New Antihypertensive Strategies to Improve Blood Pressure Control

Transcription

1 New Antihypertensive Strategies to Improve Blood Pressure Control Antonio Coca, MD, PhD,, FRCP, FESC Hypertension and Vascular Risk Unit Department of Internal Medicine. Hospital Clínic (IDIBAPS) University of Barcelona, Spain Conflict of interest concerning this presentation: None Joint Session ESC Council on HT & WG Cardiovascular Pharmacotherapy apy EuroCVP 2018 Congress.. Tel Aviv (Israel), 13 th May 2018

2 Treatment Strategies Based BP Values and Total Cardiovascular Risk High normal SBP or DBP Grade 1 SBP or DBP Grade 2 SBP or DBP Grade 3 SBP 180 or DBP 110 Recommendations No other RF Reference Low risk Moderate Classrisk High Level risk It is recommended 1-22 RF that Low decisions risk on Moderate risk treatment strategies depend on the initial Low to 3 level of total 3 RF cardiovascular moderate risk Moderate to high risk Moderate risk I High risk High risk B High risk OD, CKD stage 3 or diabetes Moderate to high risk High risk High risk High to very high risk Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs Very high risk Very high risk Very high risk Very high risk Absolute 10 year risk of CV death SCORE < 4% 4-5% 5-8% > 8% 2013 ESH/ESC Guidelines.. J Hypertens 2013; 31: ESH/ESC Guidelines. Eur Heart J 2013; 34:

3 ESH/ESC 2013 Guidelines Pharmacological Treatment Mild BP elevation Low/moderate CV risk Choose between Marked BP elevation High/very high CV risk Low-dose monotherapy If target BP not achieved Low-dose combination of two drugs Previous combination at full dose Add a third drug at low dose If target BP not achieved Combination of drugs at effective doses 2013 ESH/ESC Guidelines.. J Hypertens 2013; 31: ESH/ESC Guidelines. Eur Heart J 2013; 34:

4 Cardiovascular Risk Stratification DICOPRESS Study: 22,639 patients (>18 years) seen by GPs in Spain High normal SBP or DBP Grade 1 SBP or DBP Grade 2 SBP or DBP Grade 3 SBP 180 or DBP 110 No other RF 1-22 RF 3 3 RF OD, CKD stage 3 or diabetes 70% 4.9% High or very high risk 6.0% 3.0% hypertensive patients 7.1% 10.8% 7.0% 0.01% 1.1% 0.8% 1.9% Symptomatic CVD, CKD stage 4 or diabetes with OD/RFs 5.9% 14.3% 8.7% 3.0% Absolute 10 year risk of CV death SCORE < 4% 4-5% 5-8% > 8% Martin, Coca et al. Med Clin (Barc)) 2007; 129:

5 Prevalence of Hypertension and Associated CV Risk Factors in Spain HT Prevalence 33.3 % HT aware 59.4 % Diabetes 19.3 % Hypercholesterolemia 42.3 % Smoking 14.7 % Overweight (BMI 25-30) 42.9 % Obesity (IMC > 30) 43.3 % Central Obesity (PC 102/88 cm) 63.9 % Salt intake (> 6 gr/d) 61.4 % Hospital Clínico nico.. IDIBAPS Banegas,, Coca et al. Hypertension 2012; 60;

6 Effects of Obesity, Sedentarism and Diabetes on Blood Pressure Control PREVENCAT Study: 2,092 hypertensive patients ( years) Predictors of strict blood pressure control (BP < 140/90 or < 130/85 in DM-2) Factor Type 2 Diabetes Obesity Sedentary life OR [IC del 95%] 0.29 [ ] 0.65 [ ] 0.78 [ ] p < Coca et al. Med Clin (Barc)) 2006; 126:

7 ESH/ESC 2013 Guidelines Pharmacological Treatment Mild BP elevation Low/moderate CV risk Choose between Marked BP elevation High/very high CV risk Low-dose monotherapy 30% 70% 100% in Diabetics If target BP not achieved Low-dose combination of two drugs Previous combination at Add a third drug at full dose low dose If target BP not achieved Combination of drugs at effective doses 2013 ESH/ESC Guidelines.. J Hypertens 2013; 31: ESH/ESC Guidelines. Eur Heart J 2013; 34:

8 Pathogenic Mechanisms of Hypertension in Humans Patient A Patient B Patient C Sympathetic nervous system Renin-angiotensin-aldosterone system Intravascular volume (Na+ and water) Waeber B. Expert Rev Cardiovasc Ther 2003; 1: 43 50

9 Blood Pressure Control Achieved by Different Antihypertensive Drugs A B C Drug A Drug B Drug C % Waeber B. Expert Rev Cardiovasc Ther 2003; 1: 43 50

10 BP Reduction in Monotherapy vs Combined Therapy in 119 Placebo-controlled controlled Studies 0 SBP DBP BP Δ (mmhg) Drug Drug 2 Combination -20 Law et al. BMJ 2003; 326: 1427

11 Initial Combination Therapy and Achievement of Blood Pressure Target Retrospective analysis of 1762 patients who initiate combination therapy vs those starting in monotherapy and later shifted to combined therapy Kaplan-Meier estimates of achieving BP target with initial combination therapy 100% 90% 80% Initial Combination Therapy Add-on Patients reaching BP target (%) 70% 60% 50% 40% 30% 40,3 % 32,6 % Log-Rank P= % 10% 0% Time in Months Gradman et al. Hypertension 2013; 61:

