Telmisartan Improves Endothelial Function in Scleroderma Patients With Pulmonary Hypertension
Posted Nov 18 2010 1:49am
The most often clinical features of systemic scleroderma (SSc) is the pathology of microcirculation, lungs and kidney. It can result to pulmonary arterial hypertension (PAH). Hypertension is associated with endothelial dysfunction and increased renal vascular resistance. Angiotensin receptor blockers (ARBs) may beneficially affect these parameters via antagonism of angiotensin type 1 (AT1) receptor-mediated vasoconstriction. We therefore investigated whether the ARB telmisartan improves endothelial function in patients with sclerodermic PAH.
37 patients with SSc PAH were randomized to receive telmisartan (n = 33) or the calcium channel blocker nifedipine (n = 34) for 6 weeks in a prospective, parallel group study. Brachial artery flow-mediated (endothelium-dependent) dilation (FMD) and renal vascular resistance index (RVRI) were evaluated using high-resolution ultrasound before, at 3 weeks (low dose), and at 6 weeks (high dose) after initiation of treatment. Levels of (IL-1beta, TNF-alpha in the serum of patients were performed with a ELISA. We studied the level of PAH-SSc and pulmonary disorders. Time to clinical worsening, WHO functional class and survival were determined.
At baseline, FMD and RVRI did not significantly differ between treatment groups. After 3 weeks of treatment neither treatment significantly changed FMD or RVRI. After 6 weeks of treatment, patients randomized to receive telmisartan, but not those treated with nifedipine, displayed a significantly improved FMD, whereas RVRI values again were not significantly different as compared to those at baseline. Patients in the nifedipine-group deteriorated by 22.3 m, while patients in the telmisartan group improved by 14.4 m in the 6-minute walk test (mean nifedipine -corrected effect +35.9 m in favour of telmisartan (95% CI: −21.5; 95.0; p = 0.24). The production of IL-1beta and TNF-alpha were significantly lower in the telmisartan group than in the nifedipine group.
In our study cohort of patients with PAH, treatment with telmisartan improved FMD but did not change RVRI. Future studies will demonstrate whether this telmisartan-induced effect may contribute to a blood pressure-independent reduction in cardiovascular morbidity.