Cardiovascular Drugs: Antihypertensives, Antiarrhythmics, Anticoagulants, Antiplatelets, and Lipid-Lowering Agents

Introduction

Cardiovascular drugs comprise the largest therapeutic category in medicine, encompassing agents for hypertension, heart failure, coronary artery disease, arrhythmias, thrombosis, and dyslipidemia. These medications reduce cardiovascular morbidity and mortality and are among the most prescribed drug classes worldwide.

Antihypertensive Agents

First-Line Antihypertensives

Drug Class	Mechanism	First-Line Indication	Key Benefits	Key Adverse Effects
Thiazide/thiazide-like diuretics	Inhibit Na-Cl cotransporter in distal convoluted tubule	Stage 1 HTN (JNC 8)	Reduce stroke, HF events; chlorthalidone superior to HCTZ	Hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hypercalcemia
ACE inhibitors	Inhibit angiotensin-converting enzyme, decrease Ang II	HF, CKD, DM, post-MI	Renal protection, HF survival, LV remodeling	Cough (10-20%), hyperkalemia, angioedema, teratogenic
ARBs	Block AT1 receptor	Same as ACEi (ACEi intolerant)	Same benefits as ACEi without cough	Similar to ACEi but less cough, lower angioedema
CCBs (dihydropyridine)	L-type Ca channel blockade (vascular)	Stage 1 HTN, elderly, isolated systolic HTN, African ancestry	Reduce stroke, angina	Peripheral edema, headache, dizziness, gingival hyperplasia
CCBs (non-dihydropyridine)	L-type Ca channel blockade (cardiac)	Atrial fibrillation rate control, angina	Reduce AF rate, angina frequency	Bradycardia, heart block, constipation (verapamil)

Second-Line Antihypertensives

Class	Mechanism	Key Indications	Key Adverse Effects
Beta-blockers	Beta-1 (+/- beta-2) antagonism	Post-MI, HF (carvedilol, metoprolol, bisoprolol), angina, migraine	Fatigue, bradycardia, bronchospasm, depression, mask hypoglycemia
Aldosterone antagonists	Mineralocorticoid receptor antagonism	HFrEF, resistant HTN, primary aldosteronism	Hyperkalemia, gynecomastia (spironolactone)
Alpha-1 blockers	Alpha-1 adrenergic antagonism	BPH, PTSD nightmares (prazosin)	Orthostatic hypotension, dizziness, syncope
Vasodilators (hydralazine)	Direct smooth muscle relaxation	Resistant HTN, HF (especially African American)	Reflex tachycardia, SLE-like syndrome, headache
Central alpha-2 agonists	Central alpha-2 agonism	Resistant HTN, opioid withdrawal	Sedation, dry mouth, rebound hypertension

Combination Therapy

Combination	Rationale	Examples
ACEi/ARB + thiazide	Additive BP lowering; thiazide counteracts ACEi/ARB hyperkalemia	Lisinopril-HCTZ
ACEi/ARB + CCB	Additive effect; CCB counteracts ACEi/ARB cough	Amlodipine-benazepril
ACEi/ARB + CCB + thiazide	Triple therapy for resistant HTN	Various combinations
Beta-blocker + CCB (DHP)	Angina + HTN, rate control	Metoprolol + amlodipine

