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Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study.

ABSTRACT: AIMS:Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly treated type 2 diabetes compared with metformin. METHODS:We conducted a population-based cohort study of patients with newly treated type 2 diabetes using the UK's Clinical Practice Research Datalink. Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs metformin. RESULTS:Our cohort included 94 750 patients initiating treatment for type 2 diabetes, 17 612 on a sulfonylurea and 77 138 on metformin. After matching, sulfonylurea monotherapy, compared with metformin monotherapy, was not associated with an increased risk of myocardial infarction (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 0.85-1.25) but was associated with increased risks of ischaemic stroke (HR: 1.25, 95% CI: 1.002-1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06-1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45-1.76). This represents an additional 2.0 ischaemic strokes, 3.5 cardiovascular deaths, and 21.4 all-cause deaths per 1,000 patients per year with sulfonylureas. CONCLUSIONS:Initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischaemic stroke, cardiovascular death, and all-cause mortality.

SUBMITTER: Filion KB

PROVIDER: S-EPMC6783602 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study.

Filion Kristian B KB Douros Antonios A Azoulay Laurent L Yin Hui H Yu Oriana H OH Suissa Samy S

British journal of clinical pharmacology 20190731 10

<h4>Aims</h4>Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly treated type 2 diabetes compared with metformin.<h4>Methods</h4>We conducted a population-based cohort stud ...[more]

PMID: 31276600

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Project description:OBJECTIVE:To assess whether adding or switching to sulfonylureas is associated with an increased risk of myocardial infarction, ischaemic stroke, cardiovascular death, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy in patients with type 2 diabetes. DESIGN:Population based cohort study. SETTING:General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS:Patients with type 2 diabetes initiating metformin monotherapy between 1998 and 2013. MAIN OUTCOME MEASURES:Using the prevalent new-user cohort design we matched 1:1 patients adding or switching to sulfonylureas with those remaining on metformin monotherapy on high-dimensional propensity score, haemoglobin A1c, and number of previous metformin prescriptions. The two groups were compared using Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals for the study outcomes. RESULTS:Among 77?138 metformin initiators, 25?699 added or switched to sulfonylureas during the study period. During a mean follow-up of 1.1 years, sulfonylureas were associated with an increased risk of myocardial infarction (incidence rate 7.8 v 6.2 per 1000 person years, hazard ratio 1.26, 95% confidence interval 1.01 to 1.56), all cause mortality (27.3 v 21.5, 1.28, 1.15 to 1.44), and severe hypoglycaemia (5.5 v 0.7, 7.60, 4.64 to 12.44) compared with continuing metformin monotherapy. There was a trend towards increased risks of ischaemic stroke (6.7 v 5.5, 1.24, 0.99 to 1.56) and cardiovascular death (9.4 v 8.1, 1.18, 0.98 to 1.43). Compared with adding sulfonylureas, switching to sulfonylureas was associated with an increased risk of myocardial infarction (hazard ratio 1.51, 95% confidence interval, 1.03 to 2.24) and all-cause mortality (1.23, 1.00 to 1.50). No differences were observed for ischaemic stroke, cardiovascular death, or severe hypoglycaemia. CONCLUSIONS:Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuing metformin when introducing sulfonylureas appears to be safer than switching.

Project description:BackgroundManaging hypertension (HT) and diabetes mellitus (DM) is crucial to preventing cardiovascular diseases. Few studies have investigated the incidence and risk of cardiovascular diseases or mortality in uncontrolled HT or DM in the Asian population. Epidemiological studies of cardiovascular disease should be conducted with continuous consideration of the changing disease risk profiles, lifestyles, and socioeconomic status over time.ObjectiveWe aimed to examine the association of uncontrolled HT or DM with the incidence of cardiovascular events or deaths from any cause.MethodsThis population-based retrospective study was conducted using data from the Korean National Health Insurance Service-National Health Screening Cohort, including patients aged 40-79 years who participated in national screening from 2002 to 2003 and were followed up until 2015. The health screening period from 2002 to 2013 was stratified into 6 index periods in 2-year cycles, and the follow-up period from 2004 to 2015 was stratified accordingly into 6 subsequent 2-year periods. The incidence rates and hazard ratio (HR) for major adverse cardiovascular events (MACE) and death from any cause were estimated according to HT or DM control status. Extended Cox models with time-dependent variables updated every 2 years, including sociodemographic characteristics, blood pressure (BP), fasting blood glucose (FBG), medication prescription, and adherence, were used.ResultsAmong the total cohort of 440,249 patients, 155,765 (35.38%) were in the uncontrolled HT or DM group. More than 60% of the patients with HT or DM who were prescribed medications did not achieve the target BP or FBG. The incidence of MACE was 10.8-15.5 and 9.6-13.3 per 1000 person-years in the uncontrolled DM and uncontrolled HT groups, respectively, and increased with age. In the uncontrolled HT and DM group, the incidence of MACE was high (15.2-17.5 per 1000 person-years) at a relatively young age and showed no age-related trend. Adjusted HR for MACE were 1.28 (95% CI 1.23-1.32) for the uncontrolled DM group, 1.32 (95% CI 1.29-1.35) for the uncontrolled HT group, and 1.54 (95% CI 1.47-1.60) for the uncontrolled HT and DM group. Adjusted HR for death from any cause were 1.05 (95% CI 1.01-1.10) for the uncontrolled DM group, 1.13 (95% CI 1.10-1.16) for the uncontrolled HT group, and 1.17 (95% CI 1.12-1.23) for the uncontrolled HT and DM group.ConclusionsThis up-to-date evidence of cardiovascular epidemiology in South Korea serves as the basis for planning public health policies to prevent cardiovascular diseases. The high uncontrolled rates of HT or DM, regardless of medication prescription, have led us to suggest the need for a novel system for effective BP or glycemic control, such as a community-wide management program using mobile health technology.

