John R. Hampton

TRIAL OF TISSUE PLASMINOGEN ACTIVATOR FOR MORTALITY REDUCTION IN ACUTE MYOCARDIAL INFARCTION: Anglo-Scandinavian Study of Early Thrombolysis (ASSET)

13,318 patients admitted to fifty-two coronary care units with suspected acute myocardial infarction were considered for inclusion in a double-blind study comparing recombinant tissue-type plasminogen activator (rt-PA) 100 mg plus heparin with placebo plus heparin. 8307 (62%) were excluded, mainly because their symptoms had begun more than 5 h previously, but all excluded patients were followed up at least until hospital discharge. 2516 patients were randomly allocated to rt-PA and 2495 to placebo. At one month the overall case fatality rates were 7.2% and 9.8%, respectively, a relative reduction of 26% (95% confidence interval 11-39%). 6.3% of patients given rt-PA had a bleeding complication (1.4% major) compared with 0.8% given placebo (0.4% major). However, the incidence of stroke was similar--1.1% in the rt-PA group and 1.0% in the placebo group. Subset analysis showed that patients who had a normal electrocardiogram (ECG) at the time of randomisation (17.5% of the whole trial population) had a low case fatality rate (1.6% in those given rt-PA compared with 3.0% in those given placebo). In those with an abnormal ECG at entry, rt-PA was associated with a 24.5% relative reduction in 1 month fatality (95% confidence interval 9-37%).

Renal Function, Neurohormonal Activation, and Survival in Patients With Chronic Heart Failure

BACKGROUND Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation. METHODS AND RESULTS The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFR(c)) was calculated using the Cockroft Gault equation. GFR(c) was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFR(c) values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2. 85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFR(c) was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001). CONCLUSIONS Impaired renal function (GFR(c)) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.

Meta-analysis of randomised trials comparing coronary angioplasty with bypass surgery

A patient with severe angina will often be eligible for either angioplasty (PTCA) or bypass surgery (CABG). Results from eight published randomised trials have been combined in a collaborative meta-analysis of 3371 patients (1661 CABG, 1710 PTCA) with a mean follow-up of 2.7 years. The total deaths in the CABG and PTCA groups were 73 and 79, respectively, with a relative risk (RR) of 1.08 (95% CI 0.79-1.50). The combined endpoint of cardiac death and non-fatal myocardial infarction occurred in 169 PTCA patients and 154 CABG patients (RR 1.10 [0.89-1.37]). Amongst patients randomised to PTCA 17.8% required additional CABG within a year, while in subsequent years the need for additional CABG was around 2% per annum. The rate of additional non-randomised interventions (PTCA and/or CABG) in the first year of follow-up was 33.7% and 3.3% in patients randomised to PTCA and CABG, respectively. The prevalence of angina after one year was considerably higher in the PTCA group (RR 1.56 [1.30-1.88]) but at 3 years this difference had attenuated (RR 1.22 [0.99-1.54]). Overall there was substantial similarity in outcome across the trials. Separate analyses for the 732 single-vessel and 2639 multivessel disease patients were largely compatible, though the rates of mortality, additional intervention, and prevalent angina were slightly lower in single vessel disease. The combined evidence comparing PTCA with CABG shows no difference in prognosis between these two initial revascularisation strategies. However, the treatments differ markedly in the subsequent requirement for additional revascularisation procedures and in the relief of angina. These results will influence the choice of revascularisation procedure in future patients with angina.

Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure

BACKGROUND Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study. METHODS Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done. FINDINGS After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients. INTERPRETATION Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

Quality of Life, Employment Status, and Anginal Symptoms After Coronary Angioplasty or Bypass Surgery 3-Year Follow-up in the Randomized Intervention Treatment of Angina (RITA) Trial

BACKGROUND The Randomized Intervention Treatment of Angina (RITA) trial compares initial policies of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) in 1011 patients with angina. This report assesses the impact of these revascularization procedures on angina, quality of life (according to the Nottingham Health Profile), and employment over 3 years of follow-up. METHODS AND RESULTS Both interventions produced marked improvement in all quality-of-life dimensions (energy, pain, emotional reactions, sleep, social isolation, and mobility) and seven aspects of daily living. Patients with angina at 2 years had more quality-of-life impairment than angina-free patients, whose perceived health was similar to population norms. This reflects the close link at baseline between angina grade and quality of life. The slightly greater impairment of quality of life in PTCA compared with CABG patients is a result of their significantly higher chances of having angina, especially after 6 months. Employment status was investigated mainly for men < or = 60 years old. PTCA patients returned to work sooner (40% at 2 months compared with 10% of CABG patients), but the latter caught up by 5 months. After 2 years, 22% and 26% of CABG and PTCA patients, respectively, were not working for cardiac reasons. Patients with angina at 2 years were much more likely to be unemployed than those without. CONCLUSIONS The impact of angina on quality of life and unemployment is greatly alleviated by PTCA or CABG. Angina is avoided more successfully with CABG, but PTCA offers a speedier return to work. Both intervention strategies then produce similar benefits for quality of life and employment over several years.

Long-term results of RITA-1 trial: clinical and cost comparisons of coronary angioplasty and coronary-artery bypass grafting

Summary Background Percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) are both effective intervention strategies for patients with coronary heart disease. We report comparative long-term clinical and health-service cost findings for these interventions in the first Randomised Intervention Treatment of Angina (RITA-1) trial. Methods 1011 patients with coronary heart disease (45% single-vessel, 55% multivessel) were randomly assigned initial treatment strategies of PTCA or CABG. Information on clinical events, subsequent intervention, symptomatic status, exercise testing, and use of health-care resources is available for a median 6·5 years of follow-up. Analyses were by intention to treat. Findings The predefined primary endpoint of death or nonfatal myocardial infarction occurred in 87 (17%) PTCA-group patients and 80 (16%) CABG-group patients (p=0·64). Similarly, there was no significant treatment difference in deaths alone (39 PTCA, 45 CABG), of which 46% were cardiac related. In both groups, the risk of cardiac death or myocardial infarction was more than five times higher in the first year than in subsequent years of follow-up. 26% of patients assigned PTCA subsequently also had CABG, and a further 19% required additional nonrandomised PTCA. Most of these reinterventions occurred within a year of randomisation, and from 3 years onwards the reintervention rate averaged 4% per year. In the CABG group the reintervention rate averaged 2% per year. The prevalence of angina was consistently higher in the PTCA group, with an absolute average 10% excess compared with the CABG group (p Interpretation Initial strategies of PTCA and CABG led to similar long-term results in terms of survival and avoidance of myocardial infarction and to similar long-term healthcare costs. Choice of approach, therefore, rests on weighing the more invasive nature of CABG against the greater risk of recurrent angina and reintervention over many years after PTCA.

Quality of life four years after acute myocardial infarction: short form 36 scores compared with a normal population

OBJECTIVES To assess the impact of myocardial infarction on quality of life in four year survivors compared to data from “community norms”, and to determine factors associated with a poor quality of life. DESIGN Cohort study based on the Nottingham heart attack register. SETTING Two district general hospitals serving a defined urban/rural population. SUBJECTS All patients admitted with acute myocardial infarction during 1992 and alive at a median of four years. MAIN OUTCOME MEASURES Short form 36 (SF 36) domain and overall scores. RESULTS Of 900 patients with an acute myocardial infarction in 1992, there were 476 patients alive and capable of responding to a questionnaire in 1997. The response rate was 424 (89.1%). Compared to age and sex adjusted normative data, patients aged under 65 years exhibited impairment in all eight domains, the largest differences being in physical functioning (mean difference 20 points), role physical (mean difference 23 points), and general health (mean difference 19 points). In patients over 65 years mean domain scores were similar to community norms. Multiple regression analysis revealed that impaired quality of life was closely associated with inability to return to work through ill health, a need for coronary revascularisation, the use of anxiolytics, hypnotics or inhalers, the need for two or more angina drugs, a frequency of chest pain one or more times per week, and a Rose dyspnoea score of ⩾ 2. CONCLUSIONS The SF 36 provides valuable additional information for the practising clinician. Compared to community norms the greatest impact on quality of life is seen in patients of working age. Impaired quality of life was reported by patients unfit for work, those with angina and dyspnoea, patients with coexistent lung disease, and those with anxiety and sleep disturbances. Improving quality of life after myocardial infarction remains a challenge for physicians.

Do women with acute myocardial infarction receive the same treatment as men

Abstract Objective : To determine whether women with acute myocardial infarction in the Nottingham health district receive the same therapeutic interventions as their male counterparts. Design : Retrospective study. Setting : University and City Hospitals,20Nottingham. Patients : All patients admitted with a suspected myocardial infarction during 1989 and 1990. Main outcome measures : Route and timing of admission to hospital, ward of admission, treatment, interventions in hospital, and mortality. Results - Women with myocardial infarction took longer to arrive in hospital than men. They were less likely to be admitted to the coronary care unit and20were therefore also less likely to receive thrombolytic treatment. They seemed to have more severe infarcts, with higher Killip classes, and had a slightly higher mortality during admission. They were less likely than men to receive secondary prophylaxis by being discharged taking ß blockers or aspirin. Conclusion : Survival chances both in hospital and after discharge in women with acute myocardial infarction are reduced because they do not have the same opportunity for therapeutic intervention as men.

Evidence of inadequate investigation and treatment of patients with heart failure.

OBJECTIVE--To determine the referral rates to hospital and level of investigation of patients with heart failure, and to assess whether they are receiving optimum management. DESIGN--A retrospective survey. SETTING--Nottingham Health District. PATIENTS--505 patients receiving loop diuretic treatment prescribed by their general practitioner. MAIN OUTCOME MEASURES--Referral to hospital as an inpatient or outpatient for assessment of assumed cardiac failure; investigations--electrocardiography, chest radiography, and echocardiography; treatment with angiotensin converting enzyme inhibitors. RESULTS--Only 56% of patients prescribed loop diuretics fulfilled the diagnostic criteria for heart failure. Of these, 74% had been referred to hospital, of whom 80% had had an electrocardiograph, 75% a chest radiograph, but only 31% an echocardiogram. Only 17% of patients with heart failure were being treated with angiotensin converting enzyme inhibitors in conjunction with loop diuretics. CONCLUSIONS--Patients with heart failure in the Nottingham Health District are not being adequately investigated or receiving the optimum treatment.

Trial of early nifedipine in acute myocardial infarction: the Trent study.

Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied.