As a clinical pharmacist, you often encounter questions about choosing blood pressure medications for the initial treatment of uncomplicated hypertension. We know to turn to an ACEI or ARB, calcium channel blocker (CCB), or thiazide first, CV benefits seem similar overall. But be ready with answers to common questions about nuances...
| Table (1). Oral Drugs Commonly Used in Treatment of Hypertension | |||
|---|---|---|---|
| Drug Class | Examples | Total Daily Dose (DOSING frequency/day) | Adverse Effects |
| Diuretics | |||
| Thiazides | Hydrochlorothiazide | 6.25–50 mg (1–2) | Hypokalemia, hyperuricemia, gout, hyperglycemia, ↑ cholesterol, ↑ triglycerides |
| Thiazide-like | Chlorthalidone | 25–50 mg (1) | same as above |
| Loop diuretics | Furosemide | 40–80 mg (2–3) | Hypokalemia, hyperuricemia |
| Ethacrynic acid | 50–100 mg (2-3) | ||
| Aldosterone antagonists | Spironolactone | 25–100 mg (1–2) | Hyperkalemia, gynecomastia |
| Eplerenone | 50–100 mg (1–2) | Hyperkalemia | |
| K+-retaining | Amiloride | 5–10 mg (1–2) | |
| Triamterene | 50–100 mg (1–2) | ||
| Beta blockers | |||
| β1-selective | Atenolol | 25–100 mg (1–2) | Bronchospasm, bradycardia, heart block, fatigue, sexual dysfunction |
| Metoprolol | 25–100 mg (1–2) | same as above | |
| Nonselective | Propranolol | 40–160 mg (2) | same as above |
| Propranolol LA | 60–180 mg (1) | same as above | |
| Combined alpha/beta | Labetolol | 200–800 mg (2) | Bronchospasm, bradycardia, heart block |
| Carvedilol | 12.5–50 mg (2) | ||
| ACE inhibitors | Captopril | 25–200 mg (2) | Cough, hyperkalemia, azotemia, angioedema |
| Lisinopril | 10–40 mg (1) | ||
| Ramipril | 2.5–20 mg (1–2) | ||
| Angiotensin II receptor blockers | Losartan | 25–100 mg (1–2) | Hyperkalemia, azotemia |
| Valsartan | 80–320 mg (1) | ||
| Candesartan | 2–32 mg (1–2) | ||
| Calcium channel antagonists | |||
| Dihydropyridines | Nifedipine long-acting | 30–60 mg (1) | Edema, constipation |
| Nondihydropyridines | Verapamil long-acting | 120–360 mg (1–2) | Constipation, bradycardia, heart block |
| Diltiazem long-acting | 180–420 mg (1) | ||
Is an ACEI preferred over an ARB? Not necessarily. Overall data suggest that ARBs reduce CV risk on par with ACEIs. But ARBs cause fewer adverse effects, such as cough or angioedema, than ACEIs. And both have low-cost generics. Choose an ARB over an ACEI if starting one of these. Lean toward a long-acting ARB, such as telmisartan or olmesartan. This may reduce BP swings or help with adherence. Keep in mind, losartan is the shortest-acting ARB and often needs to be dosed BID. But don’t switch from an ACEI to an ARB for a patient who’s on an optimized regimen with an ACEI and is tolerating it well.
Is there a “go-to” CCB? Yes, generally rely on amlodipine. It’s the longest-acting dihydropyridine, causes less tachycardia and has more data for improving CV outcomes in hypertension. Keep in mind, peripheral edema is common with dihydropyridines. But don’t jump to a diuretic for CCB-induced edema, it’s due to fluid “leaking” out of blood vessels, not sodium or water retention. In this case, try reducing the CCB dose. Or consider adding an ACEI or ARB if more BP lowering is needed, this might counteract edema.
Is there a “best” thiazide? No, there’s not a clear winner. Chlorthalidone is preferred in some BP guidelines because it shows CV benefit in key hypertension studies. And data suggest indapamide reduces CV risk versus placebo in patients aged 80 and up. This MIGHT be because chlorthalidone or indapamide lasts longer, and lowers BP slightly more, than hydrochlorothiazide. But recent data don’t find benefit with chlorthalidone over hydrochlorothiazide and suggest chlorthalidone causes more hypokalemia. And some experts believe ANY thiazide will have CV benefits as long as it controls BP, especially in combo with other BP meds. Evaluate what’s practical. For many patients, consider hydrochlorothiazide. It comes in many combos, if needed and costs slightly less than chlorthalidone or indapamide.✅ Use our resource, "Overview of hypertension", for help with educating about diagnosis of HTN, lifestyle changes, tailoring BP goals, pharmacotherapy and more.
REFERENCES
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Chen R, Suchard MA, Krumholz HM, et al. Comparative First-Line Effectiveness and Safety of ACE (Angiotensin-Converting Enzyme) Inhibitors and Angiotensin Receptor Blockers: A Multinational Cohort Study. Hypertension. 2021;78(3):591-603. Available at: https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.16667
Whelton PK, Carey RM. The 2017 Clinical Practice Guideline for High Blood Pressure. JAMA. 2017;318(21):2073-2074. Available at: https://jamanetwork.com/journals/jama/article-abstract/2664351
Ishani A, Cushman WC, Leatherman SM, et al. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. N Engl J Med. 2022;387(26):2401-2410. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2212270