Contents · 13 sections
- 1. Treatment Goals
- 2. ACE Inhibitors (ACEi)
- 3. Angiotensin II Receptor Blockers (ARBs, Sartans)
- 4. Calcium Channel Blockers (CCBs)
- 5. Thiazide and Thiazide-like Diuretics
- 6. β-blockers
- 7. Mineralocorticoid Receptor Antagonists (MRAs)
- 8. Other Classes
- 9. Rational Combinations (ESC 2018/2023)
- 10. Indication-Based Selection
- 11. Hypertensive Crisis
- 12. Resistant Hypertension
- 13. FAQ
In a nutshell. The 5 main first-line drug classes for hypertension (ESC 2018/2023): ACEi, ARBs, CCBs, thiazide/thiazide-like diuretics, β-blockers. β-blockers are reserved for specific indications (CAD, HFrEF, elevated heart rate, pregnancy). Initial therapy is a 2-drug combination in a single pill (ACEi/ARB + CCB or diuretic), or monotherapy in elderly/frail patients. If efficacy is insufficient, use a "triple combination" + spironolactone (resistant hypertension). Additional classes: α1-blockers, central sympatholytics, direct vasodilators, SGLT2 inhibitors (in HF/CKD).
1. Treatment Goals
- SBP < 140 mm Hg (in most cases 120–130 mm Hg).
- DBP < 90 mm Hg (70–80 mm Hg).
- In elderly > 65 years — SBP 130–139 mm Hg.
- A reduction of 20/10 mm Hg decreases the risk of stroke by 40%, and myocardial infarction by 25%.
2. ACE Inhibitors (ACEi)
- Angiotensin-converting enzyme blockade → ↓ AII → vasodilation; ↑ bradykinin.
- Drugs: enalapril, lisinopril, ramipril, perindopril, fosinopril.
- Indications: hypertension, heart failure, post-MI, diabetic and non-diabetic nephropathy with albuminuria.
- Side effects: dry cough (5–20%, bradykinin-mediated), angioedema (0.1–0.5%, more common in African Americans), hyperkalemia, acute serum creatinine rise (up to 30% is acceptable), teratogenicity.
- Contraindications: pregnancy, bilateral renal artery stenosis, hyperkalemia, history of angioedema.
3. Angiotensin II Receptor Blockers (ARBs, Sartans)
- Direct blockade of AT1 receptors.
- Drugs: losartan, valsartan, irbesartan, telmisartan, candesartan, olmesartan, azilsartan.
- Indications are the same as for ACEi.
- Advantages: no cough; angioedema is extremely rare.
- Contraindications: pregnancy, bilateral renal artery stenosis, hyperkalemia.
- Combining ACEi + ARB is not recommended (ONTARGET trial: ↑ hyperkalemia, AKI, no benefit).
4. Calcium Channel Blockers (CCBs)
Dihydropyridines
- Amlodipine, felodipine, nifedipine (retard), lercanidipine.
- Predominant action on arterioles → vasodilation.
- Side effects: lower extremity edema (dose-dependent), flushing, tachycardia, gingival hyperplasia.
- Indications: hypertension, angina pectoris.
- Short-acting nifedipine is contraindicated (↑ mortality).
Non-dihydropyridines
- Verapamil, diltiazem.
- Negative inotropic and chronotropic effect.
- Indications: hypertension, angina pectoris, supraventricular arrhythmias.
- Contraindications: HFrEF, 2nd–3rd degree AV block, sinus bradycardia.
- Must not be combined with IV β-blockers (asystole).
5. Thiazide and Thiazide-like Diuretics
- Hydrochlorothiazide, indapamide, chlortalidone.
- Blockade of the Na-Cl cotransporter in the distal convoluted tubule.
- Indications: hypertension (especially in elderly and Black patients), isolated systolic hypertension.
- Side effects: hypokalemia, hyponatremia, hyperuricemia, lipid and glucose metabolism disorders, hypercalcemia.
- Chlortalidone and indapamide show superiority over HCTZ in reducing cardiovascular events.
- Ineffective when eGFR < 30 mL/min (except indapamide and chlortalidone).
6. β-blockers
- Nebivolol, bisoprolol, metoprolol succinate, carvedilol, atenolol (becoming obsolete).
- Indications as 1st-line for hypertension: CAD (angina, post-MI), HFrEF, heart rate > 80 bpm, pregnancy (labetalol, metoprolol), glaucoma.
- Side effects: bradycardia, bronchospasm, cold extremities, hypoglycemia masking, fatigue, sleep disturbances, erectile dysfunction, weight gain.
- Contraindications: asthma (relative for cardioselective ones), AV block II–III degree, decompensated CHF, pregnancy (atenolol).
