Acute coronary syndrome (ACS) is one of the leading causes for morbidity and mortality in the world despite advances in treatment as shown by both short- and long-term studies.1 Studies demonstrate that factors responsible for increased risk of future cardiovascular events are often ignored resulting in increased morbidity and mortality.1,2 Despite the significant reduction of in-hospital mortality in patients with ACS, the overall mortality and morbidity remains high due to missed opportunities to optimise treatment.3 The Global Registry of Acute Coronary Events (GRACE) conducted in centres in Belgium and the United Kingdom (UK) shows a long-term signal of recurrent events, such that in-hospital mortality was 3%, 4% and 5% at five-year follow up and that mortality was 15% and 18% for Belgium and UK patients, respectively.4 The GRACE study showed that patients with a higher GRACE score were at higher risk compared to low and moderate scores, and 68%, 86% and 97% deaths occurred in patients with ST-elevation myocardial infarction (STEMI), ACS and unstable angina, respectively, after initial hospital discharge. Patients with non-ST segment elevated myocardial infarction (NSTEMI) were found to have poor prognosis at six-month follow up, compared to STEMI patients, which was most likely due to patients being on less-than-optimal treatment. Medication compliance among patients is highest in the first month after ACS and Cheng et al., reported that from patients discharged on aspirin, beta blocker and statins, 34% patients had stopped at least one medicine and 12% had stopped all three medications a month after ACS.5 Only 40–45% patients were adherent with beta blocker or statins one to two years following ACS.
European Society of Cardiology (ESC) guidelines recommend low-density lipoprotein (LDL) below 1.4 mmol/L in patients post ACS, which differs from UK National Institute for Health and Care Excellence (NICE) guideline recommendations of 1.8 mmol/L and 1.4 mmol/L in very-high-risk patients only.6,7 The fifth European survey of Cardiovascular Disease prevention and Diabetes (EUROASPIRE V) survey showed that only 30% of post-ACS patients had low-density lipoprotein cholesterol (LDL-C) levels <1.8 mmol/L one year after discharge.8 The ACS EuroPath survey showed a considerable lack of physicians’ compliance with guidelines in managing lipid lowering in patients post ACS.9
UK practice
NHS patients are followed up depending on local resources within a few months to a year and, as there is no systematic approach to ensuring compliance and up-titration of secondary prevention drugs post-discharge, most patients may not receive optimal medical therapy. The heterogeneity of lipid management across various international guidelines and adherence to these guidelines varies amongst clinicians. NICE guidelines recommend high-dose atorvastatin 80 mg and to recheck lipid levels in three months’ time, with the aim to reduce LDL-C levels by at least 40%, as recommended by the Joint British Societies (JBS3).10 If statins are contraindicated or not tolerated, ezetimibe should be offered as an alternative lipid-lowering therapy and if insufficient, bempedoic acid and ezetimibe combination therapy should be initiated. If target levels are not achieved, patients should be referred to a lipid clinic for consideration of PCSK9 inhibitor therapy. Most patients who develop side effects during the first few weeks unfortunately may miss this opportunity, due to delay in initial clinic review increasing their future cardiovascular risk.
In comparison, the ESC advised different target LDL-C levels based on the patient risk and the recommended levels were <1.8 mmol/L in high-risk patients and <1.4 mmol/L in very-high-risk patients. Patients who develop an ischaemic event within two years of the previous event should have even lower target LDL-C levels <1.0 mmol/L. The latest ESC guidelines emphasise the use of combination therapies, initially with ezetimibe and then PCSK9 inhibitors. These recommendations are based mainly on the findings of FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects With Elevated Risk) and ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment with Alirocumab) trials, which showed significant risk reduction in patients who were higher risk for future cardiovascular events.11,12 The American Heart Association (AHA) and American College of Cardiologists (ACC) guidelines recommend combination therapy of statins and a non-statin therapy to achieve the target LDL-C levels <1.8 mmol/L in high-risk patients.13 These patients initially should be commenced on a maximally tolerated dose of statins and ezetimibe, and if the LDL-C levels remain >1.8 mmol/L, then they should be considered for PCSK9 inhibitor therapy.
In non-diabetic adult patients with LDL-C levels ≥1.81–4.89 mmol/L at a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% to <20%, if the decision about statin therapy is uncertain, it is recommended to consider measuring coronary artery calcification. SWEDEHEART is a nationwide registry for Swedish hospital patients that have had a MI and this showed variability from 40–75% in achieving the target LDL-C levels. The optimisation of medical therapies for secondary prevention in these patients has got worse during the COVID-19 pandemic.14
The article by Claire Jones in this issue of the BJC reports an improvement of 31% in the number of patients achieving either a 50% reduction in LDL-C or an LDL-C level of <1.4mmol/L, and patients having their admission lipid profile improved from 24.8% to 79.6% after implementation of the pathway.15 About 26% patients achieve both an LDL-C reduction of 50% and a level of below 1.4 mmol/L (increased from 17%) after attending the cardiac rehabilitation programme. Similarly, the percentage of patients achieving the target LDL-C level increased from 36% to 50%, whereas >50% reduction in LDL-C level was achieved by 56% patients in comparison to 29% pre-pathway. Remarkably, 76% of patients achieved either one or both of those targets post-pathway, compared with 45% patients pre-pathway.
