Kong I. Lie

Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels : the Regression Growth Evaluation Statin Study (REGRESS)

BACKGROUND Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. METHODS AND RESULTS REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group (P = .019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group (P = .001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events (P = .002). CONCLUSIONS In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.

PREDICTION OF UNEVENTFUL CARDIOVERSION AND MAINTENANCE OF SINUS RHYTHM FROM DIRECT-CURRENT ELECTRICAL CARDIOVERSION OF CHRONIC ATRIAL-FIBRILLATION AND FLUTTER

The present study was undertaken to reassess prospectively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter, and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion. Two-hundred forty-six patients underwent direct-current electrical cardioversion and were followed during a mean of 260 days. Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome. Cardioversion was achieved in 70% of patients with atrial fibrillation and in 96% of patients with atrial flutter. Stepwise logistic regression analysis revealed that arrhythmia duration (p less than 0.001), type of arrhythmia (fibrillation vs flutter, p less than 0.02) and age (p less than 0.05) independently influenced conversion rate. On an actuarial basis, 42 and 36% of patients remained in sinus rhythm during 1 and 2 years, respectively. Multivariate regression analysis revealed that the type of arrhythmia (p = 0.0008), low precardioversion functional class (p = 0.002) and the presence of nonrheumatic mitral valve disease (p = 0.03) independently increased the length of the arrhythmia-free episode. Rheumatic heart disease shortened this period (p = 0.03). In conclusion, patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified. This may improve the cost-benefit ratio of cardioversion.

B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS).

OBJECTIVES In this B-mode ultrasound study we assessed pravastatin treatment effects on carotid and femoral artery walls and investigated the correlations between the state and evolution of peripheral and coronary atherosclerosis. BACKGROUND The Regression Growth Evaluation Statin Study (REGRESS) was an 11-center, 2-year, double-blind, placebo-controlled, prospective study of 885 men with coronary artery disease (CAD) (total cholesterol 4 to 8 mmol/liter). The study primarily investigated pravastatin treatment effects on the coronary lumen. This report focuses on the 255 patients who participated in the REGRESS ultrasound study. METHODS Carotid and femoral artery walls were imaged at baseline and at 6, 12, 18 and 24 months. Pravastatin treatment effect was defined as the difference in progression of the combined intima-media thicknesses (IMT) between treatment groups. RESULTS Pravastatin treatment effects were highly significant (combined IMT: p = 0.0085; combined far wall IMT: p < 0.0001; common femoral artery far wall IMT: p = 0.004). Correlations between the IMTs of the arterial wall segments ranged from -0.17 to 0.81. Baseline correlations between IMT and percent coronary lumen stenoses ranged from 0.23 to 0.36. Baseline IMT correlated with the mean coronary segment diameter (r = -0.32, p = 0.001) and minimal coronary obstruction diameter (r = -0.27, p = 0.005). There were no individual correlations between IMT and coronary lumen variables (p > 0.30). CONCLUSIONS Pravastatin treatment effects on carotid and femoral artery walls were observed. B-mode ultrasound imaging studies of peripheral arterial walls could not describe the state and evolution of the coronary lumen in the individual patient, but proved to be a highly suitable tool for the assessment of antiatherosclerotic properties of agents.

THE VALUE OF CLASS IC ANTIARRHYTHMIC DRUGS FOR ACUTE CONVERSION OF PAROXYSMAL ATRIAL FIBRILLATION OR FLUTTER TO SINUS RHYTHM

