Klinik für Innere Medizin III, Universität des Saarlandes, Homburg, Germany.
Ingelheim, Germany.
Lancet. 2017 Jun 3;389(10085):2226-2237. doi: 10.1016/S0140-6736(17)30754-7. Epub 2017 Apr 5.
Studies have challenged the appropriateness of accepted blood pressure targets. We hypothesised that different levels of low blood pressure are associated with benefit for some, but harm for other outcomes.
In this analysis, we assessed the previously reported outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination, with a median follow-up of 56 months. Detailed descriptions of randomisation and intervention have already been reported. We analysed the associations between mean blood pressure achieved on treatment; prerandomisation baseline blood pressure; or time-updated blood pressure (last on treatment value before an event) on the composite outcome of cardiovascular death, myocardial infarction, stroke, and hospital admission for heart failure; the components of the composite outcome; and all-cause death. Analysis was done by Cox regression analysis, ANOVA, and χ. These trials were registered with ClinicalTrials.gov, number NCT00153101.
Recruitment for ONTARGET took place between Dec 1, 2001, and July 31, 2008. TRANSCEND took place between Nov 1, 2001, and May 30, 2004. 30 937 patients were recruited from 733 centres in 40 countries and followed up for a median of 56 months. In ONTARGET, 25 127 patients known to be tolerant to angiotensin-converting-enzyme (ACE)-inhibitors were randomly assigned after a run-in period to oral ramipril 10 mg/day (n=8407), telmisartan 80 mg/day (n=8386), or the combination of both (n=8334). In TRANSCEND, 5810 patients who were intolerant to ACE-inhibitors were randomly assigned to oral telmisartan 80 mg/day (n=2903) or placebo (n=2907). Baseline systolic blood pressure (SBP) 140 mm Hg or higher was associated with greater incidence of all outcomes compared with 120 mm Hg to less than 140 mm Hg. By contrast, a baseline diastolic blood pressure (DBP) less than 70 mm Hg was associated with the highest risk for most outcomes compared with all DBP categories 70 mm Hg or more. In 4052 patients with SBP less than 120 mm Hg on treatment, the risk of the composite cardiovascular outcome (adjusted hazard ratio [HR] 1·14, 95% CI 1·03-1·26), cardiovascular death (1·29, 1·12-1·49), and all deaths (1·28, 1·15-1·42) were increased compared with those in whom SBP was 120-140 mm Hg during treatment (HR 1 for all outcomes, n=16099). No harm or benefit was observed for myocardial infarction, stroke, or hospital admission for heart failure. Mean achieved SBP more accurately predicted outcomes than baseline or time-updated SBP, and was associated with the lowest risk at approximately 130 mm Hg, and at 110-120 mm Hg risk increased for the combined outcome, cardiovascular death, and all-cause death except stroke. A mean DBP less than 70 mm Hg (n=5352) during treatment was associated with greater risk of the composite primary outcome (HR 1·31, 95% CI 1·20-1·42), myocardial infarction (1·55, 1·33-1·80), hospital admission for heart failure (1·59, 1·36-1·86) and all-cause death (1·16, 1·06-1·28) than a DBP 70-80 mm Hg (14 305). A pretreatment and mean on-treatment DBP of about 75 mm Hg was associated with the lowest risk.
Mean achieved SBP less than 120 mm Hg during treatment was associated with increased risk of cardiovascular outcomes except for myocardial infarction and stroke. Similar patterns were observed for DBP less than 70 mm Hg, plus increased risk for myocardial infarction and hospital admission for heart failure. Very low blood pressure achieved on treatment was associated with increased risks of several cardiovascular disease events. These data suggest that the lowest blood pressure possible is not necessarily the optimal target for high-risk patients, although it is not possible to rule out some effect of reverse causality.
Boehringer Ingelheim.
已有研究对被广泛接受的血压目标值的适宜性提出了质疑。我们假设，对于某些患者而言，不同程度的低血压可能会带来获益，但对于另一些患者而言，低血压可能会带来危害。
本分析评估了先前报道的高危患者（年龄≥55 岁且有心血管病史，其中 70%有高血压）的终点事件数据，这些患者来自 ONTARGET 和 TRANSCEND 两项试验，研究对象为服用雷米普利、替米沙坦或两者联合治疗，中位随访时间为 56 个月。随机分组和干预措施的详细描述已有报道。我们分析了治疗期间的平均血压与心血管死亡、心肌梗死、卒中和心力衰竭住院复合终点；复合终点各组分；以及全因死亡之间的相关性。分析采用 Cox 回归分析、方差分析和卡方检验。这些试验在 ClinicalTrials.gov 注册，编号为 NCT00153101。
ONTARGET 研究于 2001 年 12 月 1 日至 2008 年 7 月 31 日期间开展，TRANSCEND 研究于 2001 年 11 月 1 日至 2004 年 5 月 30 日期间开展。研究共纳入来自 40 个国家的 733 家中心的 30937 例患者，中位随访时间为 56 个月。在 ONTARGET 研究中，在经过一段洗脱期后，已知能耐受血管紧张素转换酶（ACE）抑制剂的 25127 例患者被随机分配接受雷米普利 10 mg/d（n=8407）、替米沙坦 80 mg/d（n=8386）或两者联合治疗（n=8334）。在 TRANSCEND 研究中，5810 例不能耐受 ACE 抑制剂的患者被随机分配接受替米沙坦 80 mg/d（n=2903）或安慰剂（n=2907）治疗。与 120140 mm Hg 相比，收缩压（SBP）基线值≥140 mm Hg 与所有结局的发生率较高相关。相反，与所有 SBP≥70 mm Hg 相比，SBP＜70 mm Hg 与大多数结局的最高风险相关。在 4052 例治疗期间 SBP＜120 mm Hg 的患者中，与治疗期间 SBP 为 120140 mm Hg 的患者相比，复合心血管结局（调整后的危险比[HR] 1.14，95%CI 1.031.26）、心血管死亡（1.29，1.121.49）和全因死亡（1.28，1.151.42）的风险增加。对于心肌梗死、卒中和心力衰竭住院，未观察到获益或危害。与基线或时间更新的 SBP 相比，治疗期间的平均 SBP 更准确地预测结局，且与约 130 mm Hg 时的最低风险相关，当 SBP 为 110120 mm Hg 时，复合结局、心血管死亡和全因死亡的风险增加，除了卒中。治疗期间平均舒张压（DBP）＜70 mm Hg（n=5352）与复合主要结局（HR 1.31，95%CI 1.201.42）、心肌梗死（1.55，1.331.80）、心力衰竭住院（1.59，1.361.86）和全因死亡（1.16，1.061.28）的风险增加相关，而 DBP 为 70~80 mm Hg（n=14305）时的风险则较低。治疗前和治疗期间的平均 DBP 约为 75 mm Hg 时风险最低。
治疗期间 SBP＜120 mm Hg 与除心肌梗死和卒中外的心血管结局风险增加相关。DBP＜70 mm Hg 也观察到类似的模式，且与心肌梗死和心力衰竭住院风险增加相关。治疗期间实现的非常低的血压与多种心血管疾病事件的风险增加相关。这些数据表明，高危患者并非血压越低越好，尽管不能排除某些反向因果关系的影响。
勃林格殷格翰。
