钙拮抗剂降压治疗地位进展

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1、钙拮抗剂降压治疗地位进展钙拮抗剂降压治疗地位进展 从循证证据和国际治疗指南的角度从循证证据和国际治疗指南的角度影响不同种类降压药物治疗地位的决定因素影响不同种类降压药物治疗地位的决定因素 禁忌症禁忌症 循证医学证据循证医学证据 不良反应和治疗持续性不良反应和治疗持续性 效益效益/ /费用费用 种族种族各类降压药物的禁忌症各类降压药物的禁忌症(ESC/ESH,2007)(ESC/ESH,2007) 噻嗪类利尿剂 痛风 代谢综合症、糖耐量减低 妊娠-阻滞剂 哮喘、 外周血管病、代谢综合症 糖耐量异常、慢阻肺 A-V阻滞(2或3度) 运动员和强体力活动者 二氢吡啶类CCB 快速性心律失常、心力衰竭

2、非二氢吡啶类CCB A-V阻滞(2或3度) 心力衰竭 ACEI和ARB 妊娠、高血钾症 双侧肾动脉狭窄醛固酮拮抗剂 肾功能衰竭 高血钾症 绝对(强制) 相对(可能) SBP SBP differencedifference betweenbetween randomizedrandomized groupsgroups ( (mmHgmmHg) )Relative Relative riskrisk of of outcomeoutcome eventevent1.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.0

3、01.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.251.501.501.251.251.001.000.750.750.500.500.250.25StrokeStrokeMajor CVDMajor CVDCHDCHDCVD CVD deathdeathTotal Total mortalitymortality-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6

4、-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02 24 4-10-10-8-8-6-6-4-4-2-20 02 24 4BP-Lowering Treatment Trialists (WHO/ISH, 2003)Blood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.0.51.02.0Relative Risk RR (95% CI)RR (95% CI)BP Differe

5、nceBP Difference(mm Hg)(mm Hg)FavorsFavorsFirst ListedFirst ListedFavorsFavorsSecond ListedSecond ListedMajor CV eventsMajor CV eventsCV mortalityCV mortalityTotal mortalityTotal mortality 1.02 (0.98, 1.07) 1.02 (0.98, 1.07)2/02/0 ACEI vs D/BB ACEI vs D/BB 1.03 (0.95, 1.11) 1.03 (0.95, 1.11)2/02/0 A

6、CEI vs D/BB ACEI vs D/BB 1.00 (0.95, 1.05) 1.00 (0.95, 1.05)2/02/0 ACEI vs D/BB ACEI vs D/BB 1.04 (0.99, 1.08) 1.04 (0.99, 1.08)1/01/0 CA vs D/BB CA vs D/BB 1.05 (0.97, 1.13) 1.05 (0.97, 1.13)1/01/0 CA vs D/BB CA vs D/BB 0.99 (0.95, 1.04) 0.99 (0.95, 1.04)1/01/0 CA vs D/BB CA vs D/BB 0.97 (0.92, 1.0

7、3) 0.97 (0.92, 1.03)1/11/1 ACEI vs CA ACEI vs CA 1.03 (0.94, 1.13) 1.03 (0.94, 1.13)1/11/1 ACEI vs CA ACEI vs CA 1.04 (0.98, 1.10) 1.04 (0.98, 1.10)1/11/1 ACEI vs CA ACEI vs CABlood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.BP-Lowering Treatment TrialistsCompari

8、sons of Different Active Treatments RR (95% CI) Favours first listed Favours second listed0.51.02.0Relative RiskBP difference(mm Hg) 1.09 (1.00,1.18) ACEI vs. D/BB 0.93 (0.86,1.01) CA vs. D/BB 1.12 (1.01,1.25) ACEI vs. CA2/01/01/1BPLTT (2003): StrokeComparisons of different active treatmentsBlood Pr

9、essure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.0.40.40.60.60.80.81.01.01.21.21.41.40.20.21.81.82.02.0151510105 5-5-5Odds ratio for CHDACE IsALLHATALLHATACEIACEIUKPDS39UKPDS39EUROPAEUROPAPROGRESSPROGRESSPROGRESSComPROGRESSComCAMELOTCAMELOTHOPEHOPEPEACEPEACECAPPPCAPPPSTO

