Mervete Miftaraj

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes

BACKGROUND Long‐term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes. METHODS We included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population. RESULTS Among patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person‐years were as follows: death from any cause, ‐31.4 (95% confidence interval [CI], ‐56.1 to ‐6.7); death from cardiovascular disease, ‐26.0 (95% CI, ‐42.6 to ‐9.4); death from coronary heart disease, ‐21.7 (95% CI, ‐37.1 to ‐6.4); and hospitalization for cardiovascular disease, ‐45.7 (95% CI, ‐71.4 to ‐20.1). Absolute changes per 10,000 person‐years among patients with type 2 diabetes were as follows: death from any cause, ‐69.6 (95% CI, ‐95.9 to ‐43.2); death from cardiovascular disease, ‐110.0 (95% CI, ‐128.9 to ‐91.1); death from coronary heart disease, ‐91.9 (95% CI, ‐108.9 to ‐75.0); and hospitalization for cardiovascular disease, ‐203.6 (95% CI, ‐230.9 to ‐176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls. CONCLUSIONS In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.)

Glucose-lowering treatment and clinical results in 163 121 patients with type 2 diabetes: an observational study from the Swedish national diabetes register

Aims: To analyse clinical characteristics and treatment results in unselected type 2 diabetes mellitus (T2DM) patients, with non‐pharmacological treatment as well as the most commonly used pharmacological glucose‐lowering treatment regimens, in everyday clinical practice.

Clinical Use and Effectiveness of Lipid Lowering Therapies in Diabetes Mellitus—An Observational Study from the Swedish National Diabetes Register

Objectives To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice. Design Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18–75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006–30 June 2007 were included (n = 37182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined. Results Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg. Conclusions This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate.

Blood pressure and complications in individuals with type 2 diabetes and no previous cardiovascular disease: national population based cohort study.

Objectives To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. Design Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. Setting 861 Swedish primary care units and hospital outpatient clinics. Participants 187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. Main outcome measures Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. Results The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. Conclusions Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.

Aspirin treatment and risk of first incident cardiovascular diseases in patients with type 2 diabetes: an observational study from the Swedish National Diabetes Register

Objectives To investigate the benefits and risks associated with aspirin treatment in patients with type 2 diabetes and no previous cardiovascular disease (CVD) in clinical practice. Design Population-based cohort study between 2005 and 2009, mean follow-up 3.9 years. Setting Hospital outpatient clinics and primary care in Sweden. Participants Men and women with type 2 diabetes, free from CVD, including atrial fibrillation and congestive heart failure, at baseline, registered in the Swedish National Diabetes Register, with continuous low-dose aspirin treatment (n=4608) or no aspirin treatment (n=14 038). Main outcome measures Risks of CVD, coronary heart disease (CHD), stroke, mortality and bleedings, associated with aspirin compared with no aspirin, were analysed in all patients and in subgroups by gender and estimated cardiovascular risk. Propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression, and the effect of unknown covariates was evaluated in a sensitivity analysis. Results There was no association between aspirin use and beneficial effects on risks of CVD or death. Rather, there was an increased risk of non-fatal/fatal CHD associated with aspirin; HR 1.19 (95% CI 1.01 to 1.41), p=0.04. The increased risk of cardiovascular outcomes associated with aspirin was seen when analysing women separately; HR 1.41 (95% CI 1.07 to 1.87), p=0.02, and HR 1.28 (95% CI 1.01 to 1.61), p=0.04, for CHD and CVD, respectively, but not for men separately. There was a trend towards increased risk of a composite of bleedings associated with aspirin, n=157; HR 1.41 (95% CI 0.99 to 1.99). Conclusions The results support the trend towards more restrictive use of aspirin in patients with type 2 diabetes and no previous CVD. More research is needed to explore the differences in aspirins effects in women and men.

Cardiovascular safety of glucose-lowering agents as add-on medication to metformin treatment in type 2 diabetes: report from the Swedish National Diabetes Register.

To investigate the relative safety of various glucose‐lowering agents as add‐on medication to metformin in type 2 diabetes in an observational study linking five national health registers.

