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K Swedberg

Publications and source records attributed to K Swedberg.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exploring new treatment strategies in heart failure.

Heart failure remains a major and increasing cause of mortality and morbidity, even when the best available treatments are used. One of its key causes is neuroendocrine activation via the sympathetic nervous system and the renin-angiotensin system (RAS). Neuroendocrine blockers of the sympathetic nervous system (beta-blockers) and of the RAS (angiotensin-converting enzyme [ACE] inhibitors and angiotensin II type 1 [AT1] receptor blockers) therefore have an important potential therapeutic role in heart failure. The promising results from clinical trials with beta-blockers suggest that these drugs will become an established part of the future management of patients with mild to moderate symptomatic heart failure. Blockade of the RAS with ACE inhibitors has also been shown to be effective in reducing the risk of morbidity and mortality in patients with heart failure. Blockade of the AT1-receptor, with agents such as candesartan, produces more specific and, theoretically, more complete blockade of the major negative cardiovascular effects of angiotensin II than is possible using ACE inhibitors, whilst maintaining placebo-like tolerability. Furthermore, AT1-receptor blockade leads to increased stimulation of the angiotensin II type 2 (AT2) receptor, which, according to experimental data, may have favourable cardiovascular effects. Following encouraging results from two pilot studies, a major new international study programme - CHARM (Candesartan in Heart failure - Assessment of Reduction in Mortality and morbidity) - has been initiated to define the clinical benefits of candesartan cilexetil in a wide variety of patients with symptomatic heart failure. CHARM is the first study to accept all relevant heart failure patients who may benefit from RAS blockade, irrespective of their left ventricular function or tolerance of ACE inhibitors. The 6500 patients to be recruited will be divided among three integrated outcome studies. Two of these studies will examine the effect of candesartan cilexetil versus placebo in patients with an ejection fraction of 40% or less who are tolerant or intolerant of ACE inhibitors. The third study arm will examine the benefits of candesartan cilexetil in a previously seldom studied group: those with symptomatic heart failure, but with preserved left-ventricular systolic function. Recruitment of patients into the study has started.

Adrenergic beta-Antagonists↗
PubMed1999

Gender differences in survival in advanced heart failure. Insights from the FIRST study.

BACKGROUND: Previous natural history studies in broad populations of heart failure patients have associated female gender with improved survival, particularly in patients with a nonischemic etiology of ventricular dysfunction. This study investigates whether a similar survival advantage for women would be evident among patients with advanced heart failure. METHODS AND RESULTS: The study analysis is based on the Flolan International Randomized Survival Trial (FIRST) study which enrolled 471 patients (359 men and 112 women) who had evidence of end-stage heart failure with marked symptoms (60% NYHA class IV) and severe left ventricular dysfunction (left ventricular ejection fraction 18+/-4.9%). A Cox proportional-hazards model, adjusted for age, gender, 6-minute walk, dobutamine use at randomization, mean pulmonary artery blood pressure, and treatment assignment, showed a significant association between female gender and better survival (relative risk of death for men versus women was 2.18, 95% CI 1.39 to 3.41; P<0.001). Although formal interaction testing was negative (P=0.275), among patients with a nonischemic etiology of heart failure, the relative risk of death for men versus women was 3.08 (95% CI 1.56 to 6.09, P=0.001), whereas among those with ischemic heart disease, the relative risk of death for men versus women was 1.64 (95% CI 0.87 to 3.09, P=0.127). CONCLUSIONS: Women with advanced heart failure appear to have better survival than men. Subgroup analysis suggests this finding is strongest among patients with a nonischemic etiology of heart failure.

Aged↗
PubMed1999

Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST).

OBJECTIVE: To evaluate clinical characteristics and outcomes of patients with advanced heart failure receiving intravenous continuous dobutamine in the FIRST Trial (Flolan International Randomized Survival Trial). METHODS: Four hundred seventy-one patients with class IIIb to IV heart failure who were enrolled in the FIRST trial were included. Eighty patients treated with dobutamine at FIRST randomization were compared with 391 patients not treated with dobutamine at randomization. The occurrence of worsening heart failure, need for vasoactive medications, resuscitated cardiac arrest, myocardial infarction, and total mortality were compared between the 2 groups. RESULTS: The dobutamine group had a higher occurrence of first event (85.3% vs 64. 5%; P =.0006) and a higher mortality rate (70.5% vs 37.1%; P =.0001) compared with the no dobutamine group. Intravenous continuous dobutamine was an independent risk factor for death after adjusting for baseline differences. CONCLUSIONS: Dobutamine use at the time of randomization was associated with a higher 6-month mortality rate. This effect persisted after adjustment for baseline differences. This analysis challenges the concept that continuous intravenous dobutamine is beneficial to advanced heart failure patients with respect to survival.

Aged↗
PubMed1999

Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators.

BACKGROUND: Chronic heart failure (CHF) is an increasing burden to health care. Pharmacological treatment with angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalizations in patients with low left ventricular ejection fraction (LVEF). Despite these therapies, morbidity and mortality remains problematic. Furthermore, 30% to 50% of patients with CHF have a preserved LVEF. It is not known if treatments are of benefit in this group. DESIGN: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure. Patients with systolic dysfunction, tolerant or intolerant to an ACE-inhibitor, and patients with preserved systolic function are included. Specifically, the CHARM program consists of 3 independent, parallel, placebo-controlled studies in patients with (1) LVEF less than or equal to 40%, ACE-inhibitor treated (n = 2,300); (2) LVEF less than or equal to 40%, ACE-inhibitor intolerant (n = 1,700); (3) LVEF greater than 40%, not treated with ACE inhibitors (n = 2,500). The 3 studies will be combined to evaluate the effect of candesartan cilexetil on all-cause mortality in the broad spectrum of symptomatic heart failure. The primary objective in each trial is to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization. Other endpoints include the effects on myocardial infarction, all-cause hospitalization, and resource utilization. CHARM is intended to randomize 6,500 patients with symptomatic heart failure from 26 countries in Europe, the United States, Canada, South Africa, and Australia. The CHARM program started to enroll patients in March 1999. The follow-up period is a minimum of 2 years. The study is expected to end in the third quarter of 2002.

Adolescent↗
PubMed1999

Beta-blocker therapy in advanced heart failure: clinical characteristics and long-term outcomes.

AIMS: To evaluate the clinical characteristics and long-term outcomes of advanced heart failure patients (NYHA Class IIIb-IV) receiving beta-blocker therapy vs. those patients not receiving beta-blockers at randomization in the FIRST trial, a randomized, double-blind, placebo-controlled trial of epoprostenol vs. usual care in advanced heart failure. METHODS AND RESULTS: The patient population consisted of 471 patients enrolled in FIRST with Class IIIb-IV heart failure, left ventricular ejection fraction (LVEF) of <30%, advanced hemodynamic abnormalities, and standard pharmacologic treatment of ACE-inhibitor, diuretics, and/or digoxin. The study cohort consisted of 448 patients not receiving beta-blockers and 23 patients receiving beta-blockers at randomization for the FIRST trial. Patients in the beta-blocker group had decreased rates of any clinical event (P = 0.03), worsening heart failure (P = 0.001), and death or worsening heart failure (P = 0.0008) than patients not receiving beta-blockers. After adjusting for prognostically important variables, the favorable effect of beta-blockers on worsening heart failure (P = 0.02) and death or worsening heart failure (P = 0.02) persisted. CONCLUSION: Patients with advanced heart failure who receive beta-blocker therapy have a lower rate of hospitalization and are less likely to experience worsening heart failure or death at 6 months than patients who are not treated with beta-blockers. These observational data contribute to the growing body of data demonstrating a favorable effect of beta-blockers on clinical outcomes in heart failure.

Adrenergic beta-Antagonists↗
PubMed1999

Effects of the Ikr-blocker almokalant and predictors of conversion of chronic atrial tachyarrhythmias to sinus rhythm. A prospective study.

