Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors

Am J Manag Care. 2015 Sep;21(11 Suppl):S212-20.


Objectives: This study examined renin-angiotensin-aldosterone system (RAAS) inhibitor dose levels in a US patient population and investigated the impact of hyperkalemia on RAAS inhibitor dose and the association between dose levels and clinical outcomes.

Study design: De-identified medical records from a large database of electronic health records (Humedica) for patients 5 years of age or older with at least 2 serum potassium readings were analyzed (N = 205,108 patients; 1.7 million records).

Methods: Inclusion criteria required 1 RAAS inhibitor prescription and 12 months' data prior to July 1, 2009 (index date). Patients were classified by comorbidities (chronic kidney disease, heart failure, or diabetes) and RAAS inhibitor dose level at index date, as determined by prescription information. Additional analyses examined RAAS inhibitor dose changes following hyperkalemia and the frequency of cardiorenal adverse outcome/mortality or mortality alone by post index dose level.

Results: Dose level was similarly distributed irrespective of patient comorbidity status, with RAAS inhibitors prescribed at maximum dose in 19% to 26% of patients and submaximum dose in 58% to 65% of patients; RAAS inhibitors were discontinued in 14% to 16% of patients. RAAS inhibitor dose was down-titrated after 16% to 21% of hyperkalemia events and discontinued after 22% to 27% of hyperkalemia events. Cardiorenal adverse event/mortality and mortality occurred in 34.3% and 11.0% of patients who discontinued RAAS inhibitors, 24.9% and 8.2% of patients on submaximum doses, and 24.9% and 4.1% of patients on maximum doses, respectively.

Conclusions: Relatively few patients were prescribed maximum doses of RAAS inhibitors, and dose and usage declined following hyperkalemia. Patients on submaximum doses or who discontinued RAAS inhibitors had worse outcomes than patients on maximum doses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Comorbidity
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / epidemiology
  • Dose-Response Relationship, Drug
  • Electronic Health Records / statistics & numerical data
  • Female
  • Guideline Adherence / statistics & numerical data
  • Heart Failure / drug therapy*
  • Heart Failure / epidemiology
  • Humans
  • Hyperkalemia / chemically induced*
  • Hyperkalemia / epidemiology
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care / statistics & numerical data
  • Practice Guidelines as Topic
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / epidemiology
  • Renin-Angiotensin System / drug effects*
  • Retrospective Studies
  • United States


  • Angiotensin-Converting Enzyme Inhibitors