10.2 Cardiovascular Pharmacotherapy

The current TCO names cardiovascular agents as one of the 13 official drug-agent classes. Domain III Planning asks you to pick a guideline-concordant regimen. Domain IV Implementation asks whether you will sign, refuse, or monitor. This is the pharmacotherapy section. Diagnosis lived in 10.1. Lifestyle lives in 10.3. Pregnancy and frailty change the molecule in 10.4.

2025 blood-pressure treatment: PREVENT™, not the old pooled cohort

The treatment goal is <130/80 mm Hg for most adults. Use the PREVENT™ (Predicting Risk of cardiovascular disease EVENTs) equations for 10-year CVD risk. Do not reach for the retired Pooled Cohort Equations on a 2026 exam item.

Start lifestyle plus medication when the confirmed average is ≥140/90 mm Hg — always. That is stage 2, and you do not wait for a risk score to justify the first tablet.

Start medication at a confirmed average ≥130/80 mm Hg when any of these is true:

• clinical CVD
• prior stroke
• diabetes
• CKD
• PREVENT™ 10-year risk ≥7.5%

If the average is ≥130/80 and PREVENT™ risk is <7.5% with none of those conditions, prescribe lifestyle for 3–6 months. If the average is still ≥130/80, start medication. The 2017 habit of leaving some stage 1 adults untreated indefinitely is not the 2025 rule.

First-line drugs are race-neutral

Without a compelling indication, start a thiazide-type diuretic, an ACE inhibitor, an ARB, or a dihydropyridine calcium-channel blocker. That list is race-neutral. Do not teach "start a CCB or a thiazide first because the patient is Black" as the 2025 first-line rule. PREVENT™ itself dropped race in favor of clinical and social-risk inputs; the drug table followed.

For stage 2 hypertension, prefer a single-pill dual-class combination (two first-line classes in one tablet) to improve adherence and shorten time to control. Do not open with a beta blocker for uncomplicated hypertension. Do not combine an ACE inhibitor with an ARB (or add aliskiren to either) — dual renin-angiotensin blockade raises hyperkalemia and acute kidney injury without an outcome prize in primary care.

Compelling indications override the open-menu first-line list. Albuminuric CKD and diabetes with albuminuria want an ACE inhibitor or ARB (and usually an SGLT2 inhibitor in contemporary diabetes/CKD care — the RAS blocker is still the CV-class answer). Recheck creatinine and potassium in 1–2 weeks after start or a material dose increase (Section 9.2). Spironolactone is the add-on for resistant hypertension once three agents at optimal doses, including a diuretic, have failed — if eGFR and potassium allow — and it is foundational in HFrEF. Watch the potassium when an ACE inhibitor, an ARB, and spironolactone share a med list.

HFrEF in primary care is not "a little furosemide." Foundational therapy is an ARNI (or ACEI/ARB if an ARNI is not yet possible), an evidence-based beta blocker, a mineralocorticoid-receptor antagonist, and — in current GDMT — an SGLT2 inhibitor, titrated with cardiology when the regimen outruns the FNP's comfort. Loop diuretics treat congestion; they do not replace those mortality-reducing classes.

Statins: intensity by indication, risk by conversation

Teach high-intensity statin therapy as the default in four conceptual boxes, not as a brand-name trivia contest.

Start or continue high-intensity (or the maximum tolerated intensity) when there is:

1. Clinical ASCVD (ACS, revascularization, ischemic stroke/TIA, documented CAD or PAD) — this is secondary prevention.
2. LDL-C ≥190 mg/dL — treat as possible familial hypercholesterolemia; do not open with a token 10 mg.
3. Diabetes, age 40–75 — at least moderate intensity; escalate toward high intensity when additional risk is obvious.
4. Primary prevention — estimate risk with PREVENT™, talk through benefit, bleeding and diabetes risk, cost, and preference. Do not invent a single magic risk percentage if the stem does not give you a current cholesterol-guideline cutoff. Shared decision is the FNP move; silence is not.

Moderate-intensity examples you should recognize: atorvastatin 10–20 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg. Do not stack simvastatin or lovastatin with a strong CYP3A4 inhibitor (Section 9.1). Baseline ALT; recheck CK for unexplained muscle symptoms, not as a calendar ritual in an asymptomatic adult.

Antiplatelets and anticoagulants

Aspirin (typically 81 mg daily) is secondary prevention after ACS, ischemic stroke/TIA, or documented atherosclerotic disease unless it is contraindicated. It is not automatic primary prevention — especially in older adults (Section 6.1). Dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor) after a coronary stent is cardiology-owned. The FNP does not stop DAPT after a little epistaxis without calling the interventionalist, and does not extend DAPT forever because "more blood thinner feels safer."

For nonvalvular AF, a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) is preferred for most adults who need anticoagulation. Dose-adjust for age, weight, and eGFR using that molecule's label — do not copy one DOAC's cutoffs onto another. Warfarin remains required for a mechanical valve and for moderate-to-severe mitral stenosis. Do not "modernize" those patients onto a DOAC. If you inherit warfarin, you own the INR plan (Section 9.2).

Digoxin toxicity and amiodarone you did not start

You may not start digoxin often. You must recognize toxicity: anorexia, nausea, vomiting, visual change (yellow-green chromatopsia, halos), confusion, bradycardia, ventricular ectopy, or a newly "regularized" slow pulse in someone who used to be in AF. Risk explodes with renal impairment, hypokalemia, hypomagnesemia, and drugs that raise digoxin (amiodarone, verapamil). Hold the drug, correct electrolytes, check a level when it will change management, and get help for unstable rhythms. Low potassium does not exclude toxicity — it promotes it.

Amiodarone is usually a cardiology prescription that lands on your problem list. If it is already prescribed, you monitor it: TSH and free T4 and LFTs about every 6 months, a chest radiograph at baseline and for new dyspnea or cough, pulmonary function if the lung story changes, and an eye exam for visual symptoms. Counsel photosensitivity and blue-gray skin. When amiodarone starts, cut the warfarin dose (often substantially) and halve digoxin and recut the INR and the digoxin plan — do not discover the interaction after a bleed or a pause.

Vignette. A 58-year-old with diabetes, albuminuria, and confirmed BP 138/84 has a PREVENT™ 10-year risk of 11%. 2025 says start medication now, not a six-month lifestyle-only clock, and an ACE inhibitor or ARB is the compelling class. A 44-year-old with the same BP, no target-organ disease, and PREVENT™ risk 4% gets lifestyle for 3–6 months and a booked recheck — then a first-line tablet if the average is still ≥130/80. A 70-year-old with AF and a mechanical mitral valve leaves on warfarin, not apixaban.

Exam trap. The retired race-based CCB/thiazide-first rule, the retired Pooled Cohort 10% statin-or-BP threshold recited as if it were 2025, ACE-plus-ARB "for extra kidney protection," and stopping DAPT in the primary-care hallway are the items written to fail people who studied an older pocket card.