Retrospective Evaluation of LDL-C Levels Following First Treatment With Inclisiran as Part of Secondary Prevention ASCVD Risk Reduction in a Real-World Primary Care Setting

Abstract

Introduction:

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide. There is a direct relationship between increasing levels of LDL-C and increased risk of ASCVD. Guidance from the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) recommends that high-risk ASCVD patients maintain an LDL-C <1.8 mmol/L (70 mg/dL) and very high-risk patients <1.4 mmol/L (55 mg/dL). National data in England reveals that 71% of high-risk secondary prevention patients have an LDL-C >1.8 mmol/L (70 mg/dL).

Methodology:

An ASCVD risk reduction approach was initiated in a primary care clinic in December 2021. Of those patients who underwent review between December 2021 and July 2023, 102 patients were started on inclisiran treatment in a real-world setting. These patients were retrospectively reviewed to determine the initial effects of using inclisiran after the first dose as part of the patients’ ASCVD risk reduction management.

Results:

After 1 injection of Inclisiran, the patients’ mean decrease in LDL-C was 2.00 mmol/L (77.3 mg/dL) after a mean of 87 days. This represented a mean reduction of 61.7% (SD = 19.8) in their LDL-C measurements. The addition of inclisiran resulted in 79.4% of patients achieving an LDL-C target of <1.8 mmol/L (70 mg/dL) and 65.7% of patients attaining an LDL-C of <1.4 mmol/L (55 mg/dL).

Conclusion:

Healthcare providers working in primary care can achieve recommended LDL-C targets in 4 out of 5 secondary prevention patients after an initial dose of inclisiran as part of their ASCVD risk reduction approach management.

Keywords

cardiovascular disease rural health quality improvement primary care prevention patient-centeredness medications health outcomes

Introduction

Although considerable research and attention are placed on atherosclerotic cardiovascular disease (ASCVD), it remains the most common cause of death and disability globally.¹ Studies have revealed a direct relationship between elevated low-density lipoprotein cholesterol (LDL-C) and increased ASCVD with therapies targeting LDL-C helping decrease the risk of ASCVD events.^2
-4 Even small decreases in LDL-C have significant benefits. The Cholesterol Treatment Trialists Collaboration meta-analysis compared 22 different studies and found that, on average, for every 1 mmol/L (39 mg/dL) decrease in LDL-C, there was a realized decrease in all-cause mortality by 12%, a decrease in myocardial infarction by 23%, and a decrease in non-fatal stroke by 17%.³ The threshold for acceptable LDL-C levels has decreased over time due to rising evidence of LDL-C’s role in ASCVD. In 2018, the American College of Cardiology and the American Heart Association recommended that LDL-C levels be below 1.8 mmol/L (70 mg/dL). Then, in 2019, these recommendations were further lowered for very high-risk patients to 1.4 mmol/L (55 mg/dL) by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).³ The Joint British Societies’ consensus recommendations for preventing cardiovascular disease (JBS3) endorse an LDL-C below 1.8 mmol/L (70 mg/dL).¹ Recently, this target has been incorporated into England’s annual Quality and Outcome Framework (QoF) for primary care.^1,5 Many studies have indicated that there currently is no “lower limit” of LDL-C as the benefits appear to continue with any reduction in LDL-C with no evidence of adverse effects.^6,7 Unfortunately, 82% of high-risk secondary-prevention patients have not reached their LDL-C targets based on the DaVinci study.⁸ In England, a review of CVDprevent data shows that more than 71% of high-risk secondary prevention patients had an LDL-C of more than 1.8 mmol/L (70 mg/dL).⁹

Statins remain the first-line treatment for reducing LDL-C levels.⁴ However, the SANTORINI study highlighted that most patients were not reaching their LDL-C targets with mono lipid-lowering therapy (LLT), and disappointingly, 21.4% of patients were on no LLT.¹⁰ Other studies have found that half of the patients who started on statins had discontinued them by 12 months, while 70% had discontinued their statins by 24 months.^4,11,12 These studies highlighted that additional therapy beyond statins is often needed to reduce LDL-C levels to enable patients to achieve their targets.

Additional LLT therapies are available and currently used in various clinical practices. These include Ezetimibe, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). Traditional PCSK9i, such as alirocumab and evolocumab, offer an LDL-C reduction of 43% to 64% on top of statins. However, they are not widely available in primary care in England. Patients in England would generally have to be referred to secondary care to have alirocumab and evolocumab and then attend a medical facility every 2 weeks for continued therapy and monitoring.¹² This process can delay the initiation of patient treatment and may require patients to travel considerable distances to attend a specialist facility, which can lead to additional socioeconomic burdens. However, a novel injectable therapy has become available to primary care and has been incorporated into national guidance, complementing existing therapies, including statins.

Inclisiran is a novel small interfering RNA (siRNA) therapy available to primary care in England and is less expensive than traditional PCSK9i.^12,13 It was approved by the National Institute for Health & Care Excellence (NICE) for patients with established ASCVD.^4,11 This medication adheres to the RNA-induced silencing complex (RISC) of the mRNA to prevent the mRNA of PCSK9 from being translated, reducing the production of PCSK9. The decrease in PCSK9 allows more LDL-C receptors to remain on the hepatocytes, removing LDL-C from the bloodstream.² Inclisiran has been found to reduce LDL-C levels by around 50%, which has similar efficacy to high-dose statins and PCSK9i with fewer reported side effects.^4,6,11 Healthcare professionals are still familiarizing themselves with Inclisiran, for which support, resources, and education are available.⁴ As with any new medication, there needs to be real-world evidence from primary care as this helps to build confidence in its efficient and effective use, especially in already busy healthcare systems.

Objective

New LDL-C management options must be incorporated efficiently to ensure they do not place an increased burden on primary care providers but allow them to effectively manage their secondary-prevention ASCVD patients, enabling patients to achieve their recommended LDL-C targets. Due to changes in recent LDL-C target guidelines, there are large populations of patients who have yet to reach their optimal lipid levels. This is confounded by evidence suggesting that previous ways of managing lipids have left many patients undertreated.^8,10 Therefore, additional treatments beyond statins must be utilized to reach these targets and optimize lipid management. Our clinic has adopted a new approach to tackling ASCVD risk reduction by using siRNA technology to target LDL-C, an established modifiable risk factor.

We have performed an analysis of our early results. Using a retrospective approach, we reviewed the effect of 1 dose of inclisiran on LDL-C in secondary-prevention patients in a real-world primary care clinic. We aimed to identify the magnitude of LDL-C reductions and determine if inclisiran can help patients reach their recommended LDL-C targets.

Methodology

Data was extracted using a patient population from a rural primary care practice in England. The process for finding and treating patients from December 2021 to July 2023 is outlined below (Figure 1). Inclisiran data was then extracted from the electronic medical record (EMR) as a retrospective analysis to determine the response to the medication.

Figure 1.

Our ASCVD risk reduction process.

Case Finding

Patients were identified through searches in EMR explicitly targeting those with established ASCVD and an LDL-C ≥2.6 mmol/L. Searches were done using embedded tools within the EMR, and no additional electronic tools were required. These electronic tools are available to all primary care practices in England. The practice also held multidisciplinary team (MDT) education sessions to train staff on identifying high-risk patients during their usual clinics. This allowed high-risk patients to be recognized by staff during long-term reviews, health checks, test results reviews, and other opportunistic times.

Case Review

At the time the data was evaluated, patients were previously brought into the clinic with up-to-date blood tests, and an ASCVD risk reduction consultation was performed. Patients’ current medications were addressed during this consultation for compliance and optimization, other risk factors such as diet and weight were addressed, individual LDL-C targets were discussed, and treatment options were discussed. Where required, suitable treatments were initiated. Target LDL-C values were based on ESC/EAS and QoF guidelines.^1,14 QoF recommends secondary-prevention patients (including those with CKD) have an LDL-C level of <1.8 mmol/L (<70 mg/dL), while ESC/EAS further details that very high-risk patients should aim for LDL-C levels <1.4 mmol/L (<55 mg/dL).¹⁴ All LLTs were prescribed per current guidance (Figure 2) after a shared care decision was made between the patient and the healthcare provider.¹ Per Figure 2, statins were initiated and/or optimized as first-line treatment. After a patient’s statins were addressed, if they still were not to the LDL-C target (at least <1.8 mmol/L or <70 mg/dL), additional therapies were introduced. These additional therapies included ezetimibe, bempedoic acid, and inclisiran. Although all of these LLTs are used in our clinic, this paper reviews the addition of inclisiran to a patient’s treatment regimen. If a patient was suitable for and consented to Inclisiran, a 284 mg subcutaneous injection was administered. Repeat blood lipid levels were performed before the second injection at 3 months. Notably, baseline and follow-up blood tests for inclisiran only required a lipid profile. In keeping with the treatment protocol, patients were followed up 3 months after their first injection.^1-3 At this time, the patient’s lipid profiles were repeated before their second injection. This allowed for assessment of the addition of inclisiran before enhancing treatment for patients not reaching their target at 3 months. However, some patients had other blood tests depending on their concurrent long-term conditions and medications. For example, patients on statin therapy may have liver function tests with their lipid profile blood. All adverse events were recorded and submitted via the British yellow card scheme.

Figure 2.

NHS England Accelerated Access Collaborative (AAC) lipid-lowering guidelines for secondary prevention of ASCVD.¹

Data Collection

The data presented is from a retrospective analysis of information obtained from December 2021 to July 2023 for 102 patients initiated on Inclisiran. The data was collected from the EMR, and characteristics, including age, gender, BMI, and smoking status, were recorded together with comorbidities such as CVD, type 2 diabetes mellitus (T2DM), cerebral vascular accident (CVA), peripheral arterial disease (PAD), and chronic kidney disease (CKD). Patients’ LLT therapy was documented, which included all statins, Ezetimibe, bempedoic acid, and combination ezetimibe and bempedoic acid (Nustendi^®) treatment.

Patients with potential familial hypercholesterolemia (FH) were screened using the Dutch score or Simon Broome clinical criteria. The presence of FH did not alter patient management of their LDL-C compared to those without FH.

Statistical Analysis

Patient demographics were described by assessing each continuous variable’s means and standard deviation. LDL-C and total serum cholesterol levels are parametric and amenable to evaluation using a paired t-test of baseline and 3-month data for the patients. As per usual standards, only analyses resulting in a P < .05 were deemed statistically significant.

Results

Patient Demographics

In the primary care clinic, 102 patients started on inclisiran therapy were evaluated from December 2021 to July 2023. There were 50 female patients and 52 male patients included in this review. The mean age was 71 years (SD = 10). The average BMI was 29.33 kg/m² (SD = 5.53), and 20.6% of the patients were referred to multi-disciplinary weight loss programs.

Of the patients reviewed here, 59.8% had CVD, 29.4% had CVA, and 13.7% had PAD. It is of note that patients may have more than 1 condition. Other comorbidities included T2DM (18.6%), hypertension (84.3%), and CKD (42.2%). Over half of the patients were former smokers (54.9%), with 9.8% of patients current smokers, and 35.3% of patients recorded as having never smoked before. Most patients were already on LLT: 55.9% of patients were on a statin (Figures 3 and 4), 18.6% were on Ezetimibe, 2.9% were on bempedoic acid, and 34.3% of patients were on bempedoic acid and ezetimibe combination tablet (Nustendi^®).

Figure 3.

Proportion of patients on statins.

Figure 4.

Proportion of statin intensities prescribed.

The average LDL-C at the time of inclisiran initiation was 3.25 mmol/L (SD = 0.70; 125.7 mg/dL), with the minimum LDL-C being 2.6 mmol/L (100.5 mg/dL). The average total serum cholesterol was 5.52 mmol/L (SD = 0.87; 213.5 mg/dL). The average time between the first inclisiran injection and their follow-up lipid blood test was 87 days (SD = 26).

Effects of Inclisiran

Table 1 details the paired t-test calculations used to compare the initial and 3-month post-treatment levels for LDL-C and total serum cholesterol. There was a significant difference in LDL-C after 1 dose of inclisiran (mean reduction 2.00 mmol/L (77.3 mg/dL), SD = 0.79, P < .0001; Figure 5); this equates to a mean reduction of 61.69% in LDL-C blood levels. The waterfall plot demonstrates that all 102 patients reviewed experienced a fall in their LDL-C (Figure 6).

Table 1.

Paired t-test Analysis of LDL-C and Total Serum Cholesterol Pre- and Post-treatment.

LDL-C difference scores calculations	Total serum cholesterol difference scores calculations
Mean: −2.00, μ = 0 S² = SS⁄df = 63.48/(102−1) = 0.63 S²_M = S²/N = 0.63/102 = 0.01 S_M = √S²_M = √0.01 = 0.08 T-value calculation t = (M-μ)/S_M = (−2-0)/0.08 = −25.5 The value of t is −25.503467. The value of P is<.00001. The result is significant at P < .05.	Mean: −2.10, μ = 0 S² = SS⁄df = 98.16/(102−1) = 0.97 S²_M = S²/N = 0.97/102 = 0.01 S_M = √S²_M = √0.01 = 0.1 T-value calculation t = (M-μ)/S_M = (−2.10-0)/0.1 = −21.48 The value of t is −21.48173. The value of P is <.00001. The result is significant at P < .05.

Figure 5.

Box-whisker plot of LDL-C pre- (blue) and post- (green) treatment with inclisiran.

Figure 6.

Waterfall plot of percentage change in LDL-C of 102 patients after an initial dose of inclisiran at 3 months.

There was also a significant difference in total serum cholesterol with a mean reduction of 2.10 mmol/L (81.2 mg/dL), SD = 0.99, P < .0001. This equates to a mean decrease of 37.7% in total serum cholesterol.

Reviewing our data revealed that 79.4% of patients reached an LDL-C target of <1.8 mmol/L (70 mg/dL) after just 1 inclisiran injection. It was also noted that 65.7% of patients were able to achieve an LDL-C of <1.4 mmol/L (55 mg/dL), and 43.1% of patients achieved an LDL-C of <1.0 mmol/L (38.7 mg/dL) after just 1 injection.

Of those that did not reach their LDL-C target, the average LDL-C in that group was 2.38 mmol/L (SD = 0.51), and 27.3% (n = 6) in this group did achieve an LDL-C ≤2 mmol/L. This group also achieved a mean decrease in LDL-C by 1.3 mmol/L (SD = 0.67). Within the group that did not reach a target of <1.8 mmol/L (70 mg/dL), 2/3 patients (n = 14) were statin-intolerant, 57% (n = 12) were on ezetimibe and/or bempedoic acid, and 19% (n = 4) were on inclisiran as monotherapy. No significant adverse reactions were noted during the period evaluated.

Discussion

Managing patients’ LDL-C levels has become increasingly more challenging as not only have the LDL-C targets become lower, presenting a need for combination therapies but patient intolerance and resistance to using statin medication are considerable. It has been found that up to half of patients started on statins will stop their medication by 12 months, with a further 70% stopping by 24 months.^4,11,12 Around 7% to 29% of patients will experience musculoskeletal side effects severe enough to discontinue statin medication.^3,15 This review also highlighted the need for suitable statin alternatives; as previously mentioned, most of those who did not reach their target were statin-intolerant. Other non-statin oral medication alternatives exist, but injectable therapies are more effective. For example, ezetimibe leads to an average decrease in LDL-C by around 10% to 15%, and bempedoic acid shows a 17.8% to 24.5% decrease in LDL-C.^6,11,16 Compare this to Inclisiran, where a meta-analysis utilizing 3660 patients found the average drop in LDL-C to be around 51% with the medication.¹⁶

Our real-world retrospective review supports the efficacy of clinical trials, as our patients’ mean reduction in LDL-C was 61.7%. The ASCVD risk reduction approach to addressing the patient’s lipids may explain the decrease in LDL-C beyond the clinical trials. All patients were counseled on dietary and lifestyle changes during consultations. It was fully explained why their LDL-C targets were at a certain level. Medication reviews were also done during inclisiran initiation, and all patients were reminded to continue to take their current LLT.

Some patients would admit to “forgetting” or being inconsistent with using their current LLT. Various resources were utilized to address additional risk factors;20.6% of patients were referred to multi-disciplinary weight-loss services when given their first dose of Inclisiran. No significant adverse events were reported in the patients reviewed, which is in keeping with the clinical trial data where inclisiran’s adverse events were similar to placebo, apart from injection-site reactions.^2
-4

This review is limited to secondary prevention patients. The analysis duration was chosen to provide an initial assessment of inclisiran and assess patient’ ability to reach their LDL-C targets.^2,6 The ORION trials found that inclisiran yielded reductions in LDL-C of around 50% by 3 months. We wanted to compare our real-world data to the clinical trials. It was also found that LDL-C decreases with inclisiran were sustained for extended periods in Orion 9, 10, and 11, with patients having a sustained drop in their LDL-C of 47.9% by 510 days. Our 3-month data is in keeping with the initial reports in the longer-term data, but further reviews of our real-world patients would need to be undertaken to establish the longevity of action.⁶

It should be noted that inclisiran does not yet have an established cardiovascular benefit. Pooled data from Orion 9, 10, and 11 trials, which included 3655 patients over 18 months, found that inclisiran significantly reduced major adverse cardiovascular events (MACE). Further investigations are needed to establish Inclisiran’s role in reducing cardiovascular events,¹⁷ and currently, the ORION-4 CVOT study is in process, which is investigating the cardiovascular benefit of inclisiran in 15 000 patients after 5 years and is expected to be published in 2026.¹⁸

Our review addresses the feasibility of getting patients to their LDL-C targets in primary care. As the DaVinci study reported, only 18% of exceptionally high-risk patients reach their LDL-C targets.⁸ The reasons were multifactorial and included patients not being aware of hypercholesterolemia and the need to take LLT. Studies have also shown that combination LLT is underutilized, and in 2021, the International Lipid Expert Panel proposed initiating dual therapies at the time of establishing treatment to improve outcomes.^7,8 It has been suggested that if LLT were utilized appropriately, 95% of patients could reach their targets.^8,19

Current LLT options are underutilized, and access to these treatment options and their affordability may vary. Inclisiran is available on the NHS at £50 per injection following an initiative to reduce ASCVD-related deaths and reduce barriers to access to treatment. It has been found that patients in more deprived areas of England are more likely to have premature cardiovascular deaths and increased morbidity than those in non-deprived areas.²⁰ Therefore, it was essential to ensure that primary care practices were given the tools to improve ASCVD and that access to these tools was equal among practices to help address the inequality gap.²¹ As we have described previously,⁴ to overcome potential resistance to prescribing inclisiran or other LLTs within our Practice, upskilling of the entire MDT was undertaken to ensure all team members were educated on all available LLT options. More confident staff members quickly embraced newer treatments, such as inclisiran. Anecdotally, patients also reported relief in not having to take an additional daily tablet; polypharmacy commonly affects many secondary prevention patients.

We have found that our approach has improved LDL-C reductions when given the right resources. Four out of 5 of our patients (79.4%) were able to attain an LDL <1.8 mmol/L (70 mg/dL) by using medications already available to primary care practices in England (Figure 7), with a further 65.7% achieving LDL-C levels <1.4 mmol/L (55 mg/dL) in line with ESC/EAS guidelines.¹⁴ This is important as an LDL-C level below 1.8 mmol/L (70 mg/dL) is associated with plaque regression and a reduction in atheroma volume irrespective of the LLT used to achieve this target.^22,23 This review has also highlighted the potential favorable benefit of a multifactorial approach in primary care when addressing ASCVD risk reduction to reduce LDL-C levels, including dietary and lifestyle changes, ensuring patients are concordant with the medicine regimes, and providing education about their medical conditions and LDL-C targets to achieve when compared to the results reported by others using inclisiran in a secondary care setting.¹¹

Figure 7.

National data⁹ versus lipid management program data from a rural practice in England.

Conclusion

It is well documented that many patients have yet to achieve their recommended LDL-C targets, with monotherapy being ineffective in a significant proportion of the ASCVD population. Combination LLT is becoming the new standard. Our approach by adding inclisiran to patients’ treatment regimen has helped address sub-optimally managed ASCVD patients and allowed them to achieve targets in a real-world setting.

Our ASCVD risk reduction approach has been embedded into our primary care clinics as this helps mitigate excess clinical burden. Of the non-statin LLTs, inclisiran has proved to be a practical and accessible LLT. With the addition of Inclisiran, we found that the average LDL-C reduction was 2.00 mmol/L (77.3 mg/dL), and ca. 4 out of 5 (79.4%) patients reached their LDL-C targets of <1.8 mmol/L (70 mg/dL). This suggests that inclisiran can be a helpful add-on to current LLT to assist primary care practices in helping patients achieve their LDL-C targets promptly. Further real-world reviews would be beneficial to see if this trend continues over time using this siRNA medication in the primary care setting.

Footnotes

Acknowledgements

The authors would like to acknowledge the team at Marsh Medical Practice for seamlessly incorporating this new way of working into the practice.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Carl N. Deaney

References

Cegla

National Institute for Health and Care Excellence guidelines for lipid management. Heart. 2023;109(9):661-667.