7. Mineralocorticoid Receptor Antagonists (MRAs)
- Spironolactone, eplerenone, finerenone.
- Indications: resistant hypertension (4th drug), primary hyperaldosteronism, CHF.
- Side effects: hyperkalemia, gynecomastia (spironolactone).
- Finerenone — selective, for T2D + CKD (FIDELIO-DKD).
8. Other Classes
α1-blockers
- Doxazosin, prazosin.
- Application: hypertension + BPH.
- Side effects: orthostatic hypotension, "first-dose" effect.
Central sympatholytics
- Methyldopa (drug of choice in pregnancy), clonidine, moxonidine.
- Side effects: sedation, dry mouth, depression, rebound hypertension upon clonidine withdrawal.
Direct vasodilators
- Hydralazine, minoxidil.
- Application: resistant hypertension, pregnancy (IV hydralazine for severe preeclampsia).
- Side effects: reflex tachycardia, edema; for minoxidil — hypertrichosis, pericardial effusion.
Other antihypertensives
- SGLT-2 (empagliflozin, dapagliflozin) — for hypertension + T2D, CHF, CKD.
- Direct renin inhibitors (aliskiren) — limited use.
- Sacubitril/valsartan (ARNI) — for CHF with reduced EF; affects blood pressure.
- Endothelin antagonists (bosentan) — pulmonary hypertension.
9. Rational Combinations (ESC 2018/2023)
| Combination | Rationality |
|---|---|
| ACEi/ARB + CCB | Additive efficacy, ↓ CCB-induced edema |
| ACEi/ARB + thiazide | Classic, corrects diuretic-induced RAAS activation |
| CCB + thiazide | For elderly patients, isolated systolic hypertension |
| Triple (ACEi/ARB + CCB + thiazide) | When dual therapy provides insufficient control |
| + MRA | Resistant hypertension (4th drug) |
| + β-blocker | For CAD, CHF, HR > 80 |
10. Indication-Based Selection
- Hypertension + CAD: β-blocker + ACEi/ARB ± CCB.
- Hypertension + CHF with ↓EF: ARNI (or ACEi/ARB) + β-blocker + MRA + SGLT-2.
- Hypertension + T2D + CKD: ACEi/ARB + SGLT-2; finerenone if albuminuria is present.
- Hypertension + AF: β-blocker, verapamil/diltiazem.
- Hypertension + BPH: α1-blocker.
- Hypertension + pregnancy: methyldopa, labetalol, nifedipine SR.
- Hypertension in Black patients: CCBs and thiazides are more effective; ACE inhibitors are less effective, higher risk of angioedema.
11. Hypertensive Crisis
- Urgent (without TOD — no acute target organ damage): blood pressure reduction over hours; per os — captopril, clonidine, moxonidine.
- Emergency (with TOD — aortic dissection, ACS, pulmonary edema, stroke, eclampsia): IV — esmolol, nitroglycerin, nitroprusside, labetalol, urapidil.
- Goal: ↓ BP by 20–25% in the first hour, then gradually.
- For aortic dissection — ↓ SBP < 120 mm Hg + β-blocker as the primary intervention.
12. Resistant Hypertension
- BP not < 140/90 despite 3 drugs (including a thiazide) at maximal doses.
- Exclude: pseudoresistance (non-adherence, "white-coat effect"), secondary hypertension.
- Add spironolactone 25–50 mg (PATHWAY-2).
- Consider renal denervation (RDN) — approved by ESC 2023 as 4th-line therapy.
13. FAQ
Why do ACE inhibitors cause a cough?
Bradykinin accumulation in the bronchi. Frequency 5–20%, more common in women and Asians. Solution — switch to an ARB.
When to prescribe a thiazide versus a loop diuretic?
Thiazides are first-line for hypertension with normal renal function. Loop diuretics — for eGFR < 30, CHF with edema.
What is the "white-coat effect"?
Blood pressure is higher in the doctor's office than at home or on ABPM. Confirmation — home measurement or 24-hour monitoring. Often does not require pharmacological treatment, but ↑ cardiovascular risk.
When to take antihypertensives — morning or evening?
The 2022 TIME trial showed no difference in cardiovascular outcomes. Choose a convenient time; for nocturnal hypertension — in the evening (chronotherapy).
What to do in case of resistant hypertension?
Confirm compliance (DOTS, pharmacokinetics), rule out secondary forms (hyperaldosteronism, renal artery stenosis, pheochromocytoma, Cushing's syndrome, sleep apnea), add spironolactone. If ineffective — consider renal denervation.
See also: Hypertension · CHF · Diuretics · β-blockers · Pharmacology Catalog