Project description:OBJECTIVES:This study aimed to evaluate the effectiveness of multiple risk factor control (MRFC) at reducing mortality and cardiovascular events in diabetes and chronic kidney disease (CKD) in clinical practice. DESIGN:Population-based cohort study. SETTING:Primary care database in the UK, linked with inpatient and mortality data. PARTICIPANTS:Participants aged 40-79 years with type 2 diabetes and valid serum creatinine measurements, including 11?431 participants with CKD (estimated glomerular filtration rate: eGFR 15-59?mL/min/1.73?m2) and 36?429 participants with non-CKD (eGFR ?60?mL/min/1.73?m2). EXPOSURES:MRFC consisted of four components: Haemoglobin A1c (HbA1c) <53?mmol/mol (<7.0%), blood pressure <140/90?mm Hg, total cholesterol <5?mmol/L and no smoking. The main exposure variable was the number of risk factors controlled at baseline. OUTCOME MEASURES:All-cause and cardiovascular mortality in the overall participants. Cardiovascular events, including coronary heart disease and stroke, in participants limited to those without a history of cardiovascular diseases at baseline. RESULTS:In participants with CKD, 37% or 13% met three or four MRFC criteria, respectively. Increasing numbers of risk factors controlled were associated with lower relative hazards for all outcomes studied compared with those meeting no or one criterion. For participants with CKD meeting four criteria, the adjusted HR for all-cause mortality was 0.60 (95% CI 0.53 to 0.69) and the adjusted subdistribution HR for cardiovascular mortality was 0.60 (95% CI 0.50 to 0.70), considering a competing risk of non-cardiovascular death. Participants meeting four criteria also had lower relative hazards for coronary heart disease (adjusted subdistribution HR 0.73, 95%?CI 0.59 to 0.91) and stroke (0.63, 95% CI 0.45 to 0.89), considering death as a competing risk. CONCLUSIONS:MRFC may lower the increased risks for mortality and cardiovascular events in people with diabetes and CKD. Further research is needed to evaluate appropriateness of MRFC according to individual participants' health status for improved management of cardiovascular risks in this population.

Project description:The association of lipid parameters with cardiovascular outcomes and the impact of kidney function on this association have not been thoroughly evaluated in chronic kidney disease (CKD) patients with diabetes. We reviewed the National Health Insurance Database of Korea, containing the data of 10,505,818 subjects who received routine check-ups in 2009. We analyzed the association of lipid profile parameters with major adverse cardiovascular events (MACEs) risk and all-cause mortality in a nationally representative cohort of 51,757 lipid-lowering medication-naïve patients who had CKD and diabetes. Advanced CKD patients with eGFR <30 mL/min/1.73 m2 (n = 10,775) had lower serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) but higher non-HDL-c levels and triglyceride (TG) to HDL-c ratios. There was a positive linear association between serum LDL-c and MACE risk in both early and advanced CKD patients (P <0.001 for trend), except for the category of LDL-c 30-49 mg/dL in extremely low LDL-c subgroup analyses. A U-shaped relationship was observed between serum LDL-c and all-cause mortality (the 4th and 8th octile groups; lowest hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.87-1.05 and highest HR 1.14, 95% CI 1.04-1.26, respectively). A similar pattern remained in both early and advanced CKD patients. The TG/HDL-c ratio categories showed a positive linear association for MACE risk in early CKD (P <0.001 for trend), but this correlation disappeared in advanced CKD patients. There was no correlation between the serum TG/HDL-c ratio and all-cause mortality in the study patients. The LDL-c level predicted the risk for MACEs and all-cause mortality in both early and advanced CKD patients with diabetes, although the patterns of the association differed from each other. However, the TG/HDL-c ratio categories could not predict the risk for either MACEs or all-cause mortality in advanced CKD patients with diabetes, except that the TG/HDL-c ratio predicted MACE risk in early CKD patients with diabetes.

Project description:Importance:After the occurrence of nonfatal cardiovascular events, recurrent events are highly likely. Most cardiovascular outcomes trials analyze first events only; extending analyses to first and recurrent (total) events can provide clinically meaningful information. Objective:To investigate whether liraglutide is associated with reduced first and recurrent total major adverse cardiovascular events (MACE) compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. Design, Setting, and Participants:This post hoc analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) randomized, double-blind, clinical trial included data from patients with type 2 diabetes who had established or were at high risk for cardiovascular disease at 410 sites in 32 countries from August 2010, to December 2015. Data analysis was performed from August 15, 2016, to July 5, 2019. Interventions:Patients were randomized 1:1 to receive liraglutide (up to 1.8 mg per day) or placebo, both with standard care, for 3.5 to 5.0 years. Main Outcomes and Measures:Assessed outcomes were MACE (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), expanded MACE (primary MACE plus coronary revascularization and hospitalization for heart failure or unstable angina pectoris), and the individual end points. Results:The 9340 LEADER trial participants (6003 [64.3%] male; mean [SD] age, 64.3 [7.2] years) experienced 1605 total MACE (1302 first and 303 recurrent events; median follow-up, 3.8 years [range, 0-5.2 years]). Patients who experienced any MACE were older (1 MACE: mean [SD] age, 65.6 [8.0] years; >1 MACE: 65.7 [7.9] years) and had diabetes for longer duration (1 MACE: mean [SD] duration, 13.4 [8.3] years; >1 MACE: 14.4 [8.7] years) compared with patients without MACE (mean [SD] age, 64.1 [7.1] years; mean [SD] duration, 12.7 [7.9] years). Fewer first and recurrent MACE occurred in the liraglutide group (n = 4668; 608 first and 127 recurrent events) than in the placebo group (n = 4672; 694 first and 176 recurrent events). Liraglutide was associated with a 15.7% relative risk reduction in total MACE (hazard ratio [HR], 0.84; 95% CI, 0.76-0.93) and a 13.4% reduction in total expanded MACE (HR, 0.87; 95% CI, 0.81-0.93) compared with placebo. For most individual cardiovascular end points, liraglutide was associated with lower risk vs placebo. Conclusions and Relevance:These results suggest that liraglutide treatment is associated with reduced total MACE compared with placebo among patients with type 2 diabetes and high risk of cardiovascular events. This analysis supports the findings of an absolute benefit of liraglutide treatment with respect to the overall burden of cardiovascular events in this high-risk patient population. Trial Registration:ClinicalTrials.gov identifier: NCT01179048.

Project description:BackgroundPrevious studies reported the prognostic value of the atherogenic index of plasma (AIP) in the course of atherosclerosis and other cardiovascular diseases (CVDs). Still, the predictive utility of the AIP is unknown among patients with type 2 diabetes mellitus (T2DM).MethodsThis was a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, which randomized 10,251 patients with long-lasting T2DM. ROC curve analysis was used to determine an optimal threshold for AIP, and the study population was divided into high and low AIP groups. Univariable and multivariable Cox proportional hazards regression analyses were used to determine the association between AIP and primary (major adverse cardiovascular events [MACEs], including nonfatal myocardial infarction, nonfatal stroke, and/or death from cardiovascular causes) and secondary outcomes (all-cause mortality). Stratified analyses were performed to control for the confounding factors.ResultsAIP was an independent risk factor for the prognosis of T2DM (HR = 1.309; 95% CI 1.084-1.581; P = 0.005). The threshold for AIP was determined to be 0.34 in the study population. After adjustments for confounding factors, multivariable analysis showed that AIP was associated with the risk of MACEs (Model 1: HR = 1.333, 95% CI 1.205-1.474, P < 0.001; Model 2: HR = 1.171, 95% CI 1.030-1.333, P = 0.016; Model 3: HR = 1.194, 95% CI 1.049-1.360, P = 0.007), all-cause mortality (Model 1: HR = 1.184, 95% CI 1.077-1.303, P < 0.001), cardiovascular death (Model 1: HR = 1.422, 95% CI 1.201-1.683, P < 0.001; Model 3: HR = 1.264, 95% CI 1.015-1.573, P = 0.036), and nonfatal myocardial infarction (Model 1: HR = 1.447, 95% CI 1.255-1.669, P < 0.001; Model 2: HR = 1.252, 95% CI 1.045-1.499, P = 0.015; Model 3: HR = 1.284, 95% CI 1.071-1.539, P = 0.007). Subgroup stratified analyses showed that AIP might interact with sex, a classical risk factor of cardiovascular events.ConclusionsThis study showed that AIP might be a strong biomarker that could be used to predict the risk of cardiovascular events in patients with T2DM.Trial registrationURL: http://www.clinicaltrials.gov . Unique identifier: NCT00000620.

Dataset Information

Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study.

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Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study.

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