Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction.

BACKGROUND: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. METHODS: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. RESULTS: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min-1 /1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. CONCLUSION: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.

Open or endovascular revascularization in the treatment of acute lower limb ischaemia.

BACKGROUND: Consensus is lacking regarding intervention for patients with acute lower limb ischaemia (ALI). The aim was to study amputation-free survival in patients treated for ALI by either primary open or endovascular revascularization. METHODS: The Swedish Vascular Registry (Swedvasc) was combined with the Population Registry and National Patient Registry to determine follow-up on mortality and amputation rates. Revascularization techniques were compared by propensity score matching 1 : 1. RESULTS: Of 9736 patients who underwent open surgery and 6493 who had endovascular treatment between 1994 and 2014, 3365 remained in each group after propensity score matching. Results are from the matched cohort only. Mean age of the patients was 74·7 years; 47·5 per cent were women and mean follow-up was 4·3 years. At 30-day follow-up, the endovascular group had better patency (83·0 versus 78·6 per cent; P < 0·001). Amputation rates were similar at 30 days (7·0 per cent in the endovascular group versus 8·2 per cent in the open group; P = 0·113) and at 1 year (13·8 versus 14·8 per cent; P = 0·320). The mortality rate was lower after endovascular treatment, at 30 days (6·7 versus 11·1 per cent; P < 0·001) and after 1 year (20·2 versus 28·6 per cent; P < 0·001). Accordingly, endovascular treatment had better amputation-free survival at 30 days (87·5 versus 82·1 per cent; P < 0·001) and 1 year (69·9 versus 61·1 per cent; P < 0·001). The number needed to treat to prevent one death within the first year was 12 with an endovascular compared with an open approach. Five years after surgery, endovascular treatment still had improved survival (HR 0·78, 99 per cent c.i. 0·70 to 0·86) but the difference between the treatment groups occurred mainly in the first year. CONCLUSION: Primary endovascular treatment for ALI appeared to reduce mortality compared with open surgery, without any difference in the risk of amputation.

Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example.

Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different from those treated in clinical practice. Therefore, it is important to optimize real-time postmarketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases from a well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.