The addition of an antihypertensive drug from a new drug class may help hypertensive patients on an existing regimen significantly reduce systolic blood pressure (SBP), according to a study published in the BMJ.

Adam A Markovitz, BS, from the Department of Health Management and Policy at the University of Michigan School of Public Health, and colleagues conducted a study evaluating the effects of additional antihypertension medications from a new drug class.

The researchers used data from the Systolic Blood Pressure Intervention Trial (SPRINT) and a randomization method to categorize sicker patients (of the 9092 hypertensive participants) whose treatments may not have been as effective. Patients with a target SBP <120 mm Hg and <140 mm Hg were in intense and standard treatment categories, respectively.

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Hypertensive patients 50 years or older at risks for cardiovascular events were eligible candidates for participation. Additionally, eligible participants had no history of stroke, diabetes, and a SBP between 130 mm Hg and 180 mm Hg. At the start of the investigation, 9% of patients had not taken antihypertensive medications. Twenty-nine percent took medication from one drug class, 35% from two drug classes, and 26% from three or more drug classes.

Before adjustment, standard multivariable models resulted in a lower SBP, though not significant (-1.33 mm Hg). Conversely, instrumental variable models showed significantly reduced SBP (-14.42 mm Hg).

In addition to measuring SBP, the researchers also measured the effects of multiple hypertensive drug classes on major cardiovascular events. Standard multivariable models did not yield significant changes (absolute risk, 0.47), while the instrumental variable models resulted in a greatly decreased risk of major cardiovascular events (absolute risk, -6.23).

Adverse effects were associated with the instrumental variable models, including hypotension (absolute risk, 4.34), electrolyte imbalance (absolute risk, 5.51), and acute kidney injury or kidney failure (absolute, 8.26).

“These results challenge the view that the effects of antihypertensive drugs will diminish with each added drug class,” according to the authors.

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“Future research on this issue should focus on developing experimental evidence on how the strong additive reductions in blood pressure observed in our study could translate to patient benefit and harm.”


  1. Markovitz AA, Mack JA, Nallamothu BK, Ayanian JZ, Ryan AM. Incremental effects of antihypertensive drugs: instrumental variable analysis. BMJ. 2017 Dec 22. doi: 10.1136/bmj.j5542