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Biomedical subjects

J Kjekshus

Publications and source records attributed to J Kjekshus.

At least 73 records · Page 4Linked to original sources
PubMed1997

The effects of simvastatin on the incidence of heart failure in patients with coronary heart disease.

BACKGROUND: Although treatment of myocardial overload effectively reduces death from progression of heart failure, it is not known whether the retardation of progressive coronary artery disease obtained with lipid lowering treatment will prevent the onset and consequences of heart failure in patients without previous symptoms of heart failure. METHODS AND RESULTS: In the Scandinavian Simvastatin Survival Study, 4444 patients with coronary heart disease without evidence of heart failure were randomized to placebo (n = 2223) or simvastatin 20-40 mg (n = 2221) and followed for more than 5 years. Among the patients who received placebo, 228 (10.3%) were diagnosed with heart failure during follow-up evaluation compared with 184 (8.3%) of patients who received simvastatin (P < .015). Mortality was 31.9% in the placebo group and 25.5% in the simvastatin group among patients who developed heart failure. These compare with 9.2 and 6.6%, respectively, among non-heart failure patients. There were 45 hospitalizations because of acute heart failure in the placebo group and 23 in the simvastatin group (NS). Patients who developed heart failure were more likely to have suffered a recurrent myocardial infarction and have a history of diabetes, peripheral artery disease, and hypertension than patients who did not develop congestive heart failure. CONCLUSION: Long-term prevention with simvastatin reduces the occurrence of heart failure in a cohort of patients with coronary heart disease without previous evidence of congestive heart failure.

Adult↗
PubMed1997

Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.

Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.

Adult↗
PubMed1997

Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study.

The Scandinavian Simvastatin Survival Study (4S) was a double-blind, randomized placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy in patients with coronary heart disease who had total cholesterol levels between 5.5 and 8.0 mmol/l, comprising 4444 patients, equally distributed to a Simvastatin and a placebo group. Patients achieved a significant 30% relative reduction in overall mortality with Simvastatin therapy through a 42% relative reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in Scandinavian coronary heart disease patients were strikingly higher than in healthy controls. Numbers of deaths in the Simvastatin group differed significantly between quartiles of Lp(a) lipoprotein levels, the reduction in deaths being most pronounced in the second (next to lowest) quartile. Subjects with major coronary events had significantly higher Lp(a) lipoprotein levels than subjects without such events, in all groups. The relationship between Lp(a) lipoprotein level and total mortality as well as between Lp(a) lipoprotein level and major coronary events was significantly different from zero, in logistic regression analyses. The findings show that Lp(a) lipoprotein predicts major coronary events as well as death in secondary prevention with Simvastatin. This prospective study provides independent confirmation that a high Lp(a) lipoprotein level is a significant coronary heart disease risk factor.

Adult↗
PubMed1997

Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S)

OBJECTIVE: To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events. RESEARCH DESIGN AND METHODS: A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol/l, and serum triglycerides < or = 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6-18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures. RESULTS: Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30-1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27-0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43-0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58-0.87; P = 0.001), 0.68 (95% CI, 0.60-0.77; P < 0.0001), and 0.74 (95% CI, 0.68-0.82; P < 0.0001). CONCLUSIONS: The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.

Anticholesteremic Agents↗
PubMed1997

Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure.

Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.

Atrial Natriuretic Factor↗
PubMed1996

Stenting in Chronic Coronary Occlusion (SICCO): a randomized, controlled trial of adding stent implantation after successful angioplasty.

