An audit of investigation and prescribing practices in patients discharged with systolic heart failure in a tertiary referral hospital
Michael J. Bennett B Pharm MPS* |

*Medical Student, The Australian National University

Abstract

Objective: To determine the frequency of inappropriate management of systolic heart failure.

Method: A retrospective clinical audit using hospital electronic medical records was conducted. Investigations and discharge medications of patients admitted with a primary discharge diagnosis of systolic heart failure (left ventricular ejection fraction ≤ 40%) between 1st January 2008 and 31st August 2010 were compared with national guidelines for investigation and pharmacological management.

Results: Medical records of 84 patients were collected; 61 patients (71.8%) were prescribed an angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonist (ARA); 59 (69.4%) were prescribed a beta-blocker; 23 (27.1%) were prescribed a loop diuretic without an ACEI or ARA; and 12 (14.1%) were prescribed ≥ 1 contraindicated drug. Almost 1 in 5 patients (18.8%) with atrial fibrillation and heart failure were not prescribed an antithrombotic. All patients had documented evidence of at least one chest x-ray and one echocardiogram during admission or within the last 12 months. Renal function and electrolyte testing was performed in all patients during admission for heart failure.

Conclusion: Diagnostic and monitoring investigations had high concordance with guideline recommendations; however substantial gaps existed between heart failure management guidelines and clinical practice. Indicated drugs known to prolong survival and reduce readmissions (ACEIs, ARAs and betablockers) were underprescribed, while drugs known to exacerbate heart failure continued to be prescribed. Among those with heart failure and atrial fibrillation, antithrombotic agents were underprescribed.

Introduction and Aims

H

eart failure affects 1.5-2.0% of the Australian population with around 30,000 new cases diagnosed each year (1). Prevalence of the disease increases greatly with age. A 2006 population study of Canberra residents found the prevalence of symptomatic heart failure was 4.4 times greater among those aged 80-86 than 60-64 years (2).  In 2000 approximately 325,000 Australians had symptomatic heart failure requiring treatment, and an additional 214,000 had asymptomatic left ventricular systolic dysfunction (3). This asymptomatic group have a high risk of developing symptomatic disease, however early diagnosis and treatment has been shown to delay symptom onset and reduce the risk of death and hospitalisation (4).

Approximately 50% of patients with heart failure have preserved systolic function (‘diastolic heart failure’) with a left-ventricular ejection fraction (LVEF) ≥ 40% (5). This represents a problematic treatment group as limited trial data exists to guide therapy. Conversely, strong evidence exists for the effective treatment of systolic heart failure (LVEF <40%).

While the incidence of heart failure has changed little since the 1950s, survival has improved markedly since the 1980s (6,7). During this time, overwhelming evidence of the positive survival benefits of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers emerged, eventually leading to their widespread use in the management of systolic heart failure.

In 1987, the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) demonstrated a 40% reduction in mortality at six months amongst those treated with enalapril (8). This was followed by the Studies of Left Ventricular Dysfunction Treatment (SOLVD) in 1991, which found a 16% reduction in mortality and reduced rates of hospital admission among those receiving enalapril (9). Further studies including the Acute Infarction Rampiril Efficacy (AIRE) study and Trandalopril Cardiac Evaluation (TRACE) study contributed to a substantial body of evidence supporting the use of ACEIs for heart failure (10, 11).

The evidence for beta-blockers was provided by the Metoprolol CR/XL Randomised Intervention Trial for Congestive Heart Failure (MERIT-HF) study, which demonstrated a 34% reduction in mortality amongst clinically stable patients with heart failure when metoprolol was added to conventional ACEI and diuretic therapy (12). This was shortly followed by publication of the Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) study in 2001, which found the use of carvedilol was associated with a 35% reduction in the risk of death amongst those treated for heart failure (13). Overall, the benefits of beta-blockers have been evaluated in more than 20 published clinical trials, involving more than 20,000 patients with heart failure (14).

In 2006, the National Heart Foundation Guidelines for the Prevention, Detection and Management of Chronic Heart Failure in Australia were published, which underwent minor additions in July 2011.

Table 1. Baseline demographic and clinical characteristics of patients admitted from 1 January 2008 to 31August 2010 with a primary diagnosis of systolic heart failure (LVEF ≤ 40%)Key recommendations of this document included: use of ACEIs or angiotensin II receptor antagonists (ARAs) recommended in combination with use of beta-blockers in all grades of CHF; use of loop diuretics to manage fluid overload; and the avoidance of drugs known to exacerbate heart failure (15). Key investigations recommended for diagnosis and monitoring of heart failure included; echocardiogram (ECHO), electrocardiogram (ECG), chest x-ray (CXR), and measurement of electrolytes, urea, and creatinine (EUC). At the time, the underuse of ACEIs and beta-blockers, and inadvertent co-prescription of potentially contraindicated drugs were identified as gaps in management (15).

