50 Years of Thiazides: Should Thiazide Diuretics Be Considered Third-Line Hypertension Treatment?

The purpose of this report is to review available and emerging antihypertensive treatment options in light of current guidelines and evidence from large clinical trials. The published literature was reviewed for evidence regarding first-line options for antihypertensive agents, including thiazide-type diuretics, as monotherapy or as part of combination therapy. Current guidelines recommend using thiazide-type diuretics as first-line therapy alone or in combination with another agent. Other commonly used antihypertensive agents include calcium channel blockers, β-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and the direct renin inhibitor, aliskiren. These agents are associated with varying degrees of evidence that they may provide protection from cardiovascular or renal disease beyond that associated with blood pressure reduction. Thiazide diuretics are inexpensive and effective but may not be preferable to other classes of antihypertensives that reduce blood pressure to a similar extent with a better safety profile and superior reductions in cardiovascular event rates. However, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and direct renin inhibitors also show promise as initial monotherapy or as part of a combination therapy regimen. In patients requiring additional blood pressure reduction, add-on therapy with a diuretic could provide additional blood pressure-lowering efficacy.