In a single-blind randomized study, the efficacy and safety of intravenous propafenone (2 mg/kg body weight per 10 min) versus flecainide (2 mg/kg per 10 min) were assessed in 50 patients with atrial fibrillation or flutter. Treatment was considered successful if sinus rhythm occurred within 1 h. Conversion to sinus was achieved in 11 (55%) of 20 patients with atrial fibrillation treated with propafenone and in 18 (90%) of 20 with atrial fibrillation treated with flecainide (p less than 0.02). If atrial fibrillation was present less than or equal to 24 h, conversion to sinus rhythm was achieved in 8 (57%) of 14 patients in the propafenone group and 13 (93%) of 14 in the flecainide group (p less than 0.05). Atrial flutter was converted in two (40%) of five patients treated with propafenone and in one (20%) of five with flecainide (p = NS). Mean time to conversion was 16 +/- 10 min in the propafenone group versus 18 +/- 13 min in the flecainide group (p = NS). QRS lengthening (83 +/- 15 to 99 +/- 20 ms) was observed only in the patients treated with flecainide (p less than 0.001). Patients successfully treated with propafenone showed significantly higher plasma levels than those whose arrhythmia did not convert to sinus rhythm. Transient adverse effects were more frequent in the flecainide group (40%) than in the propafenone group (8%) (p less than 0.01). In conclusion, at a dose of 2 mg/kg in 10 min, flecainide is more effective than propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm. However, considering the propafenone plasma levels and very few adverse effects, the dose or infusion rate, or both, used in the propafenone group may not have been sufficient to achieve an optimal effect. Neither drug seems very effective in patients with atrial flutter.

Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study.

BackgroundSuccessful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. Methods and ResultsPatients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography <48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p<0.025; other comparisons, p=NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p<0.05; other comparisons, p=NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p<0.001; aspirin versus Coumadin, p<0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p=NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p<0.001). ConclusionsAt 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.

Comparison between New York Heart Association Classification and peak oxygen consumption in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

To compare the value of the New York Heart Association (NYHA) classification and measurement of peak oxygen consumption (VO2) in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure (CHF), 94 patients with clinically stable NYHA class II and III CHF were prospectively studied. In all patients, left ventricular ejection fraction was less than or equal to 40% (mean 22 +/- 9); 49 patients were in NYHA class II, and 45 were in NYHA class III. Mean peak VO2 was 17 +/- 5 ml/min/kg. During a follow-up period of 23 +/- 11 months, 21 patients died. The 1-, 2- and 3-year cumulative survival rates for the 94 patients were 88, 79 and 69%, respectively. Functional status, as assessed both by peak VO2 and NYHA classification, and left ventricular ejection fraction were significantly worse in the group of nonsurvivors. The most powerful independent predictor of mortality was peak VO2. Although mean peak VO2 was significantly higher in NYHA class II than in NYHA class III (20 +/- 4 vs 13 +/- 3 ml/min/kg, p less than 0.0001), categorization into subgroups on the basis of the attained peak VO2 revealed a marked discrepancy with the NYHA classification. Nevertheless, the survival curves of patients subdivided at a peak VO2 of 16 ml/min/kg showed a strong resemblance with survival curves of both NYHA classes.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of Transient Myocardial Ischemia With Pravastatin in Addition to the Conventional Treatment in Patients With Angina Pectoris

BACKGROUND Lipid-lowering therapy reduces cardiac morbidity and mortality. Less is known about its potential anti-ischemic effect. METHODS AND RESULTS In a 2-year prospective randomized placebo-controlled study, the effect of pravastatin 40 mg on transient myocardial ischemia was assessed. Forty-eight-hour ambulatory ECGs with continuous ST-segment analysis were performed in 768 male patients with stable angina pectoris, documented coronary artery disease, and serum cholesterol between 4 and 8 mmol/L (155 and 310 mg/dL). During the trial, patients received routine antianginal treatment. In the patients randomized to pravastatin, transient myocardial ischemia was present at baseline in 28% and after treatment in 19%; in the placebo group, it was found in 20% and 23% of the patients, respectively (P = .021 for change in percentage between two treatment groups; odds ratio, 0.62; 95% CI, 0.41 to 0.93). Ischemic episodes decreased by 1.23 +/- 0.25 (SEM) episode with pravastatin and by 0.53 +/- 0.25 episode with placebo (P = .047). Under pravastatin, the duration of ischemia decreased from 80 +/- 12 minutes to 42 +/- 10 minutes (P = .017) and with placebo, from 60 +/- 13 minutes to 51 +/- 9 minutes (P = .56). The total ischemic burden decreased from 41 +/- 5 to 22 +/- 5 mm.min in the pravastatin group (P = .0058) and from 34 +/- 6 to 26 +/- 4 mm . min in the placebo group (P = .24). Adjusted for independent risk factors for the occurrence of ischemia, the effect of pravastatin on the reduction of risk for ischemia remained statistically significant (odds ratio, 0.45; 95% CI, 0.22 to 0.91; P = .026). CONCLUSIONS In men with documented coronary artery disease and optimal antianginal therapy, pravastatin reduces transient myocardial ischemia.