10、P-2STOP-2ACEIACEIANBP-2ANBP-2Systolic BP difference between groups (mmHg) Verdecchia et al 20050 0NICSNICSALLHATALLHATCCBCCBPREVENTPREVENTIDNT-2IDNT-2CONVINCECONVINCEVHASVHASSystSyst-China-ChinaSYSTEURSYSTEURCAMELOTCAMELOTSTONESTONENICOLENICOLEACTIONACTIONNORDILNORDILINVESTINVESTSTOP-2STOP-2CCBCCBIN

11、SIGHTINSIGHT151510105 50 0-5-5CCBsELSAELSARelationship Between Odds Ratio for CHD and Achieved BP DifferencesCCBs and CV OutcomesNew Meta-Analysis (ACC, 2009)在在BPLTT的基础上，纳入了的基础上，纳入了2003年以后发表的年以后发表的临床试验：临床试验：ACTION, ASCOT-BPLA, CAMELOT, CASE-J, FEVER, INVEST, MOSES, HICOLE, VESPACCBs and CV OutcomesN

12、ew Meta-Analysis (ACC, 2009)CCB vs. ACEI OR ( 95% CI )Stroke 0.87 (0.78-0.97)MI 1.06 (0.98-1.18)无强制指征无强制指征Stage 1 HypertensionThiazide-type diuretics for most. May consider ACEI, ARB, BB,CCB, or combination.Stage 2 Hypertension2-drug combination for most ( thiazide-type diuretic and ACEI, or ARB, or

13、 BB, or CCB)JNC-7：降压治疗流程：降压治疗流程JNC Recommendations for an Initial Antihypertensive AgentCommittee Year RecommendationJNC 1 1977 Thiazide-type diureticJNC 2 1980 DiureticJNC 3 1984 Thiazide-type diuretic or BBJNC 4 1988 Diuretic or BB or CCB or ACEIJNC 5 1993 Diuretic or BBJNC 6 1997 Diuretic or BBJN

14、C 7 2003 Thiazide-type diuretic, either alone or in combination with ACEI.ARB,BB,or CCB 各类降压各类降压药物药物治疗高血压的地位治疗高血压的地位从JNC-6(1997)到JNC-7(2003) 利尿剂 -阻滞剂 ACEI CCB ARB -阻滞剂用于起动和持续治疗的合适降压药物(ESC/ESH, 2007) 利尿剂-阻滞剂钙拮抗剂ACE抑制剂血管紧张素II受体拮抗剂降压治疗选择降压治疗选择降压治疗选择降压治疗选择单药低剂量治疗单药低剂量治疗单药低剂量治疗单药低剂量治疗两药低剂量联合治疗两药低剂量联合治疗轻度

15、血压升高轻度血压升高轻度血压升高轻度血压升高低低低低/ /中度心血管危险中度心血管危险中度心血管危险中度心血管危险传统目标血压传统目标血压传统目标血压传统目标血压显著血压升高显著血压升高显著血压升高显著血压升高高高高高/ /很高心血管危险很高心血管危险很高心血管危险很高心血管危险更低的目标血压更低的目标血压更低的目标血压更低的目标血压如果没有达到如果没有达到如果没有达到如果没有达到目标血压目标血压目标血压目标血压先前的药物全先前的药物全先前的药物全先前的药物全剂量剂量剂量剂量转换低剂量的转换低剂量的转换低剂量的转换低剂量的不同药物不同药物不同药物不同药物先前联合药物先前联合药物先前联合药物先前

16、联合药物全剂量全剂量全剂量全剂量增加低剂量的增加低剂量的增加低剂量的增加低剂量的第第第第3 3个药物个药物个药物个药物如果没有达到如果没有达到如果没有达到如果没有达到目标血压目标血压目标血压目标血压全剂量的全剂量的全剂量的全剂量的2-32-3个个个个药物联合治疗药物联合治疗药物联合治疗药物联合治疗全剂量的全剂量的全剂量的全剂量的单药治疗单药治疗单药治疗单药治疗全剂量的全剂量的全剂量的全剂量的2-32-3个个个个药物联合治疗药物联合治疗药物联合治疗药物联合治疗2007ESH/ESC2007ESH/ESC指南推荐的降压治疗模式指南推荐的降压治疗模式b b-blockersAngiotensin r

