Impact of ACE inhibitors and Angiotensin II receptor blockers on all- cause mortality in hypertension trials Congress of the European Society of Cardiology Oral presentation. Sunday August 28, 2011 Collaborative group: Michel E. BERTRAND, MD, FRCP (London), FESC, FACC, FAHA Lille University Heart Hospital, Lille, France Jean-Jacques MOURAD, MD, PhD Avicenne Hospital, Bobigny, France Kim FOX, Professor of Clinical Cardiology Department of Cardiology, Royal Brompton Hospital, London, UK Eric BOERSMA, MSc, PhD, FESC Erasmus MC, Department of Cardiology, Rotterdam, The Netherlands Laura VAN VARK, MD, MSc Erasmus MC, Department of Cardiology, Rotterdam, The Netherlands M. Bertrand. Oral session ESC, Paris 2011

A pooled analysis of morbidity-mortality trials Inclusion criteria: Morbidity-mortality trials including ACE or ARBs inhibitors in treatment arms conducted from 2000 to June 2010 Trials including mainly hypertensive patients ( >66% of studied population, according to the trial-specific definition) All-cause mortality: a pre-specified or reported in the principal study publication (an integrative end point taking into account both the benefits and severe adverse events of treatment devoided of bias or uncertainty) Exclusion criteria: Heart failure/acute coronary syndromes/acute stroke/ hemodialysis/atrial fibrillation or post-cardiac surgery trials Objective: To evaluate the impact of RAAS inhibitors on further mortality reduction in their main indication, hypertension, in patients representative of those treated in the XXI st century. M. Bertrand. Oral session ESC, Paris 2011

Study population: patients TrialYearN Relative weight RENAAL % IDNT % LIFE % ALLHAT % ANBP % SCOPE % INVEST % JMIC-B % VALUE % MOSES % ASCOT-BPLA % JIKEI HEART % ADVANCE % HYVET ,3% PRoFESS % TRANSCEND % HIJ-CREATE % KYOTO HEART % NAVIGATOR % % M. Bertrand. Oral session ESC, Paris 2011

Perindopril 0.87 ( )* Lisinopril 0.99 ( ) Trandolapril 0.98 ( ) 0.94 ( ) Overall0.94 ( )** ACE inhibitor better Control better All-cause mortality: treatment effect of ACE inhibitors Enalapril/imidapril/ lisinopril 0, ** P=0.007 *P< ACE inhibitor trials: 88,860 patients M. Bertrand. Oral session ESC, Paris 2011

Losartan0.92 ( ) 16.9% Valsartan0.99 ( ) 35.9% Eprosartan1.08 ( ) 1.6% Telmisartan1.03 ( ) 33.2% Overall0.99 ( )* 100% Irbesartan1.04 ( ) 2.6% Candesartan1.00 ( ) 9.8% ARB better Control better Relative weight 12 ARBs trials: patients P for heterogeneity 0.75; I² 0% *P=0.75 All-cause mortality: treatment effect of ARBs M. Bertrand. Oral session ESC, Paris 2011

Conclusion Among RAAS inhibitors, only ACE inhibitors have demonstrated a further significant 6% mortality reduction in hypertensive patients (P=0.007) No significant reduction in all-cause mortality could be demonstrated with ARBs (HR, 0.99 ( ), P=0.75) Perindopril significantly reduced all-cause mortality by 13% among contemporary patients with arterial hypertension (P<0.001) Treatment with ACE inhibitors would additionally save 12 lives for every patients treated for 4 years M. Bertrand. Oral session ESC, Paris 2011