Saiz Luis Carlos, Gorricho Javier, Garjón Javier, Celaya Mª Concepción, Erviti Juan, Leache Leire
Unit of Innovation and Organization, Navarre Health Service, Pamplona, Spain.
Planning, Evaluation and Management Service, General Directorate of Health, Government of Navarre, Pamplona, Spain.
Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.
This is the second update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown.
To determine if lower blood pressure targets (135/85 mmHg or less) are associated with reduction in mortality and morbidity as compared with standard blood pressure targets (140 to 160/90 to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease).
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to November 2019: Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982), along with the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions.
We included RCTs with more than 50 participants per group that provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (135/85 mmHg or less) compared with standard targets for blood pressure (140 to 160/90 to 100 mmHg or less). Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris.
Two review authors independently assessed search results and extracted data using standard methodological procedures expected by Cochrane. We used GRADE to assess the quality of the evidence.
We included six RCTs that involved 9484 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). All RCTs provided individual participant data. None of the included studies was blinded to participants or clinicians because of the need to titrate antihypertensives to reach a specific blood pressure goal. However, an independent committee blinded to group allocation assessed clinical events in all trials. Hence, we assessed all trials at high risk of performance bias and low risk of detection bias. Other issues such as early termination of studies and subgroups of participants not predefined were also considered to downgrade the quality evidence. We found there is probably little to no difference in total mortality (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.91 to 1.23; 6 studies, 9484 participants; moderate-quality evidence) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; 6 studies, 9484 participants; moderate-quality evidence). Similarly, we found there may be little to no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 9484 participants; low-quality evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure) (RR 0.89, 95% CI 0.80 to 1.00; 6 studies, 9484 participants; low-quality evidence). The evidence was very uncertain about withdrawals due to adverse effects. However, studies suggest more participants may withdraw due to adverse effects in the lower target group (RR 8.16, 95% CI 2.06 to 32.28; 2 studies, 690 participants; very low-quality evidence). Systolic and diastolic blood pressure readings were lower in the lower target group (systolic: mean difference (MD) -8.90 mmHg, 95% CI -13.24 to -4.56; 6 studies, 8546 participants; diastolic: MD -4.50 mmHg, 95% CI -6.35 to -2.65; 6 studies, 8546 participants). More drugs were needed in the lower target group (MD 0.56, 95% CI 0.16 to 0.96; 5 studies, 7910 participants), but blood pressure targets were achieved more frequently in the standard target group (RR 1.21, 95% CI 1.17 to 1.24; 6 studies, 8588 participants).
AUTHORS' CONCLUSIONS: We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future.
这是对2017年首次发表的综述的第二次更新。高血压是导致过早发病和死亡的一个突出的可预防原因。患有高血压和已确诊心血管疾病的人风险尤其高,因此将血压降至标准目标以下可能有益。这一策略可能会降低心血管疾病的死亡率和发病率,但也可能增加不良事件。高血压合并已确诊心血管疾病患者的最佳血压目标仍不明确。
确定在治疗有心血管疾病(心肌梗死、心绞痛、中风、外周血管闭塞性疾病)病史的高血压患者时,与标准血压目标(收缩压140至160mmHg或舒张压90至100mmHg及以下)相比,更低的血压目标(收缩压/舒张压135/85mmHg及以下)是否与死亡率和发病率的降低相关。
对于本次更新的综述,Cochrane高血压信息专家检索了以下数据库以查找截至2019年11月的随机对照试验(RCT):Cochrane高血压专业注册库、CENTRAL、MEDLINE(自1946年起)、Embase(自1974年起)以及拉丁美洲和加勒比健康科学文献数据库(LILACS)(自1982年起),同时检索了世界卫生组织国际临床试验注册平台和ClinicalTrials.gov。我们还联系了相关论文的作者以获取更多已发表和未发表的研究。我们未设语言限制。
我们纳入了每组超过50名参与者且提供至少六个月随访的RCT。试验报告必须呈现至少一项主要结局的数据(全因死亡率、严重不良事件、全因心血管事件、心血管疾病死亡率)。符合条件的干预措施是将收缩压/舒张压的目标值设定得低于标准血压目标值(收缩压140至160mmHg或舒张压90至100mmHg及以下)。参与者为有高血压记录的成年人以及因心肌梗死、中风、慢性外周血管闭塞性疾病或心绞痛等心血管病史而接受高血压治疗的成年人。
两名综述作者独立评估检索结果,并使用Cochrane期望的标准方法程序提取数据。我们使用GRADE来评估证据质量。
我们纳入了六项RCT,涉及9484名参与者。平均随访时间为3.7年(范围为1.0至4.7年)。所有RCT均提供了个体参与者数据。由于需要调整抗高血压药物剂量以达到特定血压目标,纳入的研究均未对参与者或临床医生设盲。然而,一个对分组情况不知情的独立委员会评估了所有试验中的临床事件。因此,我们评估所有试验存在较高的实施偏倚风险和较低的检测偏倚风险。其他问题,如研究提前终止以及未预先定义的参与者亚组等,也被考虑用于降低证据质量等级。我们发现全因死亡率(风险比(RR)1.06,95%置信区间(CI)0.91至1.23;6项研究,9484名参与者;中等质量证据)或心血管疾病死亡率(RR 1.03,95%CI 0.
82至1.29;6项研究,9484名参与者;中等质量证据)可能几乎没有差异。同样,我们发现严重不良事件(RR 1.01,95%CI 0.94至1.08;6项研究,9484名参与者;低质量证据)或全因心血管事件(包括心肌梗死、中风、猝死、住院或因充血性心力衰竭死亡)(RR 0.89,95%CI
)0.80至1.00;6项研究,9484名参与者;低质量证据)可能也几乎没有差异。关于因不良反应导致的退出情况,证据非常不确定。然而,研究表明较低目标值组可能有更多参与者因不良反应而退出(RR 8.16,95%CI 2.06至
32.28;2项研究,690名参与者;极低质量证据)。较低目标值组的收缩压和舒张压读数更低(收缩压:平均差值(MD) -8.90mmHg,95%CI -13.24至 -4.56;6项研究,8546名参与者;舒张压:MD -4.50mmHg,95%CI -6.35至 -2.65;6项研究,8546名参与者)。较低目标值组需要更多药物(MD 0.56,95%CI 0.16至0.96;5项研究,7910名参与者),但标准目标值组更频繁地达到血压目标(RR 1.21,95%CI 1.17至1.24;6项研究,8588名参与者)。
我们发现,在高血压合并心血管疾病患者中,与标准血压目标相比,较低血压目标在全因死亡率和心血管疾病死亡率方面可能几乎没有差异。在严重不良事件或全因心血管事件方面可能也几乎没有差异。这表明较低的收缩压目标并未带来净健康益处。我们发现关于因不良反应导致退出的证据非常有限,这导致了高度的不确定性。目前,证据不足以证明在高血压合并已确诊心血管疾病的患者中采用更低的血压目标(收缩压/舒张压135/85mmHg及以下)是合理的。仍有几项试验正在进行,这可能在不久的将来为该主题提供重要的信息。