17、eceptorantagonistsThiazide diureticsCalcium antagonistsACE inhibitors-blockers欧洲高血压治疗指南欧洲高血压治疗指南(ESC/ESH,2007)(ESC/ESH,2007)合理的降压联合治疗方案合理的降压联合治疗方案Younger (55yr)Younger (55yr)Older (55yr)or Blackor BlackA: ACE Inhibitor or Angiotensin Receptor Blocker B: b b-BlockerC: Calcium Channel Blocker D: Diure

18、tic (Thiazide)Step 1Step 1A (or B*)A (or B*)C or DC or DStep 3Step 3+ + +A (or B*)A (or B*)C CD DStep 4 Step 4 Resistant HTResistant HTAdd: either Add: either a a a a- blocker or - blocker or spironolactonespironolactone or other diuretic or other diureticStep 2Step 2+ +A (or B*)A (or B*)C or DC or

19、D* combination therapy involving B & D may induce more diabetes compared with other combination therapies* combination therapy involving B & D may induce more diabetes compared with other combination therapiesBHS IV (2001) Recommendations for Blood Pressure Lowering DrugsYounger (55yr)Younger (55yr)

20、 orOlder (55yr) or Black at any Age Black at any AgeA: ACE Inhibitor or A: ACE Inhibitor or AngiotensinAngiotensin Receptor Blocker Receptor Blocker B: B: b b b b-Blocker-BlockerC: Calcium Channel BlockerC: Calcium Channel Blocker D: Diuretic ( D: Diuretic (ThiazideThiazide) )Step 1Step 1A A C or DC

21、 or DStep 2Step 2+ +A AC or DC or DStep 3Step 3+ + +A AC CD DStep 4 Step 4 Resistant HTResistant HTAdd: either Add: either a a a a- blocker or - blocker or b b b b- blocker- blocker or or spironolactonespironolactone or other diuretic or other diureticNICE / BHS (2006)Management of Hypertension Youn

22、ger (55yr)Younger (55yr) orOlder (55yr) or Black at any Age Black at any AgeA: ACE Inhibitor or A: ACE Inhibitor or AngiotensinAngiotensin Receptor Blocker Receptor Blocker B: B: b b b b-Blocker-BlockerC: Calcium Channel BlockerC: Calcium Channel Blocker D: Diuretic ( D: Diuretic (ThiazideThiazide)

23、)Step 1Step 1A A C or DC or DStep 2Step 2+ +A AC or DC or DStep 3Step 3+ + +A AC CD DStep 4 Step 4 Resistant HTResistant HTAdd: either Add: either a a a a- blocker or - blocker or b b b b- blocker - blocker or or spironolactonespironolactone or other diuretic or other diureticIn hypertensive patient

24、s aged 55 or over, or Black patients of any age, first-choice initial therapy should be a dihydropyridine calcium channel blocker; a thiazide-type diuretic is an alternative.NICE / BHS (2006)Management of HypertensionJapanese Guidelines for the Management of Hypertension(JSH, 2004 and 2009) 对对大多数高血压患者，推荐钙拮抗大多数高血压患者，推荐钙拮抗剂作为初始治疗或联合治疗的药物，除了剂作为初始治疗或联合治疗的药物，除了禁忌症和不能耐受治疗的患者。禁忌症和不能耐受治疗的患者。心血管病预防指南心血管病预防指南(WHO/ISH,2007)(WHO/ISH,2007)降压药物的选择降压药物的选择 选择低剂量利尿剂、血管紧张素转换选择低剂量利尿剂、血管紧张素转换酶抑制剂或钙拮抗剂作为降压治疗的初酶抑制剂或钙拮抗剂作为降压治疗的初始治疗药物。始治疗药物。 -阻滞剂在强适应症时可作为一线治阻滞剂在强适应症时可作为一线治疗药物使用。疗药物使用。 限制使用血管紧张素受体拮抗剂。限制使用血管紧张素受体拮抗剂。