1. Treatment-Resistant Hypertension: Magnitude of the Problem Power Over Pressure www.poweroverpressure.com

2. “Hypertension: uncontrolled and conquering the world” Volume 370, Issue 9587, August 18, 2007, Page 539 Number of People With Hypertension (millions) 2000 2025* Year 972 million (26%) 1.56 billion (29%) Lack of BP Control in Treated Hypertensive Patients † (%) 47% 59% 66% 71% 39% 50% 84% *Projected. Most of the expected increase will be in economically developing regions. † Based on a literature search of the MEDLINE database of studies from January 1980 through July 2003. 1.Kearney PM, et al. Lancet. 2005;365:217-223. 2.Kearney PM, et al. J Hypertens. 2004; 22:11-19. Hypertension: a substantial and growing problem 1 Lack of BP control is widespread, despite treatment 2 Power Over Pressure www.poweroverpressure.com

3. A particularly complex clinical challenge BP that remains above goal, in spite of… *All medications should be titrated to the maximum in-label doses or until BP control is achieved, except in cases of intolerance, in which case treatments should be optimized to the maximum tolerated doses † Patients who require  4 antihypertensive agents to achieve BP control are also considered treatment resistant, according to some sources. 1 1.Calhoun DA, et al. Circulation. 2008;117:e510-e526. 2.Mancia G, et al. Eur Heart J. 2007;28:1462-1536. Treatment-resistant hypertension is defined as: 1,2 compliance with maximum doses*… of  3 antihypertensive medications † … from different classes, ideally including a diuretic… BP Goal Reversible causes identified and addressed Power Over Pressure www.poweroverpressure.com

4. A common and increasing problem 1.Persell, S. Hypertension. 2011;57:1076-1080. 2.Hypertension and cardiovascular disease. World Heart Federation. 2011. http://www.world-heart- federation.org/cardiovascular-health/cardiovascular-disease-risk-factors/hypertension/. Accessed March 2, 2012. 3.Lloyd-Jones D, et al. Circulation. 2010;121:e46-e215. 4.Calhoun DA, et al. Circulation. 2008;117:e510-e526. 5.Egan BM, et al. Circulation. 2011;124:1046-1058. 100 million people worldwide (15% to 20% of uncontrolled hypertension) are estimated to have treatment-resistant hypertension 1,2,3 Despite focused efforts, the percentage of patients resistant to treatment has not fallen with newer medications and strategies; rather it has increased by 62% in the last 20 years* 4,5 *In the time periods 1988-1994 vs 2005-2008, the proportion of treated uncontrolled hypertensive patients reportedly taking ≥3 BP medications increased from 16% to 28%. Power Over Pressure www.poweroverpressure.com

5. Treatment-resistant hypertension is associated with a substantially increased risk of CV events CV=cardiovascular. Adapted from Pierdomenico SD, et al. Am J Hypertens. 2005;18:1422-1428. Differences between groups were apparent from very early in the follow-up period, indicating the urgent need for BP control in patients with treatment- resistant hypertension. CV Event Rate (5-year follow-up) Controlled Hypertension 5% Treatment Resistant19% Power Over Pressure www.poweroverpressure.com Note: Study did not include outcomes in untreated hypertensives or in patients with uncontrolled hypertension on 1-2 antihypertensive medications.

6. Summary: treatment-resistant hypertension Hypertension is –common and likely to increase –estimated to affect 1.56 billion people worldwide by 2025 –elusive and difficult to control even in treated patients –a risk factor for CV disease when uncontrolled Treatment-resistant hypertension is defined as BP that remains above goal despite compliance with ≥3 antihypertensive medications –100 million people worldwide are estimated to have treatment-resistant hypertension –Prevalence will likely increase due to increasingly older age and more obese populations –Diabetes and chronic kidney disease (CKD) are risk factors Patients with treatment-resistant hypertension are at increased risk of CV events –Based on a 5-year CV event follow-up, 19% of patients with treatment-resistant hypertension experienced an event compared with 5% of patients with controlled hypertension Power Over Pressure www.poweroverpressure.com