Elsevier

The Lancet

Volume 384, Issue 9943, 16–22 August 2014, Pages 591-598
The Lancet

Articles
Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data

https://doi.org/10.1016/S0140-6736(14)61212-5Get rights and content

Summary

Background

We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy.

Methods

This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11–15%, 15–21%, >21%).

Findings

11 trials and 26 randomised groups met the inclusion criteria, and included 67 475 individuals, of whom 51 917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4·0 years (IQR 3·4–4·4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6·0% (SD 2·0), 12·1% (1·5), 17·7% (1·7), and 26·8% (5·4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7–27), 15% (4–25), 13% (2–22), and 15% (5–24), respectively (p=0·30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8–21), 20 (8–31), 24 (8–40), and 38 (16–61) cardiovascular events, respectively (p=0·04 for trend).

Interpretation

Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions.

Funding

None.

Introduction

The merits of using an individual's predicted absolute risk of cardiovascular disease to inform treatment decisions for the prevention of cardiovascular disease, rather than using only the level of one cardiovascular disease risk factor, have been recognised for decades.1, 2, 3 Most countries and cardiovascular societies now regard this evidence as sufficient to recommend that lipid-lowering treatment should be based on patients' predicted cardiovascular disease risk rather than LDL cholesterol concentrations.3, 4, 5, 6 Blood pressure-lowering treatment recommendations, however, are still based mainly on blood pressure levels.7, 8, 9 The American Heart Association and the American College of Cardiology are the most recent organisations to switch to cardiovascular disease risk-based cholesterol treatment guidelines, and a Cholesterol Treatment Trialists' (CTT) Collaboration meta-analysis using individual participant data from statin trials 10 was influential in their decision to move away from treatment thresholds based mainly on LDL cholesterol concentrations. That meta-analysis involved retrospectively calculating a baseline 5-year vascular risk for all participants, which enabled the investigators to estimate the relative and absolute benefits of lipid lowering in different baseline risk categories. The findings clearly show that baseline vascular risk is a major determinant of the absolute benefits of statin treatment (figure 1 ).

The Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) has investigated the effects of blood pressure lowering on cardiovascular events in major patient subgroups, defined using individual patient data. The available data now provide a unique opportunity to compare the effects of blood pressure-lowering drugs in subgroups of patients at different levels of baseline absolute risk of cardiovascular events, in much the same way as has been done for lipid-lowering therapy in the CTT meta-analysis. 10

We postulated that the relative cardiovascular disease risk reductions achieved with blood pressure-lowering therapy would be similar across population groups with different levels of baseline cardiovascular disease risk, and therefore that the absolute risk reductions would be greater for subgroups with higher levels of baseline cardiovascular disease risk. We aimed to test this hypothesis by doing a meta-analysis of individual patient data.

Section snippets

Study eligibility

The methods used have been reported previously, 11 and only the main components are summarised here. In brief, trials were eligible if they met the original inclusion criteria specified in the protocol, 11 and were part of the subset of studies that randomly allocated patients to either a blood pressure-lowering drug or placebo, or to a more intensive or less intensive blood pressure regimen. Trials had to have a minimum of 1000 patient-years of planned follow-up in each randomised group, and

Results

11 trials and 26 randomised groups met the inclusion criteria (some trials were factorial or included more than two groups), and included 67 475 individuals (appendix).16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 Data for the calculation of the risk equations were available for 51 917 patients. The mean estimated baseline absolute 5-year risk of cardiovascular disease events in this sample was 11·7% (7·5), with the four risk groups defined as having estimated 5-year cardiovascular

Discussion

In this meta-analysis of more than 50 000 patients, pharmacological blood pressure lowering produced relative reductions in cardiovascular risk that were similar across patient groups with markedly varying levels of baseline estimated cardiovascular risk, while delivering progressively greater absolute risk reductions at higher levels of baseline risk. This same pattern was apparent in a range of subsidiary analyses done on the primary composite cardiovascular outcome after adjusting for

References (47)

  • NJ Stone et al.

    2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College Of Cardiology/American Heart Association Task Force on Practice Guidelines

    Circulation

    (2014)
  • A Cooper et al.

    Risk assessment and lipid modification for primary and secondary prevention of cardiovascular disease: summary of NICE guidance

    BMJ

    (2008)
  • J Perk et al.

    European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Developed with the special contribution of the European Association For Cardiovascular Prevention & Rehabilitation (EACPR)

    Eur Heart J

    (2012)
  • A Tonkin et al.

    Position statement on lipid management—2005

    Heart Lung Circ

    (2005)
  • T Krause et al.

    Management of hypertension: summary of NICE guidance

    BMJ

    (2011)
  • PA James et al.

    2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8)

    JAMA

    (2014)
  • The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials

    Lancet

    (2012)
  • Protocol for prospective collaborative overviews of major randomized trials of blood-pressure-lowering treatments

    J Hypertens

    (1998)
  • F Turnbull et al.

    Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system

    J Hypertens

    (2007)
  • Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials

    Lancet

    (2003)
  • Cochrane handbook for systematic reviews of interventions

    (2011)
  • MR Law et al.

    Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies

    BMJ

    (2009)
  • Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial

    Lancet

    (2007)
  • Cited by (485)

    • SEA 2024 Standards for Global Control of Vascular Risk

      2024, Clinica e Investigacion en Arteriosclerosis
    View all citing articles on Scopus

    Members are listed at the end of the paper

    View full text