In adults with symptomatic heart failure, nurse-led titration of heart failure medications significantly increased the number of participants reaching optimal dose, reduced the time taken to reach optimal dose and improved patient morbidity and survival when compared with physician-led titration. Despite mixed quality evidence, these results suggest that nurse-led titration is an effective and safe strategy for ensuring high-risk patients get the optimal medication dose.


You have a leadership role spanning primary and secondary care and are concerned about the number of people with chronic conditions not receiving optimal doses of beneficial medication. You wonder if nurse-led titration (NLT) may be a good strategy for addressing the complex barriers to patients getting the right dose of the right medications. You decide to review the evidence.


In people with chronic illness and in comparison with usual care, does nurse-led titration safely increase the number of patients receiving optimal doses of medications known to be an effective treatment for their condition?


PubMed – Clinical queries (Therapy/Narrow): nurse-led titration


Driscoll A, Currey J, Tonkin A, Krum H. Nurse-led titration of angiotensin converting enzyme inhibitors, beta-adrenergic blocking agents, and angiotensin receptor blockers for people with heart failure with reduced ejection fraction. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No.: CD009889. DOI: 10.1002/14651858.CD009889.pub2.


A Cochrane systematic review assessing the safety and effectiveness of NLT of beta-adrenergic blocking agents, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) for people with heart failure (HF). Inclusion criteria were:

Type of study: Randomised controlled trials comparing NLT with medication optimisation by another health professional involving adults with symptomatic HF and reduced ejection fraction. Uncontrolled and non-randomised studies were excluded.

Intervention: Nurse-led titration of beta-adrenergic blocking agents, ACEIs, and ARBs. Nurses were to have delegated responsibility for making protocol led changes in medication dose or were nurse practitioners titrating medications as part of their scope of practice.

Comparison: Usual care: patients under the management of a physician responsible for titration of ACEIs, ARBs, and/or beta-adrenergic blocking agents or a heart failure nurse who did not alter medication.


Primary: all-cause hospital admissions; heart failure-related hospital admissions; all-cause mortality; all-cause, event-free survival.

Secondary: time to maximum dose; adverse events associated with titration; proportion reaching target dose of medications; change in quality-of-life scores; cost-effectiveness.


Search Strategy: Reviewers searched CENTRAL, MEDLINE, EMBASE, clinical trial registries, reference lists of eligible studies and heart failure guidelines and unpublished theses. No date or language restrictions applied.

Review process: Two reviewers independently examined titles/abstracts and then full text to identify relevant studies, extracted data using a data extraction form, and assessed risk of bias in all studies. Discussion resolved any disagreement.

Quality assessment: The Cochrane Collaboration tool was used to assess risk of bias in included studies. Assessment criteria were random sequence generation, allocation concealment, blinding of participants, personnel and outcome assessment, incomplete outcome data and selective reporting.

Overall validity: A high-quality review involving studies of mixed quality and generally small sample size.


The search identified 1,016 studies. Following title review, 100 abstracts and then 18 full text articles were closely examined for eligibility, after which a further 11 studies were excluded. Seven RCTs involving 1,684 participants were included in this review. NLT occurred via nurse visits to a residential care facility (one study), telephone follow-up (one study), nurse-led clinic in primary care (one study) and outpatient clinics of tertiary hospital (four studies).

Studies involved titration of beta-adrenergic blockers (three studies), beta-adrenergic blockers and ACEIs (two studies); just two studies involved titration of beta-adrenergic blockers, ACEIs, and ARBs. Median follow-up was 12 months.

Usual care consisted of primary care physician-led titration. Participants receiving NLT experienced a 20 per cent reduction in all-cause hospital admissions, 49 per cent reduction in heart-failure related hospital admissions, and a 34 per cent reduction in all-cause mortality (see table) compared with usual care.

Participants in the NLT group were also twice as likely to reach target dose of medications (see table) and did so in a significantly shorter time (two studies, no meta-analysis). All results were statistically and clinically significant but quality of evidence was mixed.


  • NLT involved heart failure nurse specialists, was protocol-led and occurred alongside varying levels of patient education and support.
  • Low-quality evidence grading (substantial heterogeneity, small studies, risk of bias in included studies) for the outcome of proportion reaching target doses, therefore this result may change with future studies.
  • Adverse events related to the study medications were poorly reported so comparing safety of nurse-led and physician-led titration is difficult. Available data suggests that optimising therapeutic medications through NLT is safe, provided specialist nurses monitor risks associated with each medication in keeping with evidence-based prescribing guidelines.
  • People with symptomatic heart failure have high mortality and morbidity, therefore strategies for promoting optimal dosing of effective medications are crucial.

Reviewer: Cynthia Wensley RN, MHSc. Honorary Professional Teaching Fellow, the University of Auckland and PhD Candidate, Deakin University, Melbourne


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