Bjarne Sigurd

Hospital-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial

BACKGROUND Current guidelines broadly recommend comprehensive cardiac rehabilitation (CCR), although evidence for this is still limited. We investigated the 12-month effect of hospital-based CCR versus usual care (UC) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology. METHODS We conducted a centrally randomized single-center clinical trial with blinded assessment of the primary outcome: registry-based composite of total mortality, myocardial infarction, or acute first-time readmission due to heart disease. Other outcomes were hospitalization, risk profile, and quality of life. The trial included 770 participants (20-94 years) with congestive heart failure (12%), ischemic heart disease (58%), or high risk of ischemic heart disease (30%). Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months. RESULTS We randomized 380 patients to CCR versus 390 to UC. Randomization was well balanced. The primary outcome occurred in 31% of both groups (relative risk 0.96, 95% confidence interval 0.78-1.26). Compared with the UC group, CCR significantly reduced length of stay by 15% (95% confidence interval 1.1%-27.1%, P = .04), mean number of cardiac risk factors above target (4.5 vs 4.1, P = .01), patients with systolic blood pressure below target (P = .003), physically inactivity (P = .01), and unhealthy dietary habits (P = .0003). Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly. CONCLUSION At 12 months, the CCR and UC groups did not differ regarding the primary composite outcome. Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors.

Cardiac Event Rates After Acute Myocardial Infarction in Patients Treated With Verapamil and Trandolapril Versus Trandolapril Alone

Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.

The supra-additive natriuretic effect addition of theophylline ethylenediamine and bumetanide in congestive heart failure

Summary The additive natriuretic effect of oral theophylline ethylenediamine, 400 mg., and the potent diuretic bumetanide has been studied in patients with advanced congestive heart failure. Two permutation trial tests including six patients each were performed in subjects receiving long-term therapy with digoxin and bumetanide, 4 mg. daily. In the first trial, the response to supplementary theophylline ethylenediamine, 400 mg., was definitely superior to that of additional bumetanide, 2 mg., in terms of renal output of sodium, chloride, potassium, water and osmolal clearance. In the second trial the comparison was made of the effects of theophylline ethylenediamine, 400 mg. plus bumetanide, 4 mg., of theophylline ethylenediamine, 400 mg., and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. The third permutation trial test comprised six patients, who had not previously received bumetanide. In this group no additive natriuretic or diuretic effect could be demonstrated after administration of theophylline ethylenediamine. It is concluded that in patients receiving longterm treatment with the potent diuretic bumetanide the combined effects of oral theophylline ethylenediamine and bumetanide represent a supra-additive natriuretic and chloruretic effect addition. A tentative explanation for the mechanism of interaction of drugs in terms of inhibition of renal tubular sodium transport is given. Since the combined effects of the two drugs involve a tendency to development of increased kaliuresis, it is recommended that supplementary use of theophylline ethylenediamine in this setting is combined with the administration of potassium chloride. Apparently oral theophylline ethylenediamine represents an alternative possibility to thiazide diuretics when additional natriuresis and diuresis are required in patients with advanced heart failure on long-term treatment with potent diuretics like bumetanide.

Treatment with verapamil and trandolapril in patients with congestive heart failure and angina pectoris or myocardial infarction

In a double-blind, randomized trial in a consecutive group of postinfarct patients in treatment with diuretic agents for congestive heart failure, the 3 month rate of cardiac events (i.e., death, repeat infarction, unstable angina pectoris, or repeat admission because of heart failure) was 14% in patients treated with verapamil and trandolapril and 35% in patients treated with trandolapril (p = 0.01). In another study of patients with angina pectoris and left ventricular ejection fraction less than 40%, trandolapril plus verapamil improved exercise duration and left ventricular ejection fraction. These findings indicate that combined treatment with verapamil and trandolapril may be beneficial in patients with congestive heart failure.

Treatment with verapamil and trandolapril in patients with congestive heart failure and myocardial infarction

UNLABELLED EFFECTS OF VERAPAMIL AND TRANDOLAPRIL: Progression of heart failure, sudden death and death from re-infarction are the major cause of the increased mortality in postinfarct patients with congestive heart failure. Angiotensin converting enzyme (ACE) inhibitors such as trandolapril can prevent the progression of heart failure and thus improve survival. The calcium antagonist verapamil has been shown to prevent sudden death and re-infarction in postinfarct patients without congestive heart failure. HYPOTHESIS The Danish Verapamil Infarction Trial (DAVIT) study group hypothesized the combined treatment with trandolapril and verapamil might prevent cardiac events in postinfarct patients with coronary heart disease. The first double-blind randomized trial included 100 patients and supported this hypothesis, as the cardiac event rate was significantly lower after 3 months in patients treated with the combination than in those treated with trandolapril alone (14 versus 35%, respectively; P = 0.01, hazard ratio 0.35, 95% confidence interval 0.15-0.85).