Literature

Lower achieved SBP and DBP associated with more CV events

18-4-2017 • Böhm M, et al, Lancet 2017


Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials


Böhm M, Schumacher H, Teo KK, et al.
Lancet. 2017; published online ahead of print
 

Background

Guidelines recommend a target blood pressure (BP) <140/90 mmHg for the reduction of cardiovascular (CV) events, although the CV risk is also higher at low systolic blood pressure (SBP), resulting in a J-curve [1-4]. The risk reduction associated with high baseline SBP and low achieved SBP might be different for individual endpoints. In the ONTARGET and the TRANSCEND trials, in which 31 546 patients at high CV risk received ramipril, telmisartan or their combination, there were no differences in CV disease outcomes after 56 months of follow-up [5,6].
 
In this secondary analysis of the ONTARGET and TRANSCEND trials, the associations between mean BP achieved on treatment, pre-randomisation baseline BP or time-updated BP (last on treatment value before an event) and the composite outcome of CV death, myocardial infarction (MI), stroke and hospital admission for heart failure (HF), as well as all-cause death were evaluated. Given that there were no differences in outcomes between ONTARGET and TRANSCEND randomized groups, they were combined for this analysis.
 

Main results

  • The lowest risk for the combined primary outcome as well as CV death, hospital admission for HF and all-cause death, was seen at a baseline SBP of 120-140 mmHg. Those with SBP >140 mmHg or SBP <120 mmHg had higher event rates for stroke and MI.
  • The risk was highest at a baseline DBP <70 mmHg for all outcomes except stroke.
  • Patients with a baseline SBP of 140–160 mmHg and ≥160 mmHg had significantly higher event rates for all outcomes except MI, for which the risk was only increased at SBP ≥160 mmHg.
  • DBP ≥90 mmHg at baseline was associated with a lower risk for the composite outcome, MI, and hospital admission for HF compared with all lower DBP values.
  • DBP <70 mmHg at baseline was associated with higher rates of all outcomes except stroke.
  • For the mean achieved SBP values during treatment, the lowest level of risk occurred at SBP of 120–140 mmHg for all outcomes except MI.
  • For the combined primary outcome, CV death, hospital admission for HF and all-cause death, there was an increased risk at an SBP <120 mmHg during treatment.
  • For the primary outcome, all its components, and all-cause death, an increased risk was observed at SBPs of 140–160 mmHg and >160 mmHg.
  • Similar patterns were observed with DBP.
  • Analysis taking SBP as a continuous variable and using cubic spline regression revealed that the relationship between endpoints and baseline SBP (and achieved SBP) were non-linear. The risk for the primary outcome increased from a mean achieved SBP of 140 mmHg to lower SBP values. Similar results were observed for the other outcomes except for MI and stroke.
  • Regarding HRs for outcomes in different baseline SBP groups according to range of SBP changes on treatment, in which no change was reference (HR=1), the risk for the primary outcome increased with SBP reduction, when baseline SBP was <120 mmHg. Furthermore, for participants with a baseline SBP of 140-160 mmHg, reduction of SBP up to 30 mmHg was associated with reduced risk for the primary outcome, which was 50 mmHg reduction when baseline SBP was ≥160 mmHg.
 

Conclusion

In high-risk CV patients, lowering SBP to less than 130 mmHg or DBP to less than 75 mmHg, is associated with increased rates for CV death, MI and HF, but not stroke. These findings suggest that in some patients at low SBP on treatment, blood pressure medication might have to be reduced to avoid adverse outcomes, since treat to target does not mean treat under target.
 
Find this article online at  The Lancet
 

References  

1. 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.
2. Rydén L, Grant PJ, Anker SD, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular
diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and
cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration
with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34: 3035–87.
3. James PA, Oparil S, Carter BL, 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.
4. Mancia G, Grassi G. Aggressive blood pressure lowering is dangerous: the J-curve: pro side of the arguement. Hypertension 2014; 63: 29–36.
5. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358: 1547–59.
6. Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008; 372: 1174–83.
 


blood pressurehypertensionhypotensionONTARGETTRANSCEND

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