Impact of ACE Inhibition on Mortality in Hypertension Trials

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Impact of ACE Inhibition on Mortality in Hypertension Trials

Expert Commentary


The top preventable cause of premature death in the developed world is hypertension and it is well known that antihypertensive drugs reduce cardiovascular mortality. Our meta-analysis of mortality reduction with RAAS inhibition in hypertension confirmed this; ACE inhibitors and ARBs significantly reduced cardiovascular mortality by 7% (p = 0.018) and also all-cause mortality by 5% (p = 0.032). In ACE inhibitor trials, there was a statistically significant 10% reduction in all-cause mortality (p = 0.004) and a strong trend toward a 12% reduction in cardiovascular mortality (p = 0.051). No all-cause or cardiovascular mortality reduction was observed with ARBs (p = 0.68 and p = 0.13, respectively).

ACE inhibitors are effective and well tolerated in hypertension management and recommended as first line for the treatment of hypertension in British and American prescribing guidelines. The latest hypertension guidelines, the 2007 guidelines of the European Society of Hypertension and European Society of Cardiology, therefore list ACE inhibitors as an appropriate first-line choice in hypertension in monotherapy or combination. The usefulness of ACE inhibition is also underlined by the fact that European guidelines favor the use of ACE inhibitors in several conditions: heart failure, left ventricular dysfunction, post-MI, diabetic and nondiabetic nephropathy, left ventricular hypertrophy, carotid atherosclerosis, atrial fibrillation, proteinuria, microalbuminuria and metabolic syndrome.

In our meta-analysis, there was significant heterogeneity among ACE inhibitors. Treatment with perindopril, in particular, was associated with further significant all-cause and cardiovascular mortality reductions (13 and 22%, respectively). Further support for perindopril's use comes from the European guideline position statement on the choice of antihypertensive agents, which cites the importance of the drugs effect on cardiovascular risk factors and of once-a-day administration.

More extensive use of proven RAAS inhibition in hypertensive patients could save numerous lives. Thanks to a range of effects on BP, arterial stiffness and cardiovascular remodeling, ACE inhibitors – perindopril in particular – are a good choice for preventing all-cause and cardiovascular mortality in hypertension.

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