Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure.

Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.     

Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure

Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.     

Exercise therapy for older persons with cardiovascular disease

Cardiac rehabilitation with exercise training after myocardial infarction in persons younger than 70 years has been found to cause a significant decrease in all-cause mortality, cardiovascular mortality, and fatal reinfarction, but no significant difference in nonfatal reinfarction. After myocardial infarction or coronary revascularization in older individuals, such programs significantly improve physical work capacity, body mass index, percent body fat, serum lipids, behavioral characteristics, and quality of life. Exercise modalities should include aerobic, resistance, and flexibility exercises. Less intense exercise of longer duration should be performed by older persons with coronary artery disease. Exercise training programs in patients with congestive heart failure produce significant improvement in peak oxygen consumption, exercise duration, and power output. The benefits of exercise training in patients with congestive heart failure may be due to an increase in cardiac output, an improvement in skeletal muscle metabolism, and an increase in peak blood flow to the exercising limb caused by a reduction in vascular resistance.     

New insights and new approaches for the treatment of essential hypertension: selection of therapy based on coronary heart disease risk factor analysis, hemodynamic profiles, quality of life, and subsets of hypertension

The pharmacologic therapy of mild primary hypertension (diastolic blood pressure less than 105 mm Hg) has effectively reduced hypertensive arteriolar end organ disease such as cerebrovascular accidents, congestive heart failure, and nephropathy, but there has been no convincing evidence that coronary heart disease (CHD) or its complications, acute myocardial infarction or angina, have been reduced. The risks of therapy with certain antihypertensive drugs may outweigh their treatment benefits as it relates to CHD. The optimal treatment strategy should be to reduce all CHD risk factors, reverse the hemodynamic abnormalities present by lowering the systemic vascular resistance (SVR), preserving cardiac output (CO) and perfusion, and to select the best antihypertensive drug for concomitant medical diseases or problems while maintaining a good quality of life. Antihypertensive drugs that have favorable or neutral effects on CHD risk factors include alpha blockers, calcium channel blockers, central alpha agonists, and angiotensin-converting enzyme inhibitors. On the other hand, diuretics and beta blockers without intrinsic sympathomimetic activity have unfavorable effects on many CHD risk factors. Baseline and serial evaluation of the effects of these drugs on serum lipids, lipid subfractions, glucose, uric acid, electrolytes, exercise tolerance, left ventricular hypertrophy, blood pressure, SVR, CO, perfusion, concomitant diseases, and side effects is necessary to evaluate overall cardiovascular risk.     

Properties of labetalol,a combined α-and β-blocking agent,relevant to the treatment of myocardial ischemia

Summary Labetalol, a combined --adrenergic antagonist, is one of the new group of -adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike -adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to - and -adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications.     

Hemodynamic effects of felodipine at rest and during exercise in exertional angina pectoris

To examine the antianginal effects of felodipine, a new calcium antagonist, 8 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 30 minutes after oral administration of 0.1 mg/kg of felodipine. Angina pectoris was always prevented after the drug was given and the exercise intensity was increased until recurrence of angina (5 patients) or exhaustion (3 patients). Hemodynamic data were also recorded at this higher exercise capacity. At rest and during submaximal exercise, felodipine increased heart rate and decreased arterial blood pressure and systemic vascular resistance. The prevention of angina pectoris was accompanied by lower mean pulmonary capillary wedge pressure, systemic vascular resistance and ST-segment depression; the pressure-rate product was unchanged. The 20% greater exercise capacity after felodipine was attended by a 20% increase in maximal cardiac output, a 17% increase in maximal heart rate and a 13% increase in maximal pressure-rate product; the maximal arterial blood pressure and ST-segment abnormalities were unchanged and the systemic vascular resistance was lower. The relation between ST-segment depression and the pressure-rate product during exercise was favorably influenced by felodipine. Thus, felodipine is an active antianginal drug; its major mechanism of action is to lower the systemic vascular resistance. The data also suggest that it improves coronary blood flow during exercise.     

Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress.

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.     

Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease

We evaluated the cardiopulmonary exercise test results before and after long-term (16 weeks) treatment with the dihydropyridine calcium antagonist, felodipine (10 mg b.i.d., n = 9), and the ACE inhibitor, enalapril (10 mg b.i.d., n = 11), in 20 patients with New York Heart Association class III congestive heart failure. There were no significant differences at baseline. After 16 weeks patients in the enalapril group showed a significant increase in exercise duration and VO2max, without changes in arterial pressures and heart rate. In the felodipine group, exercise duration and VO2max did not change significantly, but arterial pressures and heart rate were significantly reduced at all exercise levels. Between group analysis showed a significant reduction in arterial pressures and heart rate in the felodipine group compared with enalapril, but no differences in aerobic capacity and exercise duration. These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure.     

Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: Focus on felodipine

Summary Calcium entry through L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with left ventricular dysfunction, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity. Felodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entry blockers. Hemodynamic studies in patients with hypertension, coronary artery disease, congestive heart failure, or in patients receiving beta-adrenergic blockade, show that felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore, felodipine alone or when added to a beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine calcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with heart failure indicate that felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.     

