What are the initial pharmacological treatments for patients with cardiovascular disease, including hypertension, high cholesterol, and heart failure?

Initial Pharmacological Treatment for Cardiovascular Disease

For patients with cardiovascular disease, initial pharmacological treatment should include aspirin 75-162 mg daily for antiplatelet therapy, ACE inhibitors (or ARBs if intolerant), beta-blockers, and statins for lipid management, with specific additions based on the clinical presentation (hypertension, heart failure, or acute coronary syndrome). 1

Hypertension Management

First-Line Pharmacological Therapy

• Combination therapy is recommended as initial treatment for most patients with confirmed hypertension (BP ≥140/90 mmHg), using a RAS blocker (ACE inhibitor or ARB) combined with either a dihydropyridine calcium channel blocker or thiazide/thiazide-like diuretic. 1, 2

• Fixed-dose single-pill combinations are strongly recommended to improve medication adherence. 1, 2

• For patients with BP 130-139/80-89 mmHg and high cardiovascular risk, initiate pharmacological treatment after 3 months of lifestyle intervention if BP remains uncontrolled. 2

Treatment Escalation Algorithm

• If BP is not controlled with two-drug combination, escalate to three-drug combination: RAS blocker + dihydropyridine CCB + thiazide/thiazide-like diuretic (preferably as single-pill combination). 1, 2

• If BP remains uncontrolled on three-drug combination, add spironolactone as the fourth agent. 1

• Never combine two RAS blockers (ACE inhibitor + ARB) due to increased adverse effects without additional benefit. 1, 2

Target Blood Pressure

• Target BP should be 120-129/70-79 mmHg in routine practice, though optimal target under research conditions is ≤120/70 mmHg. 1

• For patients with heart failure, target BP is <130/80 mmHg, with consideration for lowering to <120/80 mmHg in selected patients. 1

High Cholesterol Management

Statin Therapy

• Lipid-lowering drugs (HMG-CoA reductase inhibitors/statins) are recommended for patients with LDL cholesterol >130 mg/dL, with a target LDL <100 mg/dL. 1

• For patients with documented or suspected coronary artery disease and LDL 100-129 mg/dL, lifestyle and/or drug therapies should be used to lower LDL to <100 mg/dL. 1

• Atorvastatin dosing ranges from 10-80 mg daily depending on cardiovascular risk and LDL targets, with the 80 mg dose showing greater efficacy but higher rates of persistent transaminase elevations (1.3% vs 0.2% with 10 mg). 3

Heart Failure Management

Core Pharmacological Therapy (HFrEF)

• All patients with heart failure with reduced ejection fraction should receive quadruple therapy unless contraindicated: diuretics (for fluid overload), ACE inhibitors (or ARBs if intolerant), beta-blockers (bisoprolol, carvedilol, or metoprolol succinate), and mineralocorticoid receptor antagonists. 1

• Angiotensin receptor-neprilysin inhibitor (ARNI) is recommended to replace ACE inhibitor therapy in ambulatory patients who remain symptomatic despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, and MRAs. 1

Diuretic Selection

• Thiazide diuretics should be used for BP control and to reverse volume overload; in severe heart failure or severe renal impairment, loop diuretics should be used for volume control. 1

• Diuretics must be used together with an ACE inhibitor or ARB and a beta-blocker. 1

Drugs to Avoid in Heart Failure

• Nondihydropyridine calcium channel blockers (verapamil and diltiazem) are contraindicated in heart failure due to negative inotropic effects. 1

• Clonidine and moxonidine should be avoided (moxonidine was associated with increased mortality). 1

• Alpha-adrenergic blockers (such as doxazosin) should only be used if other drugs are inadequate at maximum tolerated doses. 1

Special Populations

• For African-American patients with NYHA class III or IV heart failure, add hydralazine/isosorbide dinitrate to the regimen of diuretic, ACE inhibitor or ARB, and beta-blocker. 1

Acute Coronary Syndrome Management

Immediate Antiplatelet Therapy

• Aspirin should be administered immediately to all patients with suspected acute coronary syndrome unless contraindicated, at doses of 75-162 mg daily for long-term prevention. 1, 4, 5

• Add clopidogrel as soon as possible and continue for at least 1 month (indefinitely if aspirin not tolerated). 1

• For patients receiving dual antiplatelet therapy (aspirin + clopidogrel), daily aspirin doses of 75-81 mg may optimize efficacy and safety compared to higher doses. 6

Anticoagulation

• Subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin (plus aspirin and/or clopidogrel) is recommended. 1, 7

• Platelet glycoprotein IIb/IIIa inhibition (plus aspirin and heparin) is recommended for continued ischemia or other high-risk features. 1

Additional Therapies

• ACE inhibitors are recommended for patients with heart failure, ejection fraction <40%, hypertension, or diabetes following acute coronary syndrome. 1

• Beta-blockers are recommended as initial therapy in patients with prior myocardial infarction. 1

• Statins should be initiated for lipid management. 1, 7

Common Pitfalls and Caveats

• Immediate-release dihydropyridine calcium antagonists without beta-blockade are contraindicated in acute coronary syndromes. 1

• When using ACE inhibitors, ARBs, or diuretics, monitor kidney function and electrolytes regularly. 2

• Beta-blockers should be combined with other major BP-lowering drug classes when there are compelling indications (angina, post-MI, heart failure, or heart rate control). 1

• Medication timing should be at the most convenient time of day to establish a habitual pattern and improve adherence, as diurnal timing does not affect cardiovascular outcomes. 1, 2

• For patients with hepatic impairment, start losartan at 25 mg once daily rather than the usual 50 mg dose. 8