Treatment of Mild to Moderate Hypertension is Worthwhile * * a useful question to have asked between 1970 and 1985, bu

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 1.2 - Non-smoker, non-diabetic

4. HYPERTENSION BIG PROBLEM

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 (1863-1952)

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, 12:23PMBy AUT University 182 viewsNORTH 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, 12:23PMBy AUT University 182 viewsNORTH 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. 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 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.

13. 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 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.

15. Blood Pressure and Risk of Stroke Mortality Lancet 2002;360:1903-13

16. Blood Pressure and Risk of Ischemic Heart Disease (IHD) Mortality Lancet 2002;360: 1903-13

17. Cardiovascular Mortality RiskIncreases as Blood Pressure Rises* 8x 8 7 6 5 4x CardiovascularMortality Risk 4 3 2x 2 1 0 115/75 135/85 155/95 175/105 Systolic/Diastolic Blood Pressure (mm Hg) *Measurements taken in individuals aged 40–69 years, beginning with a blood pressure of 115/75 mm Hg. Lewington S, et al. Lancet. 2002;360:1903-1913; Chobanian AV, et al. JAMA. 2003;289:2560-2572.

18. Impact of High-Normal Blood Pressure on Risk of Major Cardiovascular Events* in Men 16 14 12 10 8 6 4 2 0 Blood Pressure: High-Normal 130–139/85–89 mm Hg Normal 120–129/80–84 mm Hg Cumulative Incidence of Major Cardiovascular Events (%) Optimal <120/80 mm Hg 12 0 2 4 6 8 10 Time (Years) *Defined as death due to cardiovascular disease or as having recognized myocardial infarction, stroke, or congestive heart failure. Vasan RS. N Engl J Med. 2001;345:1291-1297.

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;289:2560-2572) Classification of Blood Pressure Category SBP DBP Normal < 120 or < 80 Prehypertension 120-139 or 80-89 Stage 1 140-159 or 90-99 Stage 2 > 160 or > 100

22. JNC 6 Guideline (Arch Int Med 1997;157:2413-16) Classification of Blood Pressure Category SBP DBP Optimal < 120 or < 80 Normal 120-129 or 80-84 High normal 130-139 or 85-89 Stage 1 140-159 or 90-99 Stage 2 160-179 or 100-109 Stage 3 >179 or > 109

23. I will arbitrarily define “Mild to Moderate” Hypertension as: 140 – 179 systolic +/- 90-109 diastolic

26. The VA Cooperative Study, 1970 VA Cooperative Study Group. JAMA. 1970;213:1143-1152.

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 140-179/ 90-109

28. What do these RCT’s (total ~ 190 000 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

30. - -

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)

34. “Old Men Making Rules to Treat Themselves”

35. CV Risk Factor Estimation Systems

36. 50 year old European female - BP averages 160/95 on multiple readings - BMI 25 - TC 6.1, HDL 1.2 - Non-smoker, non-diabetic 5 year risk 5-10%: therefore No antihypertensives No statin

38. Marma et al. Circ Cardiovasc Qual Outcomes 2010;3(1):8-14 (NHANES survey 2003-2006 – 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 1.2 - 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 1.5 - 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. 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 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 1089 40–74 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.

42. 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 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 1089 40–74 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)

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;359:2417-2428) 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 2003. Excellent BP control with 76% having BP at target at 18 months and few dropouts for side effects. 50% obese 60% diabetes mellitus www.hypertensiononline.org

46. Effects of Treatment on Systolic and Diastolic Blood Pressure over Time Jamerson K et al. N Engl J Med 2008;359:2417-2428

47. Kaplan-Meier Curves for Time to First Primary Composite End Point Jamerson K et al. N Engl J Med 2008;359:2417-2428

48. Hazard Ratios for the Primary Outcome and the Individual Components Jamerson K et al. N Engl J Med 2008;359:2417-2428

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” www.hypertensiononline.org

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)