BP before start therapy affects the relative benefit of BP-lowering therapy
Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis
Literature - Brunström M and Carlberg B. - JAMA Intern Med. 2018;178(1):28-36Background
According to medical guidelines, SBP should be treated to a target below 140 mmHg, whereas current data and meta-analyses showed that BP-lowering below this target provides additional benefit [1-3]. On the other hand, there are data showing that intensive BP-lowering may cause harm to DM patients [4].
In this systematic review and meta-analysis, the treatment effect of BP lowering on death and CVD outcomes was evaluated across SBP levels, using non-standardized methods, with RRs and SEs from raw data, derived from a broader range of studies compared with previous meta-analyses. Data on clinical characteristics, comorbidities, and interventions were collected on study level.
Relevant trials were identified based on the PRISMA guidelines. Eligible studies were those comparing drugs against placebo, or different BP targets against each other, with at least 1000 patient-years of follow-up. Studies comparing different BP-lowering drugs against each other, those including HF patients and MI patients with LV-dysfunction, as well as studies at high risk of selection bias, performance bias, or detection bias were excluded. The risk of bias was assessed using the Cochrane Collaborations risk for bias tool [5].
Main results
- 74 eligible trials were identified, including 306 273 participants and 1.2 million patient-years of follow-up. 51 trials, with 192 795 participants, were primary prevention trials.
- In primary prevention trials, treatment to lower BP reduced the risk for all-cause mortality in participants with baseline SBP from 140-159 mmHg (RR: 0.87; 95% CI: 0.75-1.00) and in participants with baseline SBP ≥160 mmHg (RR: 0.93; 95% CI: 0.87-1.00). With SBP below 140 mmHg, no treatment effect was observed (RR: 0.98, 95%CI: 0.90-1.06).
- In a meta-regression analysis, there was a linear association between baseline SBP and treatment effect for CV mortality (P=0.02). CV mortality was reduced by 15% if baseline SBP was ≥160 mmHg (RR: 0.85; 95% CI: 0.77-0.95), while no effect was seen below 140 mmHg (RR: 1.03; 95% CI: 0.87-1.20).
- The treatment association with MACE had a linear pattern across SBP levels (P=0.004). The composite end point was reduced by 22% at baseline SBP ≥160 mmHg (RR: 0.78; 95% CI: 0.70-0.87) and by 12% if baseline SBP was 140-159 mmHg (RR: 0.88; 95% CI: 0.80-0.96). At baseline SBP <140 mmHg, risk of MACE was unaffected (RR: 0.97; 95% CI: 0.90-1.04).
- While point estimates for CHD and stroke showed similar patterns, individual outcomes did not reach statistical significance in meta-regression analyses.
- In secondary prevention trials, treatment was associated with a reduced risk for MACE (RR: 0.90; 95% CI: 0.84-0.97), stroke (RR: 0.83; 95% CI: 0.73-0.96), and HF (RR: 0.83; 95% CI: 0.72-0.96), but there was no association between treatment and all-cause mortality (RR: 0.98; 95% CI: 0.89-1.07) or CV death (RR: 0.95; 95% CI: 0.84-1.09).
Conclusion
The relative benefit from treatment to lower BP depends on baseline BP. A reduced risk for death and MACE was observed in individuals with baseline SBP ≥140 mmHg. For SBP <140 mmHg, BP-lowering was not associated with any benefit in primary prevention, but may reduce the risk of non-fatal CV outcomes in secondary prevention.
Editorial comment
In their editorial article, Moran et al focus on the clinical implication of Brunström’s and Carlberg’s findings. They note that pretreatment BP alone is not enough to guide hypertension treatment, since medical history and multivariate predictors determine the BP-lowering benefit. Moreover, the absolute risk reduction, the most important measure of treatment benefit, was not reported. The authors recommend the following:
- ‘First, clinicians should not allow the ongoing debate about targeting treatment for systolic BPs lower than 140mmHg to detract from the overwhelming evidence from decades of clinical trials, observational studies, and meta-analyses (including that of Brunström and Carlberg) that supports cardiovascular benefit from treating systolic BP at or above 140mmHg. This point deserves to be underscored because current BP control rates in the United States are less than 50%...’
- ‘Second, clinicians should also understand the general points that underlie the current debate on targeting BP lower than 140mmHg.We do not know with certainty who will benefit from lower BP in this range, at least in part because we do not have good estimates of adverse effects of treatment. In the absence of firm evidence, the best approach for clinical decision making may be to align with the new AHA/ACC 2017 hypertension guidelines and to focus on those with the highest underlying cardiovascular risk…’
References
1. Mancia G, Fagard R, Narkiewicz K, et al; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-1357.
2. Wright JT Jr, Williamson JD, Whelton PK, et al; SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116.
3. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-967.
4. Brunstrom M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016;352:i717.
5. Higgins JPT, Altman DG, Gotzsche PC, et al; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ.2011;343:d5928.
6. Moran AE, Pletcher MJ, Bibbins-Domingo K. Whom to Treat for High Blood Pressure-Time for a Precision Approach. JAMA Intern Med. 2018;178(1):37-38.
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