Cardiovascular%20disease%20prevention Treatment

Cardiovascular disease (CVD) development is closely related to lifestyle characteristics and associated risk factors. There is overwhelming scientific evidence that lifestyle modifications and reduction of risk factors can slow the development of CVD both before and after the occurrence of a CV event.

CVD Prevention

• Primary prevention is aimed at the healthy population and population at risk (with ≥1 CV risk factors) that has not had a CV event while secondary prevention is instituted for those who have confirmed CVD or had a first index CV event
• Prevention and treatment goals are intensified based on the patient’s risk modifiers, 10-year CVD risk, lifetime CVD risk and benefit of treatment, comorbidities, frailty and patient preferences  
  • Lifetime CVD risk can be estimated in apparently healthy individuals, patients with established ASCVD and people with type 2 DM with specific lifetime CVD risk scores or can be approximated with age, level of risk factor, risk modifiers, etc

Selection of Patients for Clinical Intervention

• For high- to very high-risk patients as well as those with established ASCVD and/or DM, intensive lifestyle modification and appropriate drug treatment are required
  • Monitor risk profile every 3-6 months
  • High-risk patients intolerant of statin therapy should be given non-statin agents (Ezetimibe, monoclonal antibodies, bile acid sequestrants, phytosterols)
• For low- to moderate-risk patients, treatment of risk factor is generally not recommended
  • Moderate-risk patients require monitoring of risk profile every 6-12 months
  • Low-risk patients may be given conservative management, focusing on lifestyle interventions

Antiplatelet Agents

• Antiplatelet agents have been shown to reduce vascular mortality, nonfatal reinfarction of the myocardium, nonfatal stroke in patients with unstable angina (UA), acute myocardial infarction (MI), stroke, transient ischemic attacks (TIAs) or other evidence of CVD

Aspirin

Primary prevention

• Low-dose Aspirin (75-100 mg/day) should not be routinely used for primary prevention of ASCVD in patients >70 years old and in adults of any age with increased risk of bleeding
  • May be considered for primary prevention of ASCVD in select patients 40-70 years old with high ASCVD risk but without bleeding risk and in patients with DM at high or very high CVD risk without contraindications
  • Risk-benefit profile should be assessed before using Aspirin for primary prevention especially in patients with DM
• Recommended for use in men >45 years, primarily to protect against MI; and women >55 years, primarily to protect against stroke

Secondary prevention

• Good evidence shows that Aspirin therapy (75-100 mg/day) can prevent MI, stroke and CV death in men and women with established CVD
• Low dose or 75 mg/day is recommended for the high-risk group or individuals with >20% risk of MI and stroke, and in diabetic patients
• Other groups recommend Aspirin in all patients with established CVD (eg previous MI or revascularization) and in patients without a history of CVD but with >10% 10-year CVD risk
  • Low-dose Aspirin given indefinitely is recommended in patients with established CVD and after a TIA or stroke, unless contraindicated
• Long-term secondary prevention with Aspirin and a second antithrombotic drug (a P2Y₁₂ inhibitor or low-dose Rivaroxaban) should be considered in patients whose risk for ischemic events is high and risk for bleeding is low

Clopidogrel

• Recommended in combination with Aspirin in UA/NSTEMI patients wherein Ticagrelor or Prasugrel is unavailable or contraindicated
  • Initial dose of 300 mg followed by 75 mg daily for at least 1 month and ideally up to 12 months
• Recommended as an alternative to Aspirin in patients intolerant of Aspirin and may be considered in preference to Aspirin in those with established ASCVD
• Recommended in patients with TIA or non-cardioembolic ischemic stroke

Prasugrel

• Recommended in combination with Aspirin only in P2Y₁₂-inhibitor-naive patients (especially diabetics) in whom coronary anatomy is known and who will undergo percutaneous coronary intervention (PCI)
  • Initial dose of 60 mg to be given at the time of PCI, followed by 10 mg daily for 12 months

Ticagrelor

• Recommended in combination with Aspirin in UA/non-ST-segment elevation myocardial infarction (NSTEMI)/ST-segment elevation myocardial infarction (STEMI) patients with intermediate to high risk of ischemic events regardless of choice of therapy (invasive or conservative)
  • Initial dose of 180 mg then 90 mg 12 hourly for 12 months

Vorapaxar

• A protease activated receptor-1 (PAR-1) antagonist that inhibits platelet activation
• Studies showed that Vorapaxar, when given with other antiplatelet agents, significantly reduced incidences of MI, stroke, and death caused by CVD

Anticoagulants

• For COVID-19 patients requiring oral anticoagulant therapy, drug-drug interactions between oral anticoagulants and COVID-19 drugs as well as liver and renal function should be considered in order to decrease the risk of bleeding or thromboembolic complications 

