Abraham Palant

Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the bezafibrate infarction prevention trial)

Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double blind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterol < or = 45 mg/dl and triglycerides < or = 300 mg/dl. In addition, low-density lipoprotein cholesterol concentrations are required to be < or = 180 mg/dl (< or = 160 mg/dl for patients aged < 50 years). Patients needing lipid-modifying therapy, exhibiting > or = 1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of > or = 15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium antagonists and mortality in patients with coronary artery disease: A Cohort study of 11,575 patients☆

OBJECTIVES This study sought to establish the risk ratio for mortality associated with calcium antagonists in a large population of patients with chronic coronary artery disease. BACKGROUND Recent reports have suggested that the use of short-acting nifedipine may cause an increase in overall mortality in patients with coronary artery disease and that a similar effect may be produced by other calcium antagonists, in particular those of the dihydropyridine type. METHODS Mortality data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium antagonists) after a mean follow-up period of 3.2 years. RESULTS There were 495 deaths (8.5%) in the calcium antagonist group compared with 410 in the control group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence interval [CI] 0.95 to 1.24). After adjustment for the differences between the groups in age and gender and the prevalence of previous myocardial infarction, angina pectoris, hypertension, New York Heart Association functional class, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11). After further adjustment for concomitant medication, the risk ratio was estimated at 0.94 (95% CI 0.82 to 1.08). CONCLUSIONS The current analysis does not support the claim that calcium antagonist therapy in patients with chronic coronary artery disease, whether myocardial infarction survivors or others harbors an increased risk of mortality.

The prognostic significance of angina pectoris preceding the occurrence of a first acute myocardial infarction in 4166 consecutive hospitalized patients.

We examined the role of chronic (greater than 1 month) angina pectoris (AP) before acute myocardial infarction (AMI) in predicting hospital and long-term mortality rates among 4166 patients with first AMIs. The prevalence of AP in these patients was 43%. Chronic AP was more common in women (49%), patients with hypertension (49%), and diabetic patients (49%) than in men and counterparts free of the former conditions (p less than 0.005). In patients with AP the hospital course was more complicated and non-Q-wave AMI was more common than in counterparts without AP. In-hospital (16%), as well as 1 (8%)- and 5-year postdischarge (26%), mortality rates in hospital survivors were higher among patients with previous AP than in patients without previous AP (12%, 6%, and 19%, respectively) (p less than 0.01). After adjustment for age and all other predictors of increased hospital mortality rates in this cohort of patients, AP preceding AMI emerged as an independent predictor of increased hospital mortality rates (odds ratio 1.30; 90% confidence interval 1.10 to 1.53). For postdischarge mortality rates (mean follow-up 5 1/2 years), the covariate-adjusted relative risk of death in patients with AP was similar at 1.29 (p less than 0.0001; 90% confidence interval 1.16 to 1.44), according to estimation by Cox proportional hazards model. These data support the notion that preexisting AP identifies a group of patients at increased risk of death.

Cerebrovascular accident complicating acute myocardial infarction: Incidence, clinical significance, and short-long-term mortality rates

Abstract purpose: The purpose of this study was to report the incidence, the antecedents, and the clinical significance of clinically recognized cerebrovascular accidents or transient ischemic attacks (CVA-TIA) complicating acute myocardial infarction. patients and methods: During 1981 to 1983, a secondary prevention study with nifedipine (SPRINT) was conducted in 14 hospitals in Israel among 2,276 survivors of acute myocardial infarction. During the study, demographic, historical, and medical data were collected on special forms for all patients with diagnosed acute myocardial infarction in 13 of these 14 hospitals (the SPRINT registry, n=5,839). Mortality followup was completed for 99% of hospital survivors for a mean follow-up of 5.5 years (range: 4.5 to 7 years). results: The incidence of CVA-TIA was 0.9% (54 of 5,839). The latter rate increased significantly only with age, from 0.4% among patients up to 59 years old to 1.6% among those aged greater than or equal to 70 years. Multivariate analysis identified age, congestive heart failure, and history of stroke as predictors of CVA-TIA during the acute phase of myocardial infarction. Patients with CVA-TIA exhibited a complicated hospital course, with a 15-day mortality rate of 41%. Subsequent mortality rates in survivors at 1 and 5 years were 34% and 59%, respectively. Rates at the same time points in patients without CVA-TIA were 16%,11%, and 29% (p conclusion: In this large cohort of consecutive patients with myocardial infarction, CVATIA was a relatively infrequent complication of acute myocardial infarction. Factors independently favoring the occurrence of CVA-TIA were old age, previous CVA, and congestive heart failure. CVA-TIA occurring during acute myocardial infarction independently increased the risk of early death threefold as well as the risk of long-term mortality in early-phase survivors (2.5-fold).