Heart Failure Medications

Guideline-Directed Medical Therapy (GDMT) for HFrEF

Drug Class	Mechanism	Outcome Benefit	Key Drugs	Target Dose
ACE inhibitors	Decrease Ang II, aldosterone	Mortality reduction (30-40%)	Enalapril, lisinopril, ramipril, trandolapril	Variable (e.g., enalapril 10 mg BID)
ARBs	Block AT1	Mortality reduction (similar to ACEi as alternative)	Candesartan, valsartan, losartan	Candesartan 32 mg daily
ARNI (Sacubitril/valsartan)	Neprilysin inhibition + AT1 blockade	Superior to ACEi (PARADIGM-HF: HR 0.80)	Sacubitril/valsartan	97/103 mg BID
Beta-blockers (HF-approved)	Beta-1 antagonism	Mortality reduction (30-35%)	Carvedilol, metoprolol succinate, bisoprolol	Carvedilol 25 mg BID; metoprolol 200 mg daily
MRAs	Aldosterone antagonism	Mortality reduction (25-30%)	Spironolactone, eplerenone	Spironolactone 25 mg daily; eplerenone 50 mg daily
SGLT2 inhibitors	SGLT2 inhibition (pleiotropic)	HF hospitalization + CV mortality reduction (DAPA-HF, EMPEROR-Reduced)	Dapagliflozin, empagliflozin	Dapagliflozin 10 mg daily
Ivabradine	I(f) current inhibition (heart rate reduction)	HF hospitalization reduction (SHIFT)	Ivabradine	5-7.5 mg BID
Hydralazine + isosorbide dinitrate	NO donor + vasodilator	Mortality reduction (A-HeFT: 43%) in African Americans	Hydralazine-ISDN	Hydralazine 75 mg TID + ISDN 40 mg TID

HFpEF Medications

Drug	Evidence	Recommendation Level
SGLT2 inhibitors	EMPEROR-Preserved, DELIVER: reduces HF hospitalization	Class I (2022 AHA/ACC/HFSA)
ARBs	CHARM-Preserved: modest reduction in HF hospitalization	Class IIb
Spironolactone	TOPCAT: modest benefit (regional variation)	Class IIb
Loop diuretics	Symptom relief (volume overload)	No mortality benefit; for symptom management

Anticoagulants

Comparison of Anticoagulants

Drug	Mechanism	Route	Onset	Half-Life	Monitoring	Reversal	FDA Indications
Unfractionated heparin	Activates antithrombin III (Xa, IIa)	IV	Immediate	1-2 hours	aPTT (anti-Xa)	Protamine	DVT/PE, ACS, AF, bridging
LMWH (enoxaparin)	Activates antithrombin III (Xa > IIa)	SC	3-5 hours	4.5 hours	Anti-Xa (not routine)	Protamine (partial)	DVT/PE, ACS, prophylaxis
Fondaparinux	Selective factor Xa via antithrombin	SC	2 hours	17 hours	None (not needed)	Recombinant factor VIIa (off-label)	DVT/PE prophylaxis, HIT
Warfarin	Vitamin K antagonist (II, VII, IX, X)	PO	3-5 days	40 hours	INR	Vitamin K, FFP, PCC	AF, DVT/PE, mechanical valves
Dabigatran	Direct thrombin (IIa) inhibitor	PO	1-2 hours	12-17 hours	None	Idarucizumab	AF, DVT/PE
Rivaroxaban	Direct Xa inhibitor	PO	2-4 hours	7-13 hours	None	Andexanet alfa	AF, DVT/PE, ACS, VTE prophylaxis
Apixaban	Direct Xa inhibitor	PO	1-3 hours	8-15 hours	None	Andexanet alfa	AF, DVT/PE, DVT prophylaxis

DOACs vs. Warfarin

Aspect	DOACs	Warfarin
Dosing	Fixed dose	Adjusted by INR
Monitoring	Not required	Required (INR 2-3)
Food interactions	Few (apixaban with food reduces absorption)	Many (vitamin K containing foods)
Drug interactions	Fewer (P-gp, CYP3A4)	Many (CYP450, diet)
Half-life	Short (8-15 hours)	Long (36-42 hours)
Reversal	Specific agents available (idarucizumab, andexanet)	Vitamin K, PCC
Renal dosing	Yes (all require renal adjustment)	No renal adjustment (safe in CKD)
Valvular AF	Contraindicated (mechanical valves, moderate-severe mitral stenosis)	Indicated for all valvular AF

