RAAS inhibitors yield large BP reductions in obese patients with hypertension

Randomized Trial of Perindopril, Enalapril, Losartan and Telmisartan in Overweight or Obese Patients with Hypertension.

Literature - Nedogoda SV, Ledyaeva AA, Chumachok EV, et al. - Clin Drug Investig. 2013 Jun 26

Nedogoda SV, Ledyaeva AA, Chumachok EV, et al.
Clin Drug Investig. 2013 Jun 26. [Epub ahead of print]


Obesity appears to have a substantial pathophysiological effect on hemodynamic changes in hypertension. It also impairs the response to treatment of hypertension [1-3]. Despite the high prevalence of hypertension in obesity and several complicating co-morbidities [4,5], no international recommendations exist for the treatment of hypertension in obese patients.
Renin-angiotensin-aldosterone system (RAAS) inhibitors are currently the preferred class of antihypertensive treatment because of their wide range of vascular benefits [6]. Full-dose angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor blocker (ARB) therapy appear useful for lowering blood pressure as well as for prevention of cardiovascular (CV) events in hypertensive patients at high CV risk, including patients with obesity.
This phase IV trial compared four RAAS inhibitors, among which two ACE inhibitors (perindopril 10mg/day and enalapril 20 mg/day) and two ARBs (losartan 100mg/day and telmisartan 80 mg/day) to determine their impact on blood pressure, arterial stiffness and other CV risk factors in 120 overweight or obese patients with hypertension.

Main results

  • Absolute reductions in mean 24-h systolic blood pressure (SBP) at 24 weeks as compared to baseline were -22 mmHg (-14%) for perindopril, -11 mmHg (-7%) for enalapril, -12 mmHg (-8%) for losartan and -15 mmHg (-10%) for telmisartan (all P<0.05).
    Absolute reductions in mean 24-h diastolic blood pressure (DBP) at 24 weeks as compared to baseline were -13 mmHg (-13%) for perindopril, -6 mmHg (-6%) for enalapril, -13 mmHg (-13%) for losartan and -12 mmHg (-12%) for telmisartan (all P<0.05).
  • After 24 weeks, all RAAS inhibitors had improved BP dipping profiles; normal dipping profiles were restored in 85% of patients in the case of perindopril, losartan and telmisartan, while enalapril showed improvement in 65% of patients.
  • Perindopril and telmisartan improved vascular structure parameters, by week 24, since carotid-femoral pulse wave velocity (PWV) was reduced by 29 and 24% respectively (P<0.05 vs. baseline). Perindopril also reduced the carotid-radial PWV by 26% (P<0.05). Reductions in aortic pressure were 8% (P<0.05 vs. baseline) for perindopril, and non-significant <1%, 1% and 4% for enalapril, losartan or telmisartan, respectively.
  • Perindopril was the only agent that statistically significantly reduced posterior left ventricular wall thickness (by 5%) and left ventricular mass index (by 14%). The early/atrial (late) ventricular filling velocity (E/A) ratio was also significantly improved only after perindopril treatment.
  • Significant improvements in metabolic parameters were seen after 24 weeks, mostly after perindopril. Leptin was reduced by 30% after perindopril (P<0.05 vs. baseline), as opposed to 2%, 7% and 14% with enalapril, losartan and telmisartan. Perindopril and telmisartan significantly reduced C-peptide, and these two agents also improved the lipid profile. A modest favourable effect on glucose metabolism was seen after all therapies.


This is the first direct comparison of antihypertensive, nephroprotective, cardioprotective and metabolic effects of two ACE inhibitors and two ARBs in overweight or obese patients with hypertension. It shows that full-dose RAAS inhibition yields large blood pressure reductions. The different drugs showed different effects, with perindopril showing the clearest improvement in arterial elasticity and regulation of several cardiovascular disease risk factors in these patients.


1. Schmieder RE, Gatzka C, Schachinger H, et al. Obesity as a determinant for response to antihypertensive treatment. BMJ. 1993;307(6903):537–40.
2. Jordan J, Engeli S. Obesity, hypertension, and cardiovascular health: is there anything poor Cassandra tries to tell us? J Hypertens. 2012;30(6):1103–5.
3. Schmieder RE, Rockstroh JK. Obesity and hypertension. Curr Opin Nephrol Hypertens. 1994;3(5):546–9.
4.Dorresteijn JA, Visseren FL, Spiering W. Mechanisms linking obesity to hypertension. Obes Rev. 2012;13(1):17–26.
5. Kurukulasuriya LR, Stas S, Lastra G, et al. Hypertension in obesity. Med Clin North Am. 2011;95(5):903–17.
6.Jordan J, Yumuk V, Schlaich M, et al. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. J Hypertens. 2012;30(6):1047–55.

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