Does Jardiance (Empagliflozin) have cardiovascular benefits for all patients or only those with Heart Failure (HF)?

From the Guidelines

Jardiance (empagliflozin) has demonstrated cardiovascular benefits primarily in specific patient populations, including those with type 2 diabetes and established cardiovascular disease, as well as in patients with heart failure, regardless of whether they have diabetes. The medication has shown significant cardiovascular benefits in these populations, including a reduced risk of cardiovascular death and hospitalization for heart failure, with benefits seen in both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) 1. The cardiovascular benefits of Jardiance are believed to result from multiple mechanisms, including improved cardiac energy metabolism, reduced cardiac preload and afterload, anti-inflammatory effects, and improved renal function. Some key points to consider when prescribing Jardiance for cardiovascular benefits include:

• The typical dose for cardiovascular benefit is 10 mg once daily, the same as the dose used for diabetes management.
• Jardiance has been shown to reduce the risk of hospitalization for heart failure by 35% in the EMPA-REG OUTCOME trial, and by 33% in the CANVAS Program, with benefits seen in patients with and without a prior history of heart failure 1.
• The DAPA-HF trial demonstrated that dapagliflozin reduced cardiovascular mortality and hospitalization for heart failure by 17%, with consistent benefits across multiple study subgroups regardless of a prior history of heart failure 1.
• The EMPEROR-Reduced trial showed that empagliflozin reduced the risk of cardiovascular death or hospitalization for worsening heart failure by 21% in patients with NYHA class II, III, or IV heart failure and an ejection fraction of 40% or less 1. For individuals without type 2 diabetes or heart failure, Jardiance is not currently indicated and has not been proven to provide cardiovascular benefits 1.

From the FDA Drug Label

JARDIANCE significantly reduced the risk of first occurrence of primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (HR: 0.86; 95% CI 0.74,0. 99). The treatment effect was due to a significant reduction in the risk of cardiovascular death in subjects randomized to empagliflozin (HR: 0.62; 95% CI 0.49,0. to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.

The cardiovascular benefits of Jardiance are established for patients with type 2 diabetes and established cardiovascular disease or atherosclerotic cardiovascular disease, not for everyone or specifically those with heart failure (HF) only.

• The primary composite endpoint of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke was significantly reduced.
• The treatment effect was due to a significant reduction in the risk of cardiovascular death. 2

From the Research

Cardiovascular Benefits of Jardiance

• Jardiance (empagliflozin) has been shown to have cardiovascular benefits in patients with type 2 diabetes and established cardiovascular disease, as demonstrated in the EMPA-REG OUTCOME trial 3.
• The drug has been found to reduce the risk of cardiovascular death, hospitalization for heart failure, and other outcomes indicative of worsening heart failure, compared to placebo 3, 4.
• These benefits have been observed in patients with and without type 2 diabetes, and regardless of background heart failure therapies 4.

Benefits in Patients with Heart Failure

• Empagliflozin has been approved for the treatment of symptomatic chronic heart failure in adults, regardless of their left ventricular ejection fraction (LVEF) 4.
• The EMPEROR-Preserved and EMPEROR-Reduced trials demonstrated that empagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failure in patients with symptomatic heart failure and mildly reduced or preserved ejection fraction, as well as those with reduced ejection fraction 4.
• The beneficial effect of empagliflozin on cardiovascular death and hospitalization for heart failure was seen irrespective of the presence or absence of type 2 diabetes 4.

Comparison with Other SGLT2 Inhibitors

• Empagliflozin has been compared to other sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as canagliflozin and dapagliflozin, in terms of its cardiovascular benefits 5, 6.
• A cost-effectiveness analysis found that empagliflozin was projected to dominate canagliflozin and be highly cost-effective compared to dapagliflozin and standard of care in patients with type 2 diabetes and established cardiovascular disease 6.

Mechanism of Action

• The exact mechanism of action of empagliflozin's cardiovascular benefits is not fully understood, but it is thought to involve changes in haemodynamic markers, such as pulse pressure, mean arterial pressure, and cardiac workload 7.
• However, a post-hoc analysis of the EMPA-REG OUTCOME trial found that improvements in haemodynamic parameters did not substantially mediate empagliflozin's benefits on cardiovascular and kidney outcomes in patients with type 2 diabetes and established cardiovascular disease 7.