高血压治疗研究进展 优化治疗策略 张维忠

1. 高血压治疗研究进展 优化治疗策略 张维忠

2. Stroke and CHD Mortality Rate in Each Decade of Age versus Usual Systolic Blood Pressure at the Start of That Decade Age at risk (y): Age at risk (y): Stroke CHD 256 80-89 80-89 • 256 • • • • • • 128 • 70-79 • • 70-79 • • • 128 • • • • • • • • • 64 • • • • • 60-69 • 60-69 64 • • • • • • • 32 • 50-59 • 50-59 • 32 • • • • • • • • • • • • 16 • • • • 16 Stroke mortality (floating absolute risk and 95% CI) 40-49 • • • • • • • • • 8 • 8 • • • • • • • • • • • 4 4 • • • • • • 2 • 2 • • • • 1 1 • • 120 140 160 180 120 140 160 180 Usual SBP (mmHg) Usual SBP (mmHg) Lancet 2002; 360: 1903-1913

3. 100 Systolic Blood Pressure (ROC) curve 120 mmHg 130 mmHg 80 140 mmHg 60 150 mmHg Sensitivity 40 160 mmHg 20 0 0 20 40 60 80 100 False-positive error rate (%)

4. HOT Study: Risk of a major cardiovascular event reduced by 30% Achieved DBPmm Hg 105 100 95 90 85 80 0 5 83mmHg Optimal DBPreduction 10 15 20 25 30 % risk reduction Hansson, et al 1998

5. VALUE: 收缩压控制目标与终点事件 （6个月时） Odds Ratio ** Fatal/Non-fatal cardiac events 0.75 (0.67–0.83) ** Fatal/Non-fatal stroke 0.55 (0.46–0.64) ** All-cause death 0.79 (0.71–0.88) Myocardial infarction 0.86 (0.73–1.01) ** Heart failure hospitalisations 0.64 (0.55–0.74) 0.4 0.6 0.8 1.0 1.2 1.4 Controlled patients* (n = 10755) Non-controlled patients (n = 4490) Hazard Ratio 95% CI *SBP < 140 mmHg at 6 months. **P < 0.01. Weber MA et al. Lancet. 2004;363:2047–49.

6. 降压治疗更大程度获益, 应该关注或重视怎样的干预策略？

7. (一)强调早期干预控制心血管风险 REGRESS Target organ damage Asymptomatic CKD New risk factors RETARD PREVENT Target organ Damage Symptomatic Atherosclerosis Risk factors ESRD Death

8. Incidence of Major CV Events in Trials on High CV Risk Patients 50 43.5 40 40.0 34.3 30 26.9 27.0 25.4 25.6 25.4 20 17.8 16.8 19.2 15.8 14.1 14.0 16.1 13.0 12.5 12.4 12.1 14.0 13.9 13.9 11.7 11.2 11.0 10.5 12.2 12.0 11.4 11.5 10 3.5 8.5 11.0 10.6 11.7 10.5 8.3 8.0 0 Trial ACC CAM PEA EU INV JM ALL LIFE ACT CNT TR HOP VAL PROG TIA PROF PATS MOS Age (y) 68 57 64 60 66 65 67 67 64 64 67 66 67 64 65 66 60 66 DM (%) 60 18 17 - 28 2 36 13 15 37 36 38 32 13 5 28 - 37 MI (%) 23 38 55 65 32 42 16* 52 49 46 52 46 16 6 - - 8 Stroke (%) 13 4 7 3 5 - 8 - 21 22 11 20 100 100 100 100 100 Any CVD (%) - 100 100 100 100 100 52 25 100 91 91 88 60 100 100 100 100 100 LVH (%) 13 - - - 22 - 16.5 100 - 13.6 13 8.5 15 - 11 15.5 - LLT (%) 68 86 70 57 37 28 25 - 88 62 95 28 46 7 - 47 - 31 APT (%) 65 94 90 92 57 55 36 - 86 81 79 76 73 60 49 100 - 78 AHT (%) 0 139 109 102 0 0 0 0 37 118 131 101 0 50 0 103 0 0 SBP (mmHg) 132 124 129 128 131 136 135 144 130 133 136 135 139 132 150 136 143 136 Zanchetti A. J Hypertens. 2009; 27:1509-1520.