12 Initial Combination Therapy and Reduction of Cardiovascular Events Retrospective analysis of 1762 patients who initiate combination therapy vs those starting in monotherapy and later shifted to combined therapy Incident Rate of Cardiovascular Events (IRCVE) Incident rates (Initial vs. late combination) IRCVE (95% CI) All patients (1762 patients in each cohort) Acute Myocardial Infarct 0.45 vs ( ) 0.34) <.0001 Stroke/TIA 2.57 vs ( ) CHF Hospitalization 0.55 vs ( ) 0.95) All 3.34 vs ( ) 0.80) All (including death) 3.58 vs ( ) 0.84) P Initial combination better late combination better Gradman et al. Hypertension 2013; 61:

13 Cardiovascular Prevention in Early Blood Pressure Control: the VALUE Study All treatment groups Fatal and nonfatal Cardiac events Fatal and nonfatal stroke All cause mortality P < 0.05 P < 0.05 P < 0.05 Myocardial infarction Hospitalization for heart failure OR [ 95% CI] Early Responders* (n = 9336) Non Responders (n = 5663) *Previously untreated: SBP reduction > 10 mmhg at first month Previously treated: Any SBP Reduction PAS at first month Weber MA et al. Lancet 2004; 363:

14 Hypertension Treatment and Blood Pressure Control The National Health and Nutrition Examination Survey, 2005 to 2010 Adjusted Odds Ratio for BP control in the USA Treatment strategy and BP control Monotherapy Fixed-dose dose combination in a single pill Multiple pill combination BP control Treated patients 1.00 (ref) 1.55 ( )* 2.00)* 1.26 ( ) 1.55) * Significant difference compared to reference, P<0.01 Significant difference compared to reference, P<0.05 Gu et al. Circulation 2012; 126;

15 Blood Pressure Control in Hypertensive Controlpres % 13.0% 28% Combos Patients Treated by GPs in Spain Use of Combination Therapy Controlpres % 16.3% 29% Combos Controlpres % 71.2% 35% Combos 61.2% BP Control <140/90 mmhg Controlpres % 42% Combos ENRICA % 48.5% 58% Combos Coca A. Hipertension 2005; 22: Banegas,, Coca et al. Hypertension 2012; 60;

16 Number of Drugs to Achieve Target SBP Trial/SBP Achieved INVEST (136 mmhg) ALLHAT (138 mmhg) Mean 2.8 drugs (mod/high doses) IDNT (138 mmhg) RENAAL (141 mmhg) UKPDS ABCD MDRD HOT AASK (144 mmhg) (132 mmhg) (132 mmhg) (138 mmhg) (128 mmhg) Nº antihypertensive drugs Updated from Bakris GL et al. Am J Kidney Dis 2000;36:

17 New Evidence in Low and Moderate CV Risk HOPE - 3 Trial First Co-primary Outcome: composite of CV death, nonfatal MI, or nonfatal stroke Subgroup Mean SBP Can+ HCTZ events (%) Placebo events(%) Hazard Ratio (95% CI) Overall (4.1%) 279 (4.4%) 0.93 ( ) Systolic BP (3.4%) 87 (4.1%) 103 (4.8%) 62 (2.9%) 81 (3.8%) 136 (6.5%) 1.16 ( ) 1.08 ( ) 0.73 ( ) Treatment better Placebo better Lone EM, et al. N Eng J Med 2016; 374:

18 Treatment Strategies: The 2018 European Vision Mild BP elevation Low/moderate CV risk Low-dose monotherapy BP targets < 130/80 for most If target BP not achieved Marked BP elevation High/very high CV risk Low-dose combination of two drugs Previous combination at full dose Add a third drug at low dose If target BP not achieved Combination of drugs at effective doses

19 Treatment Strategies: The 2018 European Vision Relevant Antihypertensive effect CV Protection Optimal tolerability RAS Blockers ACEi or ARB (no combine) Diuretics Preferred Useful Possible Not recommended Calcium Antagonists -blockers Other Antihypertensives

20 Fixed-dose Combination Therapy Increases Compliance with Treatment Study Antihipertensive drugs Study OR (IC 95%) Clinical trials Schweizer et al, ( ) Asplund et al, ( ) Subtotal (I-squared=45.6%, p=0.175) 1.22 ( ) Cohort studies Taylor et al, ( ) Gerbino et al, ( ) Dickson et al, ( ) Subtotal (I-squared=0.0%, p=0.740) 1.21 ( ) Heterogeneity between groups: p= 0.9 Total (I-squared=0.0%, p=0.655) 1.21 ( ) Favours free-drug combinations Favours fixed-dose dose combinations Gupta et al, Hypertension 2010; 55:

21 Changes in Adherence to Treatment when Shifting from Free to Fixed Combinations P < % (n= 896) Adherence (%) % 20 0 Free Multiple-pill pill Fixed Single-pill Wang et al. Hypertension 2014; 63:

22 Number of Prescribed Antihypertensive Medications and the Risk of Nonadherence 100 Patients nonadherent to prescribed treatment United Kingdom (n= 676) % Czech Republic (n= 672) Serum and urine samples for detection of the prescribed medications Number of BP-lowering prescribed medications Gupta et al. Hypertension 2017; 69:

23 Adherence to Cardiovascular Therapy, and Mortality: Meta-analysis Relative risks (RR) for all cause mortality in good ( ( 80%) ) vs. poor (< 80%) adherence to cardiovascular disease medications No. of studies No. of participants No. of deaths RR (95% CI) Adherence to statins ,864 29, (0.46, 0.67) Adherence to antihypertensive agents ,598 12,288 0,71 (0.64, 0.78) Adherence to aspirin 3 12, (0.16, 1.29) Adherence to any CVD medication ,381 94, (0.57, 0.67) 0,3 0,5 0,7 Good adherence 1 1,2 Poor adherence Chowdhury et al. Eur Heart J 2013; 34: