Thiazide Diuretics vs. Other Antihypertensive Drug Classes

Are thiazide and thiazide-like diuretics more effective than other first-line antihypertensive drug classes in reducing mortality or cardiovascular events in patients with hypertension?

There is no mortality benefit in using thiazide or thiazide-like diuretics compared with other first-line antihypertensive drug classes; however, these diuretics most likely reduce cardiovascular events (number needed to treat [NNT] = 100; 95% CI, 63 to 333) and heart failure (NNT = 84; 95% CI, 66 to 125) compared with calcium channel blockers.¹ (Strength of Recommendation [SOR]: B, based on inconsistent or limited-quality patient-oriented evidence.) Thiazide and thiazide-like diuretics reduce stroke risk compared with angiotensin-converting enzyme (ACE) inhibitors (NNT = 167; 95% CI, 100 to 1,000). (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) Thiazides are associated with fewer withdrawals and drug discontinuations due to adverse effects compared with beta blockers, calcium channel blockers, ACE inhibitors, and alpha blockers.

The primary goal of hypertension treatment is to reduce morbidity and mortality, myocardial infarction, stroke, and renal failure while minimizing the risk of harm from medical intervention.² The ideal blood pressure target for treatment continues to be debated. The 2014 Eighth Joint National Committee guidelines and 2017 American College of Cardiology/American Heart Association guidelines agree on the drug classes that should be used as first-line therapy.^3,4 Among the three main classes of first-line antihypertensives, thiazide or thiazide-like diuretics may have advantages over calcium channel blockers and ACE inhibitors.

This Cochrane review assessed 20 trials with more than 90,000 participants between 50 and 75 years of age.¹ Participants had comorbidities, including type 2 diabetes mellitus; the trials lasted an average of five years. Cardiovascular events were a composite clinical end point referring to myocardial infarction, stroke, or death. Most trials in this review used chlorthalidone.

This review found that, compared with ACE inhibitors, thiazides and thiazide-like diuretics resulted in little to no difference in total mortality, cardiovascular events, coronary heart disease, or heart failure. Thiazide and thiazide-like diuretics decreased the risk of stroke compared with ACE inhibitors (NNT = 167; 95% CI, 100 to 1,000). Fewer patients receiving these diuretics discontinued their regimen than patients receiving ACE inhibitors (NNT = 100; 95% CI, 71 to 167). The data comparing thiazide diuretics to angiotensin receptor blockers or renin inhibitors were inadequate.

Compared with calcium channel blockers, thiazide and thiazide-like diuretics did not reduce total mortality, strokes, or coronary heart disease. They reduced total cardiovascular events (NNT = 100; 95% CI, 63 to 333) and likely reduced heart failure (NNT = 83; 95% CI, 66 to 125).

The results of this review are consistent with recommendations from current guidelines that thiazide diuretics be considered first—as opposed to alpha blockers or beta blockers—for the reduction of total cardiovascular events, stroke, and heart failure.^3,4 This review did not evaluate differences between the diuretics hydrochlorothiazide, chlorthalidone, indapamide, or metolazone (loop diuretic). Previous guidelines have recommended chlorthalidone because of its longer half-life and proven cardiovascular disease reduction.⁴

The practice recommendations in this activity are available at https://www.cochrane.org/CD008161.