ANGIOTENSIN RECEPTOR BLOCKERS ARE FIRST LINE TREATMENT : PRO Prof Xavier Girerd M.D., Ph.D., F.E.S.C. Endocrinology Department Cardiovascular Prevention Unit Groupe Hospitalier Pitié-Salpêtrière Faculté Pierre et Marie Curie, Paris 6, France Paris, August 29th 2011
Disclosures Prof Xavier Girerd Educational Board Boehringer Ingelheim X X Daiichi-Sankyo X X IPSEN Pharma X Takeda X Novartis X X August 2011
Hypertension : ARBs are first line treatment ESH/ESC guidelines state that angiotensin receptor antagonists are suitable for the initiation and maintenance of antihypertensive treatment 1 Pro
Box 10 Position statement: Choice of antihypertensive drugs The main benefits of antihypertensive therapy are due to lowering of BP per se. Five major classes of antihypertensive agents thiazide diuretics, calcium antagonists, ACE inhibitors, angiotensin receptor antagonists and b-blockers are suitable for the initiation and maintenance of antihypertensive treatment, alone or in combination. b-blockers, especially in combination with a thiazide diuretic, should not be used in patients with the metabolic syndrome or at high risk of incident diabetes. Journal of Hypertension 2007, 25:1105 1187
Document Reviewers: Gerasimos Filippatos (CPG Review Coordinator) (Greece), Stamatis Adamopoulos (Greece), Enrico Agabiti-Rosei (Italy), Ettore Ambrosioni (Italy), Vicente Bertomeu (Spain), Denis Clement (Belgium), Serap Erdine(Turkey), Csaba Farsang (Hungary), Dan Gaita (Romania), Wolfgang Kiowski (Switzerland), Gregory Lip (UK), Jean-Michel Mallion (France), Athanasios J. Manolis (Greece), Peter M. Nilsson (Sweden), Eoin O Brien (Ireland), Piotr Ponikowski (Poland), Josep Redon (Spain), Frank Ruschitzka (Switzerland), Juan Tamargo (Spain), Pieter van Zwieten (Netherlands), Margus Viigimaa (Estonia), Bernard Waeber (Switzerland), Bryan Williams (UK), Jose Luis Zamorano (Spain). Journal of Hypertension 2007, 25:1105 1187
Hypertension : ARBs are first line treatment The use of angiotensin receptor antagonists as antihypertensive therapy is frequent in Europe 2 Pro
Antihypertensive Class Usage in 2010 in EU Base: > 35 years diagnosed with HBP and using RX to treat HBP 6,5% 0,7% 5,0% 23,0% 21,9% 1,4% 4,6% 24,9% 2,4% 2,2% 22,7% 17,9% 1,5% 19,4% 32,6% 7,6% 24,2% 1,7% 6,7% 0,9% 28,3% 15,3% 28,9% 17,0% 12,0% 26,2% 5,7% 42,0% 33,8% 23,2% 12,6% 12,5% 12,7% 26,3% 16,6% 15,8% Average number of brands : 28,0% 12,4% 9,7% 27,6% 30,6% 10,5% Europe France Germany United Kingdom Italy Spain 1.4 (0.8) 1.3 (0.6) 1.4 (0.7) 1.6 (0.9) 1.3 (0.7) 1.3 (0.6) FDC Products ACE Inhibitors Beta Blockers Diuretics Calciun Channel Blockers ARBS Alpha Blockers Others 35,5% 3,0% National Health and Wellness Survey 2010 Survey administered via the Internet since 2002 in Europe 24,3% 19,0% 32,8% 9,0%
FLAHS 2010 Use of antihypertensive drugs in monotherapy in France in 2010 Prescription in treated subjects 45 % of prescription in monotherapy 40 ARB 30 30 29 20 10 0 14 BB ACEI CA DIU SPIRO 12 Cx 8 AB 3 2 1 1 DRI FLAHS 2010 - French League Against Hypertension Survey Prescritption for 1169 treated hypertensives X Girerd, ESH 2011 www.comitehta.org
Hypertension : ARBs are first line treatment The ARB s has a powerful action to decrease SBP and DBP 3 Pro
Antihypertensive efficacy of ARB s in monotherapy as evaluated by ABPM A meta-analysis of randomized trials J Am Coll Cardiol 2011;57:590 600
Hypertension : ARBs are first line treatment The majority of the ARB s have a longacting duration of action allowing a once daily prescription 4 Pro
Reduction of blood pressure during the last 4 h of the interdose period
Effects of ACEIs Trough/Peak ratio after once daily administration Ramipril (50%) Trandolapril (100%) Fosinopril (64%) Enalapril (40%) Benazepril (40%) Perindopril (35%) Lisinopril (30%) Quinapril (10%) Am J Hypertens. 1996 Jul;9(7):633-43
Comparative effect of ARB and ACEI on 24hrs blood pressure of a once daily administration in elderly hypertensives 24 hours ABPM 0-2 -4 Delta SBP (mmhg) -6-8 -10 Olmesartan Ramipril -12-14 -*- -**- H1-6 H7-12 H13-18 H19-24 Hours from drug intake J Hypertens. 2010;28:2342-50
Hypertension : ARBs are first line treatment The safety profile of the ARBs is comparable to that of placebo and better than safety profile of the ACEI 5 Pro
Specific Adverse Events The rates of cough in randomized, controlled trials were 9.9% for the ACE inhibitor group and 3.2% for the ARB group (absolute risk difference, 6.7 percentage points). Withdrawals Due to Adverse Events In studies that reported withdrawals due to adverse events, the Peto summary odds ratio favored ARBs (0.51 [CI, 0.38 to 0.70]. Given this odds ratio and a median withdrawal rate of 8% for ACE inhibitors, the expected withdrawal rate for ARBs is 3.7%. Ann Intern Med. 2008;148:16-29.
