PubMed Health⌕ Search

Biomedical subjects

John Kjekshus

Publications and source records attributed to John Kjekshus.

36 records · Page 2Linked to original sources
PubMed2004

Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction.

OBJECTIVES: We sought to determine the relationship between osteoprotegerin (OPG) and clinical outcomes in patients with heart failure (HF) after acute myocardial infarction (AMI). BACKGROUND: Arterial calcification is a prominent feature of arterial atherosclerosis and is associated with the occurrence of AMI. Osteoprotegerin is a recently discovered member of the tumor necrosis superfamily that may link the skeletal with the vascular system. METHODS: We assayed plasma OPG levels in 234 patients with AMI complicated with HF and their relation to adverse outcomes during follow-up in patients randomly assigned to angiotensin-converting enzyme inhibition or angiotensin II antagonism. Blood was sampled at baseline (median three days after AMI), one month, and at one and two years. RESULTS: Elevated plasma levels of OPG at baseline were associated with adverse outcomes during a median of 27 months follow-up; OPG remained an independent prognostic indicator also after adjustment for other known predictors of mortality and cardiovascular events after AMI (e.g., creatinine clearance, N-terminal B-type natriuretic peptide, high-sensitivity C-reactive protein). In non-survivors, plasma OPG levels were persistently elevated during longitudinal testing, suggesting that OPG may be of value for monitoring patients at risk. CONCLUSIONS: Osteoprotegerin is a novel marker for cardiovascular mortality and clinical events in patients with AMI complicated with HF. These findings are compatible with the hypothesis suggesting a possible association between mediators of bone homeostasis and cardiovascular disease.

Aged↗
PubMed2004

Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure.

This retrospective, nonrandomized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infarction compared with the effect of neither or both treatments. Early initiation of statins or beta blockers alone was associated with improved event-free survival, and the benefits of the combined treatment were additive.

Adrenergic beta-Antagonists↗
PubMed2004

The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS).

The metabolic syndrome, which is a set of lipid and nonlipid risk factors of metabolic origin linked with insulin resistance, is believed to be associated with an elevated risk for cardiovascular disease, but few have studied this association in prospective long-term cardiovascular outcomes trials. Placebo data from the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) were used post hoc to estimate the long-term relative risk of major coronary events (MCEs) associated with the metabolic syndrome, after excluding diabetes mellitus. In 4S and AFCAPS/TexCAPS, respectively, placebo-treated patients with the metabolic syndrome were 1.5 (95% confidence interval 1.2 to 1.8) and 1.4 (95% confidence interval 1.04 to 1.9) times more likely to have MCEs than those without it. Of the components of the metabolic syndrome, low high-density lipoprotein levels were associated with elevated risk of MCEs in both studies, whereas high triglycerides in 4S and elevated blood pressure and obesity in AFCAPS/TexCAPS were associated with significantly increased relative risk. Patients with the metabolic syndrome showed increased risk of MCEs irrespective of their Framingham-calculated 10-year risk score category (>20% vs </=20%). These data demonstrate that the metabolic syndrome is associated with increased risk of MCEs in both hypercholesterolemic patients with coronary heart disease in 4S and in those with low high-density lipoprotein cholesterol but without coronary heart disease in AFCAPS/TexCAPS. It appears that the metabolic syndrome is associated with risk that is not entirely accounted for by traditional risk scoring paradigms.

Anticholesteremic Agents↗
PubMed2004

Predictors of exercise capacity and the impact of angiographic coronary artery disease in heart transplant recipients.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which transplant coronary artery disease contributes to exercise intolerance in these patients has not been well defined. METHODS: This prospective study examined exercise capacity among 174 heart transplant recipients who underwent 358 exercise tests 0.3 to 13 years after surgery. Data were collected as part of routine posttransplantation treatment that each year consist of clinical and hemodynamic measurements (including ejection fraction, cardiac index, pulmonary capillary wedge pressure, and the presence of coronary artery disease) and cardiopulmonary exercise test (including measures of peak VO2). The mean follow-up was 3.5 +/- 0.2 years after transplantation. Serial exercise test data were available in 102 patients RESULTS: Peak VO2 was 19.4 +/- 0.4 mL/kg per minute, representing 70% +/- 1.3% of the age-predicted value. Exercise capacity increased significantly after transplantation and then remained stable throughout long-term follow-up. Only age, maximal systolic blood pressure, pulmonary vascular resistance, and body mass index were independent determinants of exercise capacity (R2 = 0.51), whereas specific transplant factors such as denervation, hemodynamic variables, donor characteristics, immunosuppressive drugs, biochemical parameters, and transplant coronary artery disease (TxCAD) did not contribute to the explanation of reduced exercise capacity. Although TxCAD was not related to exercise capacity in the multivariate analysis, exercise capacity declined by 17.1% (P <.05) among those in whom CAD developed during follow-up. CONCLUSIONS: Exercise capacity is reduced among heart transplant recipients, and age is the strongest determinant of aerobic performance. Specific transplant-related factors, including TxCAD, do not contribute significantly to the explanation of exercise capacity. However, the occurrence of TxCAD may contribute to reduced exercise capacity during follow-up, since peak VO2 appears to decline only among those who have TxCAD.

