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A new study investigated the benefits and side effects of common blood pressure medications. Getty Images
  • Diuretics may be a better choice for first-line treatment of high blood pressure.
  • A study found that people on ACE inhibitors had more side effects and worse outcomes than people on diuretics.
  • Researchers say more studies are needed before they make major changes to prescription guidelines.

A new multinational observational study finds that ACE inhibitors, the most popular first-line treatment for high blood pressure, may be less effective for initial treatment and carries greater side effects than an older treatment that’s been available for decades.

The findings indicate that patients who were first prescribed thiazide diuretics rather than ACE inhibitors had 15 percent fewer heart attacks, strokes, and hospitalizations for heart failure.

Those who began their treatment with thiazides also experienced fewer side effects.

“The most surprising finding is the superiority of diuretics over ACE inhibitors, which was consistent across databases and passed all our diagnostics to check for errors,” study author Dr. George Hripcsak, chair of biomedical informatics at Columbia University Vagelos College of Physicians and Surgeons told Healthline.

“The diuretics were both more effective, better reducing the risk of heart attack, stroke, and heart failure, and more safe in terms of side effects,” he said.

This research — considered the most comprehensive to compare outcomes in newly treated patients with high blood pressure — was published in The Lancet today.

However, experts caution more research is needed before changing medical guidelines for hypertension treatment.

Guidelines currently recommend high blood pressure (hypertension) treatment begins with drugs from any of 4 different classes of medication, including:

  • thiazide diuretics
  • ACE inhibitors
  • calcium channel blockers
  • angiotensin II receptor blockers (ARBs)

“ACE inhibitors help regulate blood pressure by a hormone pathway through the kidney that basically helps dilate the arteries,” explained Dr. Brian Kolski, interventional cardiologist with St. Joseph Hospital in Orange, California. “Thiazide diuretics also work on the kidneys, essentially by increasing sodium removal.”

Hripcsak and team analyzed electronic health records and claims data from almost 5 million patients who recently began drug treatment for hypertension from 1996 to 2018.

They found that people who were prescribed thiazide diuretics first had 15 percent fewer heart attacks, strokes, and hospitalizations for heart failure compared to people put on ACE inhibitors.

ACE inhibitors were also linked to certain serious side effects.

“We saw some side effects we expected based on past experience like ACE inhibitors having more angioedema, a dangerous swelling of the skin, and cough, but also a higher rate of others like high potassium, acute and chronic kidney failure, gastrointestinal bleed, and even death,” said Hripcsak.

“Diuretics, on the other hand, had a higher rate of low potassium and low sodium, as expected,” he added.

While medication to treat high blood pressure has been around for years, physicians are still working without clear evidence of what’s the best medication available.

Randomized trials have been conducted on only 31,000 patients — none of whom was just beginning treatment — resulting in guidelines based on expert opinion rather than hard data.

This observational study used an enormous amount of data to detect effects that may not have been discovered in previous randomized trials.

“We have devised a new way of doing research that allows us to test thousands of drugs on many outcomes at once, more reliably than ever before, and we can march through medicine relatively efficiently, taking on each new area,” said Hripcsak.

There were limitations to this study. One is that there was an absence of blood pressure measurements within some of the databases that were used.

This is a problem because baseline blood pressure might influence the class of drug first prescribed to patients.

Researchers used large scale data models involving information from tens of thousands of patients to make adjustments for this missing data.

“If there’s going to be criticism from studies like this, it’s that these are not randomized trials, where you take the same patients and you prescribe one arm ACE inhibitors and one arm thiazide diuretics and you study them — that’s the gold standard type of trial,” said Kolski.

He explained that when you take real world data, it can result in “selection bias” because “doctors might feel like maybe they were prescribing ACE inhibitors to a sicker patient population so the outcomes look worse, because they felt that ACE inhibitors were better.”

He added that while software can try to eliminate selection bias, “ultimately in the real world we know that computers aren’t perfect, as much as you try to use big data and AI to predict these things.”

Whether your doctor prescribes medication or lifestyle changes like weight loss, dietary adjustments, and exercise depends on how high your blood pressure is, and if you have certain risk factors, like diabetes.

“Patients that have multiple risk factors or diabetes — the blood pressure numbers are typically more aggressive so let’s say they have diabetes, then systolic blood pressure under 130 is an issue, but it’s between 135 and 140 in normal patients, that’s sort of stage 1 hypertension, where we recommend diet and lifestyle changes,” said Kolski. “But typically, a reading over 140 we recommend medication.”

However he doesn’t see a big change in how doctors will prescribe hypertension medication as a result of this research.

“I think basically we know a lot about ACE inhibitors in patients with heart failure and other cardiovascular conditions so I don’t suspect that we’ll change much there, but as a first-line agent I think you might see more thiazide diuretics being prescribed,” said Kolski.

According to Hripcsak, they don’t know for sure if diuretics are actually more effective and safe, or if the difference is due to the way people use the drugs.

“For example, if a drug has side effects, patients may stop using them, resulting in high blood pressure and its consequences,” Hripcsak said.

However he emphasized that “ACE inhibitors are effective drugs; we just have evidence that diuretics are even better.”

He explained there may be medical reasons why a patient is on an ACE inhibitor rather than a diuretic, but “according to our evidence, we should see a shift from frequent use of ACE inhibitors to diuretics or the other first-line drugs.”

New, comprehensive research involving data from millions of patients finds diuretics are safer and more effective than ACE inhibitors for the initial treatment of hypertension.

This was an observational study rather than a randomized controlled trial (the gold standard of research), however the findings of this study are considered significant.

Experts agree that this research could make diuretics more commonly prescribed for the initial treatment of hypertension.