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Quarter-dose therapy shows promise in treating hypertension
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Ultra-low-dose combination therapy using a “quadpill” was shown to significantly lower BP in patients in a small, randomized, placebo-controlled, double blind, crossover trial in Australia.
The quadpill was made of four different BP-lowering drugs each at one-quarter dose. This, taken in the context of other pervious randomized evidence also complied by the researchers, shows that the benefits of a quadpill may be additive across classes and may result in clinically significant reductions in BP, according to findings published in The Lancet.
Eighteen patients (mean age, 58 years) in western Sydney completed the study. The patients had untreated hypertension and were enrolled at four local centers mainly by general practitioners.
Patients were randomly assigned to a quadpill or a matching placebo for a 4-week duration. The quadpill consisted of irbesartan 37.5 mg, amlodipine 1.25 mg, hydrochlorothiazide 6.25 mg and atenolol 12.5 mg. This was followed by a 2-week washout. Patients who were prescribed the quadpill were then administered placebo for 4 weeks, and patients who received placebo were then prescribed the quadpill for 4 weeks.
The reduction in systolic 24-hour BP with the quadpill (placebo-corrected) was 19 mm Hg (95% CI, 14-23). Office BP was reduced with the quadpill by 22 mm Hg systolic/13 mm Hg diastolic (P < .0001).
All 18 patients achieved office BP < 140 mm Hg systolic/90 mm Hg diastolic during quadpill treatment vs. 33% of patients during placebo treatment (P = .0013).
Also, significantly lower BP levels were found with the quadpill for all the following: daytime ambulatory systolic BP, daytime ambulatory diastolic BP, nighttime ambulatory systolic BP and nighttime ambulatory diastolic BP.
Clara K . Chow, PhD, of The George Institute for Global Health, University of Sydney, and colleagues also conducted a systematic review of all randomized trials of quarter-dose BP therapy. The following databases were searched from inception to June 2016 for potentially relevant studies: Embase, MEDLINE and the Cochrane Central Registry of Controlled Trials. The websites of the FDA and the European Medicines Agency also were searched.
“Our systematic review identified 36 trials (n = 4,721 participants) of one drug at quarter-dose and six trials (n = 312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected [BP]-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both P < .0001), and there were no side effects from either regimen,” Chow and colleagues wrote.
“As far as we are aware, our findings are the first placebo-corrected results showing the full effects of four drugs at quarter-dose. Together with our systematic review finding that one or two drugs at quarter-dose produces no increase in side effects compared with placebo — our clinical trial findings suggest considerable potential advantages for a single capsule containing multiple [BP]-lowering drugs at ultra-low dose. A major novel feature of the proposed quadpill approach is the theoretical advantage of initiating therapy with a highly effective and tolerable combination vs. starting with fewer agents and titrating up (which in practice is rarely done well). ... However, as yet, there is no direct head-to-head evidence for the quadpill approach being better than that used currently, and comparison of the quadpill with existing stepped-care approaches is required in randomized clinical trials,” Chow and colleagues wrote. – by Suzanne Reist
Disclosure: Chow reports no relevant financial disclosures. Please see the full study for a list of the other researchers’ relevant financial disclosures.
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