THE FACT: A Guideline Based Medication in the Management of Hypertension JENNIFER OKPALAEZE

ANo 1 independent french pharmaceutical company Present in 146 countries over 5 continents We are a researched based organization with our eyes on what is useful for the future.

Leading factors for death According to the latest statistics, almost one-third of the adult population is hypertensive. This number is growing. 70% of treated hypertensive patients are not controlled. It is a major challenge to control their hypertension and to protect them from cardiovascular events. There are many reasons for this: a) their therapy may lack antihypertensive synergy, b) antihypertensives are prescribed in low dosages, c) compliance due to multiple dosing regimens, or d) poor tolerability due to side effects. 3

W.H.O Estimation of high blood pressure distribution (2008). The prevalence of raised blood pressure was highest in Africa, where it was 46% for both sexes combined. Both men and women have high rates of raised blood pressure in the Africa region, with prevalence rates over 40%.

High blood pressure: Powerful predictive parameter of stroke Stroke mortality Age Alors que la PAS elevée est un facteur prédictif des AVC complication qui est d’ailleurs majeure dans nos pays. Et ce peu importe l’âge. SBP(mm Hg) Floating absolute risk and 95% confidence interval. SBP, systolic blood pressure. 1. Lewington S et al. Lancet. 2002;360:1903-1913.

Last South African Recommendation « In black hypertensive patients a diuretic and a CCB is recommended.23 »1 South African hypertension practice guidelines. Décembre 2014. Vol 25 n°6. 291

WHAT DIURETIC OR THIAZIDE SHOULD I PRESCRIBE?

The right start for your hypertensive patients Ladies and gentlemen, I have a great pleasure in presenting, on behalf of Servier, a short review on the benefits of adding Natrilix SR to your uncontrolled hypertensive patients, whatever their background treatment, in terms of powerful BP control, end-organ protection, and metabolic neutrality.

Unique mechanism of action `Indapamide is highly lipophilic with a small percentage of unchanged drug excreted in the urine (5%). This intense lipophilicity explains its selective concentration in the elastin layer of the VSMCs. Its antihypertensive activity is the result of vasorelaxation, reflected by the correction of the vascular hyper-reactivity of hypertensive patients to catecholamines This vasorelaxation is obtained by: A renal saluretic effect, which allows correction of the sodium overload of the arterial wall of hypertensive patients. A direct vascular effect due to increased synthesis of PGE2 and prostacyclin. Its diuretic effect, at the dose of 1 tablet daily, is sub-clinical So, Natrilix SR is a diuretic but specifically designed for treating hypertension. HCTZ Sassard et al. Fund Clin Pharmacol. 2005:19:637-645

Powerful antihypertensive efficacy NEJM 2008 In monotherapy, Natrilix SR is an effective antihypertensive drug that provides powerful antihypertensive efficacy as shown in this study, which has been published in the NEJM 2008, with almost 30mmHg reduction in the SBP. Beckett NS, et al. N Engl J Med. 2008;358. 10.1056/NEJMoa0801369.

Superior BP reduction n=10 818 Am J Cardiovasc drugs 2005 Comparing Natrilix SR’s efficacy to different antihypertensive drugs from the major classes, at their full dose, in more than 9,000 hypertensive patients has proven that Natrilix SR provides superior BP reduction in reducing SBP, with almost the same effect on DBP as the other evaluated drugs. Natrilix SR was the only antihypertensive drugs which has shown a reduction in SBP of almost 23mmHg. All the previously mentioned studies have proven that Natrilix SR is an effective 1st line drug to control BP, but what is the case if you want to add Natrilix SR to patients who are uncontrolled on their previous treatments? Baguet. Am J Cardiovasc Drugs. 2005;5:131-140 Baguet. Am J Cardiovasc Drugs. 2005;5:131-140

