1、高血壓治療新的循證醫學證據華中科技大學協和醫院心內科廖玉華高血壓治療：新的循證醫學證據ADVANCE研究 固定復方制劑VALIDD研究 降壓與心室舒張功能A meta-analysis of RCTs中國人高血壓臨床試驗證據ADVANCE研究: 在11,140例2型糖尿病患者中進行的降壓與強化血糖控制的析因隨機臨床試驗培哚普利吲達帕胺固定復方制劑（百普樂）對重要血管事件的影響Inclusion criteria Type 2 diabetes mellitusAge 55 years or olderAdditional risk of vascular event Age 65 yearsH

2、istory of major macrovascular diseaseHistory of major microvascular diseaseFirst diagnosis of diabetes 10 years prior to entryOther major risk factor Hypertensive or normotensiveRandomised study treatmentsBlood pressure loweringDouble-blind perindopril-indapamide versus matching placebo2.0 / 0.625mg

3、 or placebo for first 3 months4.0 / 1.25mg or placebo thereafter Blood glucose lowering (ongoing)Open-label gliclazide MR-based intensive therapy targeting an HbA1c of 6.5% versus usual guideline-based careAmong patients with diabetes, does blood pressure lowering therapy:Produce additional benefits

4、 when systolic pressure is lowered below 145 mmHg?Produce similar benefits for hypertensive and non-hypertensive patients? Add to the benefits produced by other cardiovascular preventive therapies including ACE inhibitors? ADVANCE study hypothesesPerindopril-indapamide armADVANCETrial profile12877 w

5、ith type 2 diabetes registered 11140 randomised5569 assigned perindopril-indapamide combination 1737 withdrew during run-inScheduled end of follow-up: 4.3 years 4908 (88%) assessed at final visit 4081 (73%) adherent to treatment4 lost to follow-up11 lost to follow-upScheduled end of follow-up: 4.3 y

6、ears 4863 (87%) assessed at final visit 4143 (74%) adherent to treatment5571 assigned matching placebo 死亡分析心血管死亡Follow-up (months)6121824303642485460安慰劑組培哚普利/吲達帕胺組非心血管死亡Follow-up (months)6121824303642485460安慰劑組培哚普利/吲達帕胺組相對危險降低 18%; p=0.027相對危險降低 8%; p=0.415%5%Cumulative incidence (%)Coronary events

7、*2P=0.02Non-fatal MI or death from coronary heart diseaseUnstable angina requiring hospitalisation, coronary revascularisation or silent MIMajor coronary heart disease265294 11% (-6 to 24)All coronary heart disease468535 14% (2 to 24)Other coronary heart disease283324 14% (-1 to 27)*Number of events

8、Per-IndPlacebo(n=5,569)(n=5,571)Relative riskreduction (95% CI)FavoursPer-IndFavoursPlaceboHazard ratio0.51.02.0Cerebrovascular eventsMajor cerebrovascular disease215218 2% (-18 to 19)All cerebrovascular disease286303 6% (-10 to 20)Other cerebrovascular disease7999 21% (-6 to 41)2.0* *2P=0.40Non-fat

9、al stroke or death from cerebrovascular diseaseTransient ischaemic attack or subarachnoid haemorrhageNumber of eventsPer-IndPlacebo(n=5,569)(n=5,571)Relative riskreduction (95% CI)FavoursPer-IndFavoursPlaceboHazard ratio0.51.0Among patients with diabetes, does blood pressure lowering therapy:Produce

10、 additional benefits when systolic pressure is lowered below 145 mmHg?Produce similar benefits for hypertensive and non-hypertensive patients? Add to the benefits produced by other cardiovascular preventive therapies including ACE inhibitors? Blood pressure lowering in diabetes: Unresolved issues 20

11、00YESYESYESVALIDD研究The Influence of Angiotensin Receptor Blockers and Blood Pressure Lowering on Diastolic Function in Patients with Hypertension and Diastolic Dysfunction: The VALsartan In Diastolic Dysfunction 血管緊張素受體拮抗劑(ARB)對高血壓和舒張功能不全患者的作用 Solomon S. American College of Cardiology 2007 Scientifi

12、c Sessions, March 25, 2007.研究目的目的:驗證下列假說是否正確“ARB較其他非阻斷RAAS系統的降壓藥物更有效改善左室舒張功能”？Solomon S. American College of Cardiology 2007 Scientific Sessions, March 25, 2007.研究設計482例初選患者年齡大于45歲、1、2級高血壓、無心功能不全病史組織多普勒檢查，評價心肌舒張速度，確定舒張功能不全的存在 384例舒張功能不全的患者纈沙坦組(n=186)320mg/d非RAAS拮抗劑降壓治療(n=198)鈣拮抗劑、利尿劑、阻滯劑隨機分組觀察終點38周前

13、后的舒張速度、等容舒張時間（S)、加速時間、E/A、E/E左室容積質量、射血分數隨訪38周Solomon S. American College of Cardiology 2007 Scientific Sessions, March 25, 2007.ARB vs. 非RAAS阻斷劑組:改善舒張功能療效相當38周后,ARB和非RAAS阻斷類降壓藥物均顯著改善舒張功能，療效相當時間/治療前后的變化心肌舒張速度(cm/s)纈沙坦(n=186)非RAAS阻斷劑組(n=198)基線7.57.5治療38周后8.1*8.0*心肌舒張速度提高0.66*0.44*每組治療前后比較P 160/90 mmHg

14、 ，研究人員可根據判斷加用利尿劑或其他藥物（不包括鈣離子拮抗劑）FEVER：SBP變化1351 Z SBP (mmHg)隨訪 (月)142.5137.3141.6138.1安慰劑非洛地平SRFEVER：DBP變化1352 Z DBP (mmHg)隨訪 (月)85.082.583.982.3安慰劑非洛地平SR腦卒中(致死性和非致死性)的Kaplan-Meier曲線1356 Z隨訪 (月)HR = 0.732, 95% CI: 0.601-0.891, p = 0.0019 事件患者比例 (%)061218243036424854600246810安慰劑非洛地平-26.8%061218243036

15、4248546003691215所有心血管事件的Kaplan-Meier曲線1356 Z隨訪 (月)HR = 0.726, 95% CI: 0.612-0.860, p = 0.0002安慰劑非洛地平 事件患者比例 (%)-27.4%從2007ESH/ESC高血壓治療指南看FEVER研究的價值Journal of Hypertension 2007, 25:11051187FEVER研究是首個被ESH/ESC指南推舉的中國臨床研究在FEVER研究中，中危高血壓患者在基礎治療（ HCTZ12.5 mg/d ）血壓控制在160/90mmHg以下時，非洛地平與安慰劑組相比，血壓輕度下降(-3.5/-1.5mmHg)，總的心血管終點事件發生率顯著降低達28%FEVER研究結果表明，即使在中度危險的高血壓患者，與SBP降至輕微140mmHg相比，SBP降至140mmHg的保護作用更明顯，這個發現支持當收縮壓為140m