Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.

Ettehad D, Emdin CA, Kiran A et al.,
Lancet. 2015 Dec 23. pii: S0140-6736(15)01225-8. doi: 10.1016/S0140-6736(15)01225-8

Background

A continuous log-linear association between blood pressure (BP) and vascular events, to a BP of 115/75 mmHg has been found in prospective cohort studies [1]. The relationship appears to exist in diverse populations, including individuals with and without established vascular disease [1-3]. It is, however, unknown whether BP lowering treatment lowers the risk of cardiovascular (CV) disease in all patient groups.
A trend towards higher BP targets and threshold for BP lowering has been seen in recent guidelines [4-6]. The SPRINT trial reported that BP lowering to 120 mmHg was beneficial in some high-risk patient groups, but it is unclear whether the same is true for certain high-risk individuals with for instance diabetes or cerebrovascular disease [7].
This systematic review and meta-analysis aimed to combine data from all published large-scale BP lowering trials (Jan 1966-July 2015) to quantify the effects of BP lowering on CV outcomes and death in various populations, based on baseline BP levels, major comorbidities and type of treatment. 123 eligible randomised controlled trials, encompassing data of 613815 participants were included in the meta-analysis.

Main results

• Relative risk reductionsa for major CV disease events, stroke, heart failure and all-cause mortality were all found to be statistically significantly proportional to the magnitude of BP reduction achieved. This was not seen for coronary heart disease or renal failure.
• A 10 mmHg decrease in systolic BP (SBP) significantly reduced the risk of major CV disease events (RR: 0.80, 95%CI: 0.77-0.83), coronary heart disease (RR: 0.83, 95%CI: 0.78-0.88), stroke (RR: 0.73, 95%CI: 0.68-0.77), heart failure (RR: 0.72, 95%CI: 0.67-0.78) and all-cause mortality (RR: 0.87, 95%CI: 0.84-0.91).c
• When stratifying trials by mean baseline SBP, no significant trends were observed for the effect of a 10 mmHg reduction in SBP on outcomes. Proportional effects did not appear diminished in trials that included people with BP <130 mmHg.
• When stratifying trials by baseline CV disease, no evidence was seen of different proportional effects of BP lowering.
• A significant interaction (P=0.0006) was seen for baseline diabetes in the risk of major CV disease events, with larger risk reductions in those without diabetes (RR: 0.75, 95%CI: 0.70-0.80 vs. RR: 0.8, 95%CI: 0.82-0.94).
• Larger proportional risk reductions for major CV disease events were seen in populations without  chronic kidney disease (RR: 0.68, 95%CI: 0.62-0.75) than in those with (RR: 0.84, 95%CI: 0.73-0.96, P(interaction)=0.012). A significant interaction (P(interaction)=0.0008) was also seen for heart failure events, with RR: 0.48 (95%CI: 0.38-0.62) in those without chronic kidney disease, as compared with those with (RR: 0.95, 95%CI: 0.70-1.29).
• When comparing five classes of BP lowering drugs, overall the different classes were of largely similar effectiveness. Modest differential effects were observed, such that beta-blockers were less efficacious than other drugs for the prevention of major CV disease events (RR: 1.17, 95%CI: 1.11-1.24), stroke (RR: 1.24, 95%CI: 1.14-1.35) and renal failure (RR: 1.19, 95%CI: 1.05-1.34).
  Calcium channel-blockers were superior to the other classes for stroke prevention (RR: 0.90, 95%CI: 0.85-0.95), but inferior with respect to heart failure prevention (RR: 1.17, 95%CI: 1.11-1.24).
  Diuretics were superior for heart failure prevention (RR: 0.81, 95%CI: 0.75-0.88).

Conclusion

This meta-analysis shows that BP-lowering treatment significantly reduces the risk of CV disease and death in various patient populations, even in persons with lower BP. A 10 mmHg reduction in SBP lowered the risk of several CV disease manifestations by 13-28%, with broadly consistent proportional risk reductions across several high-risk populations. This suggests that BP-lowering provides rather generalizable benefits.
Unexpectedly, the proportional reduction in major CV disease events seemed larger in trials performed in individuals without diabetes or chronic kidney disease. Modest differentials effects on outcomes were observed for different BP-lowering drug classes.
The observed efficacy of BP lowering below 130 mmHg and similar proportional effects in high-risk populations are in line with the SPRINT trial, and in contrast with recent guidelines that relaxed the BP lowering thresholds.

Find this article online at The Lancet

References

1. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–13.
2. Lawes CMM, Rodgers A, Bennett DA, et al. Blood pressure and cardiovascular disease in the Asia Pacifi c region. J Hypertens 2003; 21: 707–16.
3. Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1・25 million people.
Lancet 2014; 383: 1899–911.
4.James P, Oparil S, Carter B, 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; 311: 507–20.
5. Mancia G, Fagard R, Narkiewicz K, et al. 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). Eur Heart J 2013; 34: 2159–219.
6. NICE. The clinical management of primary hypertension in adults: clinical guideline 127. London: National Institute for Health and Care Excellence, 2011.
7. Wright JTJ, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015; 373: 2103–16.