Chronic heart failure shares many risk factors with atrial fibrillation (AF), and both conditions frequently coexist (16).  Results from the Framingham study found that amongst patients with both conditions, 38% of those with AF had a prior diagnosis of heart failure, and 41% of those with heart failure had a prior diagnosis of AF (16). Both conditions are associated with an increased risk of thromboembolism and stroke (15).  To mitigate this risk, national guidelines state that all patients with heart failure who develop AF should receive long-term antithrombotic therapy (15). To predict thromboembolic events in patients with AF, and to help guide clinicians in selecting patients for antithrombotic therapy, numerous risk stratification tools have been developed. The CHADS2 tool is a widely used and validated point-based scheme, in which two points are given for a history of stroke or transient ischaemic attack, and one point is given for the presence of the following risk factors; congestive heart failure, hypertension, age >75 years, and diabetes. A total score of zero denotes low risk (1.2 strokes per 100 patient years), a score of 1 denotes moderate risk (2.8 strokes per 100 patient years), and a score ≥2 denotes a high risk (>3.6 strokes per 100 patient years) (17). As heart failure is a component risk factor of the CHADS2 tool, all patients with heart failure and concomitant AF will have a CHADS2 score of ≥1. According to guidelines current during the collection period (and at the time of writing), this score corresponds to a moderate risk of stroke and all such patients should be prescribed aspirin or warfarin for primary prevention (18,19). 

In order to quantify the extent of inappropriate management of heart failure, a retrospective clinical audit was conducted, comparing current practice with established guideline recommendations. As a secondary analysis, the use of antithrombotic therapy among heart failure patients with coexistent AF was sought for comparison with current guidelines.

Methods

Ethics approval
Approval from ACT Health Human Research and Ethics Committee was sought and granted in 2010 prior to data collection.

Table 2. Number of patients prescribed indicated and contraindicated drugs during admission for systolic heart failure between 1 January 2008 and 31 August 2010Patient selection
Hospital electronic medical record databases were searched to select patients admitted to the hospital between 1st January 2008 and 31st August 2010 with a primary diagnosis of heart failure. In those with multiple admissions during the selection period, the first admission with a primary diagnosis of Heart Failure was used. Only residents of the Australian Capital Territory (ACT) were included. To exclude those with diastolic heart failure, only patients with an ECHO report showing evidence of a LVEF ≤ 40% within the previous two years were included.

Data collection
Discharge summary reports were searched for patient age, sex, common co-morbidities, and discharge medications (see tables 1, 2). For those who died during an admission for heart failure, inpatient medication charts and progress notes were examined. Length-of-stay data was obtained by calculating the difference in days between discharge and admission dates. For those patients not prescribed an ACEI, ARA, or beta-blocker, discharge summaries and medication charts were searched for documented allergy or intolerance which could explain their underuse.

Discharge summaries and patient files were also searched for evidence of investigative procedures (ECG, CXR, EUC) performed during admission or in the previous 12 months. 

Data was coded and entered into a Microsoft Excel spreadsheet.

Data Interpretation
Descriptive statistics were calculated and prescribing rates compared with the recommendations made in the National Heart Foundation Guidelines for the Prevention, Detection and Management of Chronic Heart Failure in Australia 2006. Two consultant cardiologists confirmed that these guidelines were in use in the hospital during the collection period.

Results

Patient characteristics
Eighty five eligible patients with a primary discharge diagnosis of heart failure and LVEF ≤ 40% were identified between 1st January 2008 and 31st August 2010 (Table 1).  The patient sample included 57 men and 28 women, with a mean patient age of 73.6 years (range: 50-91 years).

Most patients had multiple co-morbidities, with the average patient having around three co-morbidities (mean: 2.8, median: 3.0). Hypertension and diabetes were the most prevalent co-morbid conditions, present in 46 (54.1%) and 38 (44.7%) patients, respectively. Atrial fibrillation, coronary artery disease, chronic obstructive pulmonary disease, and chronic kidney disease were also common, affecting more than 25% of patients. Only five patients (5.9%) had no documented co-morbidities (Table 1).

