Compared with standard monotherapy, the adjusted mean reduction in systolic blood pressure at 12 weeks was 4.8 mm Hg, a difference that approached statistical significance (95% CI -10.7 to 1.2), Mark Huffman, MD, of Washington University in St. Louis, spoke at the annual meeting of the American Heart Association. In his recent scientific report, Huffman also noted that participants in the QUARTET USA trial who took the combination pill that included low doses of four drugs had an average reduction of 4.9 mm Hg 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 goals, especially for patients and communities with a high burden of hypertension and hypertension-related diseases,” Huffman said. “QUARTET USA was the first trial of a four-drug, ultra-low-dose combination to lower blood pressure in the United States.” The original QUARTET trial was conducted in Australia and showed that treatment with the four-drug combination significantly reduced blood pressure for both systolic and diastolic measurements compared with patients treated with irbesartan 150 mg daily. This trial involved 591 patients. The US study used a comparator of candesartan (8 mg) daily compared with a combination of ultra-low-dose 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 Access Community Health Network in Chicago. In an interim analysis, patients who were unable to achieve targets could have amlodipine added to their regimen – 53.3% of patients who received candesartan monotherapy were treated with additional amlodipine compared with 18.8% of those who received the square pill, Huffman have reported. He noted that recruitment to the trial was slowed by the COVID-19 pandemic, and ultimately 62 patients were enrolled in the trial. A total of 32 patients were assigned to the square pill and 30 to candesartan monotherapy. The patients were about 52 years old and about 45% were women. About 70% of participants identified as Hispanic, and about 18% of the remainder identified as Black. More than 50% of the entire cohort reported an annual household income of less than $25,000 per year. More than 75% of patients were receiving monotherapy to control high blood pressure, yet their blood pressure averaged 138 mm Hg systolic and 84 mm Hg diastolic at baseline. Serious side effects during the trial occurred in two people taking the quad pill, but none were thought to be related to the study drug. Two patients in the quadruple pill group and eight in the candesartan monotherapy group discontinued treatment. “The direction and magnitude of the blood pressure reduction effect were similar between QUARTET and QUARTET USA, despite different study populations with lower blood pressure at baseline in the current study, thus strengthening the case for this new approach,” he said. Huffman. Commenting on the study, AHA recommended discussant LaPrincess Brewer, MD, MPH, of the 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 receive only one hypertensive drug. Initial low-dose drug combination therapy is likely a more effective and efficient approach.” In addition, he 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 important.”
Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.
Revelations Huffman disclosed financial relationships with George Medicines, Boehringer Ingelheim, Novartis, Bupa, Verily, and AstraZeneca. Brewer disclosed no industry affiliations.
