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