Should dapagliflozin be discontinued in a patient with heart failure with reduced ejection fraction (HFrEF) who experiences recurrent muscle pain both on and off the medication?

Discontinue Dapagliflozin Immediately – The Muscle Pain is Not Caused by This Medication

The temporal pattern of muscle pain occurring both when the patient was off dapagliflozin (for several months) and persisting after restarting (2 weeks ago) definitively excludes dapagliflozin as the causative agent. The medication should be continued given its critical mortality and morbidity benefits in HFrEF.

Why Dapagliflozin is Not the Culprit

• The pain occurred during the months when dapagliflozin was discontinued, which is incompatible with drug causation 1
• Muscle pain is not a recognized adverse effect of dapagliflozin in major clinical trials (DAPA-HF, DELIVER) or FDA labeling 1, 2
• The known adverse effects of dapagliflozin include genital mycotic infections (1.5-1.7%), urinary tract infections (2.3-2.7%), volume depletion (5.7%), and rarely diabetic ketoacidosis in diabetic patients—but not musculoskeletal pain 3, 1

Critical Importance of Continuing Dapagliflozin in HFrEF

Discontinuing dapagliflozin in this patient would eliminate a medication that reduces cardiovascular death by 18% and all-cause mortality by 31% in HFrEF patients 4, 1:

• Dapagliflozin reduces the composite outcome of cardiovascular death or worsening heart failure by 26% (HR 0.74,95% CI 0.65-0.85, p<0.0001) in HFrEF patients 1, 2
• First worsening heart failure events are reduced by 30%, and cardiovascular death by 18% 4
• The American College of Cardiology and American Diabetes Association strongly recommend dapagliflozin as foundational therapy for all HFrEF patients (Class I recommendation), regardless of diabetes status 5, 3, 4
• Benefits occur within weeks of initiation and are maintained regardless of background medical therapy 3, 4

Alternative Causes to Investigate

The muscle pain requires investigation for other etiologies, particularly:

• Statin-related myopathy if the patient is on lipid-lowering therapy (most common cause of muscle pain in cardiovascular patients)
• Electrolyte abnormalities (hypokalemia, hypomagnesemia) from diuretic therapy commonly used in HFrEF
• Hypothyroidism or other metabolic disorders
• Inflammatory or rheumatologic conditions
• Deconditioning from heart failure itself, which causes significant muscle dysfunction

Clinical Algorithm for This Patient

1. Continue dapagliflozin 10 mg daily without interruption 3, 4, 1
2. Obtain comprehensive metabolic panel including electrolytes, renal function, calcium, magnesium
3. Check creatine kinase (CK) if statin myopathy suspected
4. Review all concurrent medications for potential myalgic side effects (statins, fibrates, colchicine)
5. Assess thyroid function (TSH, free T4)
6. Consider rheumatologic evaluation if pain has inflammatory characteristics

Common Pitfall to Avoid

The most dangerous error would be attributing unrelated symptoms to a life-saving medication and discontinuing it based on temporal coincidence rather than causation 3, 4. The fact that pain occurred during the months off dapagliflozin provides definitive evidence against drug causation. Dapagliflozin has minimal effects on blood pressure, heart rate, potassium levels, and does not cause musculoskeletal adverse effects in clinical trials 3, 6, 1.