Ulf Stenestrand

The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)

Aims The aims of the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) are to support the improvement of care and evidence-based development of therapy of coronary artery disease (CAD). Interventions To provide users with online interactive reports monitoring the processes of care and outcomes and allowing direct comparisons over time and with other hospitals. National, regional and county-based reports are publicly presented on a yearly basis. Setting Every hospital (n=74) in Sweden providing the relevant services participates. Launched in 2009 after merging four national registries on CAD. Population Consecutive acute coronary syndrome (ACS) patients, and patients undergoing coronary angiography/angioplasty or heart surgery. Includes approximately 80 000 new cases each year. Startpoints On admission in ACS patients, at coronary angiography in patients with stable CAD. Baseline data 106 variables for patients with ACS, another 75 variables regarding secondary prevention after 12–14 months, 150 variables for patients undergoing coronary angiography/angioplasty, 100 variables for patients undergoing heart surgery. Data capture Web-based registry with all data registered online directly by the caregiver. Data quality A monitor visits approximately 20 hospitals each year. In 2007, there was a 96% agreement. Endpoints and linkages to other data Merged with the National Cause of Death Register, including information about vital status of all Swedish citizens, the National Patient Registry, containing diagnoses at discharge for all hospital stays in Sweden and the National Registry of Drug prescriptions recording all drug prescriptions in Sweden. Access to data Available for research by application to the SWEDEHEART steering group.

Long-term safety and efficacy of drug-eluting versus bare-metal stents in Sweden.

BACKGROUND The long-term safety and efficacy of drug-eluting coronary stents have been questioned. METHODS We evaluated 47,967 patients in Sweden who received a coronary stent and were entered into the Swedish Coronary Angiography and Angioplasty Registry between 2003 and 2006 and for whom complete follow-up data were available for 1 to 5 years (mean, 2.7). In the primary analysis, we compared patients who received one drug-eluting coronary stent (10,294 patients) with those who received one bare-metal stent (18,659), after adjustment for differences in clinical characteristics of the patients and characteristics of the vessels and lesions. RESULTS Analyses of outcome were based on 2380 deaths and 3198 myocardial infarctions. There was no overall difference between the group that received drug-eluting stents and the group that received bare-metal stents in the combined end point of death or myocardial infarction (relative risk with drug-eluting stents, 0.96; 95% confidence interval [CI], 0.89 to 1.03) or the individual end points of death (relative risk, 0.94; 95% CI, 0.85 to 1.05) and myocardial infarction (relative risk, 0.97; 95% CI, 0.88 to 1.06), and there was no significant difference in outcome among subgroups stratified according to the indication for stent implantation. Patients who received drug-eluting stents in 2003 had a significantly higher rate of late events than patients who received bare-metal stents in the same year, but we did not observe any difference in outcome among patients treated in later years. The average rate of restenosis during the first year was 3.0 events per 100 patient-years with drug-eluting stents versus 4.7 with bare-metal stents (adjusted relative risk, 0.43; 95% CI, 0.36 to 0.52); 39 patients would need to be treated with drug-eluting stents to prevent one case of restenosis. Among high-risk patients, the adjusted risk of restenosis was 74% lower with drug-eluting stents than with bare-metal stents, and only 10 lesions would need to be treated to prevent one case of restenosis. CONCLUSIONS As compared with bare-metal stents, drug-eluting stents are associated with a similar long-term incidence of death or myocardial infarction and provide a clinically important decrease in the rate of restenosis among high-risk patients.

