Medications Medications

Titration to maximum tolerated doses of ACE inhibitors (ACEIs), Angiotensin receptor blockers (ARBs), beta-blockers and mineralocorticoid receptor antagonists (MRAs) is recommended to reduce morbidity and mortality in left ventricular systolic HF.

Titration of medicines can be challenging as individuals with HF frequently have multiple co-morbidities, numerous medications and often move between acute and primary health-care sectors.

Other difficulties that may impact upon titration include:

  • Lack of a clear, patient-specific titration plan
  • Poor communication of medication plan between acute and primary care
  • Difficulty in managing adverse effects associated with increasing doses
  • Patient adherence issues due to the changing medication regimen

Nursing and pharmacy support can play an important role in enhancing treatment by supporting patient adherence and optimising evidence-based treatment by using tools such as a Heart failure medication titration plan. Medication titration plans should be completed by the patient’s treating healthcare team and outline a suggested schedule of titration, target doses for HF medicines, required monitoring, and management of common adverse effects.

  • Blood pressure and pulse should be reviewed prior to each dose adjustment
  • Aim to achieve recommended target dose for heart failure medications. However, if a patient is unable to tolerate the target dose, continue at the maximum tolerated dose as this may still be beneficial
  • Start at a low dose and progressively increase to the recommended target dose or to the maximum tolerated dose
  • Intervals between dose titration vary from 1 to 4 weeks, depending on the patient and medication. As a guideline, the dose can usually be doubled every 2 weeks
  • Generally, only titrate one medicine at a time; however, patients do not have to be maximised on an ACEI or ARB before initiating a beta-blocker[#hunt-sa-abraham-wt-chin-mh-et-al.-2009]
  • If adverse effects arise, consider whether these are likely to be transient, such as dizziness, in which case it is prudent to re-attempt an increase in dose at a later stage
  • Optimisation of medications may take a longer time to achieve in some patients
  • Patients over 75 years old with co-morbidities are more likely to experience adverse effects
  • Diuretics, such as frusemide, may be used in a flexible manner to achieve the minimum effective dose
  • Ensure that clinicians involved with a patient's exercise program are aware of any ongoing medicine dose titration as this may impact upon the exercise regime. See Cardiac medications that impact upon exercise response

Suggested management guidance for potential adverse effects, such as hypotension and worsening renal function, when titrating HF medicines is outlined in the Heart failure medication titration problem solving guidelines.  Practice points for dosing and titration of ACEI, ARB, beta-blockers,  mineralocorticoid receptor antagonist (MRA) and diuretics is described below.

Table 1: Medications used for HF and associated practice points

Medication Practice points
ACEIs & ARBs

ACEIs or ARBs should be commenced at a low dose as they are associated with significant first-dose hypotension.

ARBs are generally reserved as an alternative for patients who experience ACEI mediated adverse effects, such as a cough.[#national-prescribing-service.-2008]

Check electrolyte, creatinine and urea 1 week after commencing or titrating dose.

Prior to up-titration of ACEI /ARB, ensure that:

  • Systolic BP is >90mmHg
  • The patient is not symptomatically hypotensive
  • The patient does not have a significant postural drop in BP

As ACEIs may increase serum potassium, consider possible cessation of potassium supplements and potassium-sparing diuretics.

In order to avoid excessive first dose hypotension consider decreasing the dose of any diuretics or stop diuretic agents 24 hours prior to ACEI/ARB commencement, if clinically appropriate.
Beta-blockers

Beta-blockers should be started at the lowest dose and titrated slowly to the target dose as they are associated with hypotension, fatigue, and potential worsening of HF symptoms.

Prior to up-titration of beta-blockers, ensure that:

  • Systolic BP is >90mmHg
  • Heart rate is >55 beats per minute (bpm)
  • There is no evidence of decompensation such as peripheral oedema, new pulmonary crackles, wheezes or ascites
  • The patient is not experiencing excessive fatigue or lethargy
MRAs

Renal function and potassium levels must be checked prior to initiation and after dose changes of MRAs, as they may cause hyperkalaemia and renal dysfunction.

While guidelines vary in their monitoring recommendations of MRAs, the following guidance will assist with safe titration:

  • Baseline serum potassium is <5mmol/L and eGFR is>30mL/min
  • Renal function and potassium should be rechecked 1 week after commencing treatment or dose titration, monthly for 6 months and then 6 monthly thereafter once dosing is stable

Caution regarding eGFR
An eGFR may overestimate renal function in individuals with a low body weight and does not reflect accurate renal function in individuals with fluctuating creatinine levels. For these patients, a calculated CrCl using the Cockcroft-Gault formula should dictate dosing.

Diuretics

Diuretics may be used in a flexible manner but the dose should be carefully monitored in order to ensure it is sufficient to provide fluid retention symptom relief while avoiding volume depletion, hypotension, electrolyte disturbances and renal impairment. An increased diuretic dose beyond 3 days requires medical review and blood chemistry.

A decreased diuretic dose requires assessment of fluid status and blood chemistry 3-7 days post dose reduction.

Fluid overload is indicated by an increase of 2kg above stable body weight for 2 days.

Dehydration is indicated if body weight decreases by 2kg below stable weight for 2 days and there are signs of dehydration such as dizziness, postural hypotension or dry mucosa.

ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CrCl = creatinine clearance; eGFR = estimated glomerular filtration rate; HF = heart failure; MRA = mineralocorticoid receptor antagonist

  • Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119:e391-479.

    hunt-sa-abraham-wt-chin-mh-et-al.-2009
  • National Prescribing Service. (2008). Improving outcomes in chronic heart failure by early detection, drug therapy, and patient support. 57.

    national-prescribing-service.-2008