Antihypertensive Drug Efficacy Calculator Developed from 484 Clinical Trials With Nelson Wang, MD, PhD

Investigators have developed a new model to calculate the efficacy of any combination of anti-hypertensive drugs, based on results from a systematic review and meta-analysis of previous trials.

Roughly 120 million US adults have hypertension; of these, 92.9 million have uncontrolled hypertension. The condition is a leading factor for increased risk of cardiovascular disease mortality and events, such as heart attack and stroke. It is also associated with chronic kidney disease and diabetes. In previous studies, over 50% of adults with uncontrolled hypertension were unaware of the condition and were therefore untreated. An additional 70.8% of treated patients had hypertension, which remained uncontrolled.2

“Our current treatment paradigm has centered on clinicians starting low and then going slow and trying to measure the blood pressure response to treatment,” Nelson Wang, MD, PhD, academic cardiologist at Brigham and Women’s Hospital, said in an interview with HCPLive. “But what evidence suggests is that blood pressure exhibits so much variability for any given individual that it becomes extremely difficult to accurately quantify the blood pressure treatment response for a given individual.”

Investigators collected randomized, double-blind, placebo-controlled trials involving adult patients randomly assigned to angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, calcium channel blockers, or diuretics. For inclusion, studies had to have a follow-up duration of 4-26 weeks, clinic blood pressure data for the calculation of mean differences in systolic pressure between treatment groups, and a fixed antihypertensive drug treatment in all participants for ≥4 weeks before follow-up blood pressure assessment.1

The primary outcome was placebo-corrected systolic blood pressure reduction; blood pressure-lowering efficacy was estimated using fixed-effects meta-analyses standardized to the mean baseline blood pressure across all included trials. The team categorized drug regimens into low, moderate, and high intensity, which corresponded to systolic blood pressure lowering efficacy of <10 mm Hg, 10-19 mm Hg, and ≥20 mm Hg, respectively, from a 154 mm Hg baseline.1

A total of 484 trials were collected, including 104,176 participants with a mean age of 54 years (standard deviation [SD] 8). Of these, 55% (57,422) were male. Mean baseline systolic blood pressure was 154/100 mm Hg, and mean follow-up duration was 8.6 weeks (SD 5.2).1

Monotherapy at standard dose reduced systolic blood pressure by 8.7 mm Hg (95% CI, 8.2-9.2); each doubling in dose conferred an additional 1.5 mm Hg (1.2-1.7) reduction. Dual combinations at 1 standard dose conferred a 14.9 mm Hg (95% CI, 13.1-16.8) reduction in systolic blood pressure, with each doubling of both drugs adding a reduction of 2.5 mm Hg (1.4-3.7). Investigators saw each 10 mm Hg decrease in baseline systolic blood pressure reduce pressure-lowering efficacy by 1.3 mm Hg (1.0-1.5) for monotherapies, although differences between drug classes were noted.1

Among the standard dose monotherapies, 45 (79%) were classified as low intensity. Of 189 different dual combinations, 110 (58%) were classified as moderate intensity, and 21 (11%) were high intensity. Considerable differences in dose-response and baseline blood pressure response relationships between and within drug classes were also indicated. The efficacy model showed a high correlation between observed and predicted systolic pressures when validated on external trials (r = 0.76; P <.0001).1

After quantifying the blood pressure response to these medications, Wang and colleagues developed an algorithm for predicting the efficacy of combined therapies, including these treatments. The calculator can be accessed here.

“For example, if a patient had a blood pressure that was 20 mm above the desired blood pressure range, then the clinician could check with the online tool whether or not the treatment that they’re intending to prescribe will achieve, on average, the desired blood pressure reduction,” Wang explained to HCPLive. “It’s really a step forward towards using the randomized clinical trial data to inform prescribing, because to date, most of the prescribing has been a lot of trial and error.”

References

1. Wang N, Salam A, Pant R, et al. Blood pressure-lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of randomised, double-blind, placebo-controlled trials. Lancet. 2025;406(10506):915-925. doi:10.1016/S0140-6736(25)00991-2

2. Richardson LC, Vaughan AS, Wright JS, Coronado F. Examining the Hypertension Control Cascade in Adults With Uncontrolled Hypertension in the US. JAMA Netw Open. 2024;7(9):e2431997. doi:10.1001/jamanetworkopen.2024.31997