Lars Rydén

European guidelines on cardiovascular disease prevention in clinical practice: executive summary

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

Myocardial infarction redefined - A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee f or the redefinition of myocardial infarction

This document was developed by a consensus conference initiated by Kristian Thygesen, MD, and Joseph S. Alpert, MD, after formal approval by Lars Rydén, MD, President of the European Society of Cardiology (ESC), and Arthur Garson, MD, President of the American College of Cardiology (ACC). All of the participants were selected for their expertise in the field they represented, with approximately one-half of the participants selected from each organization. Participants were instructed to review the scientific evidence in their area of expertise and to attend the consensus conference with prepared remarks. The first draft of the document was prepared during the consensus conference itself. Sources of funding appear in Appendix A. The recommendations made in this document represent the attitudes and opinions of the participants at the time of the conference, and these recommendations were revised subsequently. The conclusions reached will undoubtedly need to be revised as new scientific evidence becomes available. This document has been reviewed by members of the ESC Committee for Scientific and Clinical Initiatives and by members of the Board of the ESC who approved the document on April 15, 2000.*

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society

Sidney C. Smith, Jr, MD, FACC, FAHA, FESC, Chair; Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair; Cynthia D. Adams, MSN, APRN-BC, FAHA; Jeffery L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA[‡][1]; Jonathan L. Halperin, MD, FACC, FAHA; Sharon Ann Hunt, MD, FACC, FAHA; Rick Nishimura,

Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year

OBJECTIVES We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. BACKGROUND Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. METHODS A total of 620 patients were studied: 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy. RESULTS The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 +/- 4.1 to 9.6 +/- 3.3 mmol/liter (mean +/- SD) in the infusion group during the 1st 24 h, and from 15.7 +/- 4.2 to 11.7 +/- 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046]; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). CONCLUSIONS Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).

Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas

Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study.

BACKGROUND Glycometabolic state at hospital admission is an important risk marker for long-term mortality in patients with acute myocardial infarction, whether or not they have known diabetes mellitus. Our aim was to ascertain the prevalence of impaired glucose metabolism in patients without diagnosed diabetes but with myocardial infarction, and to assess whether such abnormalities can be identified in the early course of a myocardial infarction. METHODS We did a prospective study, in which we enrolled 181 consecutive patients admitted to the coronary care units of two hospitals in Sweden with acute myocardial infarction, no diagnosis of diabetes, and a blood glucose concentration of less than 11.1 mmol/L. We recorded glucose concentrations during the hospital stay, and did standardised oral glucose tolerance tests with 75 g of glucose at discharge and again 3 months later. FINDINGS The mean age of our cohort was 63.5 years (SD 9) and the mean blood glucose concentration at admission was 6.5 mmol/L (1.4). The mean 2-h postload blood glucose concentration was 9.2 mmol/L (2.9) at hospital discharge, and 9.0 mmol/L (3.0) 3 months later. 58 of 164 (35%, 95% CI 28-43) and 58 of 144 (40%, 32-48) individuals had impaired glucose tolerance at discharge and after 3 months, respectively, and 51 of 164 (31%, 24-38) and 36 of 144 (25%, 18-32) had previously undiagnosed diabetes mellitus. Independent predictors of abnormal glucose tolerance at 3 months were concentrations of HbA(1c) at admission (p=0.024) and fasting blood glucose concentrations on day 4 (p=0.044). INTERPRETATION Previously undiagnosed diabetes and impaired glucose tolerance are common in patients with an acute myocardial infarction. These abnormalities can be detected early in the postinfarction period. Our results suggest that fasting and postchallenge hyperglycaemia in the early phase of an acute myocardial infarction could be used as early markers of high-risk individuals.

EFFECT ON MORTALITY OF METOPROLOL IN ACUTE MYOCARDIAL INFARCTION: A Double-blind Randomised Trial

The effect of metoprolol on mortality was compared with that of placebo in a double blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patients arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8.9%) and 40 deaths in the metoprolol group (5.7%), a reduction of 36% (p less than 0.03). Mortality rates are given according to the treatment group to which the patients were initially randomly allocated.

Basal insulin and cardiovascular and other outcomes in dysglycemia

BACKGROUND The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested. METHODS We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. RESULTS The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97). CONCLUSIONS When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).

Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction. Results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II)

BACKGROUND Long-term administration of angiotensin-converting--enzyme (ACE) inhibitors has been shown to improve survival in patients with symptomatic left ventricular failure and to attenuate left ventricular dilatation in patients with myocardial infarction. We studied whether mortality could be reduced during the 6 months after an acute myocardial infarction with use of the ACE inhibitor enalapril. METHODS At 103 Scandinavian centers patients with acute myocardial infarctions and blood pressure above 100/60 mm Hg were randomly assigned to treatment with either enalapril or placebo, in addition to conventional therapy. Therapy was initiated with an intravenous infusion of enalapril (enalaprilat) within 24 hours after the onset of chest pain, followed by administration of oral enalapril. RESULTS Of the 6090 patients enrolled, 3046 were assigned to placebo and 3044 to enalapril. The life-table mortality rates in the two groups at one and six months were not significantly different (6.3 and 10.2 percent in the placebo group vs. 7.2 and 11.0 percent in the enalapril group, P = 0.26). The relative risk of death in the enalapril group was 1.10 (95 percent confidence interval, 0.93 to 1.29). Death due to progressive heart failure occurred in 104 patients (3.4 percent) in the placebo group and 132 (4.3 percent) in the enalapril group (P = 0.06). Therapy had to be changed because of worsening heart failure in 30 percent of the placebo group and 27 percent of the enalapril group (P less than 0.006). Early hypotension (systolic pressure less than 90 mm Hg or diastolic pressure less than 50 mm Hg) occurred in 12 percent of the enalapril group and 3 percent of the placebo group (P less than 0.001). CONCLUSIONS Enalapril therapy started within 24 hours of the onset of acute myocardial infarction does not improve survival during the 180 days after infarction.

Glycometabolic State at Admission: Important Risk Marker of Mortality in Conventionally Treated Patients With Diabetes Mellitus and Acute Myocardial Infarction Long-Term Results From the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study

BACKGROUND The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). METHODS AND RESULTS Of 620 diabetic patients with AMI, 306 were randomly assigned to a >/=24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and beta-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0. 011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas previous AMI, hypertension, smoking, or female sex did not add independent predictive value. Metabolic control, mirrored by blood glucose and Hb AIc, improved significantly more in patients on intensive insulin treatment than in the control group. beta-Blockers improved survival in control subjects, whereas thrombolysis was most efficient in the intensive insulin group. CONCLUSIONS Mortality in diabetic patients with AMI is predicted by age, previous heart failure, and severity of the glycometabolic state at admission but not by conventional risk factors or sex. Intensive insulin treatment reduced long-term mortality despite high admission blood glucose and Hb AIc.