Patterns of drug use
Amongst the drugs indicated for use in systolic heart failure, loop diuretics were the most frequently prescribed – used by 81 patients (95.3%) (see Table 2). The proportion of patients prescribed other indicated drugs was much lower; 59 (69.4%) were prescribed a beta-blocker, 51 (60%) an ACEI, 42 (49.4%) spironolactone, 35 (41.2%) digoxin, 12 (14.1%) a thiazide diuretic, and 11 (12.9%) an ARA. Sixty-one patients (71.8%) were taking either an ACEI or ARA. No patients were prescribed amiloride.

Of the 12 patients (14.1%) taking contraindicated drugs, dihydropyridine calcium channel blockers (DHPs) were the most frequently prescribed – used by six patients (7.1%). Corticosteroids were prescribed to three patients (3.5%), tricyclic antidepressants to one (1.2%), antipsychotics to one (1.2%), and thazolidinediones to one (1.2%). No patients were prescribed non-steroidal anti-inflammatory drugs (NSAIDs).

Low-dose aspirin (≤100mg) was prescribed to 35 patients (41.2%) and warfarin was prescribed to 40 patients (47.1%).

Combinations of drugs were also examined. Fifty-eight patients (68.2%) were taking an ACEI/ARA and loop diuretic, 42 (49.4%) were prescribed either an ACEI or ARA with a beta-blocker, and 40 (47.1%) were prescribed an ACEI or ARA with both a beta-blocker and loop diuretic (see Table 2). Furthermore, 24 patients (28.2%) were not prescribed an ACEI or ARA, seven (8.2%) were taking neither an ACEI or ARA or beta-blocker, 17 (20.0%) were prescribed a beta-blocker without an ACEI or ARA, and 23 (27.1%) were prescribed a loop diuretic without an ACEI or ARA (see Table 2).

Of the 32 patients with AF, 21 (65.6%) were prescribed warfarin, 8 (25.0%) were prescribed aspirin (≤100mg daily), and three (9.4%) were prescribed aspirin and warfarin (see Table 2). Six patients (18.8%) were not prescribed warfarin or aspirin.

Discussion

The findings of this audit demonstrate the persistence of previously identified gaps in the pharmacological management of patients with systolic heart failure in a tertiary referral hospital.  Despite universal recommendations advocating the use of ACEIs in combination with beta-blockers, and the avoidance of drugs known to exacerbate heart failure, prescribing rates remain suboptimal. More than a quarter of patients (28.2%) with left ventricular systolic dysfunction were not receiving an ACEI or ARA, and almost a third of patients (30.6%) were not receiving beta-blocker therapy. In light of the cost saving and mortality benefits of these drugs, under prescribing represents a significant failure of current practice. Furthermore, no documented allergy or intolerance that would explain poor prescription rates could be found in patient discharge summaries. It is unclear whether this reflects inadequate documentation, or a true deviation from the guidelines.

These findings can be compared with figures quoted in similar Australian and international studies. A 2010 retrospective study of 667 patients treated for heart failure in a regional Australian hospital (Wagga Wagga) between January 2003 and December 2007 compared the use of cardiovascular medications with the Australian National Heart Foundation Guidelines (20). The authors reported that 58.2% of patients received an ACEI or ARA and 34.7% received a beta-blocker (20). These rates are considerably lower than those seen in the current study, suggesting greater utilisation of these agents may be occurring in the metropolitan or tertiary hospital setting.  A 2001 review of 37 international studies reported rates of ACEI use to be 43% to 90% (mean 71%) among patients who were discharged from hospital with evidence of systolic heart failure (21). This compares well with the rates observed in the ACT, suggesting local and international practices do not differ greatly.

A small number of patients (14.1%) were taking one or more contraindicated drugs, most commonly DHPs. While studies on the mortality effects of DHPs in heart failure are lacking, they are associated with reflex tachycardia and diuretic-refractory peripheral oedema. For these reasons, local and international guidelines oppose their use in the setting of systolic heart failure. Discontinuing DHP use in these patients provides an opportunity to prevent potential adverse outcomes and optimise disease management.

The use of drugs known to worsen heart failure was also noted in a 2008 audit by the National Prescribing Service (NPS). Results of this audit indicated that 20% of patients with systolic heart failure were concomitantly taking one or more contraindicated drugs, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) (22).

Further discrepancy between guidelines and prescribing practice was evident in the use of loop diuretics. Current guidelines explicitly state that loop diuretics should only be used in combination with an ACEI, and never as monotherapy for fluid overload. Contrary to this, more than a quarter of patients (27.1%) were prescribed a loop diuretic without an ACEI or ARA. While this will reduce peripheral oedema, pulmonary congestion, and increase exercise tolerance, loop diuretics alone fail to alter disease course, prolong survival, or reduce hospital readmissions (15). Urgent efforts to address this gap in current practice will promote improved health outcomes for patients and lessen the burden of heart failure on the health system.

