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Low-Dose Multidrug Shown Effective in Hypertension Trial

Blood pressure measurement


10 February 2017. A small-scale clinical trial shows a combination of four current drugs to treat hypertension, or high blood pressure, formulated in low doses, reduces blood pressure to normal levels in four weeks. A team from the George Institute for Global Health in Sydney, Australia reported its findings in the 9 February issue of the journal The Lancet (paid subscription required).

Researchers led by Clara Chow, director of the George Institute’s cardiovascular division, are seeking more reliable methods for controlling high blood pressure, a condition that affects 1 billion people worldwide, according to World Health Organization, killing some 9 million people a year.”We know that high blood pressure is a precursor to stroke, diabetes, and heart attack,” says Chow in an institute statement. “The need for even lower blood pressure levels has been widely accepted in the last few years.”

But most people now treated for high blood pressure take a single medication, with uneven results — only about half of patients respond satisfactorily — in controlling the condition. Thus an initiative at the George Institute, known as the Quartet project, is developing and testing a combination of 4 drugs in very low concentrations as an alternative treatment for high blood pressure. The low-dose formulations may also reduce the incidence or severity of side effects experienced by some patients, such as swollen ankles or kidney impairment.

The quadpill, as the test drug is called, is a combination of current drugs packed in a capsule, given once a day to control high blood pressure, but in one-quarter their usual dose: irbesartan, amlodipine, hydrochlorothiazide, and atenolol. The clinical trial enrolled 18 individuals in Sydney diagnosed with high blood pressure, but not yet taking drugs to control the condition. Half of the participants were randomly assigned to take the quadpill every day for 4 weeks, while the other half took a placebo capsule. After a 2-week break, the groups switched roles, with the former placebo recipients taking the quadpill, and original quadpill recipients taking the placebo.

Before the trial, participants’ blood pressure averaged 154 systolic and 90 diastolic, both levels considered stage 1 hypertension, where lifestyle changes and medications are often prescribed. The results show marked reductions in blood pressure for participants taking the quadpill, with all 18 individuals reaching safer systolic and diastolic levels, below 140/90, after 4 weeks. Only 6 of the 18 participants had the same results from the placebo. In addition, no serious adverse effects were reported, and participants considered the capsules easy to swallow.

To verify their findings, Chow and colleagues reviewed 36 previous clinical trials testing quarter-dose treatments for high blood pressure against a placebo in more than 4,700 participants. The results show lower systolic and diastolic readings in those trials, as well as an absence of serious adverse effects.

“What makes these result every more exciting is that these four blood pressure medications are already in use,” notes Chow. “We are increasingly finding there are opportunities to treat many common diseases hiding in plain sight. This ultimately means we will be able to deliver life changing medications much more quickly, and more affordably.”

The George Institute team now plans to expand the trials to larger numbers of participants to confirm these initial results and assess the quadpill’s long-term effectiveness.

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Disclosure: The author takes medication for high blood pressure.

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