Is PAD a Contraindication for Farxiga (Dapagliflozin)?
No, peripheral arterial disease (PAD) is not a contraindication to dapagliflozin (Farxiga); in fact, current evidence supports its use in patients with PAD and type 2 diabetes to reduce major adverse cardiovascular events (MACE) and cardiovascular death/heart failure hospitalization. 1
Evidence Supporting Use in PAD
The 2024 ACC/AHA/AACVPR guidelines explicitly endorse SGLT-2 inhibitors, including dapagliflozin, for patients with PAD and type 2 diabetes:
Multiple randomized controlled trials demonstrate cardiovascular benefit in PAD patients. In the DECLARE-TIMI 58 trial, dapagliflozin significantly reduced cardiovascular death or hospitalization for heart failure (4.9% vs 5.8%; P=0.005), though it did not show significant MACE reduction. 1
The cardiovascular benefits are consistent regardless of PAD status. Patients with PAD derive similar relative risk reductions for CV death/heart failure hospitalization (HR 0.86 in PAD patients vs 0.82 in non-PAD patients; P-interaction=0.79) and kidney disease progression (HR 0.78 vs 0.76; P-interaction=0.84). 2
Guidelines provide "robust support for use of these agents to reduce MACE among patients with PAD and type 2 diabetes." 1
Amputation Risk: The Critical Safety Question
The concern about PAD as a contraindication stems from canagliflozin data, not dapagliflozin:
Canagliflozin showed increased amputation risk in CANVAS (6.3 vs 3.4 per 1,000 patient-years; P<0.001), leading to initial FDA concerns. However, this finding was not reproduced in subsequent trials (CREDENCE) or meta-analyses. 1
The FDA removed the black box warning for canagliflozin in August 2020 due to conflicting subsequent data. 1
Dapagliflozin specifically does not increase amputation risk. In DECLARE-TIMI 58, there were no significant differences in limb ischemic adverse events (HR 1.07; 95% CI 0.90-1.26) or amputation (HR 1.09; 95% CI 0.84-1.40) with dapagliflozin versus placebo. 2
Patient-level meta-analysis of DAPA-HF and DELIVER trials (11,005 patients, 809 with PAD) confirmed that amputations were not more common with dapagliflozin compared to placebo, regardless of PAD status (PAD: placebo 4.2% vs dapagliflozin 3.7%; no PAD: placebo 0.4% vs dapagliflozin 0.4%; P-interaction=1.00). 3
When amputations occurred, infection rather than ischemia was the main trigger, even in PAD patients. 3
Clinical Algorithm for Dapagliflozin Use in PAD
Proceed with dapagliflozin in PAD patients when:
- Type 2 diabetes is present 1
- No true contraindications exist (type 1 diabetes, end-stage chronic kidney disease) 4
- Patient has established cardiovascular disease or heart failure 1
Monitor for:
- Genital and urinary tract infections (known adverse effects of SGLT-2 inhibitors) 4
- Foot care and ulcer prevention through regular inspection 1
- Signs of Fournier's gangrene (rare but serious complication) 4
Important Caveats
PAD patients have inherently higher amputation risk (adjusted HR 8.37 for limb adverse events vs non-PAD patients), but this is due to the disease itself, not the medication. 2
Comprehensive diabetes management remains essential, including coordinated foot care protocols with daily inspection, appropriate footwear, and urgent attention to any skin lesions. 1
Do not confuse class-wide concerns with drug-specific data. The amputation signal was specific to canagliflozin and has not been consistently demonstrated with dapagliflozin or empagliflozin. 1, 2, 3, 5