Pathophysiology of hypertension in the elderly

Combined systolic and diastolic arterial hypertension and isolated systolic hypertension in the elderly are proven risk factors for stroke, sudden death, coronary artery disease, and congestive heart failure. Because hemodynamics, vascular and cardiac adaptations, fluid volume, and endocrine functions are distinctly altered in the elderly hypertensive patient compared with a younger patient, antihypertensive treatment should be individualized, and an unsophisticated regimen, such as a stepped-care approach, is too rigid to be as beneficial for elderly hypertensive patients as for young hypertensive patients.     

Diuretics in the treatment of patients who present congestive heart failure and hypertension

The main operational objective of diuretic therapy in patients who present congestive heart failure and hypertension is to reduce or to suppress excess bodily fluid. Effective diuretic therapy decreases cardiac size when the heart is dilated, and it reduces lung congestion and excess water. Consequently, external respiratory work diminishes and cardiac output would be redistributed in favour of systemic vascular beds other than that of the respiratory muscles; dyspnoea decreases markedly and there is a slight reduction in fatigue. This clinical improvement and the fall in body weight caused by diuretics entail an increase in effort capacity. Subsequent exercise training ameliorates the abnormal ventilatory response to physical effort and the skeletal muscle myopathy that occur in heart failure, and thereby it attenuates dyspnoea and decreases fatigue further. Loop and/or thiazide-type diuretics may be used to augment natriuresis in patients with congestive heart failure and hypertension. The state of renal function, the existence of certain co-morbid conditions, potential untoward drug actions, and possible interactions of diuretics with nutrients and with other drugs are some of the factors that must be considered at the time of deciding on the diuretic drug(s) and dose(s) to be prescribed. Spironolactone has been found to increase life expectancy and to reduce hospitalisation frequency when added to the conventional therapeutic regimen of patients with advanced congestive heart failure and systolic dysfunction. Therefore, spironolactone should be the drug of choice to oppose the kaliuretic effect of a loop or of a thiazide-type diuretic.     

Efficacy of felodipine in chronic congestive heart failure: a placebo controlled haemodynamic study at rest and during exercise and orthostatic stress

A vascular selective calcium antagonist, felodipine, was evaluated in a randomised, double blind, crossover trial in 18 patients with chronic congestive heart failure of ischaemic cause. Felodipine (10 mg twice daily) or a corresponding placebo was added to conventional treatment. After three weeks haemodynamic function was assessed at rest, during a standard supine leg exercise, and during 45 degrees passive upright tilt. In patients in the supine resting position, felodipine reduced the mean arterial pressure (9%) and systemic vascular resistance (24%) and increased the stroke volume (25%) and cardiac index (23%). The heart rate and right and left ventricular filling pressures were unchanged. During felodipine treatment the standard exercise was accomplished at a similar cardiac index but at a substantially lower heart rate (7%), arterial pressure (10%), systemic vascular resistance (17%), and left ventricular filling pressure (19%), and a higher stroke volume (13%). During both placebo and felodipine administration there were substantial reductions in cardiac filling pressure during upright tilting. Upright tilting during the placebo phase did not increase the heart rate. It also caused a greater fall in systemic vascular resistance while the arterial pulse pressure but not the mean pressure was maintained and the cardiac index and stroke volume increased. The reduced cardiac filling pressures during the felodipine upright tilt were accompanied by reductions in arterial pulse pressure and stroke volume and the patients were able to maintain the mean arterial pressure by an increase in both the heart rate and systemic vascular resistance. Thus three weeks treatment with felodipine improved haemodynamic function at rest and during standard exercise and normalised the baroreflex mediated haemodynamic response in patients with congestive heart failure. The haemodynamic efficacy of the drug in such patients may be associated with a baroreceptor mediated effect as well as direct vasodilatation.     

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

Summary In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion.The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed.In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.Part of these data have been presented at the Second Cardiovascular Pharmacotherapy International Symposium, San Francisco, CA, 1987.     

Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure

The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic effects of molsidomine at rest and during submaximal and maximal exercise in patients with coronary artery disease limited by exertional angina pectoris

To analyze the mechanisms of action of molsidomine, a new antianginal drug, 10 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 1 hour after intravenous administration of 2 mg of molsidomine. When angina pectoris was prevented after the drug was given (6 of 10 patients), the exercise intensity was increased until the recurrence of angina (3 patients) or until exhaustion (3 patients), and hemodynamic data were recorded at this higher exercise capacity. At rest and during submaximal exercise, molsidomine increased heart rate and decreased cardiac output and mean systemic and pulmonary arterial pressures. The prevention of angina pectoris was attended by lower mean systemic and pulmonary arterial pressures and pressure-rate product; cardiac output and heart rate were unchanged. The greater exercise capacity (+26 percent) after molsidomine was attended by increases in maximal cardiac output (+19 percent) and in arteriovenous oxygen difference (+6 percent); the maximal pressure-rate product was unchanged and systemic vascular resistance was lower. The mechanisms of action of molsidomine are very similar to those of nitrates and imply a decrease in venous and arterial tone. Molsidomine deserves further study in patients with angina or congestive heart failure.     

