Speaker
Jody D. Ciolino, PhD
Associate Professor
Director, Master of Science in Biostatistics
Department of Preventive Medicine – Biostatistics
Biostatistics Collaboration Center (BCC) / Northwestern University Data Analysis and Coordinating Center (NUDACC)
Northwestern University Feinberg School of Medicine
Keywords
QUARTET, hypertension, RCT, biostatistics
Key Points
- Elevated blood pressure (>130/80) is leading cause of preventable morbidity and mortality globally. In the U.S. nearly half of adults have hypertension and prevalence rates are rising. While most Americans are aware of their hypertension and while most who are aware receive treatment (75%), less than half (47%) are controlled using a goal blood pressure of <130/<80 mmHg.
- The typical plan for treatment includes repeated clinic visits with repeated dose titrations of multiple individual drugs, which is challenging for both patients and providers. Maximizing doses of individual drugs leads to greater risk of side effects.
- QUARTET sought to investigate whether initiating treatment with ultra-low-dose quadruple-combination therapy (LDQT) will lower office blood pressure more effectively, and with fewer side effects, compared to initiating standard dose monotherapy in patients with hypertension.
- QUARTET hypothesized that a combination pill comprising 4 types of blood pressure lowering medications, each at one-quarter standard doses, will lower office blood pressure more effectively than initiating patients with standard dose monotherapy in patients with hypertension.
- Study participants came from ACCESS Community Health Network. Participants were adult, Spanish and English speakers with blood pressure withing range for Stage 1 hypertension as defined in the protocol; eventually this changed to automated blood pressure readings in clinic.
- The primary outcome was automated office systolic blood pressure (SBP) at 12 weeks and analyses will compare this change across arms for primary outcome analyses, adjusting for baseline. Secondary outcomes included automated office diastolic blood pressure (DBP) at 6 and 12 weeks; proportion of patients with hypertension control at 6 and 12 weeks; proportion of patients requiring step-up treatment; proportion of patients with adverse event-free hypertension control; medication adherence; and health-related quality of life (PROMIS Global Health).
- QUARTET planned for a total of 365 participants randomized 1:1 with a 20% dropout rate by the 12-week follow up time point. The study launched a second site in February 2020, right before the pandemic and political unrest. In August 2020, the study launched third site. All sites were in Chicago.
- QUARTET found that initiating a four-drug quarter-dose combination blood pressure lowering therapy was associated with a ~4.8/4.9mmHg greater reduction in mean change in BP from baseline to 12 weeks compared with standard-dose ARB monotherapy in patients with mild to moderate hypertension.
- Differences in SBP were not statistically significant, which may be due to limited power related to the sample size. Adverse events were more common in the intervention arm, but the rates of discontinuation were higher in the comparator arm. No SAEs were deemed related to the study drug.
- New approaches are needed to achieve lower BP targets, especially for patients and communities with a high burden of hypertension and hypertension-related diseases.
Learn More
Read more about QUARTET in the Journal of the American Heart Association.
Discussion Themes
-Did automated office blood pressure include 5-minute rest? If so, how did it differ from “research grade” BP measurement? Automated office blood pressure was according to how they measured blood pressure in the clinic with an automated cuff. Before the study started, there was some training with the research nurses on taking blood pressure from participants and there was a 5-minute rest, though I am not sure how that was adhered to. The research grade blood pressure was meant to be unattended, automated (taken 3 times), and there was an average of the 2.
Tags
#pctGR, @Collaboratory1