Marcia Reinhart, Lorri Puil, Douglas M Salzwedel, James M Wright

Key messages

• Thiazides and thiazide‐like drugs (diuretics) probably decrease some adverse cardiovascular events compared to beta‐blockers, calcium channel blockers, ACE inhibitors, and alpha‐blockers when used as the first‐line drug for the treatment of hypertension.  
• Total mortality is probably not different between diuretics and the other drug classes.
• First‐line diuretics likely reduce total cardiovascular events and heart failure compared to calcium channel blockers and alpha‐blockers.  
• First‐line diuretics likely reduce withdrawals from the studies due to unwanted or harmful (adverse) effects compared to beta‐blockers, calcium channel blockers, ACE inhibitors, and alpha‐blockers.

What is hypertension (high blood pressure)?

Hypertension is defined using resting blood pressures: mild (140 to 159/90 to 99 mmHg), moderate (160 to 179/100 to 109 mmHg), and severe (180/110 mmHg or higher). Uncontrolled high blood pressure can lead to stroke, heart attack, heart failure, and kidney damage. Blood pressure‐lowering drugs have been proven to reduce these adverse events in people aged 60 years and older with moderate to severe elevations of blood pressure; they also reduce stroke in adults under 60 years old with hypertension.

How is hypertension treated?

This review focused on blood pressure‐lowering classes of drugs given as the initial drug treatment when lifestyle interventions are insufficient. The drug classes of interest include diuretics (e.g. hydrochlorothiazide, chlorthalidone); beta‐blockers (e.g. propranolol, atenolol); calcium channel blockers (e.g. amlodipine, nifedipine); angiotensin‐converting enzyme (ACE) inhibitors (e.g. lisinopril, enalapril); angiotensin receptor blockers (e.g. candesartan, losartan); renin inhibitors (e.g. aliskiren); alpha‐blockers (e.g. doxazosin); and centrally acting drugs (e.g. clonidine).  

What did we want to find out?

We wanted to find out whether the benefits and harms of diuretics given first for hypertension differed from other drug classes.

What did we do?

We searched for studies that compared first‐line diuretics with other blood pressure‐lowering drug classes in people with hypertension. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.

What did we find?

We found 20 studies that involved over 90,000 people with hypertension and lasted five years on average.

What are the main limitations of the evidence?

More head‐to‐head trials are needed comparing low‐dose thiazides with angiotensin receptor blockers and renin inhibitors.

How up to date is this evidence?

The evidence is up to date to March 2021.