Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease: a European economic evaluation of the THEMIS trial.

To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease (CAD) from a multinational payer perspective. Cost-effectiveness and cost-utility of ticagrelor were evaluated in the overall effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial population and in the predefined patient group with prior percutaneous coronary intervention. A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost-effectiveness ratios (ICERs), which were compared with conventional willingness-to-pay thresholds [€47 000/quality-adjusted life-year (QALY) in Sweden and €30 000/QALY in other countries].Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with percutaneous coronary intervention (PCI). Increased costs and benefits translated to ICERs ranged between €27 894 and €42 252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to €18 449, €20 632, €20 233, and €13 228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit. Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost-effective in some European countries in patients with T2DM and CAD and no prior myocardial infarction (MI) or stroke. Additionally, ticagrelor is likely to be cost-effective across European countries in patients with a history of PCI.This work was supported by AstraZeneca.S

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes A Prespecified Secondary Analysis of a Randomized Clinical Trial

ImportanceSodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown.ObjectiveTo assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).Design, setting, and participantsThis secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (InterventionsDapagliflozin vs placebo.Main outcomes and measuresThe dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF.ResultsAt baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher.Conclusions and relevanceThe effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria.Trial registrationClinicalTrials.gov Identifier: NCT01730534

Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure or death from cardiovascular causes among patients with stable heart failure. However, the safety and efficacy of SGLT2 inhibitors when initiated soon after an episode of decompensated heart failure are unknown

Effect of Sotagliflozin on Total Hospitalizations in Patients With Type 2 Diabetes and Worsening Heart Failure A Randomized Trial

In the SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure) trial, sotagliflozin, a sodium-glucose cotransporter-1 and sodium-glucose cotransporter-2 inhibitor, reduced total occurrences of cardiovascular deaths, hospitalizations for heart failure, and urgent visits for heart failure relative to placebo by 33%

The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58

OBJECTIVE Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk. RESEARCH DESIGN AND METHODS DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance >60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (15 to = 30 to 300 mg/g) by treatment arm. The composite cardiorenal outcome was a >= 40% sustained decline in the estimated glomerular filtration rate (eGFR) to 15 to 300 mg/g. Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories (all P = 1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 1.45 [95% CI 1.35-1.56], P = 30 mg/g (P < 0.0125, P-interaction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, P-interaction = 0.480). CONCLUSIONS In DECLARE-TIMI 58, dapagliflozin demonstrated a favorable effect on UACR and renal-specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease

Natriuretic peptides, body mass index and heart failure risk: Pooled analyses of SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61.

AimN-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are lower in patients with obesity. The interaction between body mass index (BMI) and NT-proBNP with respect to heart failure risk remains incompletely defined.Methods and resultsData were pooled across three randomized clinical trials enrolling predominantly patients who were overweight or obese with established cardiometabolic disease: SAVOR-TIMI 53, DECLARE-TIMI 58 and CAMELLIA-TIMI 61. Hospitalization for heart failure (HHF) was examined across strata of baseline BMI and NT-proBNP. The effect of dapagliflozin versus placebo was assessed for a treatment interaction across BMI categories in patients with or without an elevated baseline NT-proBNP (≥125 pg/ml). Among 24 455 patients, the median NT-proBNP was 96 (interquartile range [IQR]: 43-225) pg/ml and the median BMI was 33 (IQR 29-37) kg/m2 , with 68% of patients having a BMI ≥30 kg/m2 . There was a significant inverse association between NT-proBNP and BMI which persisted after adjustment for all clinical variables (p 2 for NT-proBNP ranges of adj ] 7.47, 95% confidence interval [CI] 3.16-17.66, HRadj 3.22 [95% CI 2.13-4.86], and HRadj 1.87 [95% CI 1.35-2.60], respectively). In DECLARE-TIMI 58, dapagliflozin versus placebo consistently reduced HHF across BMI categories in those with an elevated NT-proBNP (p-trend for HR across BMI = 0.60), with a pattern of greater absolute risk reduction (ARR) at higher BMI (ARR for BMI 2 : 2.2% to 4.7%; p-trend = 0.059).ConclusionsThe risk of HHF varies across BMI categories for any given range of circulating NT-proBNP. These findings showcase the importance of considering BMI when applying NT-proBNP for heart failure risk stratification, particularly for patients with low-level elevations in NT-proBNP (125-<450 pg/ml) where there appears to be a clinically meaningful absolute and relative risk gradient

Cardiorenal outcomes with dapagliflozin by baseline glucose-lowering agents: Post hoc analyses fromDECLARE-TIMI58

Aim To assess the associations between baseline glucose-lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE-TIMI 58 study. Materials and methods DECLARE-TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA-based treatment interaction. Results At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase-4 inhibitors, 750 (4.4%) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP-1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP-1 RA users vs. non-users,P-interaction= .03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (P-interaction> .05). The renal-specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43-0.66]), with no interaction by baseline GLA (P-interaction> .05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium-glucose co-transporter-2 inhibitors with GLP-1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further