2.1 Cardiovascular Pharmacotherapy

Cardiovascular Pharmacotherapy

Hypertension (ACC/AHA Guidelines)

The 2017 ACC/AHA guidelines redefined hypertension staging to emphasize earlier intervention. Normal blood pressure is <120/80 mmHg. Elevated BP is 120-129/<80 mmHg, treated with nonpharmacological interventions. Stage 1 hypertension is 130-139 or 80-89 mmHg. For Stage 1, clinical ASCVD or an estimated 10-year ASCVD risk ≥10% dictates the initiation of blood pressure-lowering medication alongside lifestyle changes; otherwise, lifestyle modification alone is recommended. Stage 2 hypertension is defined as BP ≥140 or ≥90 mmHg, warranting both lifestyle modification and the initiation of two BP-lowering medications from different classes if the BP is >20/10 mmHg above target.

First-line agents include Thiazide diuretics (e.g., chlorthalidone, hydrochlorothiazide), Calcium Channel Blockers (CCBs like amlodipine), and ACE inhibitors or ARBs. African American patients without heart failure or chronic kidney disease should initially receive a thiazide or CCB. In patients with CKD (stage 3 or higher or albuminuria >300 mg/day), an ACEi or ARB is recommended for renal protection regardless of race.

Heart Failure with Reduced Ejection Fraction (HFrEF)

Guideline-directed medical therapy (GDMT) for HFrEF (LVEF ≤ 40%) focuses on four foundational pillars proven to reduce morbidity and mortality. These should be initiated rapidly and up-titrated to target doses or maximally tolerated doses.

1. Beta-Blockers: Only three beta-blockers have proven mortality benefit in HFrEF: bisoprolol, carvedilol, and sustained-release metoprolol succinate. They should be initiated in stable patients (euvolemic, not requiring IV inotropes). Carvedilol also blocks alpha-1 receptors, offering additional afterload reduction but more hypotension.
2. Renin-Angiotensin System Inhibitors: ARNI (sacubitril/valsartan) is preferred over ACEi/ARBs to further reduce morbidity and mortality. A 36-hour washout period is strictly required when switching from an ACEi to an ARNI to prevent life-threatening angioedema.
3. Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or eplerenone. Essential monitoring includes potassium and renal function. Avoid initiation if K+ > 5.0 mEq/L or eGFR < 30 mL/min/1.73m2. Eplerenone is a selective antagonist and avoids gynecomastia seen with spironolactone.
4. SGLT2 Inhibitors: Dapagliflozin and empagliflozin reduce heart failure hospitalizations and cardiovascular death regardless of the presence of diabetes. They provide diuretic synergy but increase the risk of genitourinary infections.

Other agents like Ivabradine may be considered for patients with resting HR ≥ 70 bpm in sinus rhythm who are on maximally tolerated beta-blockers. Hydralazine/Isosorbide dinitrate is recommended for self-identified African Americans with NYHA class III-IV HFrEF receiving optimal therapy with the four pillars.

Arrhythmias: Atrial Fibrillation (AFib)

Management of AFib involves three primary considerations: rate control, rhythm control, and stroke prevention.

Rate vs. Rhythm Control: The AFFIRM trial demonstrated that rate control is generally non-inferior to rhythm control for overall mortality. Rate control is typically achieved using beta-blockers (metoprolol, esmolol), non-dihydropyridine CCBs (diltiazem, verapamil), or digoxin. Digoxin is purely negative chronotropic and positive inotropic; a narrow therapeutic index requires monitoring (target 0.5-0.9 ng/mL for HF, can be higher for AFib). Non-DHP CCBs must be avoided in patients with HFrEF due to negative inotropic effects.

Rhythm control (cardioversion and antiarrhythmic maintenance) is preferred in highly symptomatic patients, younger patients, or those with tachycardia-induced cardiomyopathy. Agents include Class IC (flecainide, propafenone - strictly avoid in structural heart disease) and Class III (amiodarone, dofetilide, sotalol).

Amiodarone Therapeutic Drug Monitoring (TDM) and Toxicity: Amiodarone contains iodine and is highly lipophilic, with a massive volume of distribution and a half-life of 40-60 days. Toxicity monitoring is crucial:

• Pulmonary toxicity (baseline and annual CXR/PFTs)
• Thyroid toxicity (baseline and every 6 months TSH/free T4; can cause hyper- or hypothyroidism)
• Hepatotoxicity (baseline and every 6 months LFTs)
• Ophthalmic (optic neuropathy, corneal microdeposits) Given its myriad drug interactions (CYP3A4, 2C9, P-gp inhibitor), doses of warfarin and digoxin must be preemptively reduced by 30-50% upon amiodarone initiation.

Anticoagulation (Stroke Prevention in AFib)

Stroke risk is assessed using the CHA2DS2-VASc score.

• Congestive heart failure (1)
• Hypertension (1)
• Age ≥ 75 (2)
• Diabetes (1)
• Stroke/TIA/TE (2)
• Vascular disease (1)
• Age 65-74 (1)
• Sex category female (1)

Oral anticoagulation is recommended for a score of ≥ 2 in men or ≥ 3 in women. Direct Oral Anticoagulants (DOACs: apixaban, rivaroxaban, dabigatran, edoxaban) are preferred over warfarin unless the patient has moderate-to-severe mitral stenosis or a mechanical heart valve. Renal dosing is critical for DOACs. For example, apixaban is dosed at 2.5 mg BID if a patient has at least two of the following: Age ≥ 80, Body weight ≤ 60 kg, or Serum Creatinine ≥ 1.5 mg/dL. Rivaroxaban must be taken with the largest meal of the day to ensure absorption for the 15 mg and 20 mg doses, and should be avoided in CrCl < 15 mL/min. Bleeding risk is assessed via the HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history/predisposition, Labile INR, Elderly >65, Drugs/alcohol). A high score (≥3) should not preclude anticoagulation but highlights the need to correct modifiable bleeding risks.