towards an evidence based treatment strategy in hypertension课件

Towards an Evidence Based Treatment Strategy in Hypertension,Tony Woolley M.D. Park Nicollet Clinic Clinical Associate Professor of Medicine, University of Minnesota W,My First Lesson In Hypertension,CIRCA 1980, first Internal Med clinical rotation Begin Treatment if BP140/90 Start thiazide diuretic, 50mg qd,Towards an Evidence Based Treatment Strategy in Hypertension,What should our goal BP be, especially for special populations ( Diabetes, Renal disease, Coronary disease, other high risk populations)? What medication strategies are best supported by evidence, especially for special populations? How does the gap between clinical practice and clinical evidence grow? ( Analysis of Bias),Evidence Based Practice Major Principles,Hierarchy of Evidence Level 1 evidence= Systematic Reviews or Meta-analysis of RCTs or Single high quality RCTs (like ALLHAT or ACCORD) Tempered by Clinical Judgment and Patient Preferences,Evidence Hierarchy,More of This,And less of This,Towards an Evidence Based Treatment Strategy in Hypertension,What should our goal BP be, especially for special populations ( Diabetes, Renal disease, Coronary disease, other high risk populations)?,Current Recommendations for BP Goals,JNC 7 (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood) Pressure Goal BP 140/90 Goal with Diabetes or CKD 130/80 JNC 8 Expected Mid 2011,Hypertension. 2003;42:1206,Current Recommendations for BP Goals,JNC VII 10% ADA DM 130/80 WHO/ISH 140/90, in DM, CVD or CKD 130/80 “seems appropriate” N/DOQI 2004 CKD 130/80 BHS 140/90, 130/80 DM,CVD or CKD ESH-ESC “at least” 130/80 DM, CVD or CKD,Hypertension in Diabetes,Guidelines say: Treat to 130/80 ADA Recommends ACE/ARB first,Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial,NHLBI 10,251 Type 2 diabetics Three Trial arms Glycemic control BP 120 Lipids: Fibrate added to Statin BP arm 4,773 randomized to SBP120 or 140, March 14, 2010,Average after 1st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2,Mean # Meds Intensive: 3.2 3.4 3.5 3.4 Standard: 1.9 2.1 2.2 2.3,Primary & Secondary Outcomes,Also examined Fatal/Nonfatal HF (HR=0.94, p=0.67), a composite of fatal coronary events, nonfatal MI and unstable angina (HR=0.94, p=0.50) and a composite of the primary outcome, revascularization and unstable angina (HR=0.95, p=0.40),Primary Outcome Nonfatal MI, Nonfatal Stroke or CVD Death,Total Stroke,HR = 0.88 95% CI (0.73-1.06),HR = 0.59 95% CI (0.39-0.89) NNT for 5 years = 89,Adverse Events, Symptom experienced over past 30 days from HRQL sample of N=969 participants assessed at 12, 36, and 48 months post-randomization,The ACCORD BP trial evaluated the effect of targeting a SBP goal of 120 mm Hg, compared to a goal of 140 mm Hg, in patients with type 2 diabetes The results provide no conclusive evidence that the intensive BP control strategy reduces the rate of a composite of major CVD events in such patients.,INVEST Study,International Verapamil-Trandolapril Study Diabetic Subgroup 6400, all with CAD Achieved SBP 130, 130-139, 140+,JAMA July 7,2010;304(1)61-68,Hypertension in Diabetes,Guidelines say: Treat to 130/80 Evidence says: No renal or cardiovascular benefit with lower BP ACE/ARB therapy do improve renal outcomes in patients with proteinuria including microalbuminuria New ICSI guideline: 140/85 (consider 130/80 in patients with proteinuria),Hypertension in Coronary Artery Disease and “High Risk” Groups,AHA/ACC Guidelines say: Treat to 10% Evidence Level 5 (Expert Opinion),Framingham Risk Calculation, Ex.,Age: 65 Gender: male Total Cholesterol: 200 mg/dL HDL Cholesterol: 40 mg/dL Smoker: No Systolic Blood Pressure: 140 mm/Hg On medication for HBP: Yes Risk Score* 19% * The risk score shown was derived on the basis of an equation. Other NCEP materials, such as ATP III print products, use a point-based system to calculate a risk score that approximates the equation-based one. ATP III Executive Summary and ATP III At-a-Glance.,Hypertension in Coronary Artery Disease and “High Risk” Groups,No Intent to Treat RCT addresses this Lower Achieved BP has been associated