High blood pressure pills may work better when taken at bedtime, research suggests.

In the largest study of its kind, scientists from the University of Vigo in Spain looked at when more than 19,000 patients took their hypertension medication.

The team found those who took the pills at bedtime had nearly half the risk (45%) of dying from heart disease over the next six years compared to the participants who had the medication upon waking.

The night time regimen also reduced the patients’ risk of a heart attack, stroke and heart failure, when the organ does not pump blood around the body as effectively as it should.

Experts believe a patient’s body clock may change how they respond to the medication.

“Current guidelines on the treatment of hypertension do not mention or recommend any preferred treatment time,” lead author Professor Ramon Hermida said.

“Morning ingestion has been the most common recommendation by physicians based on the misleading goal of reducing morning blood pressure levels.

“The results of this study show patients who routinely take their anti-hypertensive medication at bedtime, as opposed to when they wake up, have better-controlled blood pressure and, most importantly, a significantly decreased risk of death or illness from heart and blood vessel problems.”

Past research by the same scientists suggests nighttime blood pressure is the “most significant and independent indication of cardiovascular disease risk”.

To learn more, the team divided 19,084 adults with high blood pressure into two groups. The first were told to take all their hypertension drugs at bedtime, while the second were instructed to have the medication upon waking.

The patients who followed for an average of around six years. At least once a year, their blood pressure was monitored continuously via a cuff over 48 hours.

Results, published in the European Heart Journal, show taking hypertension pills at bedtime reduced the participants’ risk of death caused by heart disease.

It also lowered their risk of stroke by 49%, a heart attack by 44%, heart failure by 42% and coronary revascularisation by 40%. Coronary revascularisation is surgery to widen narrowed or blocked arteries.

These patients also had lower blood pressure throughout the day, with it particularly “dipping” at night. Blood pressure should naturally decline during sleep – failure to do so can put a person at risk of heart disease.

The results remained true even after the scientists adjusted for other factors linked to poor heart health, like type 2 diabetes, smoking and high cholesterol.

“The findings indicate average blood pressure levels while asleep and nighttime blood pressure dipping, but not daytime blood pressure or blood pressure measured in the clinic, are jointly the most significant blood pressure-derived markers of cardiovascular risk,” Professor Hermida said.

“Accordingly, round-the-clock ambulatory blood pressure monitoring should be the recommended way to diagnose hypertension and to assess the risk of cardiovascular disease.”

Ambulatory monitoring involves a patient wearing a cuff that records their blood pressure at regular internals throughout the day and night.

Dr Paul Leeson, professor of cardiovascular medicine at the University of Oxford, said: “This study has the potential to transform how we prescribe blood pressure medication.

“The scale of the project, length of follow up and size of effect are impressive. Importantly, this is a ‘real world’ study where doctors were allowed to prescribe whatever they wanted and just change medication timing. This means the findings are likely to be relevant to most people who take tablets for high blood pressure.

“Where the benefit comes from remains unclear. Does this improve patterns of sleep? Are side effects less problematic at night? Does blood pressure overnight better reflect heart health?”

The scientists stress the participants all slept at night time, therefore it is unclear if the same results would occur among shift workers. All the participants were also white and of Spanish descent. Different results may apply to other ethnic groups, they added.

The team are looking into the “ideal” blood pressure readings during sleep to reduce a patient’s heart disease risk.

“If you’re taking blood pressure medication, it’s important to check with your GP or pharmacist before changing the time you take it,” Vanessa Smith, senior cardiac nurse at the British Heart Foundation, told the BBC.

“There may be specific reasons why your doctor has prescribed medication in the morning or night.”

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In high-income countries like the U.S., the standard of care for people infected with HIV is to provide antiretroviral pills when the virus is found, even when there are no symptoms of AIDS. The strategy staves off the disease and has a second — big — benefit. It has been shown to prevent the spread of HIV in sexual encounters. It’s called “treatment as prevention” (TasP in medical jargon), or “test and treat.”

But in low-income countries, “test and treat” is not the typical approach to prevention. There has been no research to support it.

So 10 years ago, researchers began planning a massive study of treatment as prevention in South Africa and Zambia. The team came from the London School of Hygiene and Tropical Medicine, Imperial College and from several other institutions in the U.S., Zambia and South Africa.

When they started, they said, there was some doubt in the AIDS research community about whether the effort would be successful. “People didn’t think we could provide antiretroviral therapy in sub-Saharan Africa at all,” says study co-leader Richard Hayes of the London School of Hygiene and Tropical Medicine. “There was a lot of skepticism.”

Helen Ayles, from the same institution and a Zambian research organization called Zambart, hit the same resistance. “People said you’ll never get communities to test, and you’ll never get communities to want to start treatment early and if you do they’ll never stay on the treatment.” That attitude sprang partly from past struggles to get people to follow a regimen of daily drugs, in both developed and developing countries — and from local mistrust when foreigners arrive in low-income countries to carry out a health mission.

