Solomon Scott D, Appelbaum Evan, Manning Warren J, Verma Anil, Berglund Tommy, Lukashevich Valentina, Cherif Papst Cheraz, Smith Beverly A, Dahlöf Björn
Cardiovascular Division, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
Circulation. 2009 Feb 3;119(4):530-7. doi: 10.1161/CIRCULATIONAHA.108.826214. Epub 2009 Jan 19.
Left ventricular (LV) hypertrophy, a marker of cardiac end-organ damage, is associated with an increased risk of cardiovascular morbidity and mortality. Inhibitors of the renin-angiotensin-aldosterone system may reduce LV mass to a greater extent than other antihypertensive agents. We compared the effect of aliskiren, the first orally active direct renin inhibitor, the angiotensin-receptor blocker losartan, and their combination on the reduction of LV mass in hypertensive patients.
We randomized 465 patients with hypertension, increased ventricular wall thickness, and body mass index >25 kg/m(2) to receive aliskiren 300 mg, losartan 100 mg, or their combination daily for 9 months. Patients were treated to standard blood pressure targets with add-on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone system and beta-blockers. Patients underwent cardiovascular magnetic resonance imaging for assessment of LV mass at baseline and at study completion. The primary objective was to compare change in LV mass index from baseline to follow-up in the combination and losartan arms; the secondary objective was to determine whether aliskiren was noninferior to losartan in reducing LV mass index from baseline to follow-up. Systolic and diastolic blood pressures were reduced similarly in all treatment groups (6.5+/-14.9/3.8+/-10.1 mm Hg in the aliskiren group; 5.5+/-15.6/3.7+/-10.7 mm Hg in the losartan group; 6.6+/-16.6/4.6+/-10.5 mm Hg in the combination arm; P<0.0001 within groups, P=0.81 between groups). LV mass index was reduced significantly from baseline in all treatment groups (4.9-, 4.8-, and 5.8 g/m(2) reductions in the aliskiren, losartan, and combination arms, respectively; P<0.0001 for all treatment groups). The reduction in LV mass index in the combination group was not significantly different from that with losartan alone (P=0.52). Aliskiren was as effective as losartan in reducing LV mass index (P<0.0001 for noninferiority). Safety and tolerability were similar across all treatment groups.
Aliskiren was as effective as losartan in promoting LV mass regression. Reduction in LV mass with the combination of aliskiren plus losartan was not significantly different from that with losartan monotherapy, independent of blood pressure lowering. These findings suggest that aliskiren was as effective as an angiotensin receptor blocker in attenuating this measure of myocardial end-organ damage in hypertensive patients with LV hypertrophy.
左心室肥厚是心脏终末器官损害的一个标志，与心血管疾病发病率和死亡率增加相关。肾素-血管紧张素-醛固酮系统抑制剂可能比其他抗高血压药物能更大程度地降低左心室质量。我们比较了阿利吉仑（首个口服活性直接肾素抑制剂）、血管紧张素受体阻滞剂氯沙坦及其联合用药对高血压患者左心室质量降低的影响。
我们将465例高血压、心室壁厚度增加且体重指数>25kg/m²的患者随机分组，分别每日服用300mg阿利吉仑、100mg氯沙坦或二者联合用药，共9个月。患者采用附加治疗使血压达到标准目标值，不包括其他肾素-血管紧张素-醛固酮系统抑制剂和β受体阻滞剂。患者在基线期和研究结束时接受心血管磁共振成像以评估左心室质量。主要目的是比较联合用药组和氯沙坦组从基线到随访时左心室质量指数的变化；次要目的是确定从基线到随访时阿利吉仑在降低左心室质量指数方面是否不劣于氯沙坦。所有治疗组的收缩压和舒张压均有相似程度的降低（阿利吉仑组为6.5±14.9/3.8±10.1mmHg；氯沙坦组为5.5±15.6/3.7±10.7mmHg；联合用药组为6.6±16.6/4.6±10.5mmHg；组内P<0.0001，组间P=0.81）。所有治疗组的左心室质量指数均较基线期显著降低（阿利吉仑组、氯沙坦组和联合用药组分别降低4.9、4.8和5.8g/m²；所有治疗组P<0.0001）。联合用药组左心室质量指数的降低与单独使用氯沙坦组无显著差异（P=0.52）。阿利吉仑在降低左心室质量指数方面与氯沙坦效果相当（非劣效性P<0.0001）。所有治疗组的安全性和耐受性相似。
阿利吉仑在促进左心室质量消退方面与氯沙坦效果相当。阿利吉仑加氯沙坦联合用药降低左心室质量与氯沙坦单药治疗相比无显著差异，与血压降低无关。这些发现表明，在减轻左心室肥厚的高血压患者心肌终末器官损害这一指标方面，阿利吉仑与血管紧张素受体阻滞剂效果相当。