with no benefit or worsened outcomes in post hoc analysis of trials INVEST DM and CAD ONTARGET Vascular disease or DM NEJM 358:1547-1559 I-PRESERVE Diastolic CHF,JAMA July 7,2010;304(1)61-68,NEJM 358:1547-1559,N Engl J Med 2008;359:245667,Hypertension in Coronary Artery Disease and “High Risk” Groups,AHA/ACC Guidelines say: Treat to 10% Evidence says: No renal or cardiovascular benefit demonstrated in this overall group 2010 ICSI guideline: 140/90,Hypertension in the Elderly,JNC7 and other Guidelines say: Treat to 140/90 High Risk Conditions: Treat to 130/80,Hypertension in the Elderly Meta-analysis RCTs in Patients 60 years,15 trials n=24,055 Frail elderly excluded from trials Results similar for isolated systolic and BP trials No trials have recruited patients with Isolated Systolic Hypertension and SBP160 Total CV Morbidity reduced RR .68, ARR 4.3% NNT 23 Total Mortality reduced RR .90 ARR 1.2% Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub2.,Issues in Treatment of the Very Elderly (80),Epidemiologic population studies show better survival with higher BP STOP-2 Worse survival in treated hypertensives with SBP140,Oates et al.Journal of the American Geriatrics Society Volume 55, Issue 3, pages 383388, March 2007,Hypertension in the Elderly Metaanalysis RCTs in Patients 80 years,9 trials n=6,798 Frail elderly excluded from trials Achieved SBP 143-148 Stroke benefit: RR .67 ARR 4% NNT 25 Total Mortality: No benefit RR .97 Citation: Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub2.,HYVET,Only HTN RCT in Patients 80 years N=3850 mean age 83 mean SBP 173 Goal SBP150, mean achieved SBP =143 Placebo vs perendipril/indapamide 18 month BP separation -15/6 mmHg,HYVET Results,Hypertension in the Elderly,JNC7 and other Guidelines say: Treat to 140/90 High Risk Conditions: Treat to 130/80 Evidence Suggests: Initiate Treatment at 160 with SBP goal,Hypertension in CKD,Guidelines say: Treat to 130/80 ACE or ARB preferred in patients with proteinuria,Hypertension in CKD,Relevant clinical trials MDRD 1994 N=884 pt with GFR 13-55 RCT MAP3g/24h proteinuria had renal outcome benefit,Hypertension in CKD,Relevant clinical trials: AASK 2002 RCT 1094 African American patients with hypertensive nephropathy assigned to MAP93 vs 102-107 Achieved BP 130/78 vs 141/86 4 year result no benefit 10 year Cohort followup: No benefit overall Protenuric subgroup 27% reduction in doubling of GFR at 10 years,Hypertension in CKD,Guidelines say: Treat to 300mg/dl) New ICSI guideline: 140/90, consider 130/80 in patients with proteinuria,Evidence Based Goals,140/90 for almost everybody Perhaps 130/80 in patients with proteinuric renal disease at risk for ESRD Perhaps a bit higher (150 systolic) in older patients with isolated systolic HTN,The gap between what we know and what we think we know or How Do We Get It so Wrong?,Theraputic Optimism The bias that the benefit of treatment exceeds the risk/harm Authority Bias Overvaluing the opinions of experts Influence of Industry More treatment/diagnosis is usually good for business, and sponsorship of research and education tends to support more rather than less treatment,The gap between what we know and what we think we know,Confirmation Bias We are much more likely to seek information that confirms rather than refutes what we believe to be true Forgetting the asymmetry of epidemiology and treatment In many (?most) instances, correcting a causal risk factor does not fully resolve associated risk,Evidence Hierarchy,More of This,And less of This,My Latest Lesson In Hypertension,CIRCA 2010 Begin Treatment if BP140/90 Start thiazide , Break it in half,Selected References,ICSI Hypertension Guideline 2010 revision /guidelines_and_more/. Treatment Blood Pressure Targets for Hypertension: Cochrane Review 2009 /o/cochrane/clsysrev/articles/CD004349/frame. html ACCORD BP Study, March 14 2010 The Effects of Intensive Blood Pressire Control in Type 2 Diabetes Mellitus /doi/pdf/10.1056/NEJMoa1001286 INVEST Diabetes Subgroup Tight Blood Pressure Control and Cardiovascular Outcomes Among Hypertensive Patients with Diabetes and Coronary Artery Disease JAMA, Vol 304, 