The study provided “test and treat” to communities containing a total of about 1 million people in South Africa and Zambia from 2013 to 2018. The $130 million project is called PopART (Population Effects of Antiretroviral Therapy to Reduce HIV Transmission).

The findings show that the practice could play a crucial role in controlling the AIDS epidemic.

“The results are fantastic,” says Ayles. “We managed to demonstrate you can reduce HIV incidence by 30 percent. That’s an amazing thing.”

“This is a landmark study,” says Judith Wasserheit, a longtime AIDS researcher and head of the Department of Global Health at the University of Washington, who was not involved in the research. “Getting communities to adopt an intervention and sustain it is one of the great challenges of global health.”

Details of the new trial were revealed at the Conference on Retroviruses and Opportunistic Infections in Seattle this spring and will be published soon. The findings are likely to be a big source of discussion at the global AIDS and HIV conference in Mexico City in July.

The scale of the trial was immense. Researchers began annual HIV testing in 14 communities of 50,000 or so people each in urban neighborhoods and towns in South Africa and Zambia. Community health workers went to people’s homes, talked to them about HIV and HIV prevention, distributed condoms and offered on-the-spot testing. Those who tested positive were offered free antiretroviral therapy. Another 300,000 or so were in the control group, which did not offer “test and treat.”

The study was funded by the U.S. government and the International Initiative for Impact Evaluation with support from the Bill and Melinda Gates Foundation (which is also a funder of NPR and this blog).

In half of the 14 communities where “test and treat” was the protocol, anyone found to be HIV-positive was offered treatment immediately. The results from these communities were not that impressive: a 7 percent drop in new HIV infections compared to communities in the control arm, where testing and treatment were sometimes available but not with the concerted, door-to-door outreach of the PopART approach.

In the other half of communities where “test and treat” took place, for the first few years treatment didn’t begin until an individual’s white blood cell counts fell below a certain level. (Partway through the study, those communities were switched to immediate treatment when national guidelines changed.)

In those seven “test and treat” communities, whose combined population was about 330,000, the incidence of new infections was 30 percent lower than in the control group communities.

“We showed it’s feasible and acceptable to deliver this kind of intervention in towns in sub-Saharan Africa,” says Hayes.

The new study does leave one major question — why was the drop only 7 percent in the group in which HIV-positive people received treatment right away as opposed to 30 percent in the other treated communities where treatment was initially delayed?

“My first reaction was that the statisticians had got it the wrong way around,” says Hayes. But four different statisticians repeated the analysis and got the same results. The PopART researchers are mining the data to try and understand the difference.

There are other findings to consider from the study. Its designers believed that community buy-in would be key to getting people to accept testing and treatment. So at the start of PopART, the researchers solicited community leaders to serve on advisory boards to oversee the project and help the researchers find and train 700-plus community members to serve as health care workers. The process, says Hayes, “was like mobilizing an army.”

The idea was that these community health workers, who understood their patients’ lives and languages, could make a difference. “What PopART has shown is how important local health workers can be,” says Maryam Shahmanesh, an associate professor at University College London and an HIV prevention and sexual health expert.

Rosemary Phiri, a Zambian with no medical training, found a listing for health workers while looking for a job in her local newspaper. She wound up overseeing 112 workers in the program and went out on community visits.

“It was an amazing experience for me,” says Phiri, now 34 years old. “At first people were not sure what was going on.” Testing centers existed in some of the towns already, but this was a door-to-door effort. “When people realized we were there to help them stop this terrible infection, they became so receptive,” she says. “They saw we were there for their own good.”

Myron Cohen, a professor at the University of North Carolina, calls the new study “a road map.” Cohen is a principal investigator in a worldwide collaboration of researchers who run clinical trials on AIDS interventions, including this one. Cohen had headed the study that in 2011 showed that intensive attention — frequent visits to the health center and counseling on risk reduction and the use of condoms — and antiretroviral drugs can stop transmission between partners when one is known to be HIV-positive.

PopART builds on Cohen’s findings and other efforts, including a major study in South Africa. That study showed that HIV transmission is less frequent in communities where treatment is available compared to similar communities where it is not, suggesting that HIV transmission could be controlled on a population level.

And in early June, a study of a single community in KwaZulu-Natal done by Doctors Without Borders showed that engaging patient groups, local health workers and political leaders encourages people to be tested and treated. The study provided preliminary evidence that widespread outreach could decrease the spread of HIV in a poor area.

The U.N. has set eliminating the public health threat of HIV as a goal for the year 2030. Is that possible? Cohen quickly says yes, if an adequate effort is made — if every HIV infected person can be found, started on treatment and persuaded to stay on treatment. PopART co-leader Richard Hayes hesitates before answering. “I think it can be done,” he finally says. “But I think it will be a real challenge.”

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