Efficacy and safety of flecainide acetate in the maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation or atrial flutter

The efficacy and safety of flecainide were studied in the maintenance of sinus rhythm after electrical cardioversion for chronic atrial fibrillation or atrial flutter. Eighty-one patients were randomized to flecainide treatment or no treatment. Baseline characteristics of both groups were comparable. Compared to previous studies, patients could be classified as difficult-to-treat patients. Multiple regression analysis showed New York Heart Association class I for exercise tolerance (p = 0.0004) and flecainide treatment (p = 0.01) to be the main factors increasing the arrhythmia-free episode. However, Mantel-Cox lifetable analysis did not reveal significant differences between arrhythmia-free survival curves of both treatment groups. In the flecainide-treated group, 9% of patients experienced side effects, mostly related to negative dromotropic effects. The incidence of ventricular proarrhythmia in this group of patients was low. Thus, flecainide may be effective in postponing arrhythmia recurrence, even in difficult-to-treat patients. Caution should be excercised in treating patients with underlying conduction disturbances, sick sinus syndrome or characteristics favoring development of ventricular proarrhythmia.

Effect of Procainamide, Propranolol and Verapamil on Mechanism of Tachycardia in Patients With Chronic Recurrent Ventricular Tachycardia

The effect of short-term intravenous administration of procainamide (12 patients), propranolol (4 patients) and verapamil (4 patients) was studied in 12 patients with chronic recurrent sustained ventricular tachycardia. In all patients tachycardia could reproducibly be initiated and terminated with programmed electrical stimulation of the heart. Procainamide (1) lengthened the effective refractory period of the right ventricle, (2) affected the tachycardia zone, (3) reduced ventricular rate during tachycardia, and (4) lengthened the interval between the tachycardia-initiating premature ventricular beat and the first QRS complex of tachycardia. No effect on the refractory period of the right ventricle or the mechanism of tachycardia was seen after administration of propranolol or verapamil. Apart from their therapeutic implications these data suggest that it may be possible to use drugs to study mechanisms of ventricular tachycardia in the human heart.

Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris : a prospective, randomized clinical study

OBJECTIVES In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation on exercise capacity and quality of life in patients with intractable angina. BACKGROUND Despite important achievements in therapy for ischemic heart disease, there remain patients with intractable symptoms of angina. In uncontrolled observations, several investigators have reported beneficial effects of spinal cord stimulation as an additional therapy for patients with angina pectoris. METHODS Seventeen patients were randomly assigned to the treatment (implantation within 2 weeks, eight patients) or control (implantation after 8 weeks, nine patients) group. Assessment of exercise capacity was performed by treadmill exercise testing. Quality of life was evaluated by daily and social activity scores and recording sublingual glyceryl trinitrate intake and angina pectoris attacks in a diary. After the 8-week study period, the control group also received the spinal cord stimulation device, and all patients were followed up for 12 months. RESULTS The treatment but not the control group demonstrated a significant increase in exercise duration (p < 0.02), rate-pressure product (p < 0.03) and time to angina (p < 0.04), with a decrease in ST segment depression (p < 0.05). This was associated with an increase in daily life (p < 0.008) and social activity (p < 0.005) scores and a reduction in glyceryl trinitrate intake (p < 0.004) and episodes of angina pectoris (p < 0.003). During the 1-year follow-up, improvement in all quality of life variables was linear for the entire group compared with baseline. The time to angina, exercise duration and ST segment depression showed a second-order trend. CONCLUSIONS Spinal cord stimulation significantly improves exercise capacity and quality of life. On the basis of an increase in exercise capacity and rate-pressure product, the mechanism by which spinal cord stimulation acts may be related to improved oxygen supply to the heart combined with an analgesic effect.