Risk Reduction

• 20–25% reduction in heart attack, stroke, or cardiovascular death per 39 mg/dL (1 mmol/L) LDL reduction

• 10% reduction in all-cause death

How they work

• Lower cholesterol production in the liver (enzyme blockade) and increase LDL clearance, which slows plaque growth and stabilizes plaque.

Who needs them

• Many patients with known coronary disease, high ASCVD risk, diabetes, or elevated LDL; often first-line for LDL lowering.

Typical dose / Implementation

• Dose varies by medication and risk level; your clinician selects intensity and target.

Side effects

• Muscle aches: 5–10%

• Serious muscle injury: ~0.1% (rare)

• Small diabetes risk: ~0.2% per year (benefits typically outweigh this)

Monitoring / Important notes

• Liver tests may be checked initially; routine ongoing monitoring is often not required unless symptoms arise.

Risk Reduction

• 15–20% reduction in major cardiovascular events

• 27–28% reduction in heart attacks

• 21–27% reduction in stroke

How they work

• Injectable medications given every 2 weeks, monthly, or twice yearly (depending on type) that dramatically lower LDL by helping the liver remove more cholesterol from the blood.

Who needs them

• People who cannot tolerate statins, have very high LDL despite maximal statin therapy, or have familial hypercholesterolemia.

Typical dose / Implementation

• Injection schedule depends on agent (q2 weeks / monthly / twice yearly).

Side effects

• Injection-site reactions (most common).

• No increase in muscle pain, cognitive problems, or diabetes. Very safe overall.

Monitoring / Important notes

• Minimal monitoring required.

Risk Reduction

• 13% reduction in heart attacks when combined with statins

How they work

• Blocks cholesterol absorption in the intestines.

Who needs them

• People needing additional LDL lowering beyond statins or unable to use higher-dose statins.

Typical dose / Implementation

• 10 mg daily.

Side effects

• Generally very well tolerated with minimal side effects.

Monitoring / Important notes

• No routine monitoring in most patients.

Risk Reduction

• FDA-approved to reduce risk of heart attack and coronary procedures.

How they work

• Oral LDL-lowering therapy through a pathway different from statins.

Who needs them

• Particularly useful for people who cannot tolerate statins.

Typical dose / Implementation

• 180 mg daily.

Side effects

• Not specified in your source texts (commonly discussed with your clinician).

Monitoring / Important notes

• Follow your clinician’s monitoring plan.

Risk Reduction

• 25% reduction in major cardiovascular events

• 31% reduction in heart attacks

• 20% reduction in cardiovascular death

• 37% reduction in stroke

How they work

• Highly purified EPA that reduces triglycerides and inflammation.

Who needs them

• People with elevated triglycerides (typically ≥135 mg/dL) despite statin therapy.

Typical dose / Implementation

• 4 grams daily (2 grams twice daily with meals).

Side effects

• Increased atrial fibrillation in about 1% of patients.

• Slightly increased bleeding risk.

Monitoring / Important notes

• Regular fish oil supplements are NOT recommended—only prescription icosapent ethyl has proven cardiovascular benefit.

Risk Reduction

• 17–22% reduction in major cardiovascular events

• 20% reduction in heart attacks

• 30% reduction in stroke

• 17% reduction in death

How they work

• Relax blood vessels and reduce strain on the heart.

Who needs them

• Many patients with hypertension, coronary disease, diabetes, kidney disease, or heart failure—per clinician judgment.

Typical dose / Implementation

• Dose varies; titrated to blood pressure and tolerance.

Side effects

• Dry cough (10–15%), dizziness, rarely swelling of face/lips.

Monitoring / Important notes

• Kidney function and potassium checked periodically.

Risk Reduction

• Similar to ACE inhibitors in many settings (17–22% reported in your Text 1)

• Also reported as ~10–13% reduction in cardiovascular events (your Text 2)

How they work

• Similar vascular benefits to ACE inhibitors via a different mechanism.

Who needs them

• Often used when ACE inhibitors cause cough or are not tolerated.

Typical dose / Implementation

• Dose varies; titrated to blood pressure and tolerance.

Side effects

• Generally well tolerated; less cough than ACE inhibitors.

Monitoring / Important notes

• Kidney function and potassium checked periodically.

Risk Reduction

• 23% reduction in death after heart attack

• 27% reduction in recurrent heart attacks (secondary prevention)

How they work

• Slow heart rate and reduce blood pressure, lowering the heart’s workload.

Who needs them

• Especially beneficial after a heart attack and/or with heart failure (and some arrhythmias), as directed by clinician.

Typical dose / Implementation

• Dose varies by medication and condition.

Side effects

• Fatigue, cold hands/feet; may worsen asthma in some patients.

Monitoring / Important notes

• Heart rate, blood pressure, symptoms monitored during titration.

Risk Reduction

• 20–23% reduction in major cardiovascular events in people with known heart disease

• 30% reduction in recurrent heart attack in secondary prevention

• Primary prevention: 10–12% reduction in heart attacks but similar increase in bleeding risk

How they work

• Prevents clotting by stopping platelets from sticking together.

