Biomedical subjects

K Dickstein

Publications and source records attributed to K Dickstein.

At least 55 records · Page 3Linked to original sources

PubMed1997

Plasma N-terminal atrial natriuretic factor: a predictor of survival in patients with congestive heart failure.

BACKGROUND: Congestive heart failure results in biatrial stretch, which stimulates myocyte release of atrial natriuretic factor (1-126). The N-terminal fragment, proatrial natriuretic factor(1-98), (proANF), is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply because of prolonged in vitro stability. Proatrial natriuretic factor has been shown to be predictive of clinical status in patients with congestive heart failure. This retrospective analysis was undertaken to evaluate the relationship between N-terminal atrial natriuretic factor(1-98) and survival in patients with stable congestive heart failure. METHODS AND RESULTS: Proatrial natriuretic factor was sampled from 316 patients (mean age, 68 (+/-) 11 years; 71% men) recruited from an outpatient heart failure clinic. The mean ejection fraction was 34 (+/-) 13%. Seventy-three deaths were registered during the period of data collection (42 months). Deaths per proANF quartile (n = 79) were as follows: 2 (2.5%) in quartile I. 13 (16.5%) in quartile II, 21 (26.6%) in quartile III, and 37 (46.8%) in quartile IV. The odds ratio estimates for death adjusted for age and sex were 7.6, 13.9, and 33.9 for the second, third, and fourth quartiles, respectively. Survival curves constructed according to proANF quartiles demonstrate significant differences in mortality rates. The correlation with death was greater for proANF as compared with left ventricular end-diastolic diameter (P < .001), systolic pulmonary artery pressure (P < .005), or ejection fraction (P < .05). CONCLUSION: These data indicate that the concentration of proANF is related to prognosis in patients with heart failure and that moderate elevation is associated with markedly decreased survival. Analysis should be of practical value in the assessment of prognosis in this heterogeneous population.

Adolescent↗

PubMed1997

Drug selection for optimal treatment of hypertension in the elderly.

Progressive aging of the world's population means that choosing the most effective drugs for the elderly is becoming increasingly important. The treatment of hypertension in the elderly is complicated because of the need to consider altered pharmacokinetics, comorbidity and multiple drug therapy in these patients. Antihypertensive treatment in the elderly has important and documented beneficial effects. However, no single drug class is suitable as the first-choice therapy for all elderly patients. The most appropriate choice of an antihypertensive drug often depends on comparative adverse effect profiles and the presence of comorbid disease.

Aged↗

PubMed1996

[Physical exercise and heart failure. A review article].

This review discusses the therapeutic value of physical exercise in patients with congestive heart failure. The possible circulatory, peripheral and metabolic mechanisms involved are discussed. Relevant clinical research in this field is reviewed. Physical training appears to be a safe and efficacious intervention in this large population.

Exercise↗

PubMed1996

Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.

BACKGROUND: Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. METHODS AND RESULTS: Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. CONCLUSIONS: These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.

Aged↗

PubMed1996

[Pro-atrial natriuretic factor is predictive for the clinical status of patients with heart failure].

This study was undertaken in order to evaluate the relationship between N-terminal proatrial natriuretic factor [1-98] and routinely available measures of clinical status. Odds ratio estimates demonstrated a much higher risk of presence of left ventricular dysfunction and dilatation, pulmonary hypertension, and New York Heart Association function class III or IV with increasing proANF values. Analysis is simple and can be of practical value as a supplement in the assessment of cardiac status in this heterogeneous population.

Adolescent↗

PubMed1996

Comparison of the effects of aqueous and gellan ophthalmic timolol on peak exercise performance in middle-aged men.