Coronary Angiography↗
PubMed2004

Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the Scandinavian Simvastatin Survival Study (4S).

OBJECTIVE: To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III). RESEARCH DESIGN AND METHODS: Subgroup analyses were performed on data from 3933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5-8.0 mmol/l, and serum triglyceride level <or=2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S), a randomized, placebo-controlled trial. End points were total mortality, coronary mortality, major CHD event, myocardial revascularization, any CHD event, stroke, and any atherosclerotic event. RESULTS: Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36-0.82), coronary mortality 0.39 (0.23-0.65), major CHD event 0.59 (0.45-0.77), and any atherosclerotic event 0.69 (0.56-0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56-0.91), 0.62 (0.45-0.84), 0.71 (0.61-0.82), and 0.76 (0.68-0.85). CONCLUSIONS: Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.

Cardiovascular Diseases↗
PubMed2003

The statin wars.

Explore the source record for details and available documents.

Coronary Disease↗
PubMed2003

N-terminal proatrial natriuretic peptide in primary care: relation to echocardiographic indices of cardiac function in mild to moderate cardiac disease.

AIMS: In patients with chronic heart failure plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) correlate to cardiac filling pressures. The aim of the present study was to examine the relation between Nt-proANP plasma levels and echocardiographic indices of cardiac dysfunction in patients recruited from primary care. METHODS AND RESULTS: After clinical examination by the primary care physician, the patients were referred to one of two centres for echocardiography and blood sampling. In patients with mild to moderate symptoms of heart failure (n=52) and in asymptomatic patients with long-standing hypertension (n=46) or previous myocardial infarction (n=97), peptide levels were most closely related to parameters of left atrial wall stress. Patients who according to echocardiographic predefined criteria had diastolic or systolic dysfunction had two- and three-fold higher Nt-proANP than controls. According to receiver operating curve (ROC) analysis, Nt-proANP measurements were helpful in ruling out left ventricular systolic dysfunction, but not diastolic dysfunction. CONCLUSION: In patients with mild to moderate cardiac disease, Nt-proANP plasma concentration was related to increased atrial wall stress. Peptide measurement could assist in ruling out the presence of LV systolic dysfunction, but was otherwise of limited value when used for diagnostic subgrouping into echocardiographically determined function categories.

Adult↗
PubMed2003

How should subgroup analyses affect clinical practice? Insights from the Metoprolol Succinate Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure (MERIT-HF).