Who needs them

• Primarily secondary prevention (prior heart attack, stroke, stent, known coronary disease). Primary prevention requires careful individualized discussion.

Typical dose / Implementation

• Loading dose (acute heart attack): 162–325 mg

• Maintenance: 75–100 mg daily (often 81 mg daily)

Side effects

• Increased bleeding risk, stomach upset, ulcers; serious bleeding ~1–2% over several years.

Monitoring / Important notes

• Watch for unusual bleeding/bruising; discuss whether benefits outweigh bleeding risk.

Risk Reduction

• ~20% reduction in cardiovascular events when combined with aspirin after heart attack or stent (dual antiplatelet therapy)

How they work

• Prevent clot formation through a different platelet pathway than aspirin.

Who needs them

• Typically prescribed 6–12 months after a heart attack or stent (sometimes longer in selected cases).

Typical dose / Implementation

• Taken daily; agent and duration chosen by clinician.

Side effects

• Increased bleeding risk, bruising.

Monitoring / Important notes

• Do not stop without medical guidance, especially if you have a stent.

Risk Reduction

• 24% reduction in major cardiovascular events when added to aspirin in stable coronary/peripheral artery disease (selected high-risk patients)

How they work

• Anticoagulant that reduces clot formation through a mechanism different from aspirin.

Who needs them

• Selected high-risk patients with coronary or peripheral artery disease after individualized bleeding-risk review.

Typical dose / Implementation

• 2.5 mg twice daily plus aspirin 81 mg daily.

Side effects

• Increased bleeding risk; major bleeding reported to increase from 1.9% to 2.7%.

Monitoring / Important notes

• Requires careful clinician-guided risk/benefit discussion.

Risk Reduction

• 23–31% reduction in major cardiovascular events

• 26% reduction in heart attacks

• 46% reduction in stroke

• After heart attack: 23% risk reduction reported

How they work

• Reduces inflammation in blood vessels that contributes to plaque buildup and rupture.

Who needs them

• People with stable coronary disease or recent heart attack, as add-on to standard therapies.

Typical dose / Implementation

• 0.5 mg daily.

Side effects

• Diarrhea/stomach upset in about 10%; often early and improves.

Monitoring / Important notes

• Minimal monitoring required.

Risk Reduction

• Major adverse cardiovascular events (MACE): 9-14% reduction in composite of MI, stroke, or cardiovascular death.

• Cardiovascular death: 14-16% reduction

• Heart failure hospitalization: 27-31% reduction (the most robust benefit of this class)

• All-cause mortality: 13-15% reduction

• Myocardial infarction: 10-11% reduction (modest effect)

• Kidney disease progression: significant reduction in people with established ASCVD, multiple risk factors, or albuminuric kidney disease.

How they work

• Reduce plasma glucose by enhancing urinary excretion of glucose through inhibition of sodium-glucose cotransporter 2 in the kidney.

• Cardiovascular and kidney benefits occur largely independent of glycemic management.

Who needs them

• People with type 2 diabetes and established ASCVD, indicators of high ASCVD risk, heart failure, or chronic kidney disease- recommended independent of A1C level, with or without metformin use.

• Individuals already at glycemic goal with other medications may benefit from switching to SGLT2 inhibitors to reduce cardiovascular and kidney risk.

• Benefits observed across the full range of heart failure risk, though greater reductions occur in those with higher baseline risk.

Typical dose / Implementation

• Oral medications taken once daily

• Glycemic efficacy is intermediate-to-high but lower at reduced eGFR[3]

• Can be used in combination with GLP-1 receptor agonists for additive cardiovascular and kidney benefits.

Side effects

• Mycotic genital infections (typically mild and treatable).

• Diabetic ketoacidosis: low incidence (0.1-0.6% in cardiovascular outcome trials vs. <0.1-0.3% with placebo).

• Not recommended in type 1 diabetesdue to significant increase in diabetic ketoacidosis and euglycemic ketoacidosis.

• Lower risk of hypoglycemia compared to other glucose-lowering agents.

Monitoring / Important notes

• Particularly important for individuals with ASCVD, heart failure, and CKD who have higher hypoglycemia risk than those without these conditions.

• FDA-approved indications include reducing cardiovascular death and heart failure hospitalization (dapagliflozin, empagliflozin) and reducing MACE in type 2 diabetes with established cardiovascular disease (canagliflozin, empagliflozin)

Agents WITHOUT demonstrated cardiovascular benefit:Lixisenatide and extended-release exenatide were not superior to placebo and are not recommended for CVD risk reduction

 

Risk Reduction

• Major atherosclerotic cardiovascular outcomes (MI, stroke, or cardiovascular death): comparable reduction to SGLT2 inhibitors in people with type 2 diabetes and established ASCVD.

• Heart failure hospitalization: reduced risk in people with established ASCVD, multiple risk factors, or albuminuric kidney disease.

• Kidney disease progression: reduced risk.

• In the GRADE trial (individuals with relatively short diabetes duration without established CVD): 30% reduction in cardiovascular events (HR 0.7, 95% CI 0.6-0.9) with liraglutide compared to insulin glargine, glimepiride, or sitagliptin.