PURPOSE: To compare the effects of 0.5% aqueous timolol and 0.5% timolol gellan on exercise performance in middle-aged men. METHODS: We evaluated the effects of 0.5% aqueous timolol (timolol solution, administered twice daily, and a 0.5% timolol gellan suspension that forms a gel on application to the conjunctiva (timolol gellan), administered once daily, on exercise performance in 42 healthy men with a mean age of 58 years (range, 55 to 65 years). Serum concentrations of timolol were assayed. Subjects exercised maximally on an upright cycle ergometer four times with ten-day intervals. After baseline testing, subjects were randomly assigned and crossed over in a double-masked manner to two and a half days of treatment with placebo, 0.5% timolol solution, and 0.5% timolol gellan. RESULTS: The serum timolol concentrations immediately after testing were 0.91 +/- 0.51 ng/ml for timolol solution compared to 0.71 +/- 0.46 ng/ml for timolol gellan (P < .05). The change from baseline in resting heart rate was -1.8 +/- 9.3 beats/min (P = .23) for placebo, -11.0 +/- 9.6 beats/min (P < .001) for timolol gellan. The change from baseline in peak heart rate was -0.1 +/- 7.3 beats/min (P = .92) for placebo, -15.6 +/- 5.6 beats/min (P < .001) for timolol solution, and -11.9 +/- 8.0 beats/min (P < .001) for timolol solution, and -8.5 +/- 7. 5 beats/min (P<.001) for timolol gellan. Pair-wise comparison demonstrated significantly less reduction in both resting (P < .05) and peak heart rate (P < .01) for timolol gellan vs timolol solution. CONCLUSIONS: Although both treatments caused reductions in testing and peak heart rate, timolol gellan was associated with significantly less reductions. The significant difference in serum concentrations of timolol between the two treatments is strong evidence that the difference in heart rate response was caused by reduced systemic absorption with timolol gellan.

Absorption↗

PubMed1996

Novel drugs and current therapeutic approaches in the treatment of heart failure.

Treatment of heart failure attempts to reduce symptoms, increase functional capacity and prolong survival. Optimal therapy usually requires a combination of several drugs. At present, ACE inhibitors are the drugs of first choice, but must be combined with diuretics in symptomatic patients. Digitalis glycosides are still an important supplement to diuretics and ACE inhibitors. Specific angiotensin receptor antagonists such as losartan have an effect comparable with that of ACE inhibitors and may possess certain advantages because of their direct effect at the receptor level. Extensive research has been conducted in the treatment of heart failure. Newer direct acting vasodilators such as flosequinan and epoprostenol have demonstrated improved exercise tolerance but have an adverse effect on mortality. Positive inotropic agents consisting of a heterogeneous group of drugs have been evaluated. Although novel agents such as xamoterol, milrinone, pimobendan and vesnarinone have demonstrated improved haemodynamics and improved symptoms, they are not advisable at present due to increased mortality related to treatment or a high incidence of adverse events. beta-Blockers, used judiciously, may improve functional capacity as well as mortality and may be an important supplement to current conventional treatment. The new generation of beta-blockers with vasodilating properties such as carvedilol and bucindolol appear promising.

Anti-Arrhythmia Agents↗

PubMed1996

Cardiac markers in the early hours of acute myocardial infarction: clinical performance of creatine kinase, creatine kinase MB isoenzyme (activity and mass concentration), creatine kinase MM and MB subform ratios, myoglobin and cardiac troponin T.

We compared early markers of acute myocardial infarction (AMI) in the first 6 h from the onset of symptoms in 133 non-traumatized patients arriving at the emergency department with chest pain suggestive of AMI. Clinical performance parameters were calculated on the basis of 45 patients with AMI and 88 patients with a non-AMI diagnosis. At admission and in the first 0-3 h after the onset of chest pain the creatine kinase-MB (CK-MB) subform ratio was the most sensitive test at a comparable specificity level of 0.95. In the time interval of 3-5 h, myoglobin, the CK-MB mass concentration and the CK-MB subform ratio were associated with the greatest areas under receiver operating characteristic (ROC) curves, but differences between these tests were small and non-significant. At 6 h from the onset of pain, differences in clinical performance between the same three tests were even smaller whether or not samples drawn after the start of thrombolytic treatment were included in the test comparison. For confirmation of AMI at 6 h after onset of pain, CK-MB (activity and mass concentration) demonstrated the highest positive likelihood ratio, and for exclusion of AMI at 6 h the CK-MB subform ratio was associated with the highest negative likelihood ratio. However, differences between the CK-MB subform ratio, CK-MB mass concentration and myoglobin were not significant as estimated by the substantial overlap between the confidence intervals of the likelihood ratios and the ROC areas at 6 h. Cardiac troponin T (cTnT) demonstrated an ROC area equal to the CK-MB isoform ratio and myoglobin at 6 h. However, the likelihood ratio for ruling out AMI was lower, mostly due to the elevated cTnT in unstable coronary disease not defined as AMI. We conclude that the CK-MB subform ratio, CK-MB mass concentration and myoglobin do not demonstrate any significant differences in clinical performance for ruling in or ruling out acute myocardial infarction at 6 h after the onset of chest pain.

