Individual management of arterial hypertension Doumas Michael, - PowerPoint PPT Presentation

Individual management of arterial hypertension Doumas Michael, Internist Doumas Michael, Internist Lecturer, Aristotle University, Thessaloniki Lecturer, Aristotle University, Thessaloniki

From Population to I ndividual From Population to I ndividual Management of Arterial Management of Arterial Hypertension Hypertension

Epidemiologic impact on mortality of blood pressure reduction in the population After Before Prevalence % Intervention Intervention Reduction in BP Reduction in % Reduction in Mortality SBP Stroke CHD Total (mmHg) 2 -6 -4 -3 3 -8 -5 -4 5 -14 -9 -7 Adapted from Whelton, P. K. et al. JAMA 2002;288:1882-1888

BP Reductions as Small as 2 mmHg Reduce the Risk of CV Events by Up to 10% • Meta-analysis of 61 prospective, observational studies • 1 million adults • 12.7 million person-years 7% reduction in risk of IHD 2 mmHg mortality decrease in mean SBP 10% reduction in risk of stroke mortality Prospective Studies Collaboration. Lancet. 2002;360:1903- 1913.

52 yr old woman non smoker TC: 202 mg/dL HDLC: 61 mg/dL No diabetes BP: 162/94 mmHg 10y CV risk: 0.6% Mrs Ariadni Low-risk BP: 157/89 mmHg 10y CV risk: 0.5%

67 yr old man Diabetes Smoker TC: 268 mg/dL HDLC: 28 mg/dL BP: 160/95 mmHg 10y CV risk: 5.3% Mr Thrasivoulos High-risk BP: 155/90 mmHg Smoking cessation BP – lipid control 10y CV risk: 5.3% 3.7%

"Individualized Care" • Risk factors considered • Non-pharmacological therapy tried • Monotherapy or combination therapy is instituted • Considerations for choice of initial therapy:  Renin status  Age  Coexisting cardiovascular conditions  Other conditions

Stratification of CV risk in four categories Blood pressure (mmHg) Normal High normal Grade 1 HT Grade 2 HT Other risk Grade 3 HT SBP ≥ 180 or factors, OD or SBP 120 ‐ 129 SBP 130 ‐ 139 or SBP 140 ‐ 159 or SBP 160 ‐ 179 or DBP ≥ 110 disease or DBP 80 ‐ 84 DBP 85 ‐ 89 DBP 90 ‐ 99 DBP 100 ‐ 109 Average Average Low No other risk Moderate High added factors added risk risk risk risk added risk Low Low Moderate Moderate Very high 1 ‐ 2 risk factors added risk added risk added risk added risk added risk 3 or more risk Moderate High added High added Very high factors, MS, OD High added risk added risk risk risk added risk or diabetes Established CV Very high Very high Very high Very high Very high or renal disease added risk added risk added risk added risk added risk SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non ‐ fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

Einstein “Not everything that can be counted counts, and not everything that counts can be counted.“ Αυτά που είναι μετρήσιμα δεν είναι πάντα χρήσιμα και αυτά που είναι χρήσιμα δεν είναι πάντα μετρήσιμα

Addressing the Complexity of Hypertension

The Challenge of Personalized Antihypertensive Treatment • How to improve prognosis to identify the patients in need of further treatment? Who to treat? Who to treat? • How to identify more effective therapeutic opportunities tailored to the individual How to treat? How to treat? patient?

J Hypertension, November 2009

Initiation of antihypertensive treatment Normal High normal Grade 1 HT Grade 2 HT Other risk Grade 3 HT SBP ≥ 180 or factors, OD or SBP 120 ‐ 129 or SBP 130 ‐ 139 or SBP 140 ‐ 159 or SBP 160 ‐ 179 or DBP ≥ 110 disease DBP 80 ‐ 84 DBP 85 ‐ 89 DBP 90 ‐ 99 DBP 100 ‐ 109 Lifestyle changes Lifestyle changes Lifestyle for several for several weeks changes + No other risk No BP No BP months then drug then drug immediate factors intervention intervention treatment if BP treatment if BP drug uncontrolled uncontrolled treatment Lifestyle changes Lifestyle changes Lifestyle for several weeks for several weeks changes + 1 ‐ 2 risk factors Lifestyle changes Lifestyle changes then drug then drug immediate treatment if BP treatment if BP drug uncontrolled uncontrolled treatment 3 or more risk Lifestyle changes Lifestyle factors, MS, Lifestyle changes and consider changes + Lifestyle changes Lifestyle changes OD or diabetes drug treatment immediate + drug treatment + drug treatment drug Lifestyle changes Diabetes Lifestyle changes treatment + drug treatment Lifestyle Established CV Lifestyle changes Lifestyle changes Lifestyle changes Lifestyle changes changes + or renal + immediate drug + immediate + immediate drug + immediate drug immediate disease treatment drug treatment treatment treatment drug treatment

