Ultralow-dose “quadpill”, a new strategy for BP lowering?

USA: Findings from the QUARTET USA trial have shown a potential use of a low-dose antihypertensive polypill for hypertension patients with no safety risk. 

In the study assessing the safety and efficacy of a polypill containing quarter doses of four antihypertensive medications for hypertension versus an angiotensin receptor blocker (ARB) monotherapy, the researchers found that the polypill was not superior to the full-dose ARB monotherapy for improving BP control in patients with mild to moderate hypertension.

The study findings were presented at the 2022 Scientific Sessions of the American Heart Association (AHA) by Mark D. Huffman.

The authors hypothesized an ultra-low-dose quadruple-combination therapy (LDQT, including amlodipine 1.25 mg, candesartan 2 mg, bisoprolol 2.5 mg and indapamide 0.625 mg) would reduce office BP more effectively than initiating patients with standard dose monotherapy (candesartan 8 mg) following current clinical practice guidelines recommendations.

The researchers conducted a controlled, randomized, parallel-group trial over 12 weeks in Chicago, Illinois. Eligible patients were randomized in a ratio of 1:1 to receive either a polypill (n = 32) or candesartan 8 mg (n = 30). Patients in the ARB group also received a daily 5 mg dose of amlodipine if their BP was above goal.

The study included adults with increased BP (SBP>130 mmHg or DBP>80 mmHg) without cardiovascular disease.

The study demonstrated the following findings:

  • The primary outcome, mean change in automated systolic BP, for polypill vs monotherapy, was: -4.8 mm Hg. Effects on 24-hour ambulatory blood pressure were similar.
  • At 12 weeks, adjusted mean change in diastolic BP at 12 weeks: -4.9 mm Hg.
  • A short-term (4-week) crossover trial of 18 participants suggests that LDQT lowers office blood pressure by 22/13 mmHg on average compared with placebo, with no difference in serious adverse events.

The trial’s findings suggest that a treatment strategy of ultra-low dosing four BP-lowering medications did not result in a statistically more significant BP reduction compared to standard-dose ARB monotherapy for patients with mild to moderate hypertension.

The authors observed adverse events as more common in the intervention arm, but higher discontinuation rates were seen in the control arm. The enrollment target was not achieved due to COVID-19, and this limited sample size led to low power.

The findings were harmonious with the international QUARTET trial and indicate a potential use of a low-dose antihypertensive polypill for hypertension patients. The following steps will be the evaluation of a hypertensive polypill for assessing clinical outcomes.


Presented by Dr Mark D. Huffman at the American Heart Association Scientific Sessions, Chicago, IL, November 6, 2022.

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