CONTEXT: The Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) have all demonstrated highly significant positive effects on total mortality as well as total mortality plus all-cause hospitalization in patients with heart failure. While none of these trials are large enough to provide definitive results in any particular subgroup, it is of interest for physicians to examine the consistency of results as regards efficacy and safety for various subgroups or risk groups. OBJECTIVE: To summarize results from both predefined as well as post-hoc subgroup analyses performed in the MERIT-HF trial, and to provide guidance as to whether any subgroup is at increased risk, despite an overall strongly positive effect, and to discuss the difficulties and limitations in conducting such subgroup analyses. For some subgroups we performed metaanalyses with data from the CIBIS II and COPERNICUS trials in order to obtain more robust data on mortality in subgroups with a small number of deaths (e.g. for women). SETTING: MERIT-HF was run in 14 countries, and randomized a total of 3,991 patients with symptomatic systolic heart failure (NYHA class II to IV with ejection fraction < or =0.40). Treatment was initiated with a very low dose with careful titration to a maximum target dose of 200 mg metoprolol succinate controlled release/extended release (CR/XL), or highest tolerated dose. MAIN OUTCOME MEASURES: Total mortality (first primary endpoint), total mortality plus all-cause hospitalization (second primary endpoint), and total mortality plus hospitalization for heart failure (first secondary endpoint) analyzed on a time to first event basis. RESULTS: Overall, MERIT-HF demonstrated a 34% reduction in total mortality ( p = 0.00009 nominal) and a 19% reduction for mortality plus all-cause hospitalization ( p = 0.00012). The first secondary endpoint of mortality plus hospitalization for heart failure was reduced by 31% ( p = 0.0000008). The results were remarkably consistent for both primary outcomes and the first secondary outcome across all predefined subgroups as well as nearly all post-hoc subgroups. Metoprolol CR/XL has been very well tolerated, overall as well as in all subgroups analyzed. Overall 87% of the patients reached a dose of 100 mg or more of metoprolol CR/XL once daily, and 64% reached the target dose of 200 mg once daily. CONCLUSION: Our results show that when carefully titrated, metoprolol CR/XL can safely be instituted for the overwhelming majority of outpatients with clinically stable systolic heart failure, with minimal side effects or deterioration. The time has come to overcome the barriers that physicians perceive to beta-blocker treatment, and to provide it to the large number of patients with heart failure in need of this therapy, including also high risk patients like elderly patients, patients with severe heart failure, and patients with diabetes. Because of the increased risk, these are the patients in whom treatment will have the greatest impact as shown by number of lives saved and number of hospitalizations avoided. The target dose should be strived for in all patients who tolerate this dose. We should expect some variation of the treatment effect around the overall estimate as we examine a large number of subgroups due to small sample size in subgroups and due to chance. However, we believe that the best estimate of treatment effect for any particular subgroup should be the overall effect observed in the trial.

Adrenergic beta-Antagonists↗
PubMed2002

Hypertension in relation to nitric oxide, asymmetric dimethylarginine, and inflammation: different patterns in heart transplant recipients and individuals with essential hypertension.

BACKGROUND: Most heart transplant (HTx) recipients develop hypertension, characterized by increased peripheral vascular tone and endothelial dysfunction. Reduced levels of nitric oxide (NO) have been found in essential hypertension, and herein we investigated the possible role of altered concentrations of NO in posttransplant hypertension. METHODS: Plasma levels of the NO-derived end products NO2(-) + NO3(-), the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha were examined in 65 stable hypertensive long-term (6 years [range 1-13]) survivors of HTx. HTx recipients were compared with 39 individuals with essential hypertension and 25 normotensive controls. RESULTS Hypertensive HTx recipients had raised NO2(-) + NO3(-) levels in plasma, positively correlated with 24-hour mean blood pressure (BP). In contrast, individuals with essential hypertension had decreased NO2(-) + NO3(-) concentration comparing controls, inversely correlated with 24-hour mean BP. Moreover, although TNF-alpha levels were significantly raised in HTx recipients compared with both healthy controls and individuals with essential hypertension, it was positively correlated to 24-hour BP and NO2(-) + NO3(-). Although only a slight increase was found in essential hypertension, no correlations were found in these nontransplant individuals. Finally, although asymmetric dimethylarginine (ADMA) tended to be raised in essential hypertension, this endogenous nitric oxide synthase (NOS) inhibitor was significantly decreased in HTx recipients compared with normotensive controls. CONCLUSION: Our findings suggest that different mechanisms may be operating in the pathogenesis of posttransplant compared with essential hypertension, with persistent inflammation, raised NO2(-) + NO3(-), and decreased ADMA levels characterizing the former group.

Arginine↗
PubMed2002

Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan.

BACKGROUND: ACE inhibitors attenuate the detrimental effects of angiotensin II, and improve survival and reduce morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system. We did a multicentre, randomised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infarction. METHODS: 5477 patients 50 years of age or older (mean age 67.4 years [SD 9.8]), with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction, were recruited from 329 centres in seven European countries. Patients were randomly assigned and titrated to a target dose of losartan (50 mg once daily) or captopril (50 mg three times daily) as tolerated. The primary endpoint was all-cause mortality. Analysis was by intention to treat. FINDINGS: There were 946 deaths during a mean follow-up of 2.7 (0.9) years: 499 (18%) in the losartan group and 447 (16%) in the captopril group (relative risk 1.13 [95% CI 0.99-1.28], p=0.07). The results for the secondary and tertiary endpoints were as follows: sudden cardiac death or resuscitated cardiac arrest 239 (9%) versus 203 (7%), 1.19 (0.98-1.43), p=0.07, and fatal or non-fatal reinfarction 384 (14%) versus 379 (14%), 1.03 (0.89-1.18), p=0.72. The all-cause hospital admission rates were 1806 (66%) versus 1774 (65%), 1.03 (0.97-1.10), p=0.37. Losartan was significantly better tolerated than captopril, with fewer patients discontinuing study medication (458 [17%] vs 624 [23%], 0.70 [0.62-0.79], p<0.0001). INTERPRETATION: Since we saw a non-significant difference in total mortality in favour of captopril, ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infarction. Losartan cannot be generally recommended in this population. However, it was better tolerated than captopril, and was associated with significantly fewer discontinuations. Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined, it can be considered in such patients.