Influence of Renal Function on the Effects of Early Revascularization in Non-ST-Elevation Myocardial Infarction Data From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)

Background— It is unknown whether patients with non–ST-elevation myocardial infarction derive a similar benefit from an early invasive therapy at different levels of renal function. Methods and Results— A total of 23 262 consecutive non–ST-elevation myocardial infarction patients ≤80 years old were included in a nationwide coronary care unit register between 2003 and 2006. Glomerular filtration rate (eGFR) was estimated with the Modification of Diet in Renal Disease Study formula. Patients were divided into medically or invasively treated groups if revascularized within 14 days of admission. A propensity score for the likelihood of invasive therapy was calculated. A Cox regression model with adjustment for propensity score and discharge medication was used to assess the association between early revascularization and 1-year mortality across renal function stages. There was a gradient, with significantly fewer patients treated invasively with declining renal function: eGFR ≥90 mL · min−1 · 1.73 m−2, 62%; eGFR 60 to 89 mL · min−1 · 1.73 m−2, 55%; eGFR 30 to 59 mL · min−1 · 1.73 m−2, 36%; eGFR 15 to 29 mL · min−1 · 1.73 m−2, 14%; and eGFR <15 mL · min−1 · 1.73 m−2/dialysis, 15% (P<0.001). After adjustment, the overall 1-year mortality was 36% lower (hazard ratio 0.64, 95% confidence interval 0.56 to 0.73, P<0.001) with an invasive strategy. The magnitude of survival difference was similar in normal-to-moderate renal function groups. The lower mortality observed with invasive therapy declined with lower renal function, with no difference in mortality in patients with kidney failure (eGFR <15 mL · min−1 · 1.73 m−2) or in those receiving dialysis (hazard ratio 1.61, 95% confidence interval 0.84 to 3.09, P=0.15). Conclusions— Early invasive therapy is associated with greater 1-year survival in patients with non–ST-elevation myocardial infarction and mild-to-moderate renal insufficiency, but the benefit declines with lower renal function, and is less certain in those with renal failure or on dialysis.

The effectiveness and cost-effectiveness of biomarkers for the prioritisation of patients awaiting coronary revascularisation: a systematic review and decision model

OBJECTIVE To determine the effectiveness and cost-effectiveness of a range of strategies based on conventional clinical information and novel circulating biomarkers for prioritising patients with stable angina awaiting coronary artery bypass grafting (CABG). DATA SOURCES MEDLINE and EMBASE were searched from 1966 until 30 November 2008. REVIEW METHODS We carried out systematic reviews and meta-analyses of literature-based estimates of the prognostic effects of circulating biomarkers in stable coronary disease. We assessed five routinely measured biomarkers and the eight emerging (i.e. not currently routinely measured) biomarkers recommended by the European Society of Cardiology Angina guidelines. The cost-effectiveness of prioritising patients on the waiting list for CABG using circulating biomarkers was compared against a range of alternative formal approaches to prioritisation as well as no formal prioritisation. A decision-analytic model was developed to synthesise data on a range of effectiveness, resource use and value parameters necessary to determine cost-effectiveness. A total of seven strategies was evaluated in the final model. RESULTS We included 390 reports of biomarker effects in our review. The quality of individual study reports was variable, with evidence of small study (publication) bias and incomplete adjustment for simple clinical information such as age, sex, smoking, diabetes and obesity. The risk of cardiovascular events while on the waiting list for CABG was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients with a mean of 59 days at risk). Risk factors associated with an increased risk, and included in the basic risk equation, were age, diabetes, heart failure, previous myocardial infarction and involvement of the left main coronary artery or three-vessel disease. The optimal strategy in terms of cost-effectiveness considerations was a prioritisation strategy employing biomarker information. Evaluating shorter maximum waiting times did not alter the conclusion that a prioritisation strategy with a risk score using estimated glomerular filtration rate (eGFR) was cost-effective. These results were robust to most alternative scenarios investigating other sources of uncertainty. However, the cost-effectiveness of the strategy using a risk score with both eGFR and C-reactive protein (CRP) was potentially sensitive to the cost of the CRP test itself (assumed to be 6 pounds in the base-case scenario). CONCLUSIONS Formally employing more information in the prioritisation of patients awaiting CABG appears to be a cost-effective approach and may result in improved health outcomes. The most robust results relate to a strategy employing a risk score using conventional clinical information together with a single biomarker (eGFR). The additional prognostic information conferred by collecting the more costly novel circulating biomarker CRP, singly or in combination with other biomarkers, in terms of waiting list prioritisation is unlikely to be cost-effective.