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

Background: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population. Methods: We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target. Results: The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93–1.85) for all-cause mortality, 1.82 (95% CI, 1.15–2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04–3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51–2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08–10.57) for all-cause mortality, 12.34 (95% CI, 7.91–19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87–23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66–18.85) for stroke. Conclusions: A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among patients with T1DM. However, risks for all outcomes were numerically higher for patients with T1DM compared with controls, even when all risk factors were at target, with risk for acute myocardial infarction and heart failure hospitalization statistically significantly higher.

Ongoing treatment with renin-angiotensin-aldosterone-blocking agents does not predict normoalbuminuric renal impairment in a general type 2 diabetes population☆

AIM To examine the prevalence and the clinical characteristics associated with normoalbuminuric renal impairment (RI) in a general type 2 diabetes (T2D) population. METHODS We included 94 446 patients with T2D (56% men, age 68.3±11.6 years, BMI 29.6±5.3 kg/m², diabetes duration 8.5±7.1 years; means±SD) with renal function (serum creatinine) reported to the Swedish National Diabetes Register (NDR) in 2009. RI was defined as estimated glomerular filtration (eGFR)<60 ml/min/1.73 m² and albuminuria as a urinary albumin excretion rate (AER) >20 μg/min. We linked the NDR to the Swedish Prescribed Drug Register, and the Swedish Cause of Death and the Hospital Discharge Register to evaluate ongoing medication and clinical outcomes. RESULTS 17% of the patients had RI, and 62% of these patients were normoalbuminuric. This group of patients had better metabolic control, lower BMI, lower systolic blood pressure and were more often women, non-smokers and more seldom had a history of cardiovascular disease as compared with patients with albuminuric RI. 28% of the patients with normoalbuminuric RI had no ongoing treatment with any RAAS-blocking agent. Retinopathy was most common in patients with RI and albuminuria (31%). CONCLUSIONS The majority of patients with type 2 diabetes and RI were normoalbuminuric despite the fact that 25% of these patients had no ongoing treatment with RAAS-blocking agents. Thus, RI in many patients with type 2 diabetes is likely to be caused by other factors than diabetic microvascular disease and ongoing RAAS-blockade.

Durability of oral hypoglycemic agents in drug naïve patients with type 2 diabetes: report from the Swedish National Diabetes Register (NDR)

Objective To analyze the durability of monotherapy with different classes of oral hypoglycemic agents (OHAs) in drug naïve patients with type 2 diabetes mellitus (T2DM) in real life. Methods Men and women with T2DM, who were new users of OHA monotherapy and registered in the Swedish National Diabetes Register July 2005–December 2011, were available (n=17 309) and followed for up to 5.5 years. Time to monotherapy failure, defined as discontinuation of continuous use with the initial agent, switch to a new agent, or add-on treatment of a second agent, was analyzed as a measure of durability. Baseline characteristics were balanced by propensity score matching 1:5 between groups of sulfonylurea (SU) versus metformin (n=4303) and meglitinide versus metformin (n=1308). HRs with 95% CIs were calculated using Cox regression models. Results SU and meglitinide, as compared with metformin, were associated with increased risk of monotherapy failure (HR 1.74; 95% CI 1.56 to 1.94 and 1.66; 1.37 to 2.00 for SU and meglitinide, respectively). When broken down by type of monotherapy failure, SU and meglitinide were associated with an increased risk of add-on treatment of a second agent (HR 3.14; 95% CI 2.66 to 3.69 and 2.52; 1.89 to 3.37 for SU and meglitinide, respectively) and of switch to a new agent (HR 2.81; 95% CI 2.01 to 3.92 and 3.78; 2.25 to 6.32 for SU and meglitinide, respectively). The risk of discontinuation did not differ significantly between the groups. Conclusions In this nationwide observational study reflecting clinical practice, SU and meglitinide showed substantially increased risk of switch to a new agent or add on of a second agent compared with metformin. These results indicate superior glycemic durability with metformin compared with SU and also meglitinide in real life.

Refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes: A nation-wide register-based study

This study aimed to describe and compare refill adherence and persistence to lipid‐lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD).