Atherosclerotic cardiovascular diseases (ASCVD) is the leading cause of death worldwide and in Saudi Arabia. Dyslipidemia is one of the main risk factors for ischemic heart disease. The overall prevalence in Saudi Arabia ranges from 20% to 40%. The highest prevalence was for triglycerides 44%. Intensive therapeutic interventions plays a major role in reduction of serious cardiovascular outcomes in patients with ASCVD.

The Ministry of Health has adopted the model of care project that was introduced as part of the new vision of our country (2030) in 2017. The model represents a method for restructuring health care through interactions between health systems and communities.

It focuses on the patient's journey through health system and help to provide an organized, coordinated, and patient centered healthcare services. The outcomes of this model will be reflected on cost reduction, decrease in morbidity and mortality from chronic diseases as well as increase the satisfaction of patients and their caregiver.

1. Level 4 category includes patients with a very high risk ASCVD : 2 major ASCVD , 1 major + multiple risk factor and patients with Triglycerides level > 1000. (Visit primary health center (PHC) & secondary care every 6 m ).
2.  Level 3 category includes patients aging from 40 -75 , LDL 70 -189 without DM and risk assessment ≥ 20 % and patients aging from 40-75 with DM and risk assessment ≥ 7.5 % and patients with LDL level ≥ 190 mg/dl and patients aging from 20-39 with family history of familial hypercholesterolemia and premature ASCVD and patients with LDL level ≥160 and patients with stable ASCVD reaching target level of LDL <70 and patients with Triglyceride level from 500 – 999 mg /dl .(Visit primary health center (PHC) & secondary care every 6 m ).
3.  Level 2 category includes patients Aging from 40-75 , LDL 70-189 mg/dl without DM and risk assessment ≥ 7.5 - < 20% and patients aging from 40-75 with DM and risk assessment <7.5 % and patients with Triglyceride level from 200- 499 mg/dl (Visit Primary care facilities).
4. Level 1 category includes patients aging from 40-75 , LDL 70 -189 mg/dl, without DM and risk assessment 5 - <7.5 % and patients with Triglyceride level 150 -199 mg/dl. (Visit Primary care facilities)
5.  Level 0 category includes patients aging from 40-75 , LDL 70-189 mg/dl, without DM and risk assessment of <5% and patients aging from 0-39 without family history of Familial hypercholesterolemia or premature ASCVD and patients with Triglyceride level < 150 mg/dl . (Visit Primary care facilities). * (ASCVD) includes acute coronary syndrome (ACS), those with history of myocardial infarction (MI), stable or unstable angina or coronary or other arterial revascularization, stroke, transient ischemic attack (TIA), or peripheral artery disease (PAD) including aortic aneurysm, all of atherosclerotic origin.

Primary Prevention link

Appendix 3: Secondary Prevention in Patients with Clinical ASCVD

Appendix 4: Very High-Risk of Future ASCVD Events

Risk Categories and Treatment Goals

1. Level 1,2,3 patient. who are not controlled for 3-6 months. - Statin-associated side effects include: CK >10 times normal limits.
2. AST, ALT more than 3 times normal limit. - Stable ASCVD on max tolerated statin and ezitemib and LDL above the target (70 mg/dL) Referred to tertiary level hospitals: Familial hypercholesteremia. 2 Major ASCVD 1 Major + multiple risk factor Triglycerides level >1000

The following patients will be referred to the tertiary Hospitals: 

1.  Familial hypercholesteremia: Two (2) major (ASCVD) Atherosclerotic Cardiovascular Diseases. . One (1) major ASCVD + multiple risk factor.  Triglycerides level >1000.
2. Recommendations for Hypertriglyceridemia In adults 20 years of age or older with moderate hypertriglyceridemia; Identification and treatment of the multiple underlying causes of elevated triglycerides: - Lifestyle causes (obesity and metabolic syndrome).
3.  Secondary Disorders: diabetes mellitus, chronic liver or kidney disease and/or nephrotic syndrome, hypothyroidism) Triglyceride-raising drugs.  In adults 40 to 75 years of age with moderate or severe hypertriglyceridemia* and ASCVD risk of ≥ 7.5%. 

 Re-evaluate ASCVD risk after lifestyle and secondary factors are addressed. 

1.  Consider a persistently elevated triglyceride level as a factor favoring initiation or intensification of statin therapy.. In adults with severe hypertriglyceridemia
2.  Addressing and eliminating the underlying factors as described in Recommendation.
3.  Implementing a very low-fat diet, avoidance of refined carbohydrates and alcohol, and adding fibrates or omega-3 fatty acids for patients with persistently elevated severe hypertriglyceridemia.
4.  Algorithm for Pharmacologic Management of Hyperlipidemia in Patients with Cardio-metabolic Risk and Diabetes.
5. Treatment objectives for elevated triglycerides.
6. Prevent pancreatitis for very high triglycerides ≥ 500 mg/dL.
7. Prevent cardiovascular disease for high or moderate hypertriglyceridemia 200-499 mg/dL.
8. Algorithm for managing severe hypertriglyceridemia (triglycerides > 1000 mg/dL), see attachment appendix.

• High, moderate and low statin therapy, see attachment appendix .

 Statin-Associated Side Effects. 

1.  Statin associated side effects, its frequency, predisposing factors, and quality of evidence, see attachment appendix
2.  Management of hypertriglyceridemia and the role of Icosapent ethyl (IPE):

Therapeutic lifestyle changes: 

• Decrease weight
•  calories
• sugar
• alcohol. 

Increase exercise .

1.  Manage secondary causes:

• Address and control conditions that raise TG and stop medications that increase TG.
•  Patients with TG 135-499 mg/dL treated maximally tolerated statins who have CVD of DM + ≥2 CVD RF should receive IPE to prevent ASCVD. (See appendix 6.5 for more specific interventions). 
• Treating LDL-C to Goal  Extreme Risk.
•  Lifestyle + high intensity statin If LDL –C > 55mg/dL, add PCSk9i, ezetimibe, colesevelam, or bempedoic acid depending on required LDL –C lowering. . If LDL –C >55mg/dL, continue to add PCSK9i, ezetimibe, colesevelam, or bempedoic acid depending on required LDL-C lowering.

1. Very High Risk  Lifestyle + high intensity statin.

•  Lifestyle + high intensity statin. 
• If LDL –C > 70mg/dL, add ezetimibe, PCSk9i, colesevelam, or bempedoic acid depending on required LDL-C lowering.  If LDL –C > 70mg/dL, continue to add ezetimibe, PCSK9i, colesevelam, or bempedoic acid depending on required LDL-C lowering. 

1.  High-Moderate Risk .

•  Lifestyle + high intensity statin.  If LDL –C > 100mg/dL, increase to high intensity statin. . If LDL –C > 100mg/dL, add ezetimibe, colesevelam, or bempedoic acid.
• If LDL –C > 100mg/dL, add agents to reach goal; consider PCSk9i. 

1. Low Risk 

•  Lifestyle If LDL –C > 130mg/dL, add moderate intensity statin. . If LDL –C > 130mg/dL, increase to high intensity statin.  If LDL –C > 130mg/dL, add ezetimibe, colesevelam, or bempedoic acid.
•  Check lipids every 3 months or more frequently when necessary. 
•  Drugs and Doses for LDL-C lowering:

1. High Intensity Statin Therapy: 

•  Atorvastatin 40-80mg / Rosuvastatin 20- 40mg 
•  Moderate – Intensity Statin Therapy .
• Rosuvastatin 5- 10mg/ Atorvastatin 10-20mg/ Simvastatin 20-40mg/ Pitavastatin 2-4mg/ Fluvastatin XL 80mg/ Fluvastatin 40mg BID/ Pravastatin 40-80mg, Lovastatin 40mg. ezetimibe 10mg. 
•  PCSk9 Inhibitors 
•  Evolocumab 140mg Q2W, 420mg Q4W/ Alirocumab 75-150mg Q2W 
•  Colesevelam 3.75mg.  Bempedoic acid 180mg.

Screening and Referral Guidelines:

• Age above or equal 40 do risk assessment 2- Age less than 40 + one of the following traditional risk factor 
•  if normal should be repeated after 3-5 y : Family history of familial hypercholesteremia Family history of premature ASCVD [ IHD in male <55Y, and female<65y] HTN, DM, smoking, etc.
• Metabolic syndrome Chronic renal disease Chronic inflammatory disease [RA, SLE, psoriasis, HIV] Woman with preeclampsia, premature menopause

Referral Guidelines

• Referred to secondary care: Level 1,2,3 pt. who are not controlled for 3-6 months. Statin-associated side effects include: - CK >10 times normal limits. - AST, ALT more than 3 times normal limit.
• Stable ASCVD on max tolerated statin and ezitemib and LDL above the target (70 mg/dL) Referred to tertiary level hospitals: Familial hypercholesteremia.
•  2 Major ASCVD 1 Major + multiple risk factor Triglycerides level >1000

• Total serum cholesterol level
• Low-density lipoprotein cholesterol (LDL-C)
• High-density lipoprotein cholesterol (HDL-C)
• Triglycerides (TG)
• Non-HDL-C will be calculated from profile (total cholesterol – HDL- C)

Liver transaminase (AST, ALT)  levels:

• should be measured before and 3 months after treatment initiation and periodically thereafter and whenever lipid therapy is restarted, increased, changed, or combined.