Long-term prognosis after acute myocardial infarction in patients with left ventricular hypertrophy on the electrocardiogram

Abstract Among 4,720 consecutive hospital survivors from acute myocardial infarction (AMI) treated in 13 coronary care units between July 1981 and August 1983, the estimated prevalence of electrocardiographic left ventricular (LV) hypertrophy was 6.1%. The prevalence of electrocardiographs LV hypertrophy increased with age and was higher in patients with previous myocardial infarction, angina and systemic hypertension. Mean age of patients with electrocardiographic LV hypertrophy was 67.2 vs 61.4 years in counterparts free of electrocardiographic LV hypertrophy. Patients with electrocardiographic LV hypertrophy had a higher rate of congestive heart failure on admission, or developing during their stay in coronary care units. The 1- and 5-year mortality rates were 19.7 and 46.6% among patients with electrocardiographic LV hypertrophy versus 8.7 and 26.2%, respectively (p

Incidence and prognostic significance of chronic atrial fibrillation among 5,839 consecutive patients with acute myocardial infarction

Abstract Paroxysmal atrial fibrillation (AF), a frequent complication of acute myocardial infarction (AMI), was found to be a weak independent predictor of the longterm mortality in surviving patients in 2 recent studies. 1,2 We are unaware of any studies on the prognostic impact of chronic AF on patients with AMI. The present study assesses the short- and long-term outcomes of patients with chronic AF having an AMI.

Frequency and prognostic significance of secondary ventricular fibrillation complicating acute myocardial infarction

The incidence of secondary ventricular fibrillation (VF) complicating acute myocardial infarction (AMI) was 2.4% in a large cohort of unselected patients with AMI (142 of 5,839). Secondary VF was more frequent in patients with recurrent AMI (4%) than in those with a first AMI (1.9%) (p < 0.01). The hospital course was more complicated and in-hospital mortality was significantly higher in patients with secondary VF than in those with the same clinical hemodynamic condition but without VF (56 vs 16%; p < 0.0001). Multivariate analyses confirmed secondary VF complicating AMI as an independent predictor of high in-hospital mortality, with an odds ratio of 7 (95% confidence interval 4.6-10.6). However, long-term mortality after discharge (mean follow-up 5.5 years) was not increased in patients with as compared with those without secondary VF (39 vs 42%). These findings were also true when patients receiving beta blockers and antiarrhythmic therapy were excluded from analysis. Thus, this life-threatening arrhythmia occurring during hospitalization is not a marker of recurrent susceptibility to VF or an indicator of increased mortality after discharge from the hospital.

Prognosis of early versus late ventricular fibrillation complicating acute myocardial infarction

Earlier studies have suggested that patients exhibiting late (> 24 h) ventricular fibrillation during acute myocardial infarction had a poorer outcome in comparison to myocardial infarction patients with early (< 24 h) ventricular fibrillation. Between August 1981 and July 1983, 5839 consecutive patients with acute myocardial infarction were hospitalized in 13 out of 21 operating coronary care units in Israel. Demographic and medical data were collected from hospitalization charts and during 1 year of follow-up. Mortality assessment was done for 99% of hospital survivors up to mid-1988 (mean, 5.5 years). The incidence of ventricular fibrillation in the SPRINT Registry was 6% (371/5839). Patients with ventricular fibrillation in the setting of cardiogenic shock (n = 107) were excluded from analysis. Patients with late ventricular fibrillation (n = 109; 41%) were older and had a more complicated hospital course than patients with early ventricular fibrillation (n = 155; 59%). In-hospital and 1-year post-discharge mortality were significantly higher in patients with late ventricular fibrillation (63% and 17%) as compared to patients with early ventricular fibrillation (26% and 4%, respectively; P < 0.05 for each). This difference vanished 5 years after hospital discharge. After multiple logistic regression analysis late occurrence of ventricular fibrillation emerged as an independent predictor of increased in-hospital mortality (Odds ratio, 4.29; 95% confidence interval, 2.11-8.74) but not for subsequent death. Patients with late ventricular fibrillation during the hospital course of acute myocardial infarction had a poorer immediate and subsequent outcome in comparison to patients with early ventricular fibrillation.

Immediate and long-term prognostic significance of a first anterior versus first inferior wall Q-wave acute myocardial infarction

Abstract Of 3,981 patients with a first Q-wave acute myocardial infarction (AMI), 1,929 (48%) had an anterior and 1,724 (43%) an inferior wall AMI. These 2 groups were well-matched with respect to age, gender and relevant history. The in-hospital mortality rate was 18%, and the 1- and 5-year postdischarge mortality rates were 9 and 25%, respectively, in patients with anterior wall AMI compared with the corresponding rates of 11, 6 and 19% in those with inferior wall AMI (p The frequency of recurrent nonfatal AMI in the year after the index AMI was 8% in the patients with anterior wall AMI compared with 4% in those with inferior wall AMI (p The findings indicate that the anatomic location of a Q-wave AMI influences immediate and short-term survival of patients with a first Q-wave AMI.

Frequency of use of thrombolytic therapy in acute myocardial infarction in Israel

Thrombolysis is now generally accepted as the initial treatment for patients with acute myocardial infarction (AMI). The extent to which this therapy is implemented in daily practice and the reasons for exclusion from thrombolytic therapy among 413 consecutive patients with AMI hospitalized in 18 coronary care units in Israel during a 1-month survey were prospectively investigated. Thrombolytic therapy administered to 145 patients (35%) was given to 38% of men versus 29% of women (p = not significant), to 38% of patients less than 75 years old compared with 18% of the very elderly (p less than 0.005), and more often to patients with a first or anterior AMI (40 and 48%) than to counterparts with recurrent or inferior AMI (23 and 31%, respectively, p less than 0.005 for both). The 2 most frequent reasons for excluding patients from thrombolysis were late arrivals to coronary care units (33%) and lack of ST elevation on the admission electrocardiogram (28%). Hospital mortality was 6% in the thrombolytic group versus 20% in patients found ineligible for thrombolysis. The significance of this difference is not clear as treatment was not randomized.