Adult↗

PubMed1995

Plasma proatrial natriuretic factor is predictive of clinical status in patients with congestive heart failure.

Atrial stretch results in myocyte release of the prohormone atrial natriuretic factor (1-126). The N-terminal (1-98) fragment, proatrial natriuretic factor (proANF) is released on an equimolar basis with the C-terminal (99-126) active hormone and may be assayed simply due to in vitro stability. This study was undertaken to evaluate the relation between proANF and routinely available measures of clinical status. ProANF was sampled from 202 patients (median age 68 years [range 15 to 85], 77% men) recruited from an active outpatient heart failure clinic. Patients were subgrouped according to New York Heart Association functional class, radionuclide ejection fraction (EF), echocardiographic left ventricular (LV) end-diastolic diameter, and Doppler-determined systolic pulmonary arterial pressure. The median proANF (pmol/L) values for patients in New York Heart Association classes I, II, III, IV were 725, 1,527, 1,750, and 5,172, respectively. The proANF value for the group with EF > 40% was 1,534 versus 1,993 for EF < or = 40% (p < 0.05). The value for the group with LV diameter < 60 mm ws 838 versus 1,751 for LV diameter > or = 60 mm (p < 0.01). The value for the group with systolic pulmonary artery pressure < 45 mm Hg was 1,241 versus 2,660 for systolic pulmonary artery pressure > or = 45 mm Hg (p < 0.01). ProANF correlated better than the other variables with New York Heart Association functional class and was more closely associated with noninvasive measurements than New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group.

BACKGROUND: The aim of the present study was to assess the short- and long-term effects of multiple doses of the angiotensin II receptor antagonist losartan in heart failure. METHODS AND RESULTS: A multicenter, placebo-controlled, oral, multidose (2.5, 10, 25, and 50 mg losartan once daily) double-blind comparison in patients with symptomatic heart failure and impaired left ventricular function (ejection fraction < 40%). Invasive 24-hour hemodynamic assessment was performed after the first dose and after 12 weeks of treatment. Clinical status and tolerability of treatment with losartan over the 12-week period were also evaluated. One hundred fifty-four patients were enrolled, of which 134 met the protocol criterion of baseline pulmonary capillary wedge pressure > or = 13 mm Hg. During short-term administration, systemic vascular resistance (SVR) (largest reduction against placebo of 197 dyne.s-1.cm-5 at 4 hours) and blood pressure fell significantly with 50 mg, lesser decreases were seen with 25 mg, and no discernible effects were seen with 2.5 and 10 mg. After 12 weeks of treatment, similar effects were seen on SVR and blood pressure (maximal fall in SVR against placebo, 318 dyne.s-1.cm-5 at 5 hours with 50 mg). In addition, pulmonary capillary wedge pressure fell with 2.5, 25, and 50 mg (largest reduction against placebo of 6.3 mm Hg at 6 hours with 50 mg), cardiac index rose with 25 and 50 mg, and heart rate was lower with all active treatment groups. Active treatment was well tolerated, and excess cough was not reported. CONCLUSIONS: This study showed that oral losartan administered to patients with symptomatic heart failure resulted in beneficial hemodynamic effects with short-term administration, with additional beneficial hemodynamic effects seen after 12 weeks of therapy. Clear effects were seen with both 25 and 50 mg, with the greatest effect seen with 50 mg.

Aged↗

PubMed1995

[Chronic left heart ventricle failure and inotropic stimulation].

Congestive left heart failure can be treated using three main strategies: change preload to optimize the Frank-Starling relationship, decrease after-load to reduce external work and increase cardiac contractility by inotropic stimulation. The third option is reviewed in this article, which discusses the pharmacological and clinical effects of different inotropic drugs as known in 1994. It is concluded that digitalis should be considered apart from other inotropic drugs. Even when in sinus rhythm, digitalis seems reasonable as an adjuvans to after-load reduction and diuretics. Chronic use of other inotropic drugs for congestive left heart failure is not recommended.

Adrenergic beta-Agonists↗

PubMed1995

Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure.

OBJECTIVES: This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment. BACKGROUND: Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents. METHODS: One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing. RESULTS: No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed. CONCLUSIONS: The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.

Adult↗

PubMed1995

Plasma proatrial natriuretic factor (1-98) concentration after myocardial infarction: relation to indices of cardiac and renal function.

