Lipid testing and treatment after acute myocardial infarction: no flags for the flagship

Br J Cardiol 2019;26:141–4doi:10.5837/bjc.2019.041 Leave a comment
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National guidelines on lipid modification for cardiovascular disease advise checking a lipid profile in all patients admitted with acute coronary syndrome (ACS). It has been demonstrated that ACS can impact lipid profiles in an unpredictable fashion, so cholesterol measurements should be taken within 24 hours of an infarct. National guidelines also recommend initiating early high-intensity lipid-lowering therapy (i.e. statins) in ACS for secondary prevention of cardiovascular disease. We first assess compliance with these guidelines in a large city-centre teaching hospital and identify the need for any improvement. Following varied interventions aimed at highlighting the need for adherence to these guidelines we demonstrate a large increase in the number of ACS patients having lipids checked within 24 hours of their admission. In some instances, baseline cholesterol was not measured (either at all or prior to statin therapy), potentially leaving familial and non-familial hypercholesterolaemia undiagnosed. Encouragingly, statins are already prescribed in accordance with guidelines for the majority of ACS patients regardless of our campaign. We ultimately demonstrate there is still much work to be done locally to improve cholesterol management in ACS and hope that our findings will encourage others to ensure compliance and ultimately improve patient outcomes.

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Introduction

Cholesterol is a key risk factor for atheroma and coronary heart disease. The evidence-base for high-intensity lipid-lowering therapy in secondary prevention of cardiovascular disease is unequivocal.1-4 Despite the introduction of novel drugs, including ezetimibe5,6 and monoclonal antibodies,7 statins remain first-line therapy.8,9 Statins decrease hepatic cholesterol synthesis by competitively inhibiting 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase receptors, as they have an affinity up to 10,000 times greater than the natural substrate.10 Through reducing intra-cellular cholesterol concentration, statins up-regulate low-density lipoprotein receptor (LDLR) expression on the hepatocyte cell surface, thereby further lowering plasma cholesterol by directly reducing low-density lipoprotein cholesterol (LDL-C). Statins may also have pleiotropic effects on atherosclerosis including reduction of plaque thrombogenicity, anti-inflammatory effects, and improvement of endothelial function.11

The National Institute for Health and Care Excellence (NICE) guidelines on lipid modification for cardiovascular disease prevention, published in 2014, emphasise the importance of initiating high-intensity lipid-lowering therapy early during hospital admission for patients with acute myocardial infarction (AMI). NICE recognises high-intensity lipid-lowering therapy as an achieved reduction in LDL-C of >40% following initiation of treatment.8 This group of statins includes atorvastatin 20–80 mg, simvastatin 80 mg and rosuvastatin 10–40 mg, however, atorvastatin 80 mg is first line in the absence of significant renal or hepatic disease. Every 1.0 mmol/L (40 mg/dL) reduction in LDL-C is associated with a corresponding 22% reduction in cardiovascular disease mortality and morbidity.12

Current NICE and European Society of Cardiology (ESC) guidelines recommend that a full lipid profile is obtained for all patients presenting with an acute coronary syndrome (ACS) and repeated at three months.9 Lipid metabolism alters 24–48 hours post-myocardial infarction, with a fall in total cholesterol (TC), LDL-C and high-density lipoprotein cholesterol (HDL-C), as well as a reciprocal increase in triglycerides (TG).13 Accepted best practice is that cholesterol levels should be determined at admission as a baseline pre-initiation of high-efficacy statin, and then reassessed after 12 weeks of therapy.14

Glasgow Royal Infirmary should be a flagship centre for cholesterol excellence. The landmark WOSCOPS (West of Scotland Coronary Prevention Study)15 and PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease)16 trials were led from here globally, along with IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial)5,6 in the UK, as well as many major data analyses, and hundreds of other smaller studies in lipid biology and medicine. Glasgow Royal Infirmary should set the benchmark at 100% for checking cholesterol in patients presenting with AMI. Anything less than 100% should be poor performance.

Therefore, we audited lipid screening and adherence to prescribing of secondary prevention post-myocardial infarction in our own cardiology department. Our primary aim was to assess lipid profiling in patients admitted with ACS. We performed this clinical audit against set standards derived from the NICE guidelines:

Standard One – all patients are to have a cholesterol measurement prior to discharge from hospital, preferably at 24 hours of admission.

Standard Two – all patients should be prescribed high-efficacy lipid-lowering therapy post-myocardial infarction for secondary prevention as tolerated, adjusting for significant comorbidities.

