• Hypertension, or high blood pressure, affects more than one billion people worldwide and almost half of all adults in the United States.
• The condition can increase the risk of heart, brain, kidney, and other diseases.
• People can often control their blood pressure through regular exercise, eating a healthy diet, and managing stress levels, but medications are sometimes necessary.
• Thiazides are diuretics that are often used to lower blood pressure.
• A large, real-world study comparing two thiazides found that both are equally effective at preventing cardiovascular disease.

Hypertension is the medical term for high blood pressure, affecting almost half of all adults in the United States.

And it is not just a disease of high-income countries. According to the World Health Organization (WHO), some 1.13 billion people worldwide have hypertension, with around two-thirds of those in low- to middle-income countries.

The condition is a primary risk factor for cardiovascular disease. People need to manage their blood pressure to reduce their risk of stroke, heart attack, heart failure, and aneurysm.

Treating hypertension

There are many ways to control blood pressure. First, there are lifestyle changes. Exercising regularly, eating a healthy diet, maintaining a healthy weight, avoiding excess alcohol, and stopping smoking are all recommended. In addition, managing stress can also help prevent high blood pressure.

Doctors can prescribe various medications that lower blood pressure if lifestyle changes are ineffective. These include diuretics, beta-blockers, and ACE inhibitors. Doctors will consider the underlying cause of hypertension and other health conditions before deciding which medication is best for a person.

Diuretics are a common treatment for hypertension, with thiazide-type diuretics being the recommended initial therapy for most patients.

Now, a large, real-world clinical trial has compared two thiazide diuretics, chlorthalidone (CTD) and hydrochlorothiazide (HCTZ). The findings suggest the drugs are equally effective in preventing cardiovascular disease and non-cancer death.

Dr. Areef Ishani, principal investigator and director of the Minneapolis VA Health Care System’s Primary Care and Specialty Care Integrated Care Community, explains why they carried out the trial:

“In 2020, Medicare reported that approximately 1.5 million people were prescribed CTD compared to 11.5 million prescribed HCTZ, despite guideline recommendations. This discrepancy between clinical guidelines and real-world usage is possibly related to the belief that CTD has a greater risk of adverse effects without clear evidence for differences in cardiovascular outcomes.”

Medical News Today spoke with Dr. Yu-Ming Ni, a cardiologist of noninvasive cardiology at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, not involved in this study.

“[HCTZ] is far more commonly prescribed than chlorthalidone, and yet previous studies suggested chlorthalidone might be better at blood pressure control,” Dr. Ni explained.

“This study helps lay to rest that idea, and shows that both diuretics can be used equally for patients with high blood pressure,” he added.

Blood pressure drugs effectiveness

This large-scale clinical trial was carried out in the Department of Veterans Affairs (VA) health system. It was a pragmatic trial — one that evaluates the effectiveness of interventions in real-life routine practice conditions — rather than a randomized control trial (RCT).

Dr. Luci Leykum, chief clinical officer at Harbor Health, who was not involved in the study, explained the benefits of this type of trial to MNT.

“In pragmatic trials, a broader group of people who would be considered for a particular treatment as part of their routine care are included, and people are not given any additional prompts or supports to encourage them to take their medications,” she told us.

“Thus, pragmatic trials allow us to see the ‘real world effectiveness’ of a medication when used in everyday care,” she added.

Thiazide diuretics have been in use for treating hypertension for more than 60 years. Although some studies, including a 2019 meta-analysis of nine studies, have shown CTD to be more effective in controlling blood pressure, others have shown no difference. However, a 2020 study found a greater risk of side effects with CTD, and doctors prescribe HCTZ far more frequently than CTD.

“Despite the data favoring chlorthalidone, a lot more physicians order HCTZ than chlorthalidone – in fact, it is orders of magnitude more. Was this happening because physicians did not know the data, or because based on their daily experiences, they thought HCTZ was preferable?”

– Dr. Lucy Leykum

This real-world trial investigated whether CTD was more effective than HCTZ at preventing cardiovascular events in patients with hypertension.

A total of 13,523 people participated in the trial. All participants, of whom almost 97% were men, were aged 65 or over and were being treated with HCTZ — 25 milligrams (mg) or 50 mg per day — for hypertension.

After obtaining consent from the participants, doctors randomly allocated them to either continue treatment with HCTZ or switch to CTD.

Following randomization, 6,767 participants remained on HCTZ, and 6,756 people changed to CTD. For those switching, the 25 mg dose of HCTZ was replaced with 12.5 mg CTD, and the 50mg HCTZ was replaced with 25 mg CTD.

Hypertension and cardiovascular events

The trial’s primary outcome was the first occurrence of a nonfatal cardiovascular disease event or non–cancer-related death. Participants were followed up until they withdrew from the trial, died, or until the end of the trial.

After a median follow-up of 2.4 years, 1,377 people experienced a primary outcome event. Of these, 702 were in the CTD group and 675 in the HCTZ group.

The researchers recorded few side effects during the trial, although those in the CTD group were more likely to have low potassium levels. For most people, this was resolved quickly with potassium supplements.

The two medications were equally effective at preventing cardiovascular disease or non-cancer death, which included heart attack, stroke, heart failure, or lack of blood flow requiring medical intervention.

Dr. Leykum did point out one important limitation of the trial: “A downside to VA studies is that there are many more male than female veterans, so that most of the participants are men. This makes it hard to extrapolate results to women. In fact, in this study, almost 97% of the participants are men.”

Both hypertension drugs equally effective

“In this real-world, routine-care context, the researchers found no difference between chlorthalidone and HCTZ in terms of their impact on preventing heart attacks or strokes,” said Dr. Leykum.

“This suggests that either medication should be acceptable for use for hypertension treatment. This is quite significant because the result is relevant for a broad group of people with hypertension, meaning that for most people, either could be used.”

– Dr. Luci Leykum

So, on the evidence of this large-scale, real-world studydoctors should considerth CTD and HCTZ when prescribing medication for controlling hypertension.

Nevertheless, Dr. Ni advised that “[p]atients on either diuretic should stick with what they take, and if switching to the other diuretic has a side benefit — for example, allowing for combination pills to reduce pill burden — then switching should be done.”

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