Gender differences in management and outcome in non-ST-elevation acute coronary syndrome

Objective: To study gender differences in management and outcome in patients with non-ST-elevation acute coronary syndrome. Design, setting and patients: Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year. Main outcome measures: Treatment intensity and in-hospital, 30-day and 1-year mortality. Results: Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge. Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15; 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in-hospital (OR 1.03; 95% CI, 0.94 to 1.13) or 30-days (OR 1.07; 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12; 95% CI, 1.06 to 1.19). Conclusion: Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long-term outcomes than men.

Improved but still high short- and long-term mortality rates after myocardial infarction in patients with diabetes mellitus : A time-trend report from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admission

Objective: The aim of the study was to compare time-trends in mortality rates and treatment patterns between patients with and without diabetes based on the Swedish register of coronary care (Register of Information and Knowledge about Swedish Heart Intensive Care Admission [RIKS-HIA]). Methods: Post myocardial infarction mortality rate is high in diabetic patients, who seem to receive less evidence-based treatment. Mortality rates and treatment in 1995–1998 and 1999–2002 were studied in 70 882 patients (age <80 years), 14 873 of whom had diabetes (the first registry recorded acute myocardial infarction), following adjustments for differences in clinical and other parameters. Results: One-year mortality rates decreased from 1995 to 2002 from 16.6% to 12.1% in patients without diabetes and from 29.7% to 19.7%, respectively, in those with diabetes. Patients with diabetes had an adjusted relative 1-year mortality risk of 1.44 (95% CI 1.36 to 1.52) in 1995–1998 and 1.31 (95% CI 1.24 to 1.38) in 1999–2002. Despite improved pre-admission and in-hospital treatment, diabetic patients were less often offered acute reperfusion therapy (adjusted OR 0.85, 95% CI 0.80 to 0.90), acute revascularisation (adjusted OR 0.78, 95% CI 0.69 to 0.87) or revascularisation within 14 days (OR 0.80, 95% CI 0.75 to 0.85), aspirin (OR 0.90, 95% CI 0.84 to 0.98) and lipid-lowering treatment at discharge (OR 0.81, 95% CI 0.77 to 0.86). Conclusion: Despite a clear improvement in the treatment and myocardial infarction survival rate in patients with diabetes, mortality rate remains higher than in patients without diabetes. Part of the excess mortality may be explained by co-morbidities and diabetes itself, but a lack of application of evidence-based treatment also contributes, underlining the importance of the improved management of diabetic patients.

Early revascularisation and 1-year survival in 14-day survivors of acute myocardial infarction: a prospective cohort study

BACKGROUND Randomised trials of early revascularisation in acute coronary syndromes have yielded conflicting results with respect to effects on survival. We assessed the association between revascularisation within 14 days after the index event and 1-year mortality in individuals who survived for at least 14 days after an acute myocardial infarction. METHODS We studied a prospective cohort of patients admitted to the coronary care units of 61 Swedish hospitals between 1995 and 1998. We obtained 1-year mortality data from the Swedish National Cause of Death Register. We assessed 21,912 individuals with first registry-recorded acute myocardial infarction, who were younger than age 80 years, and alive at day 14. Relative risk of 1-year mortality in patients who had revascularisation (n=2554) or those who did not (n=19,358) within 14 days was calculated by Cox regression analysis, adjusting for multiple covariates that affect mortality and with a propensity score that adjusted for covariates that affected the likelihood of early revascularisation. FINDINGS At 1 year, unadjusted mortality was 9.0% (1751 deaths) in the conservative group and 3.3% (84 deaths) in the early revascularisation group. In the Cox regression analysis early revascularisation was associated with a reduction in 1-year mortality (relative risk 0.47; 95% CI 0.37-0.60; p<0.001). This relative reduction of mortality was similar in all subgroups irrespective of age, sex, baseline characteristics, previous disease manifestations, or treatment. INTERPRETATION Early revascularisation in individuals with acute myocardial infarction is associated with substantial reduction in 1-year mortality. Our findings lend support to the use of an invasive approach early after an acute myocardial infarction.