OBJECTIVES: (a) To assess the relation between plasma concentrations of proatrial natriuretic factor (1-98) and non-invasively derived indices of left ventricular systolic and diastolic performance and (b) to assess the potential confounding effect of renal function and age on this relation in patients with acute myocardial infarction. DESIGN: Cross sectional comparison of biochemical and echocardiographic indices of cardiac function. SETTING: Norwegian central hospital. PATIENTS: Sixty four patients with acute myocardial infarction. MAIN OUTCOME MEASURES: Relation between plasma proatrial natriuretic factor (1-98) concentrations and echocardiographic indices of left ventricular systolic function as assessed by univariate and multivariate linear regression analysis. Sensitivity and specificity of plasma proatrial natriuretic factor (1-98) concentration as a measure of left ventricular systolic and diastolic dysfunction. RESULTS: Plasma proatrial natriuretic factor (1-98) concentrations were significantly related to left ventricular ejection fraction (r = -0.33; P = 0.008), age (r = 0.43; P < 0.001), and creatinine clearance (r = - 0.53; P < 0.001). In a multivariate model left ventricular ejection fraction and creatinine clearance were both independently related to plasma values. The mean concentration of proatrial natriuretic factor (1-98) was significantly higher in patients with an ejection fraction of < 40% than in those with an ejection fraction of > or = 40% (1876 (1151) v 1174 (530) pmol/l; P = 0.03) and in patients with an abnormal transmitral E/A ratio ( < 0.65 or > 1.65, where E/A is ratio of peak early filling velocity to peak atrial component) compared with those with a normal ratio (1572 (895) v 1137 (523) pmol/l, respectively; P = 0.02). When patients were subdivided according to the median concentration of proatrial natriuretic factor (1192 pmol/l) the sensitivity and specificity were 89% and 56% respectively for detecting a left ventricular ejection fraction of < 40% and 75% and 61% respectively for detecting an abnormal E/A ratio. Concentrations below the median had a negative predictive value of 97% in excluding an ejection fraction of < 40% and of 84% in excluding an abnormal E/A ratio. CONCLUSION: These results suggest that soon after myocardial infarction left ventricular ejection fraction and indices of renal function are independently related to plasma concentrations of proatrial natriuretic factor (1-98). Plasma concentrations of proatrial natriuretic factor (1-98) seem to reflect renal and cardiac performance rather than specific haemodynamic variables assessed by noninvasive methods. Plasma proatrial natriuretic factor (1-98) measurements may be a useful screening tool to identify patients with normal cardiac function soon after myocardial infarction.

Aged↗

PubMed1994

[Chronic heart failure. A management program. Proposal for diagnosis and treatment].

An expert meeting on the treatment of heart failure was organized by the Swedish Medical Products Agency in 1992. There were four participants from Norway. Two of these (AW, JK), in cooperation with a group of cardiologists with a special interest in heart failure, present in this article a modified Norwegian programme for treatment of chronic heart failure. When evaluating risk for patients with chronic heart failure, it is necessary to take into account both symptoms and left ventricular systolic function determined by ejection fraction. Specific recommendations are made for treatment of asymptomatic patients with left ventricular dysfunction and for symptomatic patients with mild, moderate and severe heart failure.

Chronic Disease↗

PubMed1994

Plasma neuropeptide Y levels in the acute and early convalescent phase after myocardial infarction.

The sympathetic nervous system is activated in acute myocardial infarction (MI). Scarce data exist, however, regarding the release of the sympathetic cotransmitter neuropeptide Y (NPY) during the acute and early convalescent phases after acute MI. Plasma NPY determination was obtained on days 1 and 3 after admission from 47 patients with acute MI and from eight control patients with acute chest pain without MI. Samples were also obtained on day 30 from the 39 survivors from the original MI cohort. Plasma NPY peaked on day 3 in the MI group (day 1: mean = 46.0 pmol/L, SEM = 6.4 pmol/L; day 3: mean = 60.8 pmol/L, SEM = 5.7 pmol/L; day 30: mean = 27.2 pmol/L, SEM = 4.1 pmol/L; days 1 to 3: p = 0.002; days 3 to 30: p < 0.001), whereas in the control group a nonsignificant decrease from day 1 (mean = 42.6 pmol/L, SEM = 12.3 pmol/L) to day 3 (mean = 34.0 pmol/L, SEM = 5.6 pmol/L) was observed. Plasma NPY levels were significantly increased in patients with MI on day 3 (p = 0.044), but not at baseline compared with the control group. No significant association between plasma NPY and plasma catecholamines, clinical heart failure, or 1-month survival was evident. These results suggest that increased plasma levels of the vasoconstrictory and cardiodepressant sympathetic neurotransmitter NPY are present in the recovery phase of MI, but with a plasma profile distinct from that of catecholamines.

