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Bias against higher recommended drug doses for HF may be present
The uptitration of drugs used to treat patients with chronic systolic HF was more likely to be stopped as the dosage became further away from the recommendation dose, especially with higher recommended dosages compared with lower recommended dosages, according to a brief research report published in the Annals of Internal Medicine.
Henrike Arfsten, MD, of the department of internal medicine II in the clinical division of cardiology at the Medical University of Vienna, and colleagues analyzed data from 3,737 patients (median age, 65 years; 73% men) with HF with reduced ejection fraction.
Several drugs with the greatest difference in recommended dosages were assessed, including the following:
- ACE inhibitors: 10 mg per day of ramipril compared with 40 mg per day of enalapril, lisinopril or fosinopril;
- beta-blockers: 10 mg per day of bisoprolol or nebivolol (Bystolic, Allergan) compared with 200 mg per day of metoprolol; and
- angiotensin-receptor blockers: 32 mg per day of candesartan compared with 320 mg per day of valsartan.
After 1 year, there were increases in the prescribed dosages for all three drug classes (P < .001). The maximum recommended dosage for all three classes of drugs was given to significantly fewer patients when the dosage was higher compared with when it was lower.
The results were confirmed when researchers compared the probabilities of reaching maximum dosages predicted by the logistic regression model. The difference in predicted probabilities was 10 for beta-blockers (95% CI, 7-13), 34 for ACE inhibitors (95% CI, 33-36) and 13 for angiotensin-receptor blockers (95% CI, 11-15).
Results were virtually unchanged when a subgroup of patients with ischemic HF were examined.
“We believe that the differences we observed are large enough to affect patient outcomes,” Arfsten and colleagues wrote. “If additional studies confirm our expectations, we propose that supplementing milligram-based recommendations with guidelines based on relative dosages might attenuate the differences we observed.” – by Darlene Dobkowski
Disclosures: The authors report no relevant financial disclosures.