Interventional therapy in heart failure management

The incidence and prevalence of congestive heart failure are rapidly increasing because of the progressive decrease in age-adjusted mortality rates for coronary artery disease and hypertensive heart disease, together with the progressive aging of the US population. Despite great advances in maximal medical therapy, most patients with symptomatic congestive heart failure can expect functional impairment, interludes of worsening symptomatology, and a shortened life span. Thus, it is appropriate to ask whether the interventional revolution that is under way for the management of ischemic cardiovascular disease can be applied with benefit to the management of congestive heart failure. The use of interventional therapies for the treatment of elderly patients with congestive heart failure caused by coronary artery disease, valvular heart disease, or renal vascular disease is addressed.     

Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure

Calcium sensitization increases myocardial contractility byimproving energy utlization of the myocardium, without an increasein intracellular concentrations of cyclic adenosine monophosphate.The calcium sensitizer most extensively studied up to now ispimobendan (UD-CG 115 BS). Vasodilatation results primarilyfrom phosphodiesterase III inhibition Orally administered pimobendan appears rapidly in plasma. Apeak concentration is reached 1.5 h after drug intake; eliminationfrom the plasma compartment has a half-life of 1.5 h. First-passhepatic O-desmethylation of pimobendan produces the active metaboliteUD-CG 212; plasma concentration curves of UD-CG 212 are similarto those of pimobendan, with apeak concentration 1–2 hlater than the peak concentration of the parent compound. In patients with chronic congestive heart failure, pimobendanproduces a dose-dependent and prolonged decrease in pulmonarycapillary wedge pressure and an increase in cardiac output.Maintenance doses ofpimobendan are well tolerated and may leadto lasting symptomatic improvement in patients with heart failure;open and blinded trials show that exercise tolerance increases.No attenuation of these effects is seen during long-term therapywith pimobendan. Patients in chronic congestive heart failure frequently diesuddenly; many inotropic agents increase the incidence of suddendeath in these patients. Although proarrhythmia has never beenobserved with pimobendan, arrhythmia suppression with amiodaroneseems prudent in heart failure patients receiving maintenancedoses of pimobendan.     

Recovery kinetics of oxygen uptake and heart rate in patients with coronary artery disease and heart failure.

BACKGROUND: Patients with congestive heart failure exhibit a prolonged period of recovery to baseline levels of oxygen consumption, but the decline of heart rate during recovery from exercise has been shown to be similar to that in healthy subjects, and the results of studies on the response of ventilation in recovery have been mixed. Patients with coronary artery disease have a reduced exercise capacity, but it is unknown whether the patterns of the decline in oxygen uptake (VO2), ventilation, or heart rate are similar to those in patients with heart failure. METHODS: We performed a cardiopulmonary exercise test with a ramping protocol in 18 healthy subjects, 18 patients with coronary artery disease, 19 patients with class A or B congestive heart failure, and 19 patients with class C congestive heart failure, according to the Weber classification. Peak oxygen uptake and the kinetics of oxygen uptake, ventilation, and heart rate were calculated and expressed as the slope of a single exponential relation between VO2 levels and time during the first 3 min of recovery as y(VO2) = y0Ae(-x/t). RESULTS: A difference in time of recovery of VO2 was found only between healthy subjects and patients with more severe heart failure (class C) (p < 0.05); no significant differences were observed among any of the groups in ventilation or heart rate recovery responses. CONCLUSION: VO2 recovery time is prolonged only in the presence of more severe heart failure. The presence and degree of heart disease has no effect on ventilation or heart rate recovery time.     

Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group.

OBJECTIVE--To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. PATIENTS AND DESIGN--252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. METHODS--Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. RESULTS--Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. CONCLUSION--Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.     

Comparison of effects on peak oxygen consumption, quality of life, and neurohormones of felodipine and enalapril in patients with congestive heart failure

Angiotensin-converting enzyme (ACE) inhibition is currently the cornerstone of congestive heart failure (CHF) therapy, but these drugs are not tolerated in up to 20% of patients. For these patients, therapeutic alternatives with comparable efficacy are needed. Felodipine, a vasoselective dihydropyridine calcium antagonist with a slow onset of action and a long plasma half-life, may be such an agent. Therefore, the efficacy and safety or felodipine were examined and compared with enalpril using a double-blind design. We studied 46 patients with a left ventricular ejection fraction <0.40, peak oxygen consumption <20 ml-min⁻¹·kg⁻¹, and symptoms of CHF despite therapy with diuretics and digoxin. After 16 weeks of therapy, there were no statistically significant differences in peak oxygen consumption (felodipine +1.6, enalapril +2.5 ml·min⁻¹·kg⁻¹) and exercise tolerance (felodipine +61 seconds, enalapril +64 seconds). Quality-of-life parameters were affected slightly better by felodipine man by enalapril. Plasma norepinephrine decreased by 143 pg·ml⁻¹ with enalapril and by 12 pg·ml⁻¹ with felodipine (p > 0.20 between groups). Both drugs were generally well tolerated. These data suggest that felodipine and enalapril have comparable effects on exercise parameters in patients with CHF. Neurohumoral activation was not observed with either drug.