How they work

• Activate glucagon-like peptide-1 receptors to enhance glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, and promote satiety

• Cardiovascular and kidney benefits occur largely independent of glycemic management.

Who needs them

• People with type 2 diabetes and established ASCVD, indicators of high ASCVD risk, heart failure, or chronic kidney disease- recommended independent of A1C level, with or without metformin use.

• People with type 2 diabetes, obesity, and symptomatic heart failure with preserved ejection fraction- GLP-1 RAs or dual GIP/GLP-1 RAs with demonstrated benefits are specifically recommended.

• Individuals at lower (moderate) CVD risk may still benefit from GLP-1 RA therapy to reduce future cardiovascular events.

• Individuals already at glycemic goal with other medications may benefit from switching to GLP-1 RAs to reduce cardiovascular and kidney risk.

Typical dose / Implementation

• Available as once-daily (liraglutide) or once-weekly (semaglutide, dulaglutide) subcutaneous injections

• Oral formulation of semaglutide also available with demonstrated cardiovascular benefit.

• Can be used in combination with SGLT2 inhibitors for additive cardiovascular and kidney benefits.

Side effects

• Gastrointestinal effects (nausea, vomiting, diarrhea) are common

• Lower risk of hypoglycemia compared to other glucose-lowering agents.

Monitoring / Important notes

• Particularly important for individuals with ASCVD, heart failure, and CKD who have higher hypoglycemia risk than those without these conditions.

• Cardiovascular outcome trials of the dual GIP/GLP-1 RA tirzepatide are ongoing.

• Individuals with type 2 diabetes and moderate levels of CVD risk derive cardiovascular and mortality benefits with preferential use of GLP-1 RAs compared with sulfonylureas or DPP-4 inhibitors.

Risk Reduction

• After a heart attack (Lyon Diet Heart Study):

  • Cardiovascular death reduction: 65–76%

  • All-cause death reduction: 56%

  • Recurrent heart attack reduction: 73%

  • Major cardiovascular events reduction: 70%

• Primary prevention (PREDIMED):

  • Major cardiovascular events reduction: 30%

  • Stroke reduction: 40–42%

• Overall Mediterranean diet benefits (as reported in your Text 2):

  • All deaths reduction: 28%

  • Cardiovascular death reduction: 41–45%

  • Heart attack reduction: 52%

  • Stroke reduction: 35%

How they work

• Reduces inflammation, improves cholesterol and blood pressure, and provides antioxidants that protect blood vessels.

Who needs them

• Everyone at risk for cardiovascular disease; especially powerful for people with known coronary disease.

Typical dose / Implementation

• Emphasize: vegetables, fruits, whole grains, beans, nuts, olive oil, fish

• Moderate: poultry, eggs, cheese, yogurt

• Limit: red meat, sweets, ultra-processed foods

• Use extra-virgin olive oil as primary fat

• Eat fish at least twice weekly (salmon, sardines, mackerel)

Side effects

• No meaningful adverse effects; discuss calories/weight goals if needed.

Monitoring / Important notes

Risk Reduction

• Cardiac rehabilitation (after heart attack):

  • All-cause death reduction: 13–20%

  • Cardiovascular death reduction: 26–36%

  • Heart attack reduction: 18–47%

  • Hospitalization reduction: 23–42%

  • Number needed to treat: 37 to prevent one cardiovascular death or hospitalization

• Regular physical activity (prevention):

  • Cardiovascular death reduction: 23–40%

  • All-cause death reduction: 27–31%

  • In stable heart disease with high-volume exercise (10–20 hrs/week): ~50% reduction in cardiovascular events

How they work

• Improves blood vessel function, blood pressure, insulin sensitivity, inflammation, and cardiac efficiency.

Who needs them

• Everyone; cardiac rehab is especially important after heart attack or stent.

Typical dose / Implementation

• Minimum: 150 minutes/week moderate (brisk walking) or 75 minutes/week vigorous (jogging)

• Strength training 2 days/week

• Cardiac rehab: structured, supervised program after heart attack

Side effects

• Injury risk if overdone; start gradually and follow clinician guidance.

Risk Reduction

• After heart attack:

  • Cardiovascular death reduction: 36–39%

  • Major cardiovascular events reduction: 43%

  • All-cause death reduction: 40%

  • Heart attack reduction: 36%

  • Stroke reduction: 30%

How they work

• Reduces clotting tendency, inflammation, vessel spasm, and plaque progression; improves oxygen delivery.

Who needs them

• Anyone who smokes or uses tobacco/nicotine products.

Typical dose / Implementation

• Choose a quit date; consider counseling + pharmacotherapy if needed.

Side effects

• Withdrawal symptoms (cravings, irritability, insomnia) are common early and improve over time.

Monitoring / Important notes

• Timeline of benefit:

  • After 1 year: ~50% reduction in heart disease risk

  • After 15 years: risk approaches never-smoker levels

  • Heavy smokers: may require ~25 years to reach never-smoker risk levels