Vascular Protection of ACE Inhibitors

In their enthusiastic review on the renin-angiotensin system and atherothrombotic disease,¹ Jacoby and Rader state that

This statement represents a misinterpretation of the PROGRESS data.² Despite lowering systolic pressure by 5 mm Hg, monotherapy with perindopril did not reduce the primary end point or the secondary end point in this study, as was clearly emphasized by Staessen et al.³ Only when indapamide was added to perindopril was there a significant reduction in these end points. In contrast, for the same systolic pressure reduction of 5 mm Hg, monotherapy with indapamide reduced the risk of strokes by an impressive 29% in 2841 patients in the Post-stroke Antihypertensive Treatment (PATS) study.⁴ Conceivably, most if not all of the benefits in PROGRESS can be attributed to indapamide. This could indicate that diuretics have a specific cerebroprotective effect that is not shared by other drug classes, such as ACE inhibitors or β-blockers.⁵ Thus, PROGRESS,² like the Quinapril Ischemic Event Trial (QUIET),⁶ the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT),⁷ and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT),⁸ and even the HOPE trial,⁹ do not attest to any blood pressure–independent effect of ACE inhibitors on cardiovascular morbidity and mortality or atherothrombosis.¹⁰ Only the recent EUROPA study seems to suggest some vasculoprotective properties of perindopril in patients with coronary artery disease.