OBJECTIVES: This study investigated whether stenting improves long-term results after recanalization of chronic coronary occlusions. BACKGROUND: Restenosis is common after percutaneous transluminal coronary angioplasty (PTCA) of chronic coronary occlusions. Stenting has been suggested as a means of improving results, but its use has not previously been investigated in a randomized trial. METHODS: We randomly assigned 119 patients with a satisfactory result after successful recanalization by PTCA of a chronic coronary occlusion to 1) a control (PTCA) group with no other intervention, or 2) a group in which PTCA was followed by implantation of Palmaz-Schatz stents with full anticoagulation. Coronary angiography was performed before randomization, after stenting and at 6-month follow-up. RESULTS: Inguinal bleeding was more frequent in the stent group. There were no deaths. One patient with stenting had a myocardial infarction. Subacute occlusion within 2 weeks occurred in four patients in the stent group and in three in the PTCA group. At follow-up, 57% of patients with stenting were free from angina compared with 24% of patients with PTCA only (p < 0.001). Angiographic follow-up data were available in 114 patients. Restenosis (> or = 50% diameter stenosis) developed in 32% of patients with stenting and in 74% of patients with PTCA only (p < 0.001); reocclusion occurred in 12% and 26%, respectively (p = 0.058). Minimal lumen diameter (mean +/- SD) at follow-up was 1.92 +/- 0.95 mm and 1.11 +/- 0.78 mm, respectively (p < 0.001). Target lesion revascularization within 300 days was less frequent in patients with stenting than in patients with PTCA only (22% vs. 42%, p = 0.025). CONCLUSIONS: Stent implantation improved long-term angiographic and clinical results after PTCA of chronic coronary occlusions and is thus recommended regardless of the primary PTCA result.

Angioplasty, Balloon, Coronary↗
PubMed1996

Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study.

BACKGROUND: Long-term safety is an important consideration in the selection and use of drugs, such as lipid-lowering agents, that are prescribed to reduce the risk of clinical events during long periods. METHODS: The Scandinavian Simvastatin Survival Study was designed to evaluate the effects of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease. The 4444 patients aged 35 to 70 years (mean, 58.9 years) with angina pectoris or previous myocardial infarction and serum cholesterol levels of 5.5 to 8.0 mmol/L (213-310 mg/dL) receiving a lipid-lowering diet were randomly assigned to take double-blind treatment with simvastatin, 20 to 40 mg once daily, or placebo. In addition to previously reported end-point events, detailed clinical and laboratory safety data were collected during a median follow-up period of 5.4 years (range in survivors, 4.9-6.2 years). RESULTS: The only clearly drug-related serious adverse event during the 5.4-year median follow-up period was a single reversible case of myopathy. The frequencies of persistent elevations of hepatic aminotransferase levels above 3 times the upper limit of normal and of nonviral hepatitis in the simvastatin and placebo treatment groups were not significantly different. Examination of the lens showed no between-group differences, and no previously unrecognized adverse effects of the drug were observed. There were no significant between-group differences in adverse events in any body system. In particular, the frequency of adverse events related to the central nervous system was similar in both groups. CONCLUSION: The safety profile of simvastatin, 20 to 40 mg daily, over 5 years was excellent.

Adult↗
PubMed1996

Cholesterol lowering and the use of healthcare resources. Results of the Scandinavian Simvastatin Survival Study.

BACKGROUND: Advances in the treatment of cardiovascular disease have increased costs; annual cardiovascular healthcare expenditure in the United States currently exceeds $100 billion. Physicians and third-party payers need to assess the economic impact of treatments that reduce cardiovascular morbidity and mortality. METHODS AND RESULTS: The Scandinavian Simvastatin Survival Study is a randomized, double-blind, placebo-controlled trial in which simvastatin reduced the risk of death by 30% (P=.0003) over the median follow-up period of 5.4 years in patients with previous myocardial infarction or stable angina pectoris as a result of a 42% reduction in the risk of coronary deaths (P=.00001). In the present report, data prospectively collected from hospital admissions were analyzed to evaluate the impact of simvastatin on healthcare resource use and perform a cost-minimization analysis. In the placebo group (n=2223), there were 1905 hospitalizations (average duration, 7.9 days) for acute cardiovascular events or coronary revascularization procedures among 937 patients, whereas in the simvastatin group (n=2221), there were 1403 such hospitalizations (average duration, 7.1 days) among 720 patients (all differences, P<.0001). The corresponding number of hospital days was 15089 and 9951 in the two groups, respectively (34% reduction,P<.0001). In the United States, the resulting reduction in hospitalization costs over the 5.4 years of the trial would be $3872 per patient, reducing the effective cost of simvastatin by 88% to $0.28 per day. CONCLUSIONS: In addition to reducing mortality and morbidity in coronary heart disease patients, simvastatin markedly reduces use of hospital services, thus offsetting most of its cost.