Age Factors↗

PubMed1994

Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction.

BACKGROUND: Plasma endothelin concentrations are increased in the acute phase of myocardial infarction and in chronic heart failure. Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction. METHODS AND RESULTS: We tested the hypothesis that plasma endothelin determination in the subacute phase of myocardial infarction is related to subsequent survival and assessed whether plasma endothelin measurements provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma endothelin determination was obtained from 142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented myocardial infarction and was related to 1-year mortality. Sixteen patients died during the follow-up period. In a univariate Cox proportional-hazards model, day 3 plasma endothelin concentrations were significantly related to mortality (P < .0001). Patient age, previous treatment for systemic hypertension, presence of clinical heart failure, and plasma atrial natriuretic factor levels were all related to mortality in univariate analysis but provided no additional prognostic information to that obtained from endothelin determination in a multivariate model. CONCLUSIONS: Plasma endothelin concentrations are strongly related to outcome after myocardial infarction and provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis.

Aged↗

PubMed1994

Comparison of the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide in patients with moderate hypertension.

This parallel, double-blind trial was designed to evaluate the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide (HCTZ) in patients with uncomplicated moderate to severe hypertension. Two hundred patients (aged 25-74 years) with sitting diastolic blood pressure (DBP) between 95 and 114 mm Hg after 4 week treatment with HCTZ 25 mg once daily were randomized to placebo, or moexipril 3.75, 7.5 mg, or 15 mg. BP was measured at 22-26 h postdose at biweekly visits and at 1, 2, 3, and 4 h postdose after the first dose of double-blind medication. At endpoint, adjusted mean reductions from baseline sitting DBP were 8.4, 8.8, and 8.9 mm Hg in the moexipril 3.75-, 7.5-, and 15-mg groups, respectively, as compared with a reduction of 4.6 mm Hg in the placebo group (p = 0.003). The differences in systolic BP (SBP) reductions were statistically significant in favor of each of the moexipril groups over the placebo group at all trough time-points. Adjusted mean changes in sitting SBP were 10.9, 12.0, and 11.7 mm Hg, respectively, as compared with a reduction of 0.6 mm Hg in the placebo group (p < 0.001). Our results indicate that moexipril and HCTZ constitute a clinically valuable combination in treatment of patients with moderate to severe hypertension.

Adult↗

PubMed1994

Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure.

BACKGROUND: Losartan is a specific angiotensin II receptor antagonist with no agonist properties. This agent permits evaluation of the response to selective angiotensin II antagonism in patients with congestive heart failure. OBJECTIVE: A study was designed to assess the acute hemodynamic and neurohumoral response to losartan in a controlled, blinded fashion. DESIGN: Sixty-six patients in New York Heart Association functional class II, III or IV with a radionuclide ejection fraction of < 40% were randomly allocated to treatment with placebo and then sequentially to 5, 10, 25, 75 and 150 mg losartan. Hemodynamic and neurohumoral measurements were obtained at selected times for 24 h following ingestion of a single dose of losartan. RESULTS: Treatment with losartan led to dose-dependent vasodilation. Mean arterial pressure and systemic vascular resistance decreased progressively up to a dose of 25 mg. The higher doses of 75 and 150 mg did not produce additional vasodilation. Similarly, the decrease in pulmonary capillary wedge pressure was not greater with doses exceeding 25 mg. The increase in the cardiac index was modest and similar for all doses. No variation in the heart rate was observed at any dose. The hemodynamic changes were accompanied by marked neurohumoral changes. Large dose-related increases in plasma renin activity and angiotensin II levels were observed, especially following the 150-mg dose. Moderate reductions occurred in serum aldosterone and plasma noradrenaline. The peak effect for these parameters occurred 4-6 h after the dose, with persistent changes still evident 24 h after the dose. CONCLUSIONS: These data demonstrate that selective blockade of the angiotensin II receptor with losartan causes a favorable vasodilatory and neurohumoral response in patients with heart failure. Further studies are needed to determine the most effective dose in these patients. Nevertheless, losartan should be of substantial clinical use in the management of this large population.

Angiotensin Receptor Antagonists↗