The antihypertensive efficacy of hydrochlorothiazide (HCTZ) in its daily dose (12.5 to 25 mg) measured by ambulatory blood pressure (BP) is inferior to all other drug classes, according to a systematic review published in the Feb. 1 issue of Journal of the American College of Cardiology.
“In the U.S. alone, more than 134.1 million prescriptions of HCTZ were written in the year 2008,” the authors wrote. And while the drugs are prescribed extensively, there is little evidence to outline the safety and efficacy of HCTZ to treat hypertension at the 12.5 to 25 mg dose.
Franz H. Messerli, MD, of St. Luke’s Roosevelt Hospital and Columbia University College of Physicians and Surgeons in New York City, and colleagues evaluated the antihypertensive efficacy of HCTZ by ambulatory BP monitoring in 14 studies of HCTZ dose 12.5 to 25 mg enrolling 1,234 patients and five studies of HCTZ (50 mg) with 229 enrolled patients.
The researchers found the that 24-hour BP with HCTZ (12.5 to 25 mg dose) was systolic 6.5 mmHg and diastolic 4.5 mmHg and was inferior compared to the 24-hour BP reduction of ACE inhibitors, ARBs, beta-blockers and calcium antagonists. The mean BP reductions for the aforementioned drug classes were reported to be 12.9 mmHg, 13.3 mmHg, 11.2 mmHg and 11 mmHg, respectively.
The researchers also reported no significant differences in either systolic or diastolic 24-hour BP reduction between the 12.5 mg and 25 mg HCTZ doses (5.7 mmHg vs. 7.6 mmHg). The reduction in 24-hour BP was higher for the group treated with the 50 mg dose of HCTZ, at12 mmHg.
While the researchers found that 50 mg doses of HCTZ outcomes were similar to other drug classes, biochemical adverse effects—hypokalemia, hyponatremia, hyperuricemia, insulin resistance and visceral fat accumulation—could prohibit the higher dose prescription in certain patients.
In addition, the researchers noted that HCTZ doses of more than 25 mg could increase a patients risk for sudden cardiac death.
“In its commonly used dose of 12.5 to 25 mg once a day, there has been no evidence that HCTZ reduces myocardial infarction, stroke or death,” the researchers wrote. “This lack of outcome data together with the poor antihypertensive efficacy should strongly motivate physicians to refrain from prescribing HCTZ as initial therapy in hypertension.”
However, the researchers said that HCTZ could be used in combination with an ACE inhibitor, ARBs or a direct rennin inhibitor.
“Numerous, mostly factorial design studies have shown that when combined with these drug classes, HCTZ, even at low doses, elicits a distinct incremental fall in BP,” the researchers noted.
However, because the BP lowering effects of HCTZ was found to be inferior to every drug class, “its use as a first-line antihypertensive agent is ill advised.”