Adult↗
PubMed1996

Treatment of heart failure.

Effective treatment of heart failure depends on a correct functional and aetiological diagnosis. In asymptomatic patients with cardiac dysfunction following myocardial infarction, treatment is directed to prevent recurrent infarction by aggressive lipid lowering with statins and antiplatelet drugs. Beta blockers are important to reduce sudden death. In symptomatic heart failure, clinical improvement is obtained by inhibition of the renin-angiotensin and sympathetic system. Angiotensin-converting-enzyme inhibitors in combination with diuretics reduce morbidity and mortality caused by progression of the myocardial dysfunction and recurrent myocardial infarction. Drugs that activate the neurohormonal systems are clearly counteractive. Digitalis has a definite favourable effect on systems, and in patients with atrial fibrillation, but its effect on mortality is still unsettled. Beta blockers in routine treatment of symptomatic heart failure still remains controversial, but may benefit selected patients.

Adrenergic beta-Antagonists↗
PubMed1996

Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)

An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 52.8 million Swedish kronor (SEK) (5.15 million pounds), compared with SEK 36.0 million (3.51 million pounds) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16.8 million (1.6 million pounds) or SEK 7560 (738 pounds) per patient. The net cost per patient for the duration of the study (5.4 years) was SEK 13,540 (1324 pounds). Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56,400 (5502 pounds). Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion. The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.

Anticholesteremic Agents↗
PubMed1996

Lipid-lowering therapy for patients with or at risk of coronary artery disease.

Several studies have shown that effective lipid-lowering therapy slows the progression of atherosclerotic lesions in the coronary and carotid arteries. Recent clinical trials have confirmed and extended previous work showing that lowering cholesterol reduces the risk of coronary events. A clear reduction in major coronary events during treatment for 5 years with the hydroxymethylglutaryl-coenzyme A reductase inhibitor pravastatin was observed in the West of Scotland study and in the preliminary results of the Cholesterol and Recurrent Events study. The Scandinavian Simvastatin Survival Study has provided the first unequivocal demonstration of improved survival as a result of lipid-lowering therapy. These three trials, which together included over 15,000 patients studied for 5 years, have provided good evidence that noncardiovascular mortality is not affected by substantial reductions in blood cholesterol.

Anticholesteremic Agents↗
PubMed1996

Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.

BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.

Adult↗
PubMed1996

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Analysis of Variance↗
PubMed1995

Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S).

The Scandinavian Simvastatin Survival Study (4S) was designed to evaluate the effects of cholesterol reduction with simvastatin on mortality and morbidity in patients with coronary artery disease (CAD). A total of 4,444 patients with angina pectoris or previous myocardial infarction and serum cholesterol levels of 213-310 mg/dl (5.5-8.0 mmol/liter) while treated with a lipid-lowering diet were randomly assigned to double-blind treatment with simvastatin or placebo. Over the 5.4 years of median follow-up, simvastatin produced changes in total cholesterol, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol of -25%, -35%, and +8%, respectively, with minimal adverse effects. A total of 256 patients (12%) in the placebo group died compared with 182 (8%) in the simvastatin group, a risk reduction of 30% (p = 0.0003) attributable to a 42% reduction in the risk of coronary death. Noncardiovascular causes accounted for 49 and 46 deaths in the placebo and simvastatin groups, respectively. Major coronary events were experienced by 622 patients (28%) in the placebo group and 431 patients (19%) in the simvastatin group, corresponding to a risk reduction of 34% (p < 0.00001). This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged > or = 60 years. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularization procedures. Simvastatin was beneficial regardless of whether patients had a history of myocardial infarction or whether they were smokers or had hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