Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials

Abstract

Objective: Evidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.

Methods: We conducted an individual patient-level data meta-analysis of 52 large-scale randomised clinical trials in the Blood Pressure Lowering Treatment Trialists' Collaboration using mixed models to examine treatment effects on BP over 4 years of mean follow-up.

Results: There were 363 684 participants (42% women), with baseline mean age=65 years and mean systolic/diastolic BP=152/87 mm Hg, and among whom 19% were current smokers, 49% had cardiovascular disease, 28% had diabetes and 69% were taking antihypertensive treatment at baseline. Drugs were effective in lowering BP showing maximal effect after 12 months and gradually attenuating towards later years. Based on measures taken ≥12 months postrandomisation, mean systolic/diastolic BP difference (95% CI) between more and less intense BP-lowering treatment was -11.1 (-11.3 to -10.8)/-5.6 (-5.7 to -5.4) mm Hg; between active treatment and placebo was -5.1 (-5.3 to -5.0)/-2.3 (-2.4 to -2.2) mm Hg; and between active and control arms for drug comparison trials was -1.4 (-1.5 to -1.3)/-0.6 (-0.7 to -0.6) mm Hg. BP reductions were observed across different baseline BP values and ages, and by sex, history of cardiovascular disease and diabetes and prior antihypertensive treatment use.

Conclusion: These findings suggest that BP-lowering pharmacotherapy is effective in lowering BP, up to 4 years on average, in people with different characteristics. Appropriate treatment strategies are needed to sustain substantive long-term BP reductions.

Keywords: clinical; hypertension; meta-analysis; pharmacology.

Figure 1

Blood pressure (BP) trajectories according to different trial designs. Results are in red for active group and black for control group, from 3 months to 5 years of follow-up. Estimates were based on separate models for treatment and control groups, with random intercepts at individual and trial levels, a random slope for time at the individual level (see Method for details) and adjusted for baseline BP, age and sex. Baseline systolic/diastolic BP for active and control groups were: BP-lowering trials=151/88 mm Hg; placebo-controlled trials=146/83 mm Hg and drug class comparison trials=156/90 mm Hg. Estimated BP at specific time points are shown in online supplemental table S8). Results for all BP difference trials are shown in online supplemental figure S2.

Figure 2

Effects of blood pressure (BP)-lowering treatment on mean BP at fixed follow-up time points and across all follow-up period. (A) Systolic BP; (B) Diastolic BP. For mean difference at fixed follow-up time periods, estimates were based on separate models for each time period with a fixed treatment effect and random intercept for individuals. For mean difference achieved across all time period (showing results based on all follow-up BP measures and measures obtained from 12 months until end of follow-up), estimates were based on fixed treatment effect and random intercepts at individual and trial levels, a random slope for time at the individual level. All mean difference values were adjusted for baseline BP, age and sex. The area of the square is inversely proportional to the variance of the estimated difference. Negative values indicate lower BP in the active than in the control group. Additional information provided in online supplemental table S9 and S10), and results for all BP difference trials are in online supplemental figure S3.

Figure 3

Effects of blood pressure (BP)-lowering treatment on mean BP, by baseline characteristics. (A) mean systolic BP difference; (B) mean diastolic BP difference. Estimates based on fixed treatment effect and random intercepts at individual and trial levels, a random slope for time at the individual level (see Method for details) and adjusted for baseline BP), age and sex except when these variables are used as stratification factors. The area of the square is inversely proportional to the variance of the estimated difference. Negative values indicate lower BP in the active than in the control group. Results for all BP difference trials are in online supplemental figure S4. To provide context of background BP levels, baseline BP by these subgroups are shown in online supplemental table S2.