Cardiac rehabilitation and lipid management
This study showed that cardiac rehabilitation programmes may significantly improve the lipid management of patients post-ACS, which could be due to increased patients’ adherence in the immediate post-ACS period and higher motivation. Most patients get seen at least a few months after the initial event, which might be too late to optimise medical therapies as the patient may lose motivation by that time and may also become less compliant with treatment. Hence, cardiac rehabilitation may the perfect opportunity to fill this gap and optimise secondary prevention lipid therapies. This study also rightly pointed out the difference in follow-up lipid profile checks between ESC/EAS and NICE guidelines. ESC/EAS recommends a follow-up lipid profile four to six weeks after the start of treatment, whereas NICE recommends a repeat lipid sample three months after start of the therapy. Patients who have persistently high LDL-C after four to six weeks of treatment are likely to benefit from more aggressive lipid management therapies to reduce their future ASCVD risk and cardiac rehabilitation is perhaps the best opportunity to address this. Cardiac rehabilitation nursing staff work according to specific pathways, and it provides them with the opportunity to monitor patient’s lipid profile and optimise medical therapy accordingly, due to their more frequent interaction early on with patients following ACS.
In summary, an early intervention cardiac rehabilitation-based lipid management pathway may be the best opportunity to address the challenges in managing dyslipidaemia in patients with ACS to reduce their future risk. This model can also be extrapolated to up-titration of other secondary prevention drugs including angiotensin-converting enzyme inhibitors, mineralocorticoid receptor antagonists and beta blockers. This has the advantage of early intervention aiding compliance, achieving secondary prevention targets and improving long-term clinical outcomes.
Conflicts of interest
None declared.
Editors’ note
See accompanying article by Jones in this issue.
References
1. Abu-Assi E, López-López A, González-Salvado V et al. The risk of cardiovascular events after an acute coronary event remains high, especially during the first year, despite revascularization. Rev Esp Cardiol (Engl Ed) 2016;69:11–8. https://doi.org/10.1016/j.rec.2015.06.015
2. Alnasser SMA, Huang W, Gore JM et al. Late consequences of acute coronary syndromes: Global Registry of Acute Coronary Events (GRACE) follow-up. Am J Med 2015;128:766–75. https://doi.org/10.1016/j.amjmed.2014.12.007
3. Alings M, Descamps O, Guillon B et al. Implementation of clinical practices and pathways optimizing ACS patients lipid management: Focus on eight European initiatives. Atheroscler Suppl 2020;42:e59–e64. https://doi.org/10.1016/j.atherosclerosissup.2021.01.010
4. Fox KA, Carruthers KF, Dunbar DR, et al. Underestimated and under-recognized: The late consequences of acute coronary syndrome (Grace UK-Belgian study). Eur Heart J 2010;31:2755–64 https://doi.org/10.1093/eurheartj/ehq326
5. Cheng K, Ingram N, Keenan J, Choudhury RP. Evidence of poor adherence to secondary prevention after acute coronary syndromes: Possible remedies through the application of New Technologies. Open Heart 2015;2:e000166. https://doi.org/10.1136/openhrt-2014-000166
6. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J 2019;41:111–88. https://doi.org/10.1093/eurheartj/ehz455
7. NHS Accelerated Access Collaborative. Summary of national guidance for lipid management for primary and secondary prevention of cardiovascular disease. NHS choices. Available from: https://www.england.nhs.uk/aac/publication/summary-of-national-guidance-for-lipid-management/ (last accessed 31st October 2022)
8. De Backer G, Jankowski P, Kotseva K et al. Management of dyslipidaemia in patients with coronary heart disease: Results from the ESC-EORP EUROASPIRE V survey in 27 countries. Atherosclerosis 2019;285:135–46. https://doi.org/10.1016/j.atherosclerosis.2019.03.014
9. Landmesser U, Pirillo A, Farnier M et al. Lipid-lowering therapy and low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS patient pathway project. Atheroscler Suppl 2020;42:e49–e58. https://doi.org/10.1016/j.atherosclerosissup.2021.01.009
10. JBS3 board. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart 2014;100(Suppl 2):ii1–ii67. http://doi.org/10.1136/heartjnl-2014-305693
11. Sabatine MS, De Ferrari GM, Giugliano RP, et al. Clinical benefit of evolocumab by severity and extent of coronary artery disease. Circulation 2018;138:756–66. https://doi.org/10.1161/CIRCULATIONAHA.118.034309
12. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med 2018;379:2097–107. https://doi.org/10.1056/NEJMoa1801174
13. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APHA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019;139:e1082–e1143. https://doi.org/10.1161/CIR.0000000000000625
14. Lidin M, Lyngå P, Kinch-Westerdahl A, Nymark C. Patient delay prior to care-seeking in acute myocardial infarction during the outbreak of the coronavirus SARS-CoV2 pandemic. Eur J Cardiovasc Nurs 2021;20:752–9. https://doi.org/10.1093/eurjcn/zvab087
15. Jones C. Evaluation of a lipid management pathway within a local cardiac rehabilitation service. Br J Cardiol 2022;29(4) https://doi.org/10.5837/bjc.2022.034
