Introduction
Ischemic Heart Disease (IHD), also referred to as Coronary Artery Disease (CAD), remains a leading cause of morbidity and mortality worldwide. It arises due to an imbalance between myocardial oxygen supply and demand, most commonly from atherosclerotic narrowing of coronary arteries. While revascularization strategies such as percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) play a vital role, medical therapy is the foundation of management—both for symptom relief and for improving long-term outcomes.
The goals of medical management in IHD include:
- Symptom control: Reducing angina, improving exercise tolerance, and enhancing quality of life.
- Prevention of adverse events: Reducing risk of myocardial infarction (MI), stroke, and death.
- Slowing disease progression: Addressing atherosclerosis and risk factors.
This article provides an in-depth review of the four key pillars of medical management:
- Anti-anginal therapy (nitrates, beta-blockers, calcium channel blockers)
- Antiplatelet therapy (aspirin, P2Y12 inhibitors)
- Statins and other lipid-lowering drugs
- ACE inhibitors and adjuncts
Anti-Anginal Therapy
1. Nitrates
Mechanism of Action:
- Nitrates act as vasodilators, primarily through conversion to nitric oxide (NO), which activates guanylate cyclase, increases cGMP, and relaxes vascular smooth muscle.
- They reduce preload (venodilation) and to a lesser extent afterload, thereby decreasing myocardial oxygen demand.
- They also promote coronary vasodilation, enhancing oxygen delivery.
Types:
- Short-acting nitrates: Sublingual nitroglycerin (GTN) tablets or sprays for acute angina relief.
- Long-acting nitrates: Isosorbide mononitrate, isosorbide dinitrate, transdermal GTN patches for prophylaxis.
Clinical Use:
- First-line for acute angina attacks.
- Long-acting forms used for chronic angina prophylaxis when beta-blockers or calcium channel blockers are insufficient.
Limitations:
- Tolerance: Continuous exposure leads to reduced efficacy; nitrate-free intervals are required.
- Side effects: Headache, flushing, hypotension, reflex tachycardia.
- Contraindications: Concurrent use with phosphodiesterase-5 inhibitors (sildenafil, tadalafil) due to severe hypotension risk.
2. Beta-Blockers
Mechanism of Action:
- Block β-adrenergic receptors, reducing heart rate, myocardial contractility, and blood pressure → lowering oxygen demand.
- Prolong diastole, improving coronary perfusion.
Examples:
- Cardioselective (β1): Metoprolol, bisoprolol, atenolol.
- Non-selective: Propranolol, nadolol.
- With additional vasodilatory properties: Carvedilol, nebivolol.
Clinical Use:
- First-line in chronic stable angina.
- Proven mortality benefit post-MI and in heart failure with reduced ejection fraction (HFrEF).
Limitations:
- Contraindicated in severe asthma/COPD, severe bradycardia, hypotension, advanced AV block.
- Side effects: Fatigue, depression, erectile dysfunction, cold extremities.
3. Calcium Channel Blockers (CCBs)
Mechanism of Action:
- Inhibit L-type calcium channels in vascular smooth muscle and myocardium.
- Dihydropyridines (DHPs): (Amlodipine, nifedipine) → vasodilation, reduce afterload.
- Non-DHPs: (Verapamil, diltiazem) → decrease heart rate and contractility.
Clinical Use:
- Alternative or adjunct to beta-blockers for angina.
- Effective in vasospastic (Prinzmetal) angina, where nitrates and CCBs are preferred.
- DHPs useful in hypertension with IHD.
Limitations:
- DHPs: Reflex tachycardia, edema.
- Non-DHPs: Bradycardia, AV block, contraindicated in HFrEF.
- Side effects: Constipation (verapamil), flushing, headache.
Antiplatelet Therapy
1. Aspirin
Mechanism:
- Irreversibly inhibits COX-1 enzyme → reduces thromboxane A2 production → inhibits platelet aggregation.
Clinical Evidence:
- Reduces risk of MI, stroke, and vascular death by ~25%.
- Indicated in all patients with established IHD unless contraindicated.
Dose:
- Low-dose (75–150 mg daily) sufficient for long-term therapy.
Limitations:
- Side effects: GI bleeding, peptic ulcers, hemorrhagic stroke.
