Hydrochlorothiazide ineffective first-line antihypertensive therapy
MedWire News: Meta-analysis findings indicate that hydrochlorothiazide (HCTZ) is a less effective antihypertensive agent than other antihypertensive drug classes, when used at the standard daily dose of 12.5 to 25.0 mg.
"Because of such paltry antihypertensive efficacy and the lack of outcome data at these doses, physicians should refrain from prescribing HCTZ as initial antihypertensive therapy," say Franz Messerli (St Luke's Roosevelt Hospital, New York, USA) and colleagues.
They highlight that their findings are particularly relevant given that "HCTZ remains the most commonly prescribed antihypertensive drug worldwide."
Messerli and team conducted a 19-study meta-analysis involving 1463 hypertensive patients (mean baseline blood pressure [BP] 148/92 mmHg) randomly allocated to receive HCTZ or another antihypertensive drug class, ie, an ACE inhibitor, angiotensin receptor blocker (ARB), beta blocker, or calcium-channel blocker (CCB) taken at standard doses for a mean period of 17 weeks.
HCTZ was taken at the standard daily dose of 12.5 to 25.0 mg in 14 studies and at 50.0 mg daily in five studies.
Change in BP was determined using 24-hour BP monitoring, which the researchers say "is the most thorough and objective way to assess antihypertensive efficacy."
The findings, published in the Journal of the American College of Cardiology, show that when taken at a dose of 12.5 to 25.0 mg per day, HCTZ reduced patient BP levels by a mean of 6.5/4.5 mmHg over the treatment period.
This reduction in BP was much smaller than that achieved with the use of other antihypertensives; ACE inhibitors, ARBs, beta blockers, and CCBs produced respective BP reductions of 12.9/7.7, 13.3/7.8, 11.2/8.5, and 11.0/8.1 mmHg.
However, at a dose of 50 mg per day, HCTZ demonstrated an antihypertensive efficacy similar to that of other antihypertensive drugs, producing a mean BP reduction of 12.0/5.4 mmHg over the study period.
Messerli and team highlight that although patients taking HCTZ 50 mg in a real-life setting are likely to experience better BP control than those taking standard-dose HCTZ, the risk for dose-dependent adverse effects such as hypokalemia and insulin resistance is increased at doses above 25 mg, and this deters clinicians from prescribing HCTZ 50 mg.
The researchers conclude: "The fact that our data indicate that HCTZ in its commonly used dose is a suboptimal antihypertensive drug should not prevent it from being useful in combination with a blocker of the renin-angiotensin system such as an ACE inhibitor, and ARB, or even a direct renin inhibitor."
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By Lauretta Ihonor