Sison Jorge, Vega Rosa María Ríos, Dayi Hu, Bader Giovanni, Brunel Patrick
a Medical Center Manila , Manila , Philippines.
b Hospital General Zapopan , Jalisco , Mexico.
Curr Med Res Opin. 2018 Mar;34(3):501-515. doi: 10.1080/03007995.2017.1412682. Epub 2018 Jan 22.
The aim of this post-hoc analysis was to compare the results from randomized controlled trials (RCTs) and real-world evidence (RWE) studies of valsartan/amlodipine (Val/Aml) and valsartan/amlodipine/hydrochlorothiazide (Val/Aml/HCTZ) in patients with uncontrolled hypertension (>140/90 mmHg).
Data was pooled from 15 RCTs (N = 5542) and 8 RWE studies (N = 1397) for Val/Aml; and 2 RCTs (N = 804) and 5 RWE studies (N = 9380) for Val/Aml/HCTZ. Patients who received Val/Aml (80/5, 160/5, 160/10, 320/5, or 320/10 mg), Val/Aml/HCTZ (160/5/12.5, 160/5/25, 160/10/12.5, 160/10/25, or 320/10/25 mg) or placebo were considered for this analysis. Only patients with both baseline and follow-up assessment within 60-90 days after baseline had been included in the analysis. Patients with missing values were excluded from the analysis. Using fitted linear mixed-effects model and random factors, treatment interactions and study design with mean sitting systolic blood pressure (msSBP), diastolic BP (msDBP) and pulse pressure (msPP) reductions from baseline to Week 8-12 of treatment were compared.
Baseline demographics and patient characteristics were comparable between RCT and RWE datasets and within Val/Aml and Val/Aml/HCTZ treatment groups. In both RCT and RWE studies, least-squares mean (LSM) reduction in msSBP/msDBP and msPP from baseline were significant (p < .05) across all dosages. The efficacy of Val/Aml in RCTs was statistically significantly greater than in RWE studies for msSBP/msDBP (-23.1/-13.8 vs. -17.9/-9.1 mmHg) but the difference was non-significant for msPP (-8.6 vs. -9.3 mmHg; p = .77). For Val/Aml/HCTZ, no direct comparison was available but a similar trend was observed. The difference observed for msSBP and msDBP may be due to routine practice setting, larger populations may have more confounders and different behaviors towards treatment adherence.
These findings demonstrate that the efficacy of Val/Aml and Val/Aml/HCTZ in RCTs was more pronounced compared with their effectiveness in RWE studies in different ethnic populations although the overall benefit was not different.
本事后分析的目的是比较缬沙坦/氨氯地平（Val/Aml）和缬沙坦/氨氯地平/氢氯噻嗪（Val/Aml/HCTZ）在血压控制不佳（>140/90 mmHg）患者中的随机对照试验（RCT）和真实世界证据（RWE）研究结果。
汇总了15项关于Val/Aml的RCT（N = 5542）和8项RWE研究（N = 1397）的数据；以及2项关于Val/Aml/HCTZ的RCT（N = 804）和5项RWE研究（N = 9380）的数据。接受Val/Aml（80/5、160/5、160/10、320/5或320/10 mg）、Val/Aml/HCTZ（160/5/12.5、160/5/25、160/10/12.5、160/10/25或320/10/25 mg）或安慰剂的患者纳入本分析。仅纳入在基线后60 - 90天内进行了基线和随访评估的患者。缺失值的患者被排除在分析之外。使用拟合线性混合效应模型和随机因素，比较了治疗相互作用以及研究设计对治疗第8 - 12周时平均坐位收缩压（msSBP）、舒张压（msDBP）和脉压（msPP）相对于基线降低情况的影响。
RCT和RWE数据集之间以及Val/Aml和Val/Aml/HCTZ治疗组内的基线人口统计学和患者特征具有可比性。在RCT和RWE研究中，所有剂量下msSBP/msDBP和msPP相对于基线的最小二乘均值（LSM）降低均具有统计学意义（p < 0.05）。对于msSBP/msDBP，Val/Aml在RCT中的疗效在统计学上显著高于RWE研究（-23.1/-13.8 vs. -17.9/-9.1 mmHg），但对于msPP，差异无统计学意义（-8.6 vs. -9.3 mmHg；p = 0.77）。对于Val/Aml/HCTZ，虽无直接比较，但观察到类似趋势。msSBP和msDBP观察到的差异可能归因于常规临床环境，更大的样本量可能有更多混杂因素以及对治疗依从性的不同行为。
这些发现表明，尽管总体获益无差异，但在不同种族人群中，Val/Aml和Val/Aml/HCTZ在RCT中的疗效比在RWE研究中的效果更显著。