Perceived reasons for diuretic use without combination ACEI or ARA may include potential to worsen renal function and, in the patient with acute heart failure, precipitate hypotensionAalmost 25% of study patients had a history of chronic kidney disease, which may have been perceived as a relative contraindication to the use of ACEIs or ARAs. Furthermore, the majority of patients were over 70 years, possibly with numerous risk factors for falls. In these patients the clinical benefits of ACEIs or ARAs may have been balanced against the potential for hypotensive episodes and falls. In some cases these risks may have been deemed too great to warrant the use of these drugs.  Likewise patients may have previously experienced kinin-mediated effects to ACEIs and this would justify avoiding these drugs.

A 2002 study into underuse of ACEIs found the most likely cause of under-prescribing was physician fear of worsening underlying hypotension, hyperkalaemia, or renal insufficiency (23). The authors suggested that patients with these perceived contraindications stood to derive greater benefits from ACEIs than those without perceived contraindications, and cautious use, slow dosage titration, and careful monitoring, rather than avoidance, should be recommended (23).

A secondary analysis of the data examined the use of antithrombotic agents in patients with concomitant AF. Almost one in five patients (18.8%) with systolic heart failure and AF were not prescribed aspirin or warfarin. Untreated, these patients will continue to have a moderate-to-high risk of suffering a thromboembolic event, including stroke. Addressing the underuse of antithrombotics in this patient group should be considered a priority.

Diagnostic and investigative procedures had high concordance with guideline recommendations. All patients had documented evidence of at least one CXR and one ECG during admission, or within the last 12 months. Likewise, renal function and electrolyte testing was performed in all patients during admissions for heart failure.

Further research is warranted to explore the factors determining prescribing patterns and to develop ways of improving guideline concordance. While educational initiatives directed towards prescribers are a logical and traditional measure aimed at improving guideline concordance, a multidisciplinary approach is likely to be more effective in achieving desired overall outcomes. The addition of a clinical pharmacist to heart failure management teams has been shown to optimise drug regimens and reduce hospital readmissions (24).

Study limitations
The findings of this audit were limited by several factors, including a relatively small sample size, reliance on the quality of hospital medical records, and absence of definitive outcome measures (such as mortality, or readmission). Due to the retrospective nature of the audit, there was no practical way to validate the accuracy of the documented records. In many cases contraindications and intolerances to drugs, which would have explained underprescribing, may not have been documented in patients’ medical records. Likewise, discharge summaries may not have accurately reflected the medications patients received at discharge.

The study did not consider the dosages or frequency of administration of prescribed drugs. As ACEIs, ARAs, and beta-blockers are routinely commenced at low starting dosages and up-titrated gradually, it was not feasible to investigate when such drugs were commenced or the target dosages prescribers were intending to achieve with individual agents. 

Selection bias may have also contributed to the observed results. Only patients with a documented LVEF ≤ 40% were included, and hospital ECHO reports from the previous two years were used to select patients meeting this criterion. It is likely that patients with systolic heart failure who had not had an ECHO performed, had one performed outside of the hospital setting, or had one performed more than two years ago were excluded. Similarly, only patients with a primary discharge diagnosis of heart failure were included in the study and many patients may have received treatment for heart failure during an admission for another condition. Moreover, for patients with multiple admissions for heart failure, only the initial admission was used for data collection, and treatments at subsequent admissions may have differed.

Patient consent to medical treatment was also not considered. It was assumed that every patient to whom it was offered received treatment. The possibility exists that patients may have simply refused treatment with a particular agent. This would have altered the accuracy of the observed prescribing rates.

Conclusion

This audit confirms the substantial gaps between national heart failure guidelines and clinical prescribing practice in a tertiary referral hospital. ACEIs and beta-blockers are underused in patients with systolic heart failure despite widespread availability and unequivocal evidence for their efficacy in this setting. Contraindicated drugs were prescribed to a minority of patients, however given their potential to cause costly and debilitating exacerbations of disease they exemplify an important target for clinical review by both doctors and clinical pharmacists. A large proportion of patients with systolic heart failure had concomitant AF, and consequently a moderate-to-high risk of thromboembolic disease. Currently, antithrombotic agents are under prescribed in these patients.