Aged↗
PubMed2002

Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF).

OBJECTIVES: We performed a post-hoc subgroup analysis in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF) with the aim of reporting on the heart rate (HR) response during the titration phase and clinical outcomes from the three-month follow-up visit to end of study in two dosage subgroups: one that had reached more than 100 mg of metoprolol CR/XL once daily (high-dose group; n = 1,202; mean 192 mg) and one that had reached 100 mg or less (low-dose group; n = 412; mean 76 mg). BACKGROUND: Clinicians have questioned whether patients need to reach the target beta-blocker dose to receive benefit. METHODS; Outcome (Cox-adjusted) was compared with all placebo patients with dose available at the three-month visit (n = 1,845). RESULTS: Data indicated somewhat higher risk in the low-dose group compared with the high-dose group. Heart rate was reduced to a similar degree in the two dose groups, indicating higher sensitivity for beta-blockade in the low-dose group. The reduction in total mortality with metoprolol CR/XL compared with placebo was similar: 38% (95% confidence interval [CI], 16 to 55) in high-dose group (p = 0.0022) and also 38% (95% CI, 11 to 57) in the low-dose group (p = 0.010). CONCLUSIONS: Risk reduction was similar in the high- and low-dose subgroups, which, at least partly, may be the result of similar beta-blockade as judged from the HR response. The results support the idea of an individualized dose-titration regimen, which is guided by patient tolerability and the HR response. Further research is needed to shed light on why some patients respond with a marked HR reduction and reduced mortality risk on a relatively small dose of a beta-blocker.

Adrenergic beta-Antagonists↗
PubMed2002

Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).

BACKGROUND: beta-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported. METHODS AND RESULTS: We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction <0.25, heart rate less-than-or-equal 76 bpm, and systolic blood pressure less-than-or-equal 120 mm Hg). The curves started to diverge in favor of beta-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL (P=0.037 unadjusted, P=NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction <0.25 were 7.1% and 8.0% (P=NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with beta-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase. CONCLUSIONS: When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.

Adrenergic beta-Antagonists↗
PubMed2002

The effect of aortic valve replacement on N-terminal natriuretic propeptides in patients with aortic stenosis.

BACKGROUND: Increased plasma concentrations of natriuretic peptides have been demonstrated to be associated with increased intracardiac pressure and left ventricular (LV) hypertrophy. After aortic valve replacement (AVR) in aortic stenosis patients, there is a relief of the left outflow obstruction with a substantial hemodynamic improvement. This is followed by a gradual regression of the LV hypertrophy. HYPOTHESIS: After AVR, reduction in LV filling pressure is expected to occur rapidly, while regression of LV hypertrophy will take place over a longer time period. On this basis we hypothesized that the plasma levels of N-terminal proatrial natriuretic peptide (NT-proANP) would be reduced early in the postoperative period, while N-terminal probrain natriuretic peptide (NT-proBNP), through its closer reflection of LV hypertrophy, would be sustained for a longer period. METHODS: Two groups of patients with aortic stenosis undergoing AVR were followed for 4 and 12 months, respectively. Plasma concentrations of NT-proANP and NT-proBNP were measured before and after AVR and related to preoperative findings and changes in the aortic valve area index. RESULTS: Before AVR, the patients had significantly increased plasma levels of NT-proANP and NT-proBNP. After AVR, NT- proANP was decreased at 4 and 12 months but remained elevated compared with controls. N-terminal-proBNP tended to decrease, but did not change significantly. When the patients were followed for 12 months, only those with elevated preoperative pulmonary capillary wedge pressure had decreased peptide levels (NT-proANP: p = 0.017, NT-proBNP: p = 0.058). There was no regression of LV hypertrophy. The patients with the largest postoperative valve area index [1.27 (1.10-1.55) cm2/m2] had the largest reduction of NT-proBNP (47%). Those with the smallest valve area index [0.67 (0.54-0.73) cm2/m2] had no decrease in NT-proBNP. CONCLUSIONS: Our study suggests that a reduction in left atrial pressure is the main factor causing the change of NT-proANP level after AVR. A small prosthetic valve orifice area with a high aortic valve gradient might prevent regression of LV hypertrophy, thus representing a stimulus for increased cardiac secretion of NT-proBNP.