Methods

Patients admitted to our local cardiology wards at the Glasgow Royal Infirmary between January and May 2018, and subsequently between August and December 2018 were identified from the West of Scotland Cardiac Rehabilitation Service records. Only patients fulfilling the criteria for a type 1 myocardial infarction were included.17 Excluded subjects included patients who were referred to the cardiac rehabilitation service for decompensated and chronic heart failure rather than AMI. Patients aged 85 years and over were also excluded, as the limited data available on statins for secondary prevention in the very elderly is less secure. Case notes, biochemistry results and discharge summaries were reviewed retrospectively, together with baseline demographics. Dates and details of cholesterol measurements were recorded, if applicable, in addition to medicine reconciliation at discharge.

Departmental and junior doctor education was delivered between audit cycles in order to improve our clinical practice. Our intervention following ‘cycle one’ was an interactive, face-to-face teaching session for nursing staff and doctors of all grades working in cardiology at the Glasgow Royal Infirmary. This was delivered at our departmental meeting in July 2018. Following the meeting we displayed illustrative reminders throughout the cardiology department in efforts to consolidate learning and encourage junior doctors on future rotations to the cardiology department to continue to check lipids post-ACS. Our collective findings from this clinical audit were presented locally in poster format at the Glasgow Royal Infirmary Research Symposium in March 2019.

Outcomes between audit cycles were compared using Fisher’s exact test in R, version 3.6.0. No patient identifiable data were stored.

Results

A pilot study ‘cycle one’ was initially carried out to determine our local cardiology department’s compliance with current NICE guidelines on lipid modification for cardiovascular disease prevention. We delivered a number of interventions in order to improve our practice. ‘Cycle two’ was subsequently conducted to assess effect.

Cycle one: January to May 2018

Table 1. Patient demographics across both cycles

Age group (years) Cycle one Cycle two
Male Female Male Female
< 45 6 4 12 2
45–54 15 4 21 9
55–64 34 11 48 24
65–74 24 8 17 15
75–84 20 19 17 15
Total 99 46 115 65

There were 145 patients admitted to our cardiology receiving ward with ACS during this four-month period. Table 1 details the demographics of these patients. The mean age in cycle one was 65 years. Of these, only 80 patients had their TC checked during admission (55%), and 67 patients had their TC checked within the first 24 hours of admission (46%). A full lipid profile was ordered in 47 patients (32%), which comprised of TC, TG, HDL-C and LDL-C. These figures demonstrate a lack of adherence with Standard One. When we reviewed discharge documents for secondary prevention medications, we found somewhat better compliance with Standard Two, with 129 patients (89%) sent home on high-efficacy lipid-lowering therapy.

Cycle two: August to December 2018

During this second four-month period, 180 patients under the age of 85 years were identified who were admitted to our cardiology receiving ward with ACS. Table 1 illustrates patient demographics. The mean age of the cycle two group was 62 years.

Regarding Standard One, 115 patients with ACS had their TC measured during their admission (64%): 110 patients had their TC checked in the first 24 hours of their admission (61%). A full lipid profile comprising of TC, TG, HDL-C and LDL-C, was measured in just 64 patients (36%). Disappointingly, 65 of our patients had no lipid screen of any kind (36%), and 19 of these patients were under 55 years of age (29%). Of the patients who had their cholesterol measured in the first 24 hours of admission, 77 patients (67%) had a TC level >4.1 mmol/L.18 Our analysis of TC by age group is illustrated in figure 1. Patients aged <45 years had a median cholesterol of 5.4 mmol/L and maximum cholesterol of 7.2 mmol/L. Patients aged 45–64 years had a median cholesterol of 5.4 mmol/L and a maximum cholesterol of 7.9 mmol/L. There were 19 patients across these age groups (41%) who did not have their cholesterol measured. Ezetemibe was added to lipid-lowering therapy to optimise high-intensity therapy in five patients <55 years due to the severity of their hypercholesterolaemia, in line with NICE guidance.19

Brady - Figure 1. Patient cholesterol levels measured during admission in cycle two
Figure 1. Patient cholesterol levels measured during admission in cycle two

Following our intervention, there was a statistically insignificant increase in the total number of patients who had their cholesterol measured during admission (9%, p=0.113). We did, however, identify a statistically significant 15% increase in the total number of patients who had their TC measured in the first 24 hours of admission (p<0.007).

