Department of Nephrology and Hypertension, University Hospital Erlangen, Ulmenweg 18, 91054 Erlangen, Germany.
Charité Research Organisation, Berlin, Charité Research Organisation GmbH, Charitéplatz 1, 10117 Berlin (Mitte), Germany.
Eur Heart J. 2017 Nov 21;38(44):3308-3317. doi: 10.1093/eurheartj/ehx525.
Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated.
This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure. Magnetic resonance imaging scans were used to assess LV mass and local aortic distensibility, at baseline and at 12 and 52 weeks after initiation of treatment. Central pulse and systolic pressure were determined using a SphymoCor® XCEL device at each time point. A total of 114 patients were included, with 57 in each treatment group. The mean age was 59.8 years, and 67.5% were male. Demographic characteristics did not vary between the two sets of patients. Left ventricular mass index decreased to a greater extent in the sacubitril/valsartan group compared to the olmesartan group from baseline to 12 weeks (-6.36 vs. -2.32 g/m2; P = 0.039) and from baseline to 52 weeks (-6.83 vs. -3.55 g/m2; P = 0.029). These differences remained significant after adjustment for systolic blood pressure (SBP) at follow-up (P = 0.036 and 0.019 at 12 and 52 weeks, respectively) and similar signals (though formally non-significant) were observed after adjusting for changes in SBP (P = 0.0612 and P = 0.0529, respectively). There were no significant differences in local distensibility changes from baseline to 12 or 52 weeks between the two groups; however, there was a larger reduction in central pulse pressure for the sacubitril/valsartan group compared to the olmesartan group (P = 0.010).
Since LV mass change correlates with cardiovascular prognosis, the greater reductions in LV mass indicate valuable advantages of sacubitril/valsartan compared to olmesartan. The finding that LV mass index decrease might be to some extent independent of SBP suggests that the effect of the dual-acting agent may go beyond those due to its BP-lowering ability.
未经治疗，主动脉逐渐变硬最终会导致左心室（LV）肥大和心力衰竭。抗高血压药物已被证明在一定程度上可以逆转这种情况。沙库巴曲缬沙坦（LCZ696），一种双重作用的血管紧张素受体阻断剂（ARB）和 Neprilysin 抑制剂，对动脉僵硬和 LV 重塑的影响尚未被研究过。
这是一项随机、多中心、双盲、双模拟、阳性对照、平行组研究，旨在比较沙库巴曲缬沙坦与奥美沙坦对高血压伴脉压升高患者心血管重塑的影响。基线时、治疗开始后 12 周和 52 周时，使用磁共振成像扫描评估 LV 质量和局部主动脉可扩张性。在每个时间点，使用 SphymoCor® XCEL 设备测量中心脉搏和收缩压。共纳入 114 例患者，每组 57 例。平均年龄为 59.8 岁，67.5%为男性。两组患者的人口统计学特征无差异。与奥美沙坦组相比，沙库巴曲缬沙坦组从基线到 12 周（-6.36 与-2.32 g/m2；P=0.039）和从基线到 52 周（-6.83 与-3.55 g/m2；P=0.029）时 LV 质量指数下降幅度更大。在调整随访时收缩压（SBP）后，这些差异仍然具有统计学意义（12 周和 52 周时分别为 P=0.036 和 0.019），并且在调整 SBP 变化后也观察到类似的信号（尽管没有统计学意义）（分别为 P=0.0612 和 P=0.0529）。两组之间从基线到 12 周或 52 周的局部可扩张性变化没有显著差异；然而，沙库巴曲缬沙坦组的中心脉搏压降低幅度大于奥美沙坦组（P=0.010）。
由于 LV 质量变化与心血管预后相关，因此 LV 质量的较大降低表明沙库巴曲缬沙坦与奥美沙坦相比具有更有价值的优势。LV 质量指数下降在一定程度上可能独立于 SBP，这表明双重作用药物的作用可能不仅仅是由于其降低血压的能力。