PURPOSE: To assess the efficacy of the Ikr-blocker almokalant attempting to convert chronic atrial tachyarrhythmias, and to find predictors of conversion, to sinus rhythm. METHODS: The electrophysiological effects of a 6-hour infusion of almokalant, to a total dose of 25 +/- 4 mg, were assessed by ECG and transesophageal atrial electrograms (TAE) in 100 consecutive patients with atrial fibrillation/flutter (n = 95/5) of 8 +/- 12 months' duration (range 1 to 99 months). RESULTS: The conversion rate was 32%. The time to conversion was 3.5 +/- 2.2 hours. During infusion increases in QTtop (292 +/- 35 to 335 +/- 44 ms, p < 0.001, after 30 minutes), QT (387 +/- 40 to 446 +/- 60 ms, p < 0.001), corrected QT (425 +/- 30 to 487 +/- 44 ms, p < 0.001), and QT dispersion (21 +/- 12 to 29 +/- 31 ms, p = 0.02), were paralleled by decreases in T wave amplitude (0.31 +/- 0.19 to 0.23 +/- 0.16 mV, p < 0.001), and atrial rate (425 +/- 78 to 284 +/- 44 beats per minute (bpm) on ECG, and 396 +/- 72 to 309 +/- 44 bpm on TAE), with no differences between converters to sinus rhythm and non-converters. Patients with aberrantly conducted beats, and T wave variation, also increased. Calcium antagonists were more common among converters. A decreasing T wave amplitude predicted conversion. Four patients developed torsades de pointes. CONCLUSIONS: This study demonstrates class III action of almokalant, with a conversion rate of 32% of long-standing, chronic atrial tachyarrhytmias. An early decrease in T wave amplitude was associated with conversion to sinus rhythm.

Aged↗
PubMed1999

Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I.

BACKGROUND: The CONSENSUS trial was the first study to show prognostic improvement by an ACE inhibitor. Patients in NYHA class IV heart failure were treated with enalapril or placebo. After study completion (average 183 days) all patients were offered open-label enalapril therapy. This paper reports on the survival at the 10-year follow up of the patients randomized in the CONSENSUS trial. METHODS: All 35 participating centres in CONSENSUS I were asked to complete a questionnaire on the survival status at 1 November 1996 of patients randomized in CONSENSUS. RESULTS: At 10-year follow up, one patient was lost to follow-up. Five patients, all in the enalapril group, were long-term survivors (P = 0.004). Averaged over the duration of the trial (double-blind plus open-label extension) the risk reduction was 30% (P = 0.008), with a 95% confidence interval of 11% to 46%. At the end of the double-blind study period, mortality was considerably higher among patients who did not receive open ACE inhibitor therapy compared to those who did. CONCLUSION: After a treatment period of, on average, 6 months, enalapril was shown to be effective. The effect was sustained for at least 4 years i.e. for another 3.5 years. The present follow-up is the first heart failure trial where the full life-cycle has been followed from randomization. In severe heart failure, mortality is significantly reduced by enalapril. On average, the beneficial effect is maintained for several years and overall survival time is prolonged by 50% (from 521 to 781 days).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry.

AIMS: The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry. METHODS AND RESULTS: Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions </=35%. The median age of the 9580 Registry patients was 66 years, 26% were women, the median ejection fraction was 27%, and the primary aetiology of left ventricular dysfunction was ischaemic (63%). Eighty percent of patients were receiving ACE inhibitors. The most common reason for non-use of ACE inhibitors was intolerance (9%). CONCLUSION: The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction. The contemporary use of ACE inhibitors (80%) appears to be higher than previously reported and the main reason for non-use is perceived intolerance (9%).

Aged↗
PubMed1998

[Study and treatment of heart failure require new approaches. Natriuretic peptides can be safe and simple diagnostic and outcome measures].

Analysis of plasma natriuretic peptides and related propeptide fragments may be a cost-effective aid to diagnostic evaluation and treatment follow-up in cases of heart failure. In diagnostic potential such variables may constitute first-line measures of high negative predictive value, allowing further examination, e.g. by echocardiography, in cases where values are above the respective cut-off levels. However, in many cases evaluation of published reports is rendered difficult by their omission of information on such pre-analytical variables as blood sampling and storage, and drug therapy. Moreover, different analytical methods may yield widely divergent results. Thus, before such assays are introduced in general use, their long-term validity needs to be ensured, for instance by consistency in calibration, and measurements need to be made in representative series of unselected patients for the determination of appropriate cut-off levels.

Amino Acid Sequence↗