Regarding Standard Two and statin therapy, 165 of our patients (91.7%) were on appropriate secondary prevention, in accordance with the NICE guidelines, at time of discharge. Given already good compliance in cycle one, this was a statistically insignificant increase between cycles (p=0.45).

There were 68 patients (38%) already on a statin at admission; the vast majority of these (62, 91%) were switched to or continued on high-efficacy lipid-lowering therapy as previously described. Of the 112 patients (62%) who were not on a statin at admission, 103 patients (92%) were commenced on atorvastatin 40–80 mg or rosuvastatin 10–40 mg. Three patients were commenced on statin therapy, however, where chosen drug and/or dose of drug did not adhere to our set standard. Two patients who were not started on a statin had intolerance documented in their case notes. The remaining four patients had no reason documented for not being commenced on a statin for secondary prevention.

Discussion

We examined lipid screening and prescribing of secondary prevention in all patients presenting with ACS to the acute cardiology receiving ward of a large city hospital in Glasgow. This was a single-site audit carried out over two separate, equal time periods during 2018, with a view to improve our clinical practice against agreed national standards.

During our cycle one pilot study, we found that only approximately 50% of our patient population had their cholesterol measured prior to discharge, and less than half of our patients had their cholesterol checked in the first 24 hours of admission, falling far short of accepted guidelines. Following staff education, we demonstrated an increase in the number of ACS patients having their cholesterol measured in the first 24 hours of admission (p<0.05). Although we have demonstrated better compliance with Standard One in cycle two of our clinical audit, further work is required in order to sustain this change in our department. Despite improvement, the number of patients getting their cholesterol measured during admission for ACS remains poor, which shows a lack of adherence to the NICE and ESC guidelines.

The discrepancy between patients who had a full lipid profile measured (TC, TG, HDL-C and LDL-C) and patients who had a single TC measurement can be attributed to the electronic selection process when ordering cholesterol biochemistry. Although a complete lipid profile offers much more baseline information and should be encouraged, a single TC measurement fulfills the basic standard to adhere with national guidelines. Yet, neglecting to check HDL-C and TG means that patients with low HDL-C and high cardiovascular risk, common in the West of Scotland, are not identified.

Somewhat worryingly, young patients admitted with ACS did not always undergo cholesterol measurement. It is important to identify these patients early so that they can be referred for ongoing investigation and management, as well as organising screening for first-degree relatives where appropriate.20

When reviewing secondary prevention, we were able to demonstrate good compliance with Standard Two in prescribing high-dose statins. Nonetheless, there were 13 patients (7%) that were not managed in accordance with approved standards. This was either due to suboptimal dosing of statins after adjusting for patient comorbidities or statin intolerance due to side effects, where documented. Prescribing of ezetimibe was poor, despite the now substantial evidence base,4-6 clear NICE guidance on its usage,19 and the presence of one of the IMPROVE-IT steering committee in our own department.

Conclusion

Baseline, pre-statin lipids are of prognostic value and should guide post-myocardial infarction treatment. Despite its established importance, measuring lipids remains poorly performed in patients presenting with an ACS, even in what should be an international flagship centre for cholesterol management. Further work is required in order to achieve sustainable and long-lasting improvement in lipid profiling in our patients. In addition to continued staff education, lipids will be added to the electronic laboratory bundle for ‘chest pain’ admission bloods when troponin is elevated.

Encouragingly, at least high-efficacy lipid-lowering therapy is commenced immediately during acute admission in the majority of patients, likely as clinicians treat empirically for secondary prevention using the standard treatment regimen recommended by NICE. Although statins remain the backbone of cholesterol-lowering therapy, it may sometimes be necessary to intensify treatment with non-statin drugs in high-risk patients, and consideration should be given to ezetimibe, and eventually emerging protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Key messages

  • High cholesterol is a key risk factor for coronary heart disease
  • Baseline lipids are of prognostic value in acute coronary syndrome and should be measured within 24 hours of admission
  • Aggressive lipid-lowering therapy should be commenced following acute coronary syndrome

Conflicts of interest

None declared.

Funding

None.

Acknowledgement

We would like to acknowledge Gillian Armstrong, our lead for the West of Scotland Cardiac Rehabilitation Service, who provided the hospital identification numbers of all patients who presented with an acute coronary syndrome to the Glasgow Royal Infirmary between January 2018 and May 2018, and subsequently between August 2018 and December 2018.

Study approval and consent

Ethical approval was not required to carry out this local clinical audit. Patient confidentiality was maintained throughout the undertaking of this improvement project.

References

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