied treatments (p = 0.11). A significant difference (p = 0.02) was disclosed because of an increased incidence of combined end point events in discordant patients. In the multivariate Cox hazard model, clinical judgment was a powerful predictor of outcome (p = 0.01) even after adjustment for other covariates. The main subgroup explaining this difference was a significant shift toward a worse outcome in the subgroup of discordant patients who underwent percutaneous coronary intervention (PCI) (p = 0.003). Angiographic variables were more often used in making clinical decisions regarding PCI than clinical variables, and the only independent predictor of concordance status in the PCI group was the number of diseased vessels (p = 0.01). Our data are a reminder that physician judgment remains an important predictor of outcomes.

Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction.

Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.