Do the Effects of Antihypertensives Diminish With Each Added Drug Class?

Patients often require multiple antihypertension medications
Patients often require multiple antihypertension medications

Adding a new antihypertensive drug class resulted in large reductions in systolic blood pressure (BP) and major cardiovascular events among patients already taking antihypertensive drugs (0 or more agents from other classes) at high risk for cardiovascular events but without diabetes, according to an analysis published in The BMJ

Previous observational studies have suggested that adding additional antihypertensives may lead to diminishing benefits. In order to assess the incremental effects of adding additional agents, researchers from Michigan analyzed data from SPRINT (Systolic Blood Pressure Intervention Trial). Patients' randomization status was either standard treatment (systolic BP target <140mmHg) or intensive treatment (systolic BP target <120mmHg); the randomization status was used to adjust for confounding by indication. 

The secondary analysis included 9,092 SPRINT patients with hypertension and increased cardiovascular risk but without a history of diabetes or stroke. According to standard multivariable models (unadjusted for confounding), adding an antihypertensive from a new class was associated with a small –1.3mmHg reduction in systolic BP (95% CI: –1.6 to –1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% CI: –1.5 to 2.3). 

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According to instrumental variable models, adding an antihypertensive from a new class was associated with a clinically meaningful –14.4mmHg (95% CI: –15.6 to –13.3) reduction in systolic BP and a reduction in major cardiovascular events (absolute risk –6.2, 95% CI: –10.9 to –1.3). Patients who were taking no baseline drugs
(–13.90mmHg reduction) or drugs from ≥3 drug classes (–15.11mmHg reduction) still experienced incremental systolic BP reductions that were "large and similar in magnitude." The effects on systolic BP were consistent for all patient subgroups, the authors noted. 

Regarding safety, adding a new antihypertensive drug class was not associated with adverse effects in either the standard (absolute risk 4.89 events per 1000 patient years, 95% CI: –2.11 to 12.09) or variable models (absolute risk 12.66 events per 1000 patient years, 95% CI: –5.04 to 31.05).

"Collectively, these findings suggest that antihypertensive drugs can be used to lower blood pressure effectively with the addition of a first, second, third, or fourth class of drug or more to a patient's regimen," the authors concluded.

For more information visit bmj.com.