December 04, 2023

2 min read

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Key takeaways:

  • There were no differences in most CVD outcomes over more than 2 decades between three antihypertensive agents.
  • ACE inhibitors were linked to greater risk for stroke and stroke mortality vs. diuretics.

In adults with hypertension and at least one CHD risk factor followed for up to 23 years, three antihypertensive medications did not differ in CVD mortality, according to long-term results of the ALLHAT trial.

However, participants assigned ACE inhibitors had elevated risk for stroke compared with those assigned thiazide-type diuretics, researchers reported in JAMA Network Open.

Pills in shape of heart_Adobe Stock
There were no differences in most CVD outcomes over more than 2 decades between three antihypertensive agents.
Image: Adobe Stock

The ALLHAT trial compared a thiazide-type diuretic (chlorthalidone), an ACE inhibitor (lisinopril), a calcium channel blocker (amlodipine) and an alpha-blocker (doxazosin). In the initial results, the alpha-blocker arm was stopped early because of an elevated rate of CV events, but there was no difference between the other three groups in fatal CHD or nonfatal MI during 4.9 years of follow-up.

For the long-term analysis, participants from the diuretic, ACE inhibitor and calcium channel blocker groups were followed until December 2017, a maximum of 23.9 years. Posttrial follow-up data were gathered from the National Death Index, Social Security Administration and CMS databases.

The cohort included 32,804 adults aged 55 years or older at baseline (mean age, 67 years; 53% men; 36% Black) who had hypertension (defined as BP at least 140/90 mm Hg) and at least one CHD risk factor (prior MI or stroke, left ventricular hypertrophy by ECG or echocardiogram, type 2 diabetes, current smoking or low HDL). All participants were followed for all-cause mortality and 22,754 participants (mean age, 69 years; 56% women; 36% Black) were followed for CVD morbidity outcomes.

The mean follow-up was 13.7 years and the maximum follow-up was 23.9 years.

At 23 years, the rates of CVD mortality were 23.7 per 100 persons in the diuretic group, 21.6 per 100 persons in the calcium channel blocker group and 23.8 per 100 persons in the ACE inhibitor group (adjusted HR for calcium channel blockers vs. diuretics = 0.97; 95% CI, 0.89-1.05; aHR for ACE inhibitors vs. diuretics = 1.06; 95% CI, 0.97-1.15), Jose-Miguel Yamal, PhD, associate professor at the Coordinating Center for Clinical Trials, department of biostatistics and data science, School of Public Health, The University of Texas Health Science Center at Houston, and colleagues wrote.

There were no differences between the groups in the following secondary outcomes: all-cause mortality and both mortality and morbidity for CHD, HF, end-stage renal disease and cancer.

However, compared with the diuretic group, the ACE inhibitor group had elevated risk for stroke mortality (aHR = 1.19; 95% CI, 1.03-1.37) and combined fatal and nonfatal stroke (aHR = 1.11; 95% CI, 1.03-1.2), the researchers found.

“The use of administrative data has gained increased popularity in clinical trials and has been recognized by the [FDA] as important to advance the development of therapeutic products,” Yamal and colleagues wrote. “Ascertainment of these long-term posttrial outcomes in a large study such as ALLHAT using traditional methods would have been very expensive and resource-intensive. Although limited, the use of administrative data has made this type of analysis feasible. … [In the long-term analysis,] we found similar results as those found during the ALLHAT [trial]. [ACE inhibitors] were associated with an increased risk of stroke outcomes … compared with diuretics, and this effect persisted well beyond the trial period.”