ACE inhibitor-induced angioedema. This adverse effect of ACE inhibitors, irrespective of the chemical structure, can occur early in treatment as well as after prolonged exposure for up to several years. The incidence of angioedema is low (0.1 to 0.2%) but can be considered as a potentially life-threatening adverse effect of ACE inhibitor therapy. The actual incidence can be far higher because of poorly recognised presentation of angioedema as a consequence of its late onset in combination with usually long term therapy. The incidence can be even higher (up to 3-fold) in certain risk groups, for instance Black Americans. Drug Saf 1998 Mar;18(3):171-88
ACE inhibitor-induced angioedema. a noticeable incidence of angioedema under combined therapy with ACEi and other drugs Dipeptidyl Peptidase-IV Inhibitor Use Associated With Increased Risk of ACE Inhibitor-Associated Angioedema. Hypertension. 2009;54:516-523. vildagliptin use was associated with a significantly increased risk of angioedema (OR 4.57 [95% CI 1.57 to 13.28]) Increased incidence of angioedema with ACE inhibitors in combination with mtor inhibitors in kidney transplant recipients. (6.6%, 3.8 per 100 treatment years) Clin J Am Soc Nephrol.2010 Apr;5(4):703-8.
Dipeptidyl Peptidase-IV Inhibitor Use Associated With Increased Risk of ACE Inhibitor-Associated Angioedema. Hypertension. 2009;54:516-523
Hypertension : ARBs are first line treatment Compared with controls (active treatment or placebo), ARBs reduce the risk of stroke, heart failure, and new onset diabetes. 6 Pro
Relative risk estimates of coronary heart disease events and stroke in 46 drug comparison trials comparing each of the five classes of blood pressure lowering drug with any other class of drug Greater preventive effect of calcium channel blockers than other drugs, and a lesser effect of β blockers in the prevention of stroke. No advantage of any one drug over others in the prevention of CHD. BMJ 2009;338;b1665;
Objectives : To evaluate the cardiovascular outcomes and other outcomes associated with angiotensin receptor blockers. Results : Compared with controls, angiotensin receptor blockers were associated with a reduction in the risk of stroke (0.90, 0.84 to 0.98), heart failure (0.87, 0.81 to 0.93), and new onset diabetes (0.85, 0.78 to 0.93), with similar results when compared with placebo or with active treatment. When compared with controls (placebo/active treatment), placebo, or active treatment, angiotensin receptor blockers were not associated with an increase in the risk of myocardial infarction (0.99, 0.92 to 1.07), death, cardiovascular death, or angina pectoris. BMJ 2011;342:d2234
Hypertension : ARBs are first line treatment Studies consistently showed that persistence (patients continuing therapy after the initial prescription) with ARBs was better than persistence with other antihypertensive drugs (including ACEI). 7 Pro
Hypertensive patients initiated on an ARB had greater persistence to antihypertensive treatment J Human Hypertension (2005) 19, 607 613
A fixe-dose combination is more likely to be initiated after an ARB in monotherapy % 100 90 80 70 60 50 40 30 20 10 0 *p<0.0001; ARB vs. Others * ARB ACEI CA Diuretic Persistence after 5 years FDC administration X.Girerd 2011 (in press)
Hypertension : ARBs are first line treatment How to choose between ARB or ACEI to initiate antihypertensive treatment Effect on BP Action on 24Hrs Side effects profile Cardiovascular Prevention Persistence ACEI +++ ++ ++ +++ ++ ARB +++ +++ +++ +++ +++ +++ : Best choice X.Girerd 2011