What new cardiovascular drugs have been FDA‑approved in the past five years, and what are their indications and dosing?

New Cardiovascular Drugs Approved in the Past Five Years

The most clinically significant cardiovascular drugs approved in the past five years include SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) and GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) with proven cardiovascular mortality reduction, along with the angiotensin receptor-neprilysin inhibitor valsartan/sacubitril and the If-channel inhibitor ivabradine for heart failure. 1, 2, 3

SGLT2 Inhibitors with Cardiovascular Indications

These agents represent a paradigm shift in cardiovascular risk reduction, demonstrating benefits beyond glycemic control:

Empagliflozin

• FDA-approved for cardiovascular death reduction in patients with type 2 diabetes and established cardiovascular disease 1
• Reduced cardiovascular death by 38% (HR 0.62,95% CI 0.49-0.77) in the EMPA-REG OUTCOME trial 1
• Reduced the composite outcome of MI, stroke, and cardiovascular death by 14% (HR 0.86,95% CI 0.74-0.99) 1
• Dosing: 10 mg or 25 mg once daily 1

Canagliflozin

• Demonstrated significant reduction in cardiovascular death, MI, or stroke (HR 0.86,95% CI 0.75-0.97) in combined CANVAS program analysis 1
• Critical caveat: Associated with increased risk of lower-limb amputation (HR 1.97,95% CI 1.41-2.75), requiring careful patient selection and monitoring 1
• Dosing: 100 mg or 300 mg once daily 1

Dapagliflozin

• Approved for cardiovascular risk reduction in patients with type 2 diabetes and multiple cardiovascular risk factors 1
• Part of the three FDA-approved SGLT2 inhibitors with proven cardiovascular benefit 1

GLP-1 Receptor Agonists with Cardiovascular Benefits

Not all GLP-1 receptor agonists provide cardiovascular benefit—this is NOT a class effect. Only specific agents have demonstrated mortality reduction in cardiovascular outcomes trials. 2, 4

Semaglutide (Injectable)

• FDA-approved to reduce major adverse cardiovascular events including heart attack 1, 2
• Reduced primary composite outcome by 26% (HR 0.74,95% CI 0.58-0.95) in SUSTAIN-6 trial 1, 2
• Preferred agent for once-weekly dosing and greater cardiovascular risk reduction 2
• Dosing: 0.5 mg or 1.0 mg subcutaneously once weekly 1
• Gastrointestinal side effects occur in 15-20% but are typically transient 2

Liraglutide

• Reduced cardiovascular death by 22% (HR 0.78,95% CI 0.66-0.93) in LEADER trial 1, 2
• Reduced primary composite outcome from 14.9% to 13.0% (HR 0.87,95% CI 0.78-0.97) 1, 2
• Preferred for patients with chronic kidney disease (eGFR <60 mL/min/1.73 m²) due to greater MACE reduction in this subgroup 2
• Dosing: 1.8 mg subcutaneously once daily 1

Dulaglutide

• Demonstrated cardiovascular benefit in large cardiovascular outcomes trials 1, 2
• Included in guideline recommendations for patients with established atherosclerotic cardiovascular disease 1, 2
• Dosing: 0.75 mg to 1.5 mg subcutaneously once weekly 1

Agents WITHOUT Proven Cardiovascular Benefit

• Lixisenatide, exenatide, and albiglutide showed neutral or non-significant results in cardiovascular outcomes trials 1, 4
• These should NOT be selected when cardiovascular risk reduction is the goal 4

Heart Failure Medications

Valsartan/Sacubitril (Angiotensin Receptor-Neprilysin Inhibitor)

• First-in-class combination approved for heart failure with reduced ejection fraction (HFrEF) 3
• Reduces cardiovascular death and heart failure hospitalization 3
• Represents a novel mechanism combining angiotensin receptor blockade with neprilysin inhibition 3

Ivabradine (If-Channel Inhibitor)

• FDA-approved for chronic HFrEF in patients with elevated heart rate 3
• Reduces cardiovascular death and heart failure hospitalization 3
• Mechanism: Selectively inhibits the If current in the sinoatrial node, reducing heart rate without negative inotropic effects 3

Mineralocorticoid Receptor Antagonist

Finerenone

• Non-steroidal mineralocorticoid receptor antagonist approved for patients with type 2 diabetes and chronic kidney disease 1
• Reduces cardiovascular outcomes and CKD progression 1
• Key advantage: Lower risk of hyperkalemia compared to spironolactone 1

Lipid-Lowering Agents

PCSK9 Inhibitors (Evolocumab, Alirocumab)

• Monoclonal antibodies that dramatically lower LDL cholesterol 5
• Provide incremental cardiovascular risk reduction in high-risk patients who cannot achieve LDL targets with statins and ezetimibe 5
• Represent biological agents (BLAs) rather than traditional small molecules 6

Bempedoic Acid

• ATP citrate lyase inhibitor approved for LDL cholesterol reduction 7
• Recent label expansion based on cardiovascular outcomes data 7
• Advantage: Does not cause myalgias like statins, useful for statin-intolerant patients 7

Inclisiran (siRNA Therapy)

• Small interfering RNA targeting PCSK9 synthesis 5
• Administered twice yearly after initial loading doses 5
• Represents novel biological approach to lipid management 6, 5

Hypertension Agents

Nebivolol

• Cardioselective beta-blocker with vasodilatory properties through nitric oxide-induced vasodilation 1
• Dosing: 5-40 mg once daily 1
• Preferred in patients requiring beta-blockade with concurrent vasodilation 1

Clinical Algorithm for Drug Selection

For patients with type 2 diabetes and established cardiovascular disease:

1. First priority: SGLT2 inhibitor (empagliflozin preferred for mortality reduction) OR GLP-1 receptor agonist (semaglutide or liraglutide) 1, 2
2. Consider combination therapy with both an SGLT2 inhibitor and GLP-1 receptor agonist for maximal cardiovascular and renal protection 1
3. For chronic kidney disease: Add finerenone if eGFR permits 1

For heart failure with reduced ejection fraction:

1. Foundation: Valsartan/sacubitril (replacing ACE inhibitor or ARB) 3
2. Add ivabradine if heart rate remains ≥70 bpm despite beta-blocker optimization 3
3. Add SGLT2 inhibitor (dapagliflozin or empagliflozin) regardless of diabetes status 1

For high cardiovascular risk requiring aggressive LDL lowering:

1. Maximize statin therapy first 5
2. Add ezetimibe if LDL target not achieved 5
3. Add PCSK9 inhibitor or inclisiran for further LDL reduction in very high-risk patients 7, 5
4. Consider bempedoic acid for statin-intolerant patients 7

Critical Pitfalls to Avoid

• Do not assume class effects: Cardiovascular benefits of GLP-1 receptor agonists are agent-specific, not universal across the class 2, 4
• Monitor for amputations with canagliflozin: This SGLT2 inhibitor carries unique amputation risk requiring foot care vigilance 1
• Avoid thiazolidinediones in heart failure: These agents consistently increase heart failure risk and should be avoided in symptomatic patients 1
• Document cardiovascular disease explicitly when prescribing semaglutide or liraglutide to facilitate insurance approval, citing FDA-approved cardiovascular indications 2
• Titrate GLP-1 receptor agonists slowly to minimize gastrointestinal side effects, which affect 15-20% of patients 2