Episode 207: 207. Medical Update-- DOAC, Warfarin, diabetes, venous thromboembolism, EMPA-KIDNEY, Empagliflozin

Efficacy and Safety of Intensive Versus Nonintensive Supplemental Insulin With a Basal-Bolus Insulin Regimen in Hospitalized Patients With Type 2 Diabetes: A Randomized Clinical Study | Diabetes Care | American Diabetes Association (diabetesjournals.org)

randomized noninferiority study from Emory University, 224 hospitalized patients with longstanding type 2 diabetes

Both groups received basal/bolus insulin; both the starting dose and subsequent changes were specified by the study protocol. Additional premeal SSI was added to scheduled premeal bolus doses.

randomized to either intensive SSI (at BG >140 mg/dL) or nonintensive SSI (at BG >260 mg/dL) before meals and at bedtime.

Mean baseline glycosylated hemoglobin (HbA1c) was 9%, and 60% of patients were using insulin at home. Patients with a presenting glucose level of >400 mg/dL or diabetic ketoacidosis were excluded.

Outcome---Mean daily BG level, hypoglycemia, severe hyperglycemia, percent of BGs in the target range (70–180 mg/dL), and the amount of total, basal, or prandial insulin used did not differ between groups. However, significantly fewer patients in the nonintensive group than in the intensive group received SSI (34% vs. 91%).

COMMENT

Although this is a single-center study, its results are persuasive and suggest that a less-intense SSI regimen can achieve similar glucose outcomes in hospitalized patients with type 2 diabetes who are receiving basal/bolus insulin. It also could decrease nursing treatment burden. As we move slowly toward more continuous glucose monitoring in hospitals, reducing use of SSI is another opportunity to achieve similar results with less staff burden and more patient comfort.

Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation: A Multinational Population-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 11 (acpjournals.org)

In a retrospective study, investigators accessed five electronic health databases from Europe and the U.S. to compare >500,000 new DOAC users with newly diagnosed atrial fibrillation. Follow up varied from 1.5 to 4.5 years.

In propensity score–adjusted analyses, patients who received apixaban had significantly less gastrointestinal (GI) bleeding did those who received any of the other three drugs (hazard ratios, 0.7–0.8). This result was consistent among older patients and those with chronic kidney disease (CKD). Risk for stroke or other systemic embolism, intracranial hemorrhage, and all-cause mortality did not differ significantly among DOACs.

COMMENT

This is the largest comparison of individual DOACs, and it demonstrates similar efficacy among all agents. Although apixaban was associated with less GI bleeding, absolute percentages of GI bleeds ranged from ≈2% to ≈3.5% for all DOACs; therefore, apixaban's statistically significant safety benefit might amount to marginal clinical benefit for any individual patient. I might turn to apixaban for patients at high risk for GI bleeding (and those with CKD), but all DOACs remain reasonable options for preventing thromboembolism in most patients with atrial fibrillation.

Ellenbogen MI et al. Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study. J Hosp Med 2022 Oct; 17:809. (https://doi.org/10.1002/jhm.12926. opens in new tab)

. In an industry-funded retrospective study, investigators used a national database (years, 2014–2018) and propensity score–adjusted analysis to compare outcomes among >11,500 patients with ESRD and newly diagnosed VTE who received either apixaban or warfarin.

Only 2% of patients received apixaban in 2014, but 47% received apixaban in 2018.

during the 6 months following initiation of therapy, apixaban — compared with warfarin

associated with significantly lower incidence of major bleeding (10% vs. 14%), including intracranial bleeding (1.8% vs. 2.5%) and gastrointestinal bleeding (8.6% vs. 10.4%).

Recurrent VTE and all-cause mortality were similar in the two groups.

VTE and creatine clearence less than 30 then I think apixaban is the drug of choice—I would like to see this study don’t with afib and done with exclusively <15 gfr but we take what we can get and the take home is venous thromboembolism (VTE) and gfr <30 go ahead and fire away with apixaban

The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N Engl J Med 2022 Nov 4; [e-pub]. (https://doi.org/10.1056/NEJMoa2204233. opens in new tab)

dapagliflozin is FDA-approved to slow progression of chronic kidney disease (CKD)

empa wanted in on the fun and money

industry-supported researchers randomized 6600 patients with or without type 2 diabetes. with CKD to receive empagliflozin (10 mg daily) or placebo.

Enrollment criteria included estimated glomerular filtration rate (GFR) between 20 and 45 mL/minute/1.73 m2 regardless of proteinuria, or GFR between 45 and 90 mL/minute in patients with substantial proteinuria.

follow-up of 2 years,

primary composite outcome — largely comprising a 40% decline in GFR or cardiovascular-related or renal-related death

was significantly lower with empagliflozin than with placebo (13% vs. 17%).

Less progression of CKD with empagliflozin accounted for this difference; no significant differences between groups were noted for mortality

Normally I would say a decrease progression of CKD is a bs ending and this isn’t patient oriented outcome. HOWEVER,

Initiation of dialysis or receipt of a renal transplant occurred significantly less often with empagliflozin than with placebo (3.3% vs. 4.8%). At a NNT of 66.

But once again empag cost 560$ per month. Follow up was 24 months. Which means 65 people have to take a $500 per month drug for 2 years which is This is a whopping 873,000$ spent for one person to be saved renal transplant or starting dialysis.

Zheng J et al. Cost-effectiveness of empagliflozin in patients with heart failure with preserved ejection fraction. JAMA Intern Med 2022 Nov 7; [e-pub]. (https://doi.org/10.1001/jamainternmed.2022.5010. opens in new tab)

At its current price, this drug provides low value in patients with heart failure with preserved ejection fraction.

The authors did something great here and said hey if you assume a 9% reduction in cardiovascular-related mortality (the nonsignificant reduction noted in the trial), cost-effectiveness would have been somewhat more acceptable

However they also usethe cost as 327$ per month… which is very generous as I can not find that number any place!!! So even with their generous calculation it still is not worth it-- yet