CONFLICT OF INTEREST
None declared.
Blood pressure (BP) control relies on the use of effective drugs in the right combination and dosage. Antihypertensive agents can be increased either by increasing dosage or by adding another class of drug for synergic effect, although multiplying and complexifying medical prescriptions is associated with poor compliance and negative outcomes.1, 2, 3
SPRINT (Systolic Blood Pressure Intervention Trial) (NCT01206062) aimed to evaluate BP control with a systolic BP target of 120 mm Hg, regarding the primary composite outcome of myocardial infarction, acute decompensated heart failure, or death from cardiovascular causes, by comparing an intensive management with a standard one (control group). The management of BP was strictly guided by an algorithm: the addition of another class of BP class was dependent on the BP measured during a visit, with higher thresholds for the standard group as compared with the intensive group and, conversely, treatment could be decreased.
SPRINT concluded that a lower BP threshold (120 mm Hg) was preferable to that of a higher value (140 mm Hg).4
With data obtained during the SPRINT Data Analysis Challenge,5 this study assessed whether the way BP target was reached had an influence on the incidence of clinical outcomes. To do so, the association between the number of additions to antihypertensive treatment and incidence of cardiovascular outcomes was analyzed using regression analyses.
Because of the indication bias (ie, BP control), the number of antihypertensive treatment modifications that was required by the study protocol was computed: for the standard group, systolic BP ≥ 160 mm Hg once (or ≥140 mm Hg twice) (respectively 140 and 120 mm Hg for the intensive group) or diastolic BP ≥ 100 mm Hg once (or ≥90 mm Hg twice). This way, BP control was computed by analyzing BP values at all time points for every patient. Interactions between variables were also tested.
All SPRINT patients were included in the analysis (n = 9361). There were more additions of antihypertensive agents in the intensive group as compared with the control group (1.4 ± 1.1 vs 1.2 ± 1.1, respectively; P = .001). BP variations showed that protocol required more treatment upscaling in the intensive group as compared with the control group (6.0 ± 3.7 vs 2.2 ± 2.4, respectively; P < .0001).
Cox multivariable regression analysis showed that the number of additions to antihypertensive agents was significantly associated with the primary outcome, independently of age, cardiovascular risk estimated by Framingham, estimated glomerular filtration rate (as defined in the original SPRINT publication), treatment arm (intensive or control), patients’ average BP, and BP control (adjusted hazard ratio per addition, 1.22, 95% confidence interval, 1.13–1.31; P < .0001) (Figure 1).
Figure 1.
Cumulative survival (event‐free) of Systolic Blood Pressure Intervention Trial patients based on the number of antihypertensive drugs added during follow‐up. Cox multivariable regression analysis showed the number of additions to antihypertensive agents was significantly associated with the primary outcome, independently of age, cardiovascular risk estimated by Framingham, estimated glomerular filtration rate, treatment arm (intensive or control), patients’ average blood pressure, and blood pressure control (adjusted hazard ratio per addition, 1.22; 95% confidence interval [CI], 1.13–1.31 [P < .0001]).
These results were confirmed in subgroup analysis (per treatment arm). Changes in the number of BP medication classes were associated with the outcome in the intensive group: adjusted hazard ratio, 1.17 (95% confidence interval, 1.03–1.32, P = .01) and in the control group: adjusted hazard ratio, 1.25 (confidence interval, 1.13–1.39, P < 0.0001). There were no interactions between additions in BP medications, treatment arm (intensive or control), changes required by the study protocol, and average BP during follow‐up regarding the primary outcome.
In this large cohort of patients with high‐risk hypertension, increasing the number of antihypertensive agents was associated with an increased risk of myocardial infarction, acute decompensated heart failure, or death from cardiovascular causes, regardless of the treatment arm, average systolic BP, and BP control.
Hence, in addition to the SPRINT conclusions, these findings may incite physicians to use fewer but more potent drugs to keep the number of medications at a minimum.
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