Lower achieved SBP and DBP associated with more CV events
Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials
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
- 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.
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.