Warfarin

• May be used in post-MI patients for stroke prevention when clinically indicated (such as atrial fibrillation or left ventricle [LV] thrombus, dilated LV with poor systolic function)
• May be considered for paroxysmal or chronic atrial fibrillation or atrial flutter
• Warfarin with either Aspirin or Clopidogrel increases risk of bleeding and should be monitored closely by checking prothrombin time (PT)/INR
• Monitor international normalized ratio (INR) when using Warfarin

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs)

• Also called novel oral anticoagulants, new oral anticoagulants or direct oral anticoagulants
• Direct-acting inhibitors of either thrombin (Dabigatran) or factor Xa (Apixaban, Edoxaban, Rivaroxaban)
• May be used in the prevention and treatment of VTE and in the prevention of stroke and systemic embolism in patients with ACS and non-valvular atrial fibrillation
• Please see Ischemic Stroke, Venous Thromboembolism - Management and Venous Thromboembolism - Prevention disease management charts for specific dosing recommendations.

Antihypertensive Agents

• Initiation of drug therapy¹ is recommended for patients with a BP of ≥130/80 mmHg and ≥10% estimated 10-year ASCVD risk, and those with a BP of ≥140/90 mmHg and <10% estimated 10-year ASCVD risk
• Include angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) with calcium channel blockers, thiazide diuretics or beta-blockers, either alone or in combination
• If BP is uncontrolled despite treatment with 3 antihypertensive medications at maximally tolerated doses, consider adding an aldosterone antagonist, an alpha blocker, a centrally acting agent or a vasodilator
• Many antihypertensive agents are available. Specific formulations and prescribing information may be found in the latest MIMS. Please see Hypertension disease management chart for specific dosing recommendations.

¹Recommendations for treatment initiation may vary between countries. Please refer to available guidelines from local health authorities.

Lipid-lowering Agents

• Includes statins, fibrates, bile acid binding resins, Niacin, anti-sense apolipoprotein B oligonucleotide (Mipomersen), microsomal transfer protein inhibitor (Lomitapide), PCSK9 monoclonal antibodies and selective cholesterol absorption inhibitors (Ezetimibe)
• May halt progression or induce regression of coronary atherosclerosis
• Statins are drugs of choice and have been shown not only to reduce hyperlipidemia but also to reduce CV events and mortality
  • A high-intensity statin is recommended to be given at the highest tolerated dose to achieve the LDL-C goals set for a specific risk group
• Use of statin therapy may benefit patients who undergo coronary artery bypass grafting (CABG), preoperatively and postoperatively
• Statin therapy recommendations per target LDL-C reductions as follows:
  • High-intensity statin therapy (eg Atorvastatin [80 mg], Rosuvastatin [20 mg]) for approximately ≥50% LDL-C reduction
    • May be given to patients with ≥20% 10-year ASCVD risk
  • Moderate-intensity statin therapy (eg Atorvastatin [10 mg], Rosuvastatin [10 mg], Simvastatin [20-40 mg], Pravastatin [40 mg], Lovastatin [40 mg], Fluvastatin [40 mg 12 hrly], Pitavastatin [1-4 mg]) for goals of <50% lower LDL-C levels
    • May be given to patients with 7.5-19.9% 10-year ASCVD risk
  • Low-intensity statin therapy (eg Simvastatin [10 mg], Pravastatin [10-20 mg], Lovastatin [20 mg], Fluvastatin [20-40 mg]) for <30% reduced LDL-C levels
• If LDL-C goals are not reached, it is recommended to combine a maximally tolerated statin dose with Ezetimibe  
• Many lipid-lowering agents are available. Specific formulations and prescribing information may be found in the latest MIMS. Please see Dyslipidemia disease management chart for further information and for specific dosing recommendations.

PCSK9 Monoclonal Antibodies

• Eg Alirocumab, Evolocumab
• Indicated for the prevention of CV events 
  • Alirocumab reduces the risk of MI, stroke, and unstable angina requiring hospitalization in patients with established CVD 
  • Evolocumab reduces the risk of MI, stroke, peripheral arterial disease, and coronary revascularization in patients with established ASCVD 
• Recommended in patients with familial hypercholesterolemia who are intolerant of statins or in very high-risk familial hypercholesterolemia patients whose treatment with a maximally tolerated statin dose plus Ezetimibe did not achieve target goal
• As human monoclonal antibody, it inhibits the binding of PCSK9 to low-density lipoprotein receptors (LDLRs) thus increasing the number of available LDLRs to clear LDL thereby decreasing LDL-C concentration 
• Alirocumab may be given as an adjunct to diet, alone or in combination with other lipid-lowering therapies 
• Evolocumab may be given as an adjunct to diet and correction of other risk factors: In combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated

Other Agents

• Colchicine at a low dose (0.5 mg/day) may be considered in secondary prevention of CVD, particularly if other risk factors are insufficiently controlled or if recurrent CVD events occur with optimal therapy
  • Reduces the risk of MI, stroke, coronary revascularization and CV death in adult patients with established atherosclerotic disease or with multiple risk factors for CVD