Relation between renal function, presentation, use of therapies and in-hospital complications in acute coronary syndrome: data from the SWEDEHEART register.

Abstract.  Szummer K, Lundman P, Jacobson SH, Schön S, Lindbäck J, Stenestrand U, Wallentin L, Jernberg T, for SWEDEHEART. (Karolinska Institute, Karolinska University Hospital, Stockholm; Karolinska Institute, Danderyd Hospital, Danderyd; Ryhov County Hospital, Jönköping; University Hospital, Uppsala and University Hospital, Linköping; Sweden) Relation between renal function, presentation, use of therapies and in‐hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med 2010; 268:40–49.

Digoxin and mortality in atrial fibrillation: a prospective cohort study

ObjectiveThe Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study showed that rhythm-control treatment of patients with atrial fibrillation (AF) offered no survival advantage over a rate-control strategy. In a subgroup analysis of that study, it was found that digoxin increased the death rate [relative risk (RR) = 1.42), but it was suggested that this may have been attributable to prescription of digoxin for patients at greater risk of death, such as those with congestive heart failure (CHF). No study has investigated a priori the effect of digoxin on mortality in patients with AF. This study aimed to address this question.MethodsUsing data from the Registry of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), we studied the 1-year mortality among patients admitted to coronary care units with AF, CHF, or AF+CHF with or without digoxin (n = 60,764) during 1995–2003. Adjustment for differences in background characteristics and other medications and treatments was made by propensity scoring.ResultsTwenty percent of patients with AF without CHF in this cohort were discharged with digoxin. This group had a higher mortality rate than the corresponding group not given digoxin [adjusted RR 1.42 (95% CI 1.29–1.56)], whereas no such difference was seen among patients with CHF with or without AF, although these patients had a nearly three-times higher mortality.ConclusionThe results suggest that long-term therapy with digoxin is an independent risk factor for death in patients with AF without CHF.

Differences in Restenosis Rate With Different Drug-Eluting Stents in Patients With and Without Diabetes Mellitus: A Report From the SCAAR (Swedish Angiography and Angioplasty Registry)

OBJECTIVES Our aim was to evaluate restenosis rate of drug-eluting stents (DES) in patients with and without diabetes mellitus (DM) in a real-world setting. BACKGROUND DES seem less effective in patients with DM. METHODS The SCAAR (Swedish Coronary Angiography and Angioplasty Registry) includes all patients undergoing percutaneous coronary intervention in Sweden. From April 1, 2004, to April 20, 2008, all restenoses detected at a subsequent angiography and all DES types implanted at more than 500 occasions were assessed using Cox regression. RESULTS Four DES types qualified for inclusion. In total, 35,478 DES were implanted at 22,962 procedures in 19,004 patients and 1,807 restenoses were reported over a mean 29 months follow-up. In the entire population, the restenosis rate per stent was 3.5% after 1 year and 4.9% after 2 years. The adjusted risk of restenosis was higher in patients with DM compared with that in patients without DM (relative risk [RR]: 1.23, 95% confidence interval [CI]: 1.10 to 1.37). In patients with DM, restenosis was twice as frequent with the zotarolimus-eluting Endeavor stent (Medtronic, Minneapolis, Minnesota) compared with that in the other DES types. The Endeavor stent and the sirolimus-eluting Cypher stent (Cordis, Johnson & Johnson, Miami, Florida) had higher restenosis rates in patients with DM compared with those in patients without DM (RR: 1.77, 95% CI: 1.29 to 2.43 and RR: 1.25, 95% CI: 1.04 to 1.51). Restenosis rate with the paclitaxel-eluting Taxus Express and Liberté (Boston Scientific, Natick, Massachusetts) stents was unrelated to DM. Mortality did not differ between different DES. CONCLUSIONS Restenosis rate with DES was higher in patients with DM compared with that in patients without DM. There seem to be important differences between different brands of DES.