New late-breaking science presented at ESC Congress 2024 in London adds to the growing body of evidence looking at the potential benefits of single combination pills in managing hypertension, as well as whether evening vs. morning administration of blood pressure (BP)-lowering medications affects cardiovascular outcomes.

On the medication-timing front, two separate trials – the BedMed and BedMed-Frail trials – found no major differences in major cardiovascular events or safety among both primary care and nursing home patients taking blood pressure medications in the morning vs. the evening.

"We found bedtime vs. morning administration [provided] no difference in MACE, nor in potential hypotensive, visual, cognitive or other safety events in a general population and importantly, in frail older patients, a subgroup who are generally excluded from clinical trials," said Principal Investigator Scott Garrison, MD. "We can now dismiss the treatment timing as being important and advise patients to take their BP medication when they are least likely to forget."

In the first of three trials looking at combination pills, a single-pill combination (GMRx2) containing low doses of telmisartan, amlodipine, and indapamide "showed good tolerability and clinically relevant BP reductions" in early treatment of patients with mild to moderate hypertension compared with placebo. The trial, which was simultaneously published in JACC, randomized participants in a 2:2:1 ratio to GMRx2 1/4 dose (telmisartan 10 mg/amlodipine 1.25 mg/indapamide 0.625 mg), GMRx2 1/2 dose (telmisartan 20 mg/amlodipine 2.5 mg/indapamide 1.25 mg), or placebo.

"GMRx2 reduced BP quickly in mild-to-moderate hypertension and more effectively than dual therapy in a broad, large hypertensive population, without safety concerns," said Principal Investigator Anthony Rodgers, MBCHB, MPH, PhD. "The availability of a single-pill combination could help to reduce current therapeutic inertia, helping patients achieve BP control quickly in a small number of steps, with potential benefits for improved adherence."

In a related editorial comment, Oyere K. Onuma, MD, MSc, FACC, noted that the results from the trial are the first in a series of studies aimed at obtaining regulatory approval for the combination pill and highlighted the "need for additional further research to assess its efficacy against usual care strategies in higher risk populations and to define the best strategies to support widespread implementation in target populations." Onuma writes: "In the face of tremendous innovations and progress in many facets of cardiovascular care, time is overdue for a major paradigm shift in BP control. Low-dose single pill combinations can and should be a key component of that change."

A second study out of Nigeria and simultaneously published in JAMA compared the efficacy and safety of GMRx2 in triple one-quarter, one-half, and standard doses (10/1.25/0.625 mg; 20/2.5/1.25 mg; and 40/5/2.5 mg) with standard care among Black African adults with uncontrolled hypertension.

"We found that the effects of GMRx2 in Nigerian patients appeared consistent with those seen in broader populations, demonstrating excellent effectiveness, even when compared against a standard-care protocol that achieved much better results than usually seen in routine practice," said main investigator Dike Ojji, MD.

In a related editorial comment also published in JAMA, George A. Mensah, MD, FACC, said the greatest value from the Nigerian study and others like it "will come when the low-dose, triple-drug combination pill protocols become widely available and used sustainably in the long term by all who need it." He writes: "As the old African proverb teaches, a sick man who eats many herbs may not know what made him well – but if the concoction is available, accessible, affordable, acceptable, safe and effective, and if it brings him good health, he will gladly take it every time. So it will be for the low-dose combination pills for hypertension."

In a third trial – QUADRO – researchers found that adding isoprolol to a combination of three other BP-lowering drugs in a quadruple single-pill combination was more effective at reducing BP than taking the same three drugs in separate pills in patients with resistant hypertension.

According to the trial investigators, individuals with resistant hypertension typically need to take multiple medications to control their hypertension, which often contributes to greater non-adherence. "The availability of a quadruple single-pill combination could help with non-adherence and provide much-needed effective BP control in resistant or difficult-to-treat hypertension," they said.