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Blood Pressure-Lowering Treatment Based on Cardiovascular Risk: A Meta-Analysis of Individual Patient Data
Study Questions:
Are the benefits of blood pressure (BP)-lowering drugs proportional to baseline cardiovascular risk, and can absolute risk be used to inform treatment decisions for BP-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 BP-lowering drugs or placebo, or to more intensive or less intensive BP-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. The variables included age, sex, body mass index, systolic BP, diastolic BP, other antihypertensive treatment, current smoking, diabetes, and history of cardiovascular disease. Lipid data were not available. 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%, and >21%).
Results:
A total of 11 trials and 26 randomized groups met the inclusion criteria, and included 67,475 individuals, of whom 51,917 had available data for the calculation of the risk equations. Trials were combined regardless of drug class. A total of 4,167 (8%) people had a cardiovascular event during a median of 4.0 years (interquartile range, 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% (standard deviation 2.0), 12.1% (1.5), 17.7% (1.7), and 26.8% (5.4). In each consecutive higher risk group, BP-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% confidence interval, 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p = 0.30 for trend). However, in absolute terms, treating 1,000 patients in each group with BP-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).
Conclusions:
Lowering BP 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 BP-lowering treatment decisions.
Perspective:
The authors also conclude that a risk-based approach is likely to be more cost-effective than a BP-based approach, and could simultaneously reduce the numbers of patients needing treatment, and control drug costs, while increasing the numbers of averted strokes and heart attacks. Available data suggest that while over 60% of persons require at least two drugs, the cost of generic antihypertensive drugs is low, suggesting that simply an elevated BP without other risk factors should be considered an appropriate indication. Whilst the absolute risk reduction may be lower when treating hypertension in low-risk patients, the safety of treatment is very well established. Further, there is evidence that treating mild hypertension prevents worsening of hypertension later (blunts BP progression) and prevents later onset of left ventricular hypertrophy, which may reduce the very common and costly heart failure with preserved ejection fraction in the elderly.
Keywords: Hypertrophy, Left Ventricular, Stroke, Follow-Up Studies, Lipids, Numbers Needed To Treat, Risk Factors, Drug Costs, Smoking, Body Mass Index, Heart Failure, Confidence Intervals, Hypertension, Diabetes Mellitus
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