1, 61-67,Selected References,Hypertension in the Very Elderly Trial (HYVET) 2008 N Engl J Med 2008; 358(18):1887-98. Pharmacotherapy of Hypertension in the Elderly: Cochrane Review 2010 /o/cochrane/clsysrev/articles/CD000028/frame. html AASK 10 year follow up 2010 Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease N Engl J Med 2010; 363:918-929 First Line Drugs for Hypertension: Cochrane Review 2009 /o/cochrane/clsysrev/articles/CD001841/frame. html,Additional Slides, Treatment,These will not be discussed in the presentation,Drug Rx for HTN,Where is the evidence pointing us?,Drug Rx for HTN,JNC 7 Thiazides for most Other First line drugs ACE/ARB Beta Blockers CCB,Cochrane Review, Drugs for HTN,57 trials, n=58,040 Conclusion: Low dose thiazides reduce all morbidity and mortality outcomes. ACEI and Calcium blockers may be similarly effective but the evidence is less robust. Beta blockers and high dose thiazides are inferior to low dose thiazides,Cochrane Review, Drugs for HTN,The Cochrane Library 2009, issue 3. http/,Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group,Chlorthalidone Amlodipine Lisinopril,Nonfatal MI + CHD Death Subgroup Comparisons RR (95% CI),Beta blockers: What Happened to My Atenolol?,Meta-analysis of trials comparing beta blockers with other antihypertensives Outcome RR w/beta blockers 95% CI Stroke 1.16 1.04-1.30 MI 1.020 .93-1.12 All-cause mort. 1.030 .99-1.08,Lindholm LH, Carlberg B, and Samuelsson O. Should blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366(9496):1545-1553,Atenolol vs other antihypertensives,Lindholm LH, Carlberg B, and Samuelsson O. Should blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet 2005; 366(9496):1545-1553,Beta Blockers Are Now 3rd Line Therapy,After diuretic, ACE/ARB, CCB Benefit in clinical trials demonstrated mainly in combination therapy Appear less effective than other classes at preventing stroke Are less effective in older patients Monotherapy mainly in patients with compelling indications (like angina, post-MI, tachyarrhythmias),The Big 3 Concept,Thiazides, ACEI and CCBs All appear about equally effective Work well together,Diuretics in HTN,Thiazides are most effective; optimal dose 6.25-25mg Metolazone can be used if Cr CL30 Spironolactone works well for many who dont tolerate thiazide Loop diuretics (except torsemide) need to be given twice a day,ACE Inhibitors/ARBs: Special Roles,In a broad range of patients ACE/ARBs appear to contribute to improved endpoints beyond antihypertensive effects LV Systolic Dysfunction (CHF) Diabetes with microalbuminuria Proteinuric renal ? Post MI Not in diastolic CHF, diabetes without proteinuria or non-proteinuric renal disease.,ACEI/ARBs: One or the other, not both The ONTARGET Study,RCCT N=17,118 high risk patients with DM or vascular disease Ramipril, Telmisartan or both for 56 months No additional benefit in combined vascular events Combination therapy caused higher rate of adverse events (hypotensive symptoms (4.8% vs. 1.7%, P0.001), syncope (0.3% vs. 0.2%, P=0.03), and renal dysfunction (13.5% vs. 10.2%, P0.001) Similar findings in CHF trials,NEJMVolume 358:1547-1559, April 10, 2008,Dihydropyridine CCBs: The Swiss Army Knife of BP meds,No contraindicating medical conditions (CHF, diabetes, CKD, arrhythmias etc) Effective in all age and ethnicity groups Good dose response curve Can be used with any other drug class, including non-dihydropyridine CCBs,Dihydropyridine CCBs: Clinical Trials,Equivalent to Thiazide and ACE in ALLHAT (including 15,297 diabetics) Outperformed thiazide in combination with ACE (ACCOMPLISH) Superior to ACE in African Americans (ALLHAT) Superior to ACE in pts with CAD (CAMELOT) Highly effective in elderly isolated systolic HTN, including 76% reduction in CV mortality in diabetic subgroup (Syst-Eur),JAMA. 2004;292(18):2217-2222 NEJM 2008 359:2417-2428 JAMA. 2002;288:2981-2997 NEJM. 1999;340:677-684,Dihydropyridine CCBs: The Swiss Army Knife of BP meds,Amlodipine 2.5-20 mg qd Felodipine 2.5-20 mg qd Isradipine 5-20 mg qd Nicardipine SR 30-120 mg qd Nifedipine ER 30-120 mg qd Nisoldipine 20-60 mg qd,A Modest Proposal: 3 Drug