HYPERTENSION MANAGEMENT 2015MOSTAFA ALSHAMIRIASSISTANT PROFESSOR KING SAUD UNIVERSITY RIYADH CONSULTANT CARDIOLOGISTDIRECTOR OF CORONARY CARE andQUALITY CARDIOVASCULERKING FAHD CARDIAC CENTER ABHA JUNE 2015

Disclosure

Agenda Definition of hypertension ?What is the prevalence of hypertension ? Do we do a good job to reach the goal ?Is hypertension harmful ?Is the treatment effective in reducing cardiovascular adverse outcome ?How to reduce BP ?What are the strategy of treatment of hypertension ?conclusion

What is the definition of hypertensionInternational WHOESH , ESCNICEJNC 7JNC 8

Recommendation 1 (Strong recommendation)

Recommendation 2 (Strong recommendation)

Recommendation 3 (Expert opinion)General population 60 yearsSBP 150 mm Hgor DBP 90 mm Hg SBP

What is the prevalence of Hypertension ?

ItalySwedenEnglandSpainFinlandGermanyPrevalence of Hypertension in US and European Adults Aged 3564 YearsAge- and sex-adjustedHypertension defined as BP 140/90 mmHg or on treatmentWolf-Maier et al. JAMA 2003;289:23639Prevalence of hypertension (%)US

Prevalence of Hypertension by Age and GenderKearney et al. Lancet 2005;365:21723Data for established market economies (US, Canada, Spain, England, Germany, Greece, Italy, Sweden, Australia, Japan)Prevalence of hypertension (%)2029703039404950596069Age (years)

Prevalence of Hypertension in Saudi ArabiaAL-Nozha et al in a cross-sectional cluster sampling & house hold survey on 13700 Saudis of both sexes Kingdomwide Ann Saudi Med, Vol 17, No2.1997

Comparative Prevalence of hypertension and the expected hypertension population in each country

Journal of Hypertension 2005, Vol 23 No 6Among ACS SPACE 48% HYPERTENSIVE

Benefits of Lowering BPAverage Percent ReductionStroke incidence 3540% Myocardial infarction 2025%

Heart failure50%

Blood Pressure Reduction of 2 mmHg Decreases the Risk of Cardiovascular Events by 710%Meta-analysis of 61 prospective, observational studies1 million adults12.7 million person-years

2 mmHg decrease in mean SBP10% reduction in risk of stroke mortality7% reduction in risk of IHD mortalityLewington et al. Lancet 2002;360:190313

HOW TO REDUCES THE BP ?

From Elliott. J Clin Hypertens 2003;5(Suppl. 2):313Copyright 2003, with permission from Blackwell PublishingControlling blood pressure with medication is unquestionably one of the most cost-effective methods of reducing premature CV morbidity and mortality

Unmet Need in the Treatment of Hypertension.Is it important to reduce BP for observed benefits or for reaching the goals ?..WHAT IS THE WOURLD WIDE PERCENTAGE OF HYPERTENSION REACH THE GOAL ?

Approximately 70% of Patients* Who Receive Treatment Do Not Reach BP Goal in EuropeWolf-Maier et al. Hypertension 2004;43:1017*Treated for hypertensionBP goal is

What are the strategy for hypertension treatment ?

Current Guidelines Acknowledge that Combination Therapy is Required by the Majority of Patients to Reach BP GoalJNC 7 guidelines state1:Although effective BP control can be achieved in most patients who are hypertensive, the majority will require two or more antihypertensive drugs.ESH/ESC guidelines state2:Regardless of the drug employed, monotherapy allows to achieve BP target in only a limited number of hypertensive patients. Use of more than one agent is necessary to achieve target BP in the majority of patients.

1Chobanian et al. Hypertension 2003;42:120652 2Mancia et al. J Hypertens 2007:25:110587ESH = European Society of HypertensionESC = European Society of Cardiology JNC = Joint National Committee

Current Guidelines Recommend Initiating Combination Therapy Early in Patients with Stage 2 Hypertension or High Cardiovascular RiskJNC 7 guidelines state1:When BP is more than 20 mmHg above systolic goal or 10 mmHg above diastolic goal, consideration should be given to initiate therapy with 2 drugs...ESH/ESC guidelines state2:A combination of two drugs at low doses should be preferred as first step treatment when initial BP is in the grade 2 or 3 range or total cardiovascular risk is high or very high.1Chobanian et al. Hypertension 2003;42:120652 2Mancia et al. J Hypertens 2007:25:110587ESH = European Society of HypertensionESC = European Society of Cardiology JNC = Joint National Committee

JNC8-DECEMBER 2014

Rationale for Single-pill Combination Therapy in Hypertension

Defined as the total number of days of therapy for medication dispensed/365 days of study follow-upGerbino & Shoheiber. Am J Health System Pharm 2007;64:127983 Compliance Single-pill Combination VS Free-combination TherapySingle-pill combination(amlodipine/benazepril)(n=2,839)Free combination(ACEI + CCB)(n=3,367)Medication possession ratio (MPR)p

Average no. of antihypertensive medications1234Multiple Antihypertensive Agents are Needed to Reach BP GoalTrial (SBP achieved)Bakris et al. Am J Med 2004;116(5A):30S8; Dahlf et al. Lancet 2005;366:895906 Jamerson et al. Blood Press 2007;16:806; Jamerson et al. N Engl J Med 2008;359:241728 ASCOT-BPLA (136.9 mmHg)ALLHAT (138 mmHg)IDNT (138 mmHg)RENAAL (141 mmHg)UKPDS (144 mmHg)ABCD (132 mmHg)MDRD (132 mmHg)HOT (138 mmHg)AASK (128 mmHg)ACCOMPLISH (132 mmHg)Initial 2-drug combination therapy

Advantages of Multiple-mechanism TherapyEnhanced antihypertensive efficacyPotential for attenuation of certain class-specific adverse eventsRecommended by treatment guidelines

What drugs can be recommended for Combination Therapy in Hypertension ?

DiureticsCCBS) ARBAngiotensin-converting enzyme (ACE) inhibitorsb-blockersa-blockersAvailable as a single-pill combinationLess frequently used/combination used as necessaryTask Force for ESHESC. J Hypertens 2007;25:110587ESHESC Recommendations for Combining BP-lowering Drugs and Availability as Single-pill CombinationsACEI DIURETIC)

ACCOMPLISH: Superior CV Outcomes with RAS Blocker/Amlodipine Versus RAS Blocker/HCTZ Single-pill Combination (SPC)-based RegimensMonths06121824303642Patients at risk (N) Benazepril/amlodipine5,5125,3175,1414,9594,7392,8261,447Benazepril/HCTZ5,4835,2745,0824,8924,6552,7491,3900.160.120.080.040Cumulative event rate01823665477319121,0961,277Benazepril/amlodipine (552 patients with events: 9.6%)Benazepril/HCTZ (679 patients with events: 11.8%)Time to first CV mortality/morbidity (days)HR 0.80 (95%CI 0.720.90); p

Defined as the total number of days of therapy for medication dispensed/365 days of study follow-upGerbino & Shoheiber. Am J Health System Pharm 2007;64:127983 Compliance Single-pill Combination VS Free-combination TherapySingle-pill combination(amlodipine/benazepril)(n=2,839)Free combination(ACEI + CCB)(n=3,367)Medication possession ratio (MPR)p

Tolerability and Risk Factor Modification: CCB-induced Peripheral Edema Minimized by the ARBSingle mode of action of the CCBDual mode of action of the CCB/ARB Illustration modified from www.lotrel.comARB dilates arteries and veinsReduces CCB-induced peripheral edemaCapillary overload forces fluid into surrounding tissueCCB dilates arteriesVeins remain constrictedMesserli et al. Am J Hypertens 2001;14:9789

WHAT GUIDELINES SAID ABOUT DRUG COMBINATIONS RATIONALE ?

National Institute for Health and Clinical Excellence (NICE) (2006)Hypertension: management of hypertension in adults in primary care (Quick Reference Guide).London: NICE. Available from www.nice.org.uk/034. Reproduced with permission Updated UK NICE Guidelines for the Treatment of Newly Diagnosed Hypertension*If ACE inhibitor (ACEI) not toleratedACEI (or ARB*) + CCB orACEI (or ARB*) + thiazide diuretic

Recommendation 4 (Expert opinion)

Recommendation 5 (Expert opinion)

Recommendation 6 (Moderate recommendation)Population with CKD 18 yearsSBP 140 mm Hgor DBP 90 mm Hg SBP

ONTARGET: ARB Therapy was Non-inferior to ACE Inhibitor Therapy with Respect to the Primary Endpoint of CV Morbidity/Mortality*The primary outcome occurred in 1,412 (16.5%) patients in the ramipril group and in 1,423 (16.7%) patients in the telmisartan armTelmisartan was associated with lower rates of cough and angioedema compared with ramiprilThe ONTARGET Investigators. N Engl J Med 2008;358:154759Primary composite outcome*RR (95%)Telmisartan betterRamipril better0.80.91.01.11.2p=0.003Non-inferiority margin*Composite of CV death, myocardial infarction, stroke, or hospitalization for heart failure; p value is for the comparison with non-inferiority margins; RR = relative risk; CV = cardiovascular; ONTARGET = Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial

SUMMERY Hypertension prevalence is increasing

The control rate of hypertension still low Compliance is important

Control of hypertension has an impact in preventing cardiovascular complication Single pill combination is recommended to better control of BP and compilance

Thanks for your Attention!

ASSESS for hypertension (130/80 mmHg)TREAT to target 20 mmHg above target or diastolic blood pressure >10 mmHg above target

2013Hypertension Checklist Canadian Diabetes Association Clinical Practice Guidelines

*Lower doses generally used in single-pill combinations**An increasing number of single-pill combinations are becoming available with a range of doses+ = potential advantageAdvantages of Single-Pill Versus Free Combinations of Two Antihypertensive Drugs

Single pillFreeSimplicity of treatment+Compliance+Efficacy++Tolerability +*Price+Flexibility +**++

Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009A total of 4071 individuals, with hypertension or normotensives, and without previous history of diabetes mellitus were investigated between January 2004 and September 2009.A subgroup of 1856 hypertensive patients who had at least one additional cardiovascular risk factor took part in the treatment analysis. To adjust for potential cofounders, a propensity score matched analysis was performed using the logistic regression model. The population was finally divided as follows: 321 patients for ACE inhibitor users and 321 patients for ARB users.The primary end point was the cumulative incidence of new-onset diabetes mellitus.*Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009In this study by Wolf-Maier et al., data from national sample surveys were analyzed to provide age- and sex-adjusted estimates of BP and prevalence of hypertension (BP 140/90 mmHg or treatment with antihypertensive medication) by country and region (Europe compared with North America).

Data showed that the prevalence of hypertension was similar for the US and Canada (28% and 27%, respectively; data for Canada not shown on the slide), but was markedly higher in European countries (44.2% overall).

ReferenceWolf-Maier K, et al. Hypertension prevalence and blood pressure levels in 6 European countries, Canada, and the United States. JAMA 2003;289:23639.

Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009This slide shows the results of an analysis of worldwide data (from published literature dated 1980 to 2002) on the prevalence of hypertension (age- and gender-specific).1

Hypertension was defined as systolic BP 140 mmHg, or diastolic BP 90 mmHg or the use of antihypertensive medication. Only data for the established market economies (i.e. US, Canada, Spain, England, Germany, Greece, Italy, Sweden, Australia, Japan) are given on this slide. Other data (not shown) are available for former socialist economies (Slovakia), India, Latin America and the Caribbean, Middle East, Asia, and sub-Saharan Africa.

As illustrated, the prevalence of hypertension increases with advancing age. At young ages, the prevalence was higher in males than in females; from age 60, however, the trend was reversed, with prevalence higher in women than in men. The reasons for gender differences in BP are not known, although it has been suggested (but not proven) that estrogen may be responsible for lower BP in younger women.2

References Kearney PM, et al. Global burden of hypertension: analysis of worldwide data. Lancet 2005;365:21723.

August P, et al. Hypertension in women. J Clin Endocrinol Metab 1999;84:18626.

Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009Trials have shown that BP lowering can produce rapid reductions in cardiovascular disease risk. In fact, even a 2 mmHg decrease in systolic BP would result in approximately 7% lower mortality risk from ischemic heart disease and a 10% lower mortality risk from stroke.

ReferenceLewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:190313.Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009Amlodipine/Valsartan Speaker Slide Resource Item code: EXF09.203; Release Date: March 2009This slide shows the age-adjusted control rates in treated hypertensive patients aged 3564 years.

As shown, the majority of patients treated for hypertension in Europe do not attain target BP goals of