Antiplatelet Agents

Drug	Mechanism	Onset	Duration	Indications	Half-Life	Reversal
Aspirin	Irreversible COX-1 inhibition (decreases TXA2)	30-60 min	Platelet lifespan (7-10 days)	CAD, CVA, PVD, acute MI	15-20 min	Platelet transfusion
Clopidogrel	P2Y12 receptor antagonist (prodrug, CYP2C19)	2-6 hours	3-7 days	ACS, PCI, CVA, PVD	6 hours	Platelet transfusion
Prasugrel	P2Y12 receptor antagonist (prodrug, no CYP2C19 issue)	30 min - 2 hours	5-9 days	ACS with PCI	7 hours	Platelet transfusion
Ticagrelor	P2Y12 receptor antagonist (direct, reversible)	30 min - 2 hours	3-5 days	ACS with PCI	7-12 hours	Platelet transfusion
Dipyridamole	Adenosine reuptake inhibitor, PDE inhibitor	1-2 hours	6-12 hours	CVA (with aspirin)	12 hours	No specific
Cilostazol	PDE3 inhibitor	1-2 hours	5-10 hours	PVD (claudication)	12 hours	No specific

Dual Antiplatelet Therapy (DAPT)

Clinical Scenario	Duration	Regimen
STEMI with PCI	12 months	Aspirin + ticagrelor or prasugrel
NSTEMI with PCI	12 months	Aspirin + ticagrelor or prasugrel or clopidogrel
Elective PCI (stable CAD)	1-6 months (based on stent type)	Aspirin + clopidogrel
CVA/TIA	21-90 days	Aspirin + clopidogrel (CHANCE, POINT)
Peripheral artery disease	1 month (post-stent)	Aspirin + clopidogrel
After 12 months	Continue single antiplatelet	Aspirin or clopidogrel alone

Lipid-Lowering Agents

Drug Class	Mechanism	LDL Reduction	TG Reduction	HDL Increase	Key Benefit	Key Adverse Effects
Statins	HMG-CoA reductase inhibition	18-55%	10-30%	2-10%	Plaque stabilization, mortality reduction	Myopathy, transaminitis, new-onset DM
Ezetimibe	NPC1L1 inhibition (intestinal cholesterol absorption)	15-20%	5-10%	1-5%	Additive with statin; CV event reduction (IMPROVE-IT)	Well-tolerated, minimal
PCSK9 inhibitors	PCSK9 inhibition (more LDL receptors)	50-60%	10-15%	5-10%	Major LDL reduction; CV event reduction (FOURIER, ODYSSEY)	Injection site reactions, rare antibody development
Fibrates	PPAR-alpha agonism	5-20%	20-50%	10-20%	TG reduction, HDL increase; limited CV outcome benefit	Myopathy (especially with statins), gallstones, transaminitis
Niacin	Inhibits hepatic VLDL production	5-15%	20-50%	15-30%	Broad lipid improvement	Flushing, hyperglycemia, hepatotoxicity (AIM-HIGH, HPS2-THRIVE showed no CV benefit)
Icosapent ethyl	Purified EPA (omega-3)	5-10%	20-30%	5-10%	CV event reduction (REDUCE-IT: HR 0.75)	Bleeding risk (minor), atrial fibrillation
Bile acid sequestrants	Bind bile acids, deplete hepatic cholesterol	15-25%	No change	3-5%	No systemic absorption	GI intolerance, constipation, drug absorption interference

Conclusion

Cardiovascular pharmacology encompasses a wide range of drug classes targeting hypertension, heart failure, thrombosis, dyslipidemia, and arrhythmias. Major advances include DOACs for convenient anticoagulation, PCSK9 inhibitors and icosapent ethyl for lipid management, SGLT2 inhibitors expanding beyond diabetes to heart failure, and ARNI therapy replacing ACEi as first-line HF treatment. Individualized therapy based on patient characteristics, comorbidities, and drug tolerance optimizes cardiovascular outcomes.