Contributor: Alec Coston, MD

Educational Pearls:

For patients presenting to the emergency room with hypertension, clinicians should determine if it is isolated and uncomplicated, or involves comorbidities with more complex underlying pathophysiology.

For uncomplicated and isolated hypertension, first-line treatment is thiazide diuretics.

How do thiazide diuretics work to treat hypertension?

• Thiazide diuretics work by blocking sodium and chloride resorption in the kidneys. "Where sodium goes, water follows," thus promoting diuresis and lowering blood pressure.

Examples of thiazide diuretics and their benefits?

• Hydrochlorothiazide (HCTZ): First-line medication in uncomplicated and chronic hypertensive states. Cheaper and fewer significant adverse effects compared to chlorthalidone.
• HCTZ can be associated with decreased risk of stroke and myocardial infarction.
• However, for more complicated hypertension, especially in the setting of heart failure, Angiotensin Converting Enzyme (ACE) Inhibitors should be considered.

How do ACE Inhibitors manage blood pressure?

• The body's kidneys drive the Renin-Angiotensin-Aldosterone-System (RAAS) to regulate blood pressure.
• It is easiest to understand RAAS as being pro-hypertensive as a response to decreased renal perfusion. As renal perfusion decreases, renin is released and activates angiotensin I, which is converted by ACE to Angiotensin II, which causes release of aldosterone.
• ACE Inhibitors prevent the conversion of Angiotensin I to Angiotensin II, thus decreasing the kidneys' production of Angiotensin II and Aldosterone levels.

Why, in the context of heart failure, are ACE Inhibitors preferred?

• In heart failure, especially left-sided or left-ventricular heart failure, a vicious cycle can develop wherein the left ventricle fails to perfuse the kidneys due to over-dilation.
• The kidneys are hypoperfused and activate RAAS to try to retain volume and increase peripheral vasoconstriction, promoting renal perfusion.
• The increase in blood pressure puts further strain on the heart, thereby further decreasing cardiac output. The cycle develops, and extremely elevated blood pressures can develop.
• ACE Inhibitors can directly block this cycle, hence their preference in heart failure.

Big takeaway?

• In uncomplicated hypertensive patients, consider thiazide diuretics. When comorbidities, especially heart failure, are introduced, then consider ACE Inhibitors.

References

1. Carey RM, Moran AE, Whelton PK. Treatment of Hypertension: A Review. JAMA. 2022;328(18):1849-1861. doi:10.1001/jama.2022.19590
2. Fan M, Zhang J, Lee CL, Zhang J, Feng L. Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter. Nature. 2023;614(7949):788-793. doi:10.1038/s41586-023-05718-0
3. Hripcsak G, Suchard MA, Shea S, et al. Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Internal Medicine. 2020;180(4):542-551. doi:10.1001/jamainternmed.2019.7454
4. Yu D, Li JX, Cheng Y, et al. Comparative efficacy of different antihypertensive drug classes for stroke prevention: A network meta-analysis of randomized controlled trials. PLoS One. 2025;20(2):e0313309. doi:10.1371/journal.pone.0313309

Summarized by Dan Orbidan, OMS2 | Edited by Dan Orbidan & Jorge Chalit, OMS4

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