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Treatment of Mild to Moderate Hypertension is Worthwhile* * a useful question to have asked between 1970 and 1985, but not in 2011 *the most evidence-based.

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Presentation on theme: "Treatment of Mild to Moderate Hypertension is Worthwhile* * a useful question to have asked between 1970 and 1985, but not in 2011 *the most evidence-based."— Presentation transcript:

1 Treatment of Mild to Moderate Hypertension is Worthwhile* * a useful question to have asked between 1970 and 1985, but not in 2011 *the most evidence-based statement in all of medicine

2 50 year old European female - BP averages 160/95 on multiple readings - BMI 25 - TC 6.1, HDL Non-smoker, non-diabetic

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4 BIG PROBLEM HYPERTENSION

5 Hypertension specialists retired or died from the 1980’s – 1990’s. Cardiologists deemed hypertension not to be an important specialty, shut down the hypertension clinics, and devolved hypertension management entirely to primary care ↓ Cardiologists and other medical specialists lost hypertension management skills ↓ No-one left to educate medical students, trainee physicians and GP’s ↓ GP’s don’t know how to treat simple or complex hypertension and have nowhere to refer their difficult patients

6 Because no-one in the Pharmac corridors of power is interested in hypertension our patients are missing out on badly needed modern (and some old) antihypertensive drug therapies Reserpine Aldactazide Amiloride Minoxidil Moxonidine Eplerenone Aliskerin Combinations containing chlorthalidone rather than HCTZ Modern fixed-dose combinations ACE-inhibitor – CCB ARB-CCB ACE-inhibitor – CCB – thiazide ARB – CCB – thiazide

7 We are not interested in prevention Public awareness BP health risk - All time Low 99% of resource - High tech treatments and complications Coronary angiography and intervention Cardiac surgery Stroke units and rehab ($450 million per year inpatient costs) Heart failure clinics

8 “Those who cannot remember the past are doomed to repeat it” George Santayana, philosopher ( )

9 “They that sow the wind shall reap the whirlwind” Hosea 8:7

10 Increasing stroke numbers in New Zealand an 'epidemic' says leading AUT researcher Tuesday 30 November 2010, 12:23PM By AUT University 182 views NORTH SHORE CITY NORTH SHORE CITY Urgent measures are needed to reduce the growing number of stroke victims in New Zealand, says Professor Valery Feigin, Director of the new National Institute for Stroke and Applied Neuroscience, which is officially being launched today by Associate Minister of Health, the Hon Dr Jonathan Coleman at AUT’s North Shore Campus. Currently costing the country over $450 million per year in hospital and rehabilitation-related costs alone, stroke incidence in New Zealand is the second highest amongst developed countries and numbers are only increasing, says Feigin. x

11 Increasing stroke numbers in New Zealand an 'epidemic' says leading AUT researcher Tuesday 30 November 2010, 12:23PM By AUT University 182 views NORTH SHORE CITY NORTH SHORE CITY Urgent measures are needed to reduce the growing number of stroke victims in New Zealand, says Professor Valery Feigin, Director of the new National Institute for Stroke and Applied Neuroscience, which is officially being launched today by Associate Minister of Health, the Hon Dr Jonathan Coleman at AUT’s North Shore Campus. Currently costing the country over $450 million per year in hospital and rehabilitation-related costs alone, stroke incidence in New Zealand is the second highest amongst developed countries and numbers are only increasing, says Feigin. x NZ stroke rates increasing and second highest in OECD

12 Abstract Background Cardiovascular mortality is higher in New Zealand compared to Australia, but reasons for this difference are uncertain. This study describes differences in cardiovascular risk factors and cardiovascular mortality in Australians and New Zealanders with stable coronary artery disease stratified by socioeconomic status. Journal of the New Zealand Medical Association, 15-February-2008 Vol 121 No 1269 Differences in cardiovascular mortality between Australia and New Zealand according to socioeconomic status: findings from the Long- Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Ralph A H Stewart, Fiona M North, Katrina J Sharples, R John Simes, Andrew M Tonkin, Harvey D White; for the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Investigators

13 Abstract Background Cardiovascular mortality is higher in New Zealand compared to Australia, but reasons for this difference are uncertain. This study describes differences in cardiovascular risk factors and cardiovascular mortality in Australians and New Zealanders with stable coronary artery disease stratified by socioeconomic status. Journal of the New Zealand Medical Association, 15-February-2008 Vol 121 No 1269 Differences in cardiovascular mortality between Australia and New Zealand according to socioeconomic status: findings from the Long- Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Ralph A H Stewart, Fiona M North, Katrina J Sharples, R John Simes, Andrew M Tonkin, Harvey D White; for the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Investigators Cardiovascular mortality 40% higher in NZ than Australia

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15 Blood Pressure and Risk of Stroke Mortality Lancet 2002;360:

16 Blood Pressure and Risk of Ischemic Heart Disease (IHD) Mortality Lancet 2002;360:

17 Lewington S, et al. Lancet. 2002;360: ; Chobanian AV, et al. JAMA. 2003;289: Cardiovascular Mortality Risk Increases as Blood Pressure Rises * Cardiovascular Mortality Risk Systolic/Diastolic Blood Pressure (mm Hg) /75135/85155/95175/105 2x 4x 8x * Measurements taken in individuals aged 40–69 years, beginning with a blood pressure of 115/75 mm Hg.

18 *Defined as death due to cardiovascular disease or as having recognized myocardial infarction, stroke, or congestive heart failure. Cumulative Incidence of Major Cardiovascular Events (%) Time (Years) Optimal <120/80 mm Hg Normal 120–129/80–84 mm Hg High-Normal 130–139/85 – 89 mm Hg Impact of High-Normal Blood Pressure on Risk of Major Cardiovascular Events * in Men Vasan RS. N Engl J Med. 2001;345: Blood Pressure:

19 Continuum of increasing CV risk from SBP 115mmHg CV mortality doubles for every 10/5 increase in BP > 120/70mmHg High BP causes - 35% of all cardiovascular deaths - 50% of all stroke deaths - 25% of all CAD deaths - 50% of all congestive heart failure - 25% of all premature deaths - commonest cause of chronic kidney disease

20 What is “Mild to Moderate Hypertension”??? No accepted medical definition

21 JNC 7 Guidelines (JAMA 2003;289: ) Classification of Blood Pressure CategorySBPDBP Normal < 120or< 80 Prehypertension or80-89 Stage or Stage 2 > 160or > 100

22 JNC 6 Guideline ( Arch Int Med 1997;157: ) Classification of Blood Pressure CategorySBPDBP Optimal < 120or< 80 Normal or80-84 High normal or Stage or Stage or Stage 3 >179 or > 109

23 I will arbitrarily define “Mild to Moderate” Hypertension as: 140 – 179 systolic +/ diastolic

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26 The VA Cooperative Study, 1970 Cohort380 men Mean age50 years EligibilityDiastolic BP mmHg Design Double blind; placebo control Therapy HCTZ, reserpine, hydralazine Duration5.5 years (mean=3.8 yrs) BP change Diastolic BP -19 mmHg VA Cooperative Study Group. JAMA. 1970;213:

27 Apart from the 1967 trial of treatment of in individuals with severe hypertension, the majority of RCT’s of drug treatment in hypertension have involved individuals broadly within the “mild to moderate” category /

28 What do these RCT’s (total ~ pts) of hypertension drug treatment show? Major cardiovascular events (MI, stroke, heart failure) reduced by ave. 25% (Stroke 40%, MI 15-20%, CHF 50%) Relative risk reduction similar in all age groups Arch Int Med 1993;153:578 BMJ 2008;336:1121

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30 -

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32 Basis for this is that active (pharmacological) treatment is suggested if 5 year risk of cardiovascular event is > 15% But “Isolated single risk factors” do not mandate therapy unless extremely abnormal (BP > 170/100, total cholesterol > 8mmol/l etc)

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34 “Old Men Making Rules to Treat Themselves”

35 SystemGeographic AreaAge (yrs) Time Horizon (yrs) FraminghamUS ScoreEurope AssignScotland Q RiskGeneral Practice ProcamEurope WHO/ISH ReynoldsWHS-PHS NZ CV Risk Guideline New Zealand CV Risk Factor Estimation Systems

36 50 year old European female - BP averages 160/95 on multiple readings - BMI 25 - TC 6.1, HDL Non-smoker, non-diabetic 5 year risk 5-10%: therefore No antihypertensives No statin

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38 Marma et al. Circ Cardiovasc Qual Outcomes 2010;3(1):8-14 (NHANES survey – US adults aged 20-79) Short term cardiovascular risk - low < 10% 10 year - high >= 10% 10 years or diagnosed diabetes Long term cardiovascular risk - low < 39% lifetime - high >= 39% lifetime Population divided in to 3 groups - low short term/ low long term (26%) - low short term/ high long term (56%) - high short term/ high long term (18%)

39 For example 50 year old female - BP 160/95 - TC 6.1, HDL Non-smoker, non-diabetic NZ Risk Score 5-10% 5years – no treatment Lifetime cardiovascular risk – 50% 50 year old female - BP 115/75 - TC 4, HDL Non-smoker, non- diabetic NZ Risk Score <2.5% - no treatment Lifetime cardiovascular risk – 8%

40 If we had the means to reduce the risk of breast cancer in women at high lifetime risk by 42% - would we employ it? Causes of death in NZ women - cardiovascular disease 40% - breast cancer 5%

41 Abstract Aim To determine whether use of cardiovascular medications by a sample of mid-life and older women is consistent with New Zealand cardiovascular risk guidelines. Method Retrospective analysis of risk factor data collected during the Women’s Lifestyle Study involving –74 year old women. Outcome measures included: 5-year cardiovascular (CVD) risk score calculated using the adjusted Framingham equation and self-reported use of cardiovascular medications. Results Seven percent (76/1089) of women had established CVD, and a further 3% (33/1089) had a risk score greater than 15% (high risk). Of the 109 women at high risk (risk score ≥15% or established CVD); 36% (39/109) were taking aspirin, 55% (60/109) were taking blood pressure-lowering medication, 45% (49/109) were taking lipid-lowering medications and 17% (19/109) were taking all three medications. Triple therapy was being taken by 12% of women (4/33) for primary prevention (5-year risk score ≥15%) and only 19.7% of women for secondary prevention (15/76). Conclusion These results suggest that women at high-risk are not receiving cardiovascular medications as recommended by the guidelines, reflecting a ‘treatment gap.’ Modifiable barriers to the management of women at risk for CVD need to be identified and addressed to reduce cardiovascular morbidity and mortality among women. Journal of the New Zealand Medical Association, 19-February-2010, Vol 123 No 1309 Are at-risk New Zealand women receiving recommended cardiovascular preventive therapy? Olivia Bupha-Intr, Sally B Rose, Beverley A Lawton, C Raina Elley, Simon A Moyes, Anthony C Dowell