Aged↗
PubMed2002

Inflammatory predictors of mortality in the Scandinavian Simvastatin Survival Study.

BACKGROUND AND HYPOTHESIS: The predictive value of specific markers of infection and autoimmunity for coronary events, such as the effects of statins on inflammation, is still controversial. METHODS: A case-control design was used to compare C-reactive protein (CRP) levels, seropositivity for Chlamydia pneumoniae and Helicobacter pylori, and anti-oxidized low-density lipoprotein (oxLDL) antibody levels in prerandomization blood samples from 129 participants in the Scandinavian Simvastatin Survival Study who died (cases), and from 129 matched participants who were alive during 5-year follow-up (controls). RESULTS: Patients with CRP levels in the highest quartile had an increased risk of death compared with those in the first through third quartile (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.3-4.8). Seropositivity for Chlamydia pneumoniae or Helicobacter pylori and anti-oxLDL antibody levels were similar in cases and controls (p = NS). At a 4-month control, simvastatin reduced CRP levels (p = 0.009) while placebo did not (p = NS). However, the risk of death associated with high baseline CRP levels was similar in patients randomized to placebo (OR = 2.36, 95% CI 1.06-5.26) or simvastatin (OR = 3.13, 95% CI 1.06-9.21). CONCLUSIONS: Elevated CRP levels, but not seropositivity for Chlamydia pneumoniae or Helicobacter pylori, nor levels of anti-oxLDL antibodies, predict the risk of death in patients with stable ischemic heart disease. Simvastatin treatment reduces CRP levels, but without affecting the increased risk conferred by higher CRP levels at baseline.

Aged↗
PubMed2001

Debate: Statins should be used in patients with heart failure.

Treatment to prevent progression of heart failure has been targeted to reverse the consequences of heart failure and to a lesser extent the cause - the atherosclerotic plaque itself. Less than 50% of patients with heart failure are treated with lipid intervention. Heart failure (New York Heart Association [NYHA] functional classes I and II) is associated with an increase in low-density lipoproteins (LDL) and triglycerides while high-density lipoproteins (HDL) is lowered. In NYHA class IV, cholesterol is reduced due to depressed production in the liver. Although lipoproteins, especially LDL and HDL, may have some protective effect in binding and neutralising endotoxins released from the intestine during terminal heart failure, observational studies in patients with heart failure strongly suggest that lipid modification with statins may reduce progression of heart failure as well as reducing heart failure mortality.

Journal Article↗
PubMedDate not supplied

Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S).

BACKGROUND: The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5-6-year trial periods are unknown. We extended post-trial follow-up of participants in the Scandinavian Simvastatin Survival Study (4S) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial. METHODS: 4S was a randomised double-blind trial of simvastatin or placebo in patients with coronary heart disease, serum total cholesterol 5.5-8.0 mmol/L, and serum triglycerides 2.5 mmol/L or lower. The double-blind period lasted for a median of 5.4 years (range for survivors 4.9-6.3) and ended in 1994. After the trial, most patients in both groups received open-label lipid-lowering treatment. National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years (range for survivors 9.9-11.3). Analysis was by intention to treat. FINDINGS: 414 patients originally allocated simvastatin and 468 assigned placebo died during the 10.4-year follow-up (relative risk 0.85 [95% CI 0.74-0.97], p=0.02), a difference largely attributable to lower coronary mortality in the simvastatin group (238 vs 300 deaths; 0.76 [0.64-0.90], p=0.0018). 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group (0.81 [0.60-1.08], p=0.14), and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group (0.88 [0.73-1.05], p=0.15). Incidence of any specific type of cancer did not rise in the simvastatin group. INTERPRETATION: Simvastatin treatment for 5 years in a placebo-controlled trial, followed by open-label statin therapy, was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only. No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group.

Adult↗