Acknowledgements
No financial grants or funding in any form were provided to the author. This audit formed the basis of a year 1 and 2 research project as part of the MBBS degree at The Australian National University. The contributions of Dr Mary Ann Kulh and Mr Timothy Rose are acknowledged.

Conflicts of Interest
None

Sources of support (grants, equipment, drugs)
None

References

  1. Australian Institute of Health and Welfare. Heart, stroke and vascular diseases — Australian facts 2004. Canberra: AIHW and National Heart Foundation of Australia, 2004.
  2. Abhayaratna WP, Smith WT, Becker NG, Marwick TH, Jeffery IM, McGill DA. Prevalence of heart failure and systolic ventricular dysfunction in older Australians: the Canberra Heart Study. Med J Aust. 2006;184(4):151.
  3. Clark RA, McLennan S, Dawson A, Wilkinson D, Stewart S. Uncovering a hidden epidemic: a study of the current burden of heart failure in Australia. Heart Lung Circ. 2004; 13: 266-73.
  4. The SOLVD Investigators. Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions. N Engl J Med. 1992;327:685-91.
  5. Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC. Clinical Presentation, Management, and In-Hospital Outcomes of Patients Admitted With Acute Decompensated Heart Failure With Preserved Systolic Function: A Report From the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol. 2006; 47: 76-84.
  6. Redfield MM. Heart Failure — An Epidemic of Uncertain Proportions. N Engl J Med. 2002; 347: 1442-4.
  7. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KL, et al. Long-Term Trends in the Incidence of and Survival with Heart Failure. N Engl J Med. 2002; 347: 1397-402.
  8. Swedberg K, Eneroth P, Kjekshus J. Effects of Enalapril on Mortality in Severe Congestive Heart Failure. N Engl J Med. 1987;316(23):1429-35.
  9. The SOLVD Investigators. Effect of Enalapril on Survival in Patients with Reduced Left Ventricular Ejection Fractions and Congestive Heart Failure. N Engl J Med. 1991;325(5):293-302.
  10. The Acute Infarction Ramipril Efficacy  (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342(8875):821-8.
  11. Køber L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, et al. A Clinical Trial of the Angiotensin-Converting–Enzyme Inhibitor Trandolapril in Patients with Left Ventricular Dysfunction after Myocardial Infarction. N Engl J Med. 1995;333(25):1670-6.
  12. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in-Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001-7.
  13. Packer M, Coats AJS, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of Carvedilol on Survival in Severe Chronic Heart Failure. N Engl J Med. 2001;344(22):1651-8.
  14. MEMBERS WC, Hunt SA, Abraham WT, Chin MH, Feldman AM, Francis GS, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation. 2005 September 20, 2005;112(12):e154-e235.
  15. National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand. Quick reference guide. Diagnosis and management of chronic heart failure. Updated October 2011..
  16. Wang TJ, Larson MG, Levy D, Vasan RS, Leip EP, Wolf PA, et al. Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality. Circulation. 2003;107(23):2920-5.
  17. Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ. Validation of Clinical Classification Schemes for Predicting Stroke. JAMA. 2001 June 13, 2001;285(22):2864-70.
  18. Medi C, Hankey GJ, Freedman SB. Atrial Fibrillation. Med J Aust. 2007; 186: 197-202.
  19. Samardhi H, Santos M, Denman R, Walters DL, Bett N. Current Management of Atrial Fibrillation. Aust Presc. 2011; 34: 100-4.
  20. Yao DK, Wang LX, Curran S, Ball P. Adherence to treatment guidelines in the pharmacological management of chronic heart failure in an Australian population. Am J Geriatr Cardiol. 2011;8(2):88-92.
  21. Bungard TJ, McAlister FA, Johnson JA, Tsuyuki RT. Underutilisation of ACE Inhibitors in Patients with Congestive Heart Failure. Drugs. 2001;61(14):2021-33.
  22. National Prescribing Service. NPS Prescribing Practice Review 56: Heart Failure.  2011 [cited 2011 12 May 2012]; Available from: http://www.nps.org.au/health_professionals/publications/prescribing_practice_review/
    current/heart_failure
    .
  23. Ahmed A, Kiefe CI, Allman RM, Sims RV, DeLong JF. Survival Benefits of Angiotensin‐Converting Enzyme Inhibitors in Older Heart Failure Patients with Perceived Contraindications. J Am Geriatr Soc. 2002;50(10):1659-66.
  24. Gattis WA, Hasselblad V, Whellan DJ, O'Connor CM. Reduction in Heart Failure Events by the Addition of a Clinical Pharmacist to the Heart Failure Management Team: Results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study. Arch Intern Med. 1999; 159: 1939-45