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CHICAGO -- A pill aimed at controlling hypertension by combining four blood pressure-lowering agents appeared to be effective in a U.S. population, researchers reported here.

Compared with standard monotherapy, the adjusted mean systolic blood pressure decrease at 12 weeks was 4.8 mm Hg, a difference that trended toward statistical significance (95% CI -10.7 to 1.2), Mark Huffman, MD, of Washington University in St. Louis, reported at the annual meeting.

In his late-breaking science report, Huffman also noted that participants in the QUARTET USA trial taking the combination pill that included low doses of four medicines had a mean 4.9 mm Hg reduction in diastolic blood pressure -- a difference that was statistically significant (95% CI -8.6 to -1.1).

"New approaches are needed to achieve lower blood pressure targets, especially for patients and communities with high burden of hypertension and hypertension-related diseases," Huffman said. "QUARTET USA was the first trial of a four-drug, ultra-low-dose blood pressure-lowering combination in the United States."

The original QUARTET trial was performed in Australia and showed that treatment with the four-drug combination significantly lowered blood pressure for both systolic and diastolic measurement when compared with patients who were being treated with 150 mg daily of irbesartan. There were 591 patients in that trial.

The U.S. study used a comparator of candesartan (8 mg) daily compared with an ultra-low-dose combination of candesartan (2 mg) plus amlodipine (1.25 mg), indapamide (0.625 mg), and bisoprolol (2.5 mg) daily over the course of 12 weeks. The study was conducted among patients treated at the Access Community Health Network in Chicago.

At an interim analysis, patients who were not able to meet the goals could have amlodipine added to their regimen – 53.3% of the patients assigned to candesartan monotherapy were treated with add-on amlodipine compared with 18.8% of those on the quad pill, Huffman reported.

He noted that recruitment to the trial was slowed due to the COVID-19 pandemic, and eventually 62 patients were enrolled in the trial. A total of 32 patients were assigned to the quad pill and 30 to candesartan monotherapy. Patients were about 52 years old, and about 45% were women. About 70% of the participants identified as Hispanic, and about 18% of the others as Black.

More than 50% of the entire cohort reported a household annual income of less than $25,000 a year. More than 75% of the patients were on monotherapy for high blood pressure control, and yet their blood pressure averaged 138 mm Hg systolic and 84 mm Hg diastolic at baseline.

Serious adverse events during the trial were experienced by two individuals taking the quad pill, but neither case was deemed to have been related to the study medication. Two patients in the quad pill group and eight in the candesartan monotherapy group discontinued treatment.

"The direction and magnitude of blood pressure lowering effect were similar between QUARTET and QUARTET USA, despite different study populations with lower baseline blood pressure in the current study, thus strengthening the case for this new approach," Huffman said.

In commenting on the study, AHA-designated discussant LaPrincess Brewer, MD, MPH, of Mayo Clinic School of Medicine in Rochester, Minnesota, said, "Most adults in the United States with hypertension do not have it under control. About 40% of patients with uncontrolled hypertension are taking only one hypertensive medication. Upfront low-dose, drug combination therapy is likely a more effective and efficient approach."

In addition, she said, in the QUARTET USA trial, "there was a greater reduction in blood pressure among the intervention group versus the control group. The difference in systolic blood pressure reduction was not statistically significant, but it is clinically meaningful."

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