9. FEVER: Fatal and non-fatal stroke in groups with or without previous history of CVD On-treatment SBP/DBP (mmHg) Patient groups No. Felodipine Placebo HR HR 95% CI p CVD-Yes 4111 137.9/82.4 142.2/84.4 0.84 0.2217 CVD-No 5600 138.1/82.8 142.2/85 0.64 0.0015 0.4 0.6 0.8 1.0 1.5 2.0 Felodipine better Placebo better

10. (二)关注治疗过程的血压控制质量 age, ethnicity, male sex, obesity, genetic factors, low socioeconomic status, low birth weight  BP Variability  BP Levels CV Diseases

11. Intra-individual SBP Variability during Treatment Low High mmHg mmHg 160 160 B 6 12 18 24 30 36 42 48 B 6 12 18 24 30 36 42 48 Months Months Treatment Treatment

12. ELSA: Clinic and ambulatory BP control SBP <140 mmHg and DBP < 90 mmHg DBP < 90 mmHg SBP <140 mmHg 100 100 100 % % % 80 80 80 60 60 60 Clinic BP 40 40 40 20 20 20 0 0 0 All years All years All years 1 2 3 4 1 2 3 4 1 2 3 4 Year Year Year SBP <125 mmHg and DBP < 80 mmHg DBP < 80 mmHg SBP <125 mmHg 100 100 100 % % % 80 80 80 60 60 60 24 h 40 40 40 20 20 20 0 0 0 All years All years All years 1 2 3 4 1 2 3 4 1 2 3 4 Year Year Year Zanchetti A, et al. J Hypertens 2007;25:2463

13. INVEST: Blood pressure and CV outcomes According to the percentage of visits with BP <140/90 mmHg % of visits with BP < 140/90 mmHg HR (95% CI), MI Reduced Risk Increased Risk <25% (n=3838) 1.00 25 to <50% (n=3757) 0.70 (0.57-0.86) 50 to < 75% (n=6664) 0.68 (0.56-0.81) ≥ 75% (n=8316) 0.58 (0.48-0.69) HR (95 CI), Stroke < 25% (n=3838) 1.00 25 to <50% (n=3757) 0.89 (0.67-1.19) 50 to < 75% (n=6664) 0.70 (0.52-0.92) ≥ 75% (n=8316) 0.50 (0.37-0.68) 0.40 0.60 0.80 1.00 1.20 HR (95% CI) Mancia G, et al. Hypertens 2007;50:299

14. Clinical outcome by proportion of visits with BP control Primary endpoint CV morbidity/ mortality MI (F+NF) Stroke (F+NF) % 25 % 25 % 10 % 10 20 20 8 8 15 15 6 6 10 10 4 4 5 5 2 2 0 0 0 0 ≥25% to <50% ≥25% to <50% ≥25% to <50% ≥25% to <50% <25% <25% ≥50% to <75% ≥50% to <75% ≥75% ≥75% <25% <25% ≥50% to <75% ≥50% to <75% ≥75% ≥75% Proportion of Visits with BP Control (%) VALUE: Quality of BP Control and Outcomes

15. (三)重视心血管风险标记指导治疗 Aging Smoking BP LDL/HDL Diabetes Oxidative Stress LDL/HDL Inflammation BP CV Events Genetics Endothelial Dysfunction Atherosclerosis Small Artery Elasticity Pulse Pressure PWV Large Artery Elasticity

16. LIFE-ECHO substudyImpact on LVH regression on outcomes Hazard Ratio: 0.58 (0.38-0.86) p< .008 Devereux R, et al. JAMA. 2004;292:2350-2356

17. ONTARGET and TRANSCED: Reduction in albuminuria translates to reduction in CV events Patients with vascular disease, n=23,480, 32 months FU All cause mortality 0.026 decrease > 50% vs minor change Minor change increase > 100% vs minor change <0.0001 CV deaths 0.140 decrease > 50% vs minor change Minor change increase > 100% vs minor change <0.0001 Composite CV endpoint 0.032 decrease > 50% vs minor change Minor change increase > 100% vs minor change <0.0001 Combined renal endpoint 0.015 decrease > 50% vs minor change Minor change increase > 100% vs minor change 0.005 Risk ratio 0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 Adjusted to age, sex, BMI, aicobet, eGFR, Plasma glucose, SBP, DBP, HR, diabetes, smoking and eGFR changes at 2 yrs Schmieder et al. JASN 2011

18. 降压治疗策略的新理念 ◆以长期高质量血压控制和预防或逆转靶器官损害为目标的优化治疗，更有利于指导降压治疗，并可能获得更大程度的益处。

19. 不同治疗方案影响终点事件的临床试验 ● LIFE (2001) ● IDNT (2001) ● ASCOT-BPLA (2005) ● ACCOMPLISH (2008) ● COPE (2011)

20. 优化治疗策略的意义 ◆优化治疗策略需要优化降压治疗的基本 元素、剂量，以及联合治疗方案与路径， Preferred drugs，Preferred combinations。 ◆RAS阻滞剂±钙拮抗剂±噻嗪类利尿剂 联合成为临床上主要的优化治疗方案。 ◆ 新观念和新思路将开拓高血压治疗的新 靶点，推动新药与新制剂研发。