42 Abstract Aim To determine whether use of cardiovascular medications by a sample of mid-life and older women is consistent with New Zealand cardiovascular risk guidelines. Method Retrospective analysis of risk factor data collected during the Women’s Lifestyle Study involving –74 year old women. Outcome measures included: 5-year cardiovascular (CVD) risk score calculated using the adjusted Framingham equation and self-reported use of cardiovascular medications. Results Seven percent (76/1089) of women had established CVD, and a further 3% (33/1089) had a risk score greater than 15% (high risk). Of the 109 women at high risk (risk score ≥15% or established CVD); 36% (39/109) were taking aspirin, 55% (60/109) were taking blood pressure-lowering medication, 45% (49/109) were taking lipid-lowering medications and 17% (19/109) were taking all three medications. Triple therapy was being taken by 12% of women (4/33) for primary prevention (5-year risk score ≥15%) and only 19.7% of women for secondary prevention (15/76). Conclusion These results suggest that women at high-risk are not receiving cardiovascular medications as recommended by the guidelines, reflecting a ‘treatment gap.’ Modifiable barriers to the management of women at risk for CVD need to be identified and addressed to reduce cardiovascular morbidity and mortality among women. V mortality 40% higher on NZ than Australia and death from IHD 25% higher) Journal of the New Zealand Medical Association, 19-February-2010, Vol 123 No 1309 Are at-risk New Zealand women receiving recommended cardiovascular preventive therapy? Olivia Bupha-Intr, Sally B Rose, Beverley A Lawton, C Raina Elley, Simon A Moyes, Anthony C Dowell Even the minimalistic recommendations of the NZ CV risk guideline are not being followed

43 “A low dose thiazide diuretic remains an acceptable option for first-line therapy in many people without contraindications or indications for one of the other treatment options” NZ CV Risk Guideline 2009

44 ACE inhibitor + Thiazide vs ACE inhibitor + CCB

45 ACCOMPLISH ( NEJM 2008;359: ) was a large (11 400) outcome study of high risk hypertensives > 55 yrs and SBP > 160. Many obese and 60% diabetic. Pts randomised to Benazepril/HCTZ or Benazepril/Amlodipine combinations. Primary endpoint – composite of death from cardiovascular causes, nonfatal MI, nonfatal stroke, hospitalisation for angina, resuscitation after cardiac arrest, and coronary revascularisation Pts randomised from Excellent BP control with 76% having BP at target at 18 months and few dropouts for side effects. 50% obese 60% diabetes mellitus

46 Effects of Treatment on Systolic and Diastolic Blood Pressure over Time Jamerson K et al. N Engl J Med 2008;359:

47 Kaplan-Meier Curves for Time to First Primary Composite End Point Jamerson K et al. N Engl J Med 2008;359:

48 Hazard Ratios for the Primary Outcome and the Individual Components Jamerson K et al. N Engl J Med 2008;359:

49 Trial stopped early in October 2007 by data safety and monitoring committee following interim analysis of 60% of expected information from the trial. Over a mean f/u of 39 months, cardiovascular morbidity/mortality was reduced by 20% with the ACEI/CCB compared with the ACEI/HCTZ “The benazepril-amlodipine combination was superior to the benazepril hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events”

50 The days of the primacy of diuretics in hypertension may be numbered Provisos:  they remain an extremely important part of combination therapy and most regimens of > 2 drugs should contain a thiazide  when used they need to be adequately dosed (..no outcome studies have ever shown benefit with HCTZ 12.5mg daily)

51 Conclusions “Mild to moderate hypertension” is the most important (remediable) cause of cardiovascular disease and death Most of the cardiovascular risks of mild to moderate hypertension can be avoided by treating to target blood pressure – this has been repeatedly demonstrated in multiple RCT’s involving hundreds of thousands of patients Aggressive management (at all ages) with a combination of lifestyle intervention and pharmacotherapy is mandatory Hypertension is poorly managed in New Zealand principally because of a failure of clinical leadership in the cardiology and primary care communities The NZ cardiovascular Risk Guideline needs to be urgently updated

52 Waitemata Hypertension Clinic Risk Factor Management Guideline No smoking at any time Fasting blood glucose < 5.5mmol/l Antihypertensive drug treatment of all (irrespective of age, gender, smoking or lipid status) with sustained BP >= 140/90, and > =130/80 for diabetes, CKD,or history of MI, stroke or PVD Statins for all (irrespective of age, gender, BP or smoking status) with LDL-C > 2.5mmol/l +/- TC/HDLC ratio > 4, and irrespective of lipid profile in diabetics, CKD or history of MI, stroke or PVD Low dose aspirin in all over 50 on treatment for hypertension or dyslipidaemia, and irrespective of age in all individuals with a history of MI, stroke, or PVD


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