Brandts

Ray

KK.

Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. Nat Rev Cardiol. 2023; 20(9):600-616.

Raschi

Casula

Cicero

, et al. Beyond statins: new pharmacological targets to decrease LDL-cholesterol and cardiovascular events. Pharmacol Ther. 2023;253:108507.

Deaney

Donaldson

Meskauskiene

Implementing an innovative lipid management technique using siRNA LDL-C lowering therapy: lessons learned in an NHS primary care practice with worked case examples. J Prim Care Community Health. 2023;14:21501319231172709.

Adeniyi

Olofinbiyi

Ojo

, et al. A critical appraisal of cardiovascular disease picture in the United Kingdom; an experience tool for low resource settings. 2023.

Albosta

Grant

Taub

Blumenthal

Martin

Michos

. Inclisiran: a new strategy for LDL-C lowering and prevention of atherosclerotic cardiovascular disease. Vasc Health Risk Manag. 2023;19:421-431.

Ray

Reeskamp

Laufs

, et al. Combination lipid-lowering therapy as the first-line strategy in very high-risk patients. Eur Heart J. 2022;43(8):830-833.

Banach

Penson

PE.

Adherence to statin therapy: it seems we know everything, yet we do nothing. Eur Heart J Open. 2022;2(6):oeac071.

CVDPREVENT. Data Explorer: Cholesterol: CVD treated to threshold (CVDP007CHOL). Accessed November 2023. https://www.cvdprevent.nhs.Uk/data-explorer?period=9&area=1&indicator=30. Mach

, et al. Eur Heart J 2020;41(1):111-188.

10.

Catapano

Manu

Burden

Ray

KK.

(2022). LDL-C goal achievement and lipid-lowering therapy in patients by atherosclerotic cardiovascular disease subtype: the SANTORINI study. Eur Heart J. 2022;43(2):ehac544-2373.

11.

Padam

Barton

Wilson

, et al. Lipid lowering with inclisiran: a real-world single-centre experience. Open Heart. 2022;9(2):e002184.

12.

LaFratte

Peasah

Huang

Hall

Patel

Good

CB.

Association of PCSK9 inhibitor initiation on statin adherence and discontinuation. J Am Heart Assoc. 2023;12(18):e029707.

13.

Michaeli

Boch

Michaeli

Cost-effectiveness of icosapent ethyl, evolocumab, alirocumab, ezetimibe, or fenofibrate in combination with statins compared to statin monotherapy. Clin Drug Investig. 2022;42(8):643-656.

14.

Mach

Baigent

Catapano

, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-188.

15.

Nissen

Lincoff

Brennan

, et al. Bempedoic acid and cardiovascular outcomes in statin-intolerant patients. N Engl J Med. 2023;388(15):1353-1364.

16.

Jain

Traditional and novel non-statin lipid-lowering drugs. Indian Heart Journal. 2023. doi:10.1016/j.ihj.2023.11.003

17.

Ray

Raal

Kallend

, et al.; ORION Phase III Investigators. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J. 2023;44(2):129-138.

18.

Arnold

Koenig

PCSK9 inhibitor wars: how does inclisiran fit in with current monoclonal antibody inhibitor therapy? Considerations for patient selection. Curr Cardiol Rep. 2022;24(11):1657-1667.

19.

Cannon

De Lemos

Rosenson

, et al.; GOULD Investigators. Use of lipid-lowering therapies over 2 years in GOULD, a registry of patients with atherosclerotic cardiovascular disease in the US. JAMA Cardiol. 2021;6(9):1060-1068.

20.

Heart

. Prioritising the prevention of cardiovascular disease (CVD) - heart UK. Prioritising the prevention of cardiovascular disease (CVD). 2019. Accessed December 2023. https://www.heartuk.org.uk/downloads/health-professionals/heart-uk-cvd-prevention-policy-paper—july-2019.pdf

21.

Beech

Bottery

Charlesworth

, et al. Closing the Gap. Key Areas for Action on the Health and Care Workforce. The King’s Fund; 2019.

22.

Nissen

Nicholls

Sipahi

, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295(13):1556-1565.

23.

Di Giovanni

Nicholls

. Intensive lipid lowering agents and coronary atherosclerosis: insights from intravascular imaging. Am J Prevent Cardiol. 2022;11:100366.