1. 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

2. 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

3. Study population: 165 971 patients TrialYearN Relative weight RENAAL 2001 15130.9% IDNT 2001 11460.7% LIFE 2002 91935.5% ALLHAT 2002 2430914.6% ANBP-2 2003 60833.7% SCOPE 2003 49373% INVEST 2003 2257613.6% JMIC-B 2004 16501% VALUE 2004 152459.2% MOSES 2005 13520.8% ASCOT-BPLA 2005 1925711.6% JIKEI HEART 2007 30811.9% ADVANCE 2007 111406.7% HYVET 2008 38452,3% PRoFESS2008 20332 12.3% TRANSCEND 2008 59263.6% HIJ-CREATE 2009 20491.2% KYOTO HEART 2009 30311.8% NAVIGATOR 2010 93065.6% 165 971100.0% M. Bertrand. Oral session ESC, Paris 2011

4. Perindopril 0.87 (0.81-0.94)* Lisinopril 0.99 (0.92-1.06) Trandolapril 0.98 (0.89-1.08) 0.94 (0.78-1.14) Overall0.94 (0.90-0.98)** ACE inhibitor better Control better All-cause mortality: treatment effect of ACE inhibitors Enalapril/imidapril/ lisinopril 0,8 0.91.01.11.2 ** P=0.007 *P<0.001 7 ACE inhibitor trials: 88,860 patients M. Bertrand. Oral session ESC, Paris 2011

5. Losartan0.92 (0.82-1.03) 16.9% Valsartan0.99 (0.91-1.07) 35.9% Eprosartan1.08 (0.74-1.57) 1.6% Telmisartan1.03 (0.95-1.12) 33.2% Overall0.99 (0.95-1.04)* 100% Irbesartan1.04 (0.77-1.40) 2.6% Candesartan1.00 (0.86-1.17) 9.8% ARB better Control better Relative weight 12 ARBs trials: 77111 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

6. 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 (0.95-1.04), 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 1 000 patients treated for 4 years M. Bertrand. Oral session ESC, Paris 2011