Quarter-dose quadpill a promising antihypertensive approach
medwireNews: A pilot randomized crossover trial suggests that giving patients a single pill composed of four antihypertensives at a quarter of their usual dose is a promising means of controlling blood pressure.
As well as being easier to take and titrate than multiple individual medications, “[a] quadpill also addresses the individual variation in responsiveness to different agents through provision of a combination with a range of modes of action,” say Clara Chow (The George Institute for Global Health, Sydney, New South Wales, Australia) and co-authors of the study, which is published in The Lancet.
The 24-hour ambulatory blood pressure of the 18 trial participants was, on average, 18.7/12.4 mmHg lower during the 4 weeks of quadpill treatment than the 4 weeks of placebo treatment, and office blood pressure was 22.4/13.1 mmHg lower. There was a 2-week washout period between the treatments, which were given in a randomly assigned order.
The participants had average baseline 24-hour blood pressure of 140/87 mmHg and office blood pressure of 154/90 mmHg, but were not taking any antihypertensives. All patients achieved office blood pressure below 140/90 mmHg while taking the quadpill, compared with 33% while taking placebo, and 83% versus 39% achieved ambulatory blood pressure below 135/85 mmHg.
The quadpill contained irbesartan 37.5 mg, amlodipine 1.25 mg, hydrochlorothiazide 6.25 mg, and atenolol 12.5 mg, and was taken once daily. Adverse events were mild and mostly unrelated to treatment. Patients had significant increases in creatinine, urate, and glucose levels during the quadpill phase, but by no more than 12%. All 18 study participants said it was either likely or very likely that they would take the quadpill were it available for use.
“A major novel feature of the proposed quadpill approach is the theoretical advantage of initiating therapy with a highly effective and tolerable combination versus starting with fewer agents and titrating up (which in practice is rarely done well),” write the researchers.
“Thus, initiation of combination therapy at very low doses might, for a worthwhile proportion of patients, achieve the blood pressure targets seen in SPRINT without the multiple titration steps.”
They stress, however, that the quadpill needs direct comparison with stepped-care approaches, to which commentator Alan Gradman (Temple University School of Medicine, Philadelphia, Pennsylvania, USA) adds that it should be compared against currently available two- and three-drug combination pills.
He is positive about the approach overall, noting that “[u]se of one-pill combinations also takes much of the guesswork out of drug selection by providing clinicians with combinations that have undergone rigorous testing and have been judged safe and effective.”
But Gradman stresses that “careful study will be needed to establish if there is additional overall benefit gained by increasing the number of targeted pharmacological pathways to four.”
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