-30% -21% -23% -39% Beckett NS et al. N Engl J Med 2008;358:1887-1898

60 INVEST INVEST ONTARGET ONTARGET 30 3 (CAD pts) (CAD pts) (high risk pts, mainly with CAD) (high risk pts, mainly with CAD) 50 40 CV events (%) CV events (%) CV events (%) CV events (%) 20 2 Adjusted HR Adjusted HR 30 20 10 1 10 0 0 0 110 >110 >120 >130 >140 >150 >160 110 >110 >120 >130 >140 >150 >160 112 121 126 130 133 136 140 144 149 160 to 120 to 120 to 130 to 130 to 140 to 140 to 150 to 150 to 160 to 160 On- -treatment SBP (mmHg) treatment SBP (mmHg) On- -treatment SBP (mmHg) treatment SBP (mmHg) On On VALUE VALUE TNT TNT 30 35 5 (High risk pts) (CAD pts) (High risk pts) (CAD pts) 30 Cardiac events (%) 4 Cardiac events (%) 20 CV events (%) 25 CV events (%) Adjusted HR Adjusted HR 3 20 15 2 10 10 1 5 0 0 0 < 120 >120 >130 >140 >150 >160 >160 >170 >170 ≥ ≥ 180 180 < 120 >120 >130 >140 >150 ≤ ≤ 60 60 61- 61 -70 70 71- 71 -80 80 81 81- -90 90 91- 91 -100 100 > 100 > 100 to 130 to 130 to 140 to 140 to 150 to 150 to 160 to 160 to 170 to 170 to 180 to 180 On- On -treatment SBP (mmHg) treatment SBP (mmHg) On- On -treatment DBP (mmHg) treatment DBP (mmHg) J hypertension 2009; 2009;27: 27:2121–58 121–58

Should low-risk hypertensive patients be treated? Young patients? Mild hypertension?

One point of view “individual treatment can only be  justified if there is individual benefit”

Stroke and blood pressure lowering: subgroup analysis from 17 RCTs Trial % Events Odds ratio (Relative risk red.) group control treatment Younger 43 % patients Older 34 % patients 1º prev. 38 % 2º prev. 38 % 0 0.5 1.0 1.5 MacMahon & Rogers J Vasc Med Biol 1993;4:265-71

Stroke and blood pressure lowering: subgroup analysis from 17 RCTs Trial % Events Odds ratio (Relative risk red.) group control treatment Younger 2.3 % 1.3 % 43 % patients 1% Older 7.0 % 4.6 % 34 % patients 2.4% 1º prev. 3.2 % 2.0 % 38 % 1.2% 2º prev. 27.3 % 18.8 % 38 % 8.5% 0 0.5 1.0 1.5 MacMahon & Rogers J Vasc Med Biol 1993;4:265-71

Drug Costs in the US Drug Costs in the US Drug name Cost for 30 day supply Drug name Cost for 30 day supply Enalapril 5 mg - -20 mg 20 mg $4 Enalapril 5 mg $4 HCTZ 12.5- -25 mg 25 mg $4 HCTZ 12.5 $4 Atenolol 25 mg- - 100 mg $4 Atenolol 25 mg 100 mg $4 Amlodipine (Norvasc) 5 mg $75 Amlodipine (Norvasc) 5 mg $75 Amlodipine (generic) 5 mg $21 Amlodipine (generic) 5 mg $21

To treat or not to treat “mild hypertension” “treat risk not blood pressure” “only absolute risks and benefits are relevant to patients” “the payer should choose the threshold”

High-risk patients ‘The earlier – The better’ Attention to all CV risks

To treat or not to treat “mild hypertension” “the payer should not choose the threshold”

The Challenge of Personalized Antihypertensive Treatment • How to improve prognosis to identify the patients in need of further treatment? • How to identify more effective therapeutic opportunities tailored to the individual How to treat? How to treat? patient?

The Many Faces of HT Therapy Today s s B B C C C C Centrally acting agents Centrally acting agents ARBs ARBs Diuretics Diuretics ACE – ACE – inhibitors inhibitors Beta blockers Beta blockers Hypertension Hypertension

Reductions in Systolic Blood Pressure Among All Patients Reductions in Systolic Blood Pressure Among All Patients VA Cooperative Study of Responses to Single- VA Cooperative Study of Responses to Single -Drug Therapy Drug Therapy Hydrochlorothiazide Prazosin Captopril Clonidine Diltiazem Atenolol Placebo n = 177 188 182 186 176 188 186 0 Change in SBP (mm Hg) -5 -10 from Baseline -15 -20 * -25 * -30 * * P ≤ 0.05 vs. captopril -35 SBP = systolic blood pressure Materson BJ, et al. N Engl J Med. 1993;328:914-921.