Published in Nature Medicine, the study, led by DPhil Student Qianqian Yang, Professor Kazem Rahimi and colleagues from the Nuffield Department of Women's & Reproductive Health, analysed individual participant data from 358,642 participants across 51 randomised controlled trials from the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC).
Research method
The study used individual data from 358,642 participants across 51 randomised controlled trials, making it the largest body of randomised evidence assembled to examine how the cardiovascular benefits of blood pressure treatment change over time.
Participants were followed for a median of 4.2 years.
Blood pressure lowering is already known to reduce the risk of cardiovascular disease. However, a longstanding question has been whether those benefits continue to build the longer a person remains on treatment, in a similar way to what has been observed for cholesterol-lowering drugs such as statins.
The significance of the study
The findings suggest that the relative cardiovascular benefit of blood pressure-lowering treatment is established early in treatment, rather than increasing over time.
Researchers found that a 5 mm Hg reduction in systolic blood pressure was associated with a 12% lower risk of major cardiovascular events in the first year of treatment. Rather than growing over time, this relative benefit remained broadly stable or attenuated slightly across subsequent years of follow-up.
The same pattern was seen across five major classes of blood pressure-lowering drugs: ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers and thiazide diuretics, and across age groups ranging from under 55 to 85 and over.
The findings were confirmed through additional analyses that accounted for differences in patient characteristics, treatment adherence and the way follow-up time was modelled.
Key findings
- A 5 mm Hg reduction in systolic blood pressure was associated with a 12% lower risk of major cardiovascular events in the first year of treatment.
- The relative benefit remained broadly stable or attenuated slightly over subsequent years.
- The same pattern was seen across ACE inhibitors, ARBs, beta-blockers, calcium channel blockers and thiazide diuretics.
- The findings were consistent across age groups from under 55 to 85 and over.
- Additional analyses supported the robustness of the results across different assumptions and methods.
Implications of the findings
Importantly, the researchers stress that the absence of growing relative benefits does not mean there is no value in continuing treatment.
When measured on the absolute scale and anchored to the original trial populations, the total amount of disease prevented continued to increase over time. For major cardiovascular events, the absolute risk reduction rose from around 0.3% at one year to 1.25% at five years, meaning the number of people who needed to be treated to prevent one event fell from 337 to 80 over that period.
The findings stand in contrast to cholesterol-lowering therapy. Evidence from statin trials has shown that the relative benefits of lowering cholesterol increase year on year, with larger proportional risk reductions emerging the longer treatment continues. This study found no similar pattern for blood pressure lowering, with the relative benefit present early and not increasing with longer follow-up.
The results suggest that treatment decisions should continue to be guided primarily by a person’s baseline cardiovascular risk and expected absolute benefit. They do not support changing treatment thresholds solely on the assumption that earlier exposure produces progressively larger proportional benefits, and they suggest that targeting individuals at higher cardiovascular risk may be more efficient than expanding treatment to lower-risk individuals on that basis.
The key message is not to delay or discontinue effective treatment. Blood pressure lowering provides cardiovascular protection soon after it is started, and maintaining treatment allows the absolute benefit to accumulate. However, our findings challenge the assumption that the relative cardiovascular benefit necessarily become greater simply because treatment is continued for longer."
Qianqian Yang, first author and DPhil student in the Deep Medicine research group
There is growing enthusiasm for treating blood pressure earlier in life, partly on the assumption that longer exposure delivers ever-greater benefit. Our findings don’t support that assumption and suggest that treatment should go to those who are most likely to benefit - guided by a person's underlying cardiovascular risk, not by an expectation that the benefit compounds over time." Professor Kazem Rahimi, corresponding author, Director of the Deep Medicine programme and Chair of the Blood Pressure Lowering Treatment Trialists’ Collaboration
Outlook
These findings provide an important perspective on how the benefits of blood pressure-lowering treatment change over time. The research team note that the early establishment of relative benefit, together with the continued accrual of absolute risk reduction, supports the rationale for early and sustained treatment. Later interval estimates should be interpreted in the context of changing risk sets over time.
Contributions & Collaborations
This research was funded by the British Heart Foundation and led by researchers at the Nuffield Department of Women's & Reproductive Health as part of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), an international research collaboration.
The research team included Qianqian Yang (first author), Professor Kazem Rahimi (corresponding author), Dr Milad Nazarzadeh, Professor Mark Woodward and Dr Zeinab Bidel.