Alex Z. Fu

Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)

Background -Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin in type 2 diabetes patients with atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose lowering drugs (oGLDs) in six countries to determine if these benefits are seen in real-world practice, and across SGLT-2i class. Methods -Data were collected via medical claims, primary care/hospital records and national registries from the US, Norway, Denmark, Sweden, Germany and the UK. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios (HRs) for HHF, death and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany. Results -After propensity matching, there were 309,056 patients newly initiated on either SGLT-2i or oGLD (154,528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42% and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the two groups. There were 961 HHF cases during 190,164 person-years follow up (incidence rate [IR] 0.51/100 person-years). Of 215,622 patients in the US, Norway, Denmark, Sweden, and UK, death occurred in 1334 (IR 0.87/100 person-years), and HHF or death in 1983 (IR 1.38/100 person-years). Use of SGLT-2i, versus oGLDs, was associated with lower rates of HHF (HR 0.61; 95% CI 0.51-0.73; p<0.001); death (HR 0.49; 95% CI 0.41-0.57; p<0.001); and HHF or death (HR 0.54; 95% CI 0.48-0.60, p<0.001) with no significant heterogeneity by country. Conclusions -In this large multinational study, treatment with SGLT-2i versus oGLDs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of T2D patients in real-world practice (NCT02993614). Clinical Trial Registration -URL: ClinicalTrials.gov; Unique Identifier: NCT02993614.Background: Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class. Methods: Data were collected via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios for HHF, death, and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany. Results: After propensity matching, there were 309u2009056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154u2009528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the 2 groups. There were 961 HHF cases during 190u2009164 person-years follow-up (incidence rate, 0.51/100 person-years). Of 215u2009622 patients in the United States, Norway, Denmark, Sweden, and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100 person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years). Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51–0.73; P<0.001); death (hazard ratio, 0.49; 95% confidence interval, 0.41–0.57; P<0.001); and HHF or death (hazard ratio, 0.54; 95% confidence interval, 0.48–0.60; P<0.001) with no significant heterogeneity by country. Conclusions: In this large multinational study, treatment with SGLT-2i versus other glucose-lowering drugs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of patients with type 2 diabetes mellitus in real-world practice. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02993614.

Association Between Hospitalization for Heart Failure and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes: An Observational Study

OBJECTIVE To examine, among patients with type 2 diabetes, the association between hospitalization for heart failure (hHF) and treatment with dipeptidyl peptidase 4 inhibitors (DPP-4is) versus sulfonylureas (SUs), and treatment with saxagliptin versus sitagliptin. RESEARCH DESIGN AND METHODS This was a retrospective, observational study using a U.S. insurance claims database. Patients initiated treatment between 1 August 2010 and 30 August 2013, and had no use of the comparator treatments in the prior 12 months (baseline). Each comparison consisted of patients matched 1:1 on a propensity score. Time to each outcome was compared between matched groups using Cox models. Analyses were stratified by the presence of baseline cardiovascular disease (CVD). Secondary analyses examined associations between comparator treatments and other selected cardiovascular events. RESULTS After matching, the study included 218,556 patients in comparisons of DPP-4i and SU, and 112,888 in comparisons of saxagliptin and sitagliptin. The hazard ratios (HRs) of hHF were as follows: DPP-4i versus SU (reference): HR 0.95 (95% CI 0.78–1.15), P = 0.580 for patients with baseline CVD; HR 0.59 (95% CI 0.38–0.89), P = 0.013 for patients without baseline CVD; saxagliptin versus sitagliptin (reference): HR 0.95 (95% CI 0.70–1.28), P = 0.712 for patients with baseline CVD; HR 0.99 (95% CI 0.56–1.75), P = 0.972 for patients without baseline CVD. Comparisons of the individual secondary and composite cardiovascular outcomes followed a similar pattern. CONCLUSIONS In patients with type 2 diabetes, there was no association between hHF, or other selected cardiovascular outcomes, and treatment with a DPP-4i relative to SU or treatment with saxagliptin relative to sitagliptin.

Bevacizumab use and risk of cardiovascular adverse events among elderly patients with colorectal cancer receiving chemotherapy: a population-based study

BACKGROUNDnCardiovascular risk attributable to bevacizumab (Avastin(®), BEV) for treatment of metastatic colorectal cancer (CRC) remains unclear. We conducted a population-based cohort study to assess the safety of BEV use among patients aged ≥ 65.nnnPATIENTS AND METHODSnWe identified CRC patients diagnosed from 2005 to 2007 who received chemotherapy and were followed until 31 December 2009. Outcomes were 3-year risk of arterial thromboembolic events (ATEs), cardiomyopathy or congestive heart failure (CM/CHF), and cardiac death (CD) after chemotherapy initiation. We fitted Cox-proportional hazards (PHs) models with inverse-probability-of-treatment-weights and calculated hazard ratios (HRs) for the risk of adverse events.nnnRESULTSnWe identified 6803 CRC patients (median age: 73 years). Those with cardiac comorbidity were less likely to receive BEV (P < 0.0001). BEV is associated with an elevated risk of ATEs (HR = 1.82, 95% CI = 1.20-2.76, P < 0.001; rate difference: 3.5 additional cases/1000 person-years). We observed no association between BEV and CD or CM/CHF.nnnCONCLUSIONSnIn general practice, the cardiovascular risk of BEV in elderly CRC is modest. The observed ATEs risk is lower than reported in clinical trials, which may be due to careful patient selection. Our findings may facilitate clinical decision-making of BEV use in elderly patients.

Disease burden of urinary tract infections among type 2 diabetes mellitus patients in the U.S.

AIMSnType 2 diabetes is a reported risk factor for more frequent and severe urinary tract infections (UTI). We sought to quantify the annual healthcare cost burden of UTI in type 2 diabetic patients.nnnMETHODSnAdult patients diagnosed with type 2 diabetes were identified in MarketScan administrative claims data. UTI occurrence and costs were assessed during a 1-year period. We examined UTI-related visit and antibiotic costs among patients diagnosed with UTI, comparing those with versus without a history of UTI in the previous year (prevalent vs. incident UTI cases). We estimated the total incremental cost of UTI by comparing all-cause healthcare costs in patients with versus without UTI, using propensity score-matched samples.nnnRESULTSnWithin the year, 8.2% (6,014/73,151) of subjects had ≥1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among prevalent versus incident cases were, respectively,

Cardiovascular Events Associated With SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL 2 Study

603 versus

Risk characterization for urinary tract infections in subjects with newly diagnosed type 2 diabetes

447 (p=0.033) for outpatient services,

Initial Sulfonylurea Use and Subsequent Insulin Therapy in Older Subjects with Type 2 Diabetes Mellitus

1,607 versus

Treatment intensification for patients with type 2 diabetes and poor glycaemic control.

1,819 (p=NS) for hospitalizations, and

Healthcare cost attributable to recently-diagnosed breast cancer in a privately-insured population in the United States.

61 versus

Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study.

35 (p<0.0001) for antibiotics. UTI was associated with a total all-cause incremental cost of