- Contraindicated in aspirin allergy, severe bleeding disorders.
2. P2Y12 Inhibitors
Mechanism:
- Inhibit the ADP receptor (P2Y12) on platelets, preventing aggregation.
Agents:
- Clopidogrel: Irreversible, widely used.
- Prasugrel: More potent, faster onset, higher bleeding risk.
- Ticagrelor: Reversible, rapid action, superior to clopidogrel in ACS.
Clinical Use:
- Dual antiplatelet therapy (DAPT) with aspirin after PCI (stent placement).
- Alternative in aspirin-intolerant patients.
- ACS management (NSTEMI, STEMI).
Limitations:
- Bleeding risk, dyspnea with ticagrelor.
- Clopidogrel resistance due to CYP2C19 polymorphisms.
Statins and Lipid-Lowering Therapy
1. Statins
Mechanism:
- Inhibit HMG-CoA reductase, lowering LDL cholesterol.
- Improve endothelial function, stabilize plaques, reduce inflammation and thrombosis.
Examples:
- High-intensity: Atorvastatin (40–80 mg), rosuvastatin (20–40 mg).
- Moderate-intensity: Simvastatin, pravastatin.
Clinical Evidence:
- Statins reduce risk of recurrent MI, stroke, and cardiovascular death.
- First-line in all patients with IHD regardless of baseline LDL.
Limitations:
- Side effects: Myopathy, liver enzyme elevation, rare rhabdomyolysis.
- Monitor LFTs, CK in symptomatic patients.
2. Ezetimibe
- Inhibits intestinal absorption of cholesterol.
- Used as add-on to statins if LDL goals not achieved.
- Shown in IMPROVE-IT trial to reduce events when combined with simvastatin.
3. PCSK9 Inhibitors
- Alirocumab, evolocumab: Monoclonal antibodies that increase LDL receptor recycling.
- Reduce LDL by up to 60%, effective in high-risk or statin-intolerant patients.
- High cost limits widespread use.
4. Other Lipid-Lowering Agents
- Bempedoic acid: Oral ATP citrate lyase inhibitor, reduces LDL.
- Fibrates: Lower triglycerides, modest HDL increase.
- Omega-3 fatty acids: Reduce triglycerides, modest CV benefits in selected patients.
ACE Inhibitors and Other Adjuncts
1. ACE Inhibitors (ACEIs)
Mechanism:
- Inhibit conversion of angiotensin I to angiotensin II.
- Reduce afterload, preload, and adverse ventricular remodeling.
- Improve endothelial function and reduce progression of atherosclerosis.
Examples:
- Ramipril, lisinopril, perindopril.
Clinical Evidence:
- Mortality benefit in IHD patients with LV dysfunction, diabetes, hypertension, or prior MI.
- HOPE trial: Ramipril reduced cardiovascular death and MI in high-risk patients.
Side Effects:
- Cough (due to bradykinin), hyperkalemia, renal dysfunction, angioedema.
2. Angiotensin Receptor Blockers (ARBs)
- Used when ACEIs are not tolerated.
- Examples: Losartan, valsartan.
- Similar benefits with lower risk of cough.
3. Aldosterone Antagonists
- Spironolactone, eplerenone.
- Indicated in patients with LV dysfunction post-MI, on top of ACEI and beta-blocker.
- Reduce mortality and prevent remodeling.
4. Other Adjunctive Therapies
- Ranolazine: Late sodium current inhibitor, used in refractory angina. Improves exercise tolerance without affecting heart rate or BP.
- Ivabradine: Inhibits If current in sinoatrial node → lowers HR without reducing contractility; useful in angina patients intolerant of beta-blockers.
- Anticoagulants: Reserved for patients with atrial fibrillation or LV thrombus.
- Diabetes management: SGLT2 inhibitors and GLP-1 receptor agonists have shown cardiovascular benefit.
Comprehensive Approach
Effective management of IHD requires integration of these therapies:
- Symptom relief: Nitrates, beta-blockers, CCBs, ranolazine, ivabradine.
- Event prevention: Antiplatelets, statins, ACEIs/ARBs, aldosterone antagonists.
- Risk factor modification: Lifestyle, diabetes, hypertension, dyslipidemia control.
- Patient education: Adherence, recognizing symptoms, participation in cardiac rehabilitation.
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