Unsurpassed efficacy in uncontrolled patients More than 80% of patients below 140 mmHg Journal of hypertension 2006 *p<0.0001 vs. baseline Systolic Baseline 80 100 120 140 160 Blood pressure (mm Hg) * -34 mm Hg 3 - months This study provides the evidence that you can count on Natrilix SR for your uncontrolled hypertensive patients. Natrilix SR has shown an unsurpassed efficacy and reduced SBP by 34mmHg in more than 2,000 patients, and 8 out of 10 achieved their target SBP after 3 months. 2050 uncontrolled on monotherapy antihypertensive treatment Akram J. J Hypertens. 2006;24(suppl 4):S93

Protects against end-organ damage So, achieving the target BP will be much easier with the addition of Natrilix SR, whatever the background therapy that your uncontrolled hypertensive patients is taking. But this is not all! Natrilix SR goes beyond BP control and protects against end-organ damage at the level of he heart, kidney, & brain. Let me show you how

Significantly superior to enalapril in regression of LVH Journal of hypertension 2000 -1.9 (NS) -3 1 tablet daily Enalapril, 20 mg daily Regression LVMI (g/m²) -6 -8.4 The LIVE study demonstrates clearly that Natrilix SR is significantly more effective than the ACE inhibitor enalapril in the regression of LVMI over the long-term, with equivalent BP control. (***) -9 n=411 Duration: 9+4 months ** * P<0.05 ** P<0.01 (LVMI: left ventricular mass index) Gosse P, Guez D, Guéret P, et al. J Hypertens. 1998;16:531-535

Significant regression in microalbuminuria 6.2 Albumine-creatinine urinary ratio (mg/mmol) 4 8 Baseline 6.2 Albumine-creatinine urinary ratio (mg/mmol) -35%* 4 8 Baseline Journal of hypertension 2004 *P<0.05 Duration=1 year The results after 1-year have shown that Natrilix SR is the first antihypertensive diuretic which has been proven in an international, large-scale study to significantly reduce microalbuminuria in type II diabetic hypertensives, with a 35% reduction in terms of albumin/creatinine ratio. n=283 type 2 diabetic hypertensive patients with microalbuminuria Marre M, et al. J Hypertens. 2004;22:1613-1622 18

fatal or non-fatal stroke -30% P=0.03 Read the figure Beckett NS, et al. N Engl J Med. 2008;358. 10.1056/NEJMoa0801369.

HYVET STUDY CONT’D Prevention of Stroke mortality by 39% Prevention of CV Events by 34% Prevention of All Cause Mortality by 21% Reduction of Heart Failure by 72%

Preserves lipid & glucose metabolism Good acceptability for the antihypertensive drug is something crucial if we take into consideration that hypertension is a life-long disease. It is well-established that the use of conventional thiazides is accompanied by some adverse metabolic side effects. This is not the case with Natrilix SR, which is a result of an innovative formulation developed mainly to improve the efficacy/acceptability ratio. Natrilix SR controls BP without replacing one risk factor by another and preserves lipid & glucose metabolism

Lipid and glucose neutral, over the long term 0 12 weeks 52 weeks 7 6 5 4 3 2 1 6.2 5.4 6.1 5.7 mmol/L 1.7 1.5 Total cholesterol Fasting blood glucose Triglycerides NS This study confirms that there is no modification of cholesterol, triglycerides or fasting blood glucose with 1-year treatment with Natrilix SR. This metabolic neutrality makes Natrilix SR suitable for all hypertensive patients, including those with diabetes and dyslipidemia. Ambrosioni E, et al. J Hypertens. 1998;16:1677-1684

NATRILIX SR VS HCTZ

NICE has updated the Hypertension Clinical Guidelines August 2011 NEW “If a diuretic is required, choose a thiazide-like diuretic, such as chlorthalidone or INDAPAMIDE in preference to a conventional thiazide diuretic such as hydrochlorothiazide”. Hypertension,The clinical management of primary hypertension in adults.Clinical Guideline Methods,evidence and recommendations. Commissioned by the National Institute for Health and Clinical Excellence August 2011

RECOMMENDATION If a “thiazide-type” diuretic is indicated,either INDAPAMIDE or chlorthalidone should be selected. Messerli FH et al. J Am Coll Cardiol. 2011;57:590-600.

Thank you