Vilken evidens finns för att blodtrycksmålet 130/80 mmhg leder till färre komplikationer än systoliskt blodtryck under 140 mmhg vid DM2?

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1 Kardiovaskulära Vårmötet Örebro 2011 Vilken evidens finns för att blodtrycksmålet 130/80 mmhg leder till färre komplikationer än systoliskt blodtryck under 140 mmhg vid DM2? Peter M Nilsson Institutionen för kliniska vetenskaper Akutcentrum Skånes Universitetssjukhus Malmö

2 PRO CON Risk reduction proven for stroke and CVD events Increased costs and side effects Less retinopathy shown in UKPDS Increased CHD risk in susceptible patients? PN 2010

3 Hypertension in type 2 diabetes Lancet 2007 Combined analysis in Diabetes Care 2009

4 Summary of treatment effects in antihypertensive trials Uncomplicated HT SBP (mmhg) Elderly PL SBP (mmhg) BP Benefit Partial benefit Active BP Benefit Partial benefit No benefit SBP (mmhg) OS HDFP AUS MRC FEV Diabetes EW SBP (mmhg) SHEP MRC S. China SCOPE CW STOP S. Eur HYVET JATOS Previous CVD PL Stroke CHD PL Active BP Benefit Partial benefit No benefit Active BP Benefit Partial benefit No benefit HOT UKPDS ADV ABCD IDNT IDNT S. Eur REN SHEP HOPE PROG HT NT IR AM PATS ACC PROG PROF HOPE CAM-AM PREV CAM-EN EU TR ACT PEA Mancia G, et al. J Hypertens 2009

5 ONTARGET T v R: Pre-specified Subgroup Analysis No. of Patients Incidence of Primary Outcome in Ramipril Group Primary Composite Hx of CVD No Hx of CVD SBP < > Diabetes No Diabetes HOPE Risk Score Low Medium High Age < > Male Female Telmisartan better Ramipril better Relative Risk in Telmisartan Group (95% Confidence Interval)

6 Primary outcome CV mortality MI Stroke In-trial SBP (mmhg) In-trial SBP (mmhg) Redon J, et al, 2011

7 ACCORD ADV UKPDS SBP

8 Blood Pressure Trial (42% of ACCORD participants) 4,200 patients of different ethnic background Age-eligible, high-risk people with type 2 diabetes 2,100 to Intensive Group < 120 mmhg SBP (SBP Target < 120 mm Hg) 2,100 to Standard Group < 140 mmhg SBP (SBP Target < 140 mm Hg) Treated and followed for > 4 years (mean 5.5 yrs) MAJOR CVD EVENTS Results were presented during ACC in March 2010

9 Mean # Meds Intensive: Standard: Average : Standard vs Intensive, Delta = 14.2 mmhg Cushman W, et al. N Engl J Med Nilsson PM (Editorial) N Engl J Med 2010

10 Primary and secondary outcomes Intensive Events (%/yr) Standard Events (%/yr) HR (95% CI) P Primary 208 (1.87) 237 (2.09) 0.89 ( ) 0.20 Total Mortality 150 (1.28) 144 (1.19) 1.07 ( ) 0.55 Cardiovascular Deaths 60 (0.52) 58 (0.49) 1.06 ( ) 0.74 Nonfatal MI 126 (1.13) 146 (1.28) 0.87 ( ) 0.25 Nonfatal Stroke 34 (0.30) 55 (0.47) 0.63 ( ) 0.03 Total Stroke 36 (0.32) 62 (0.53) 0.59 ( ) 0.01 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) Cushman W, et al. N Engl J Med 2010

11 Primary Outcome Non-fatal MI, Non-fatal Stroke or CVD Death Total Stroke HR = % CI ( ) P = 0.20 HR = % CI ( ) P = 0.01 NNT for 5 years = 89 Cushman W, et al. N Engl J Med 2010

12 INVEST: Methods Patients with diabetes at baseline grouped according to mean on-treatment SBP Tight Control Usual Control Not Controlled <130 mm Hg 130-<140 mm Hg 140 mm Hg Sep 97- Mar 03 Apr 03- Nov 08 Tight Control INVEST follow up Evaluated time to primary and secondary outcomes according to group Extended follow up (US Cohort) - National Death Index search to evaluate long term effect on mortality Further categorized on-treatment SBP in 5 mm Hg segments to evaluate effect of very low SBP Cooper-DeHoff RM, et al. Tight blood pressure control and cardiovascular outcomes among hypertensive patients with diabetes and coronary artery disease. JAMA 2010 Jul 7;304:61-8.

13 Results: Outcome Rates INVEST Follow Up n=6400 Tight Control n=2,255 Usual Control n=1,970 Not Controlled n=2,175 Outcome # of Events (Event Rate %) p value Primary Outcome 286 (12.7) 249 (12.6) 431 (19.8) < Nonfatal MI 29 (1.3) 33 (1.7) 67 (3.1) Nonfatal Stroke 22 (1.0) 26 (1.3) 52 (2.4) Total MI 108 (4.8) 100 (5.0) 185 (8.5) < Total Stroke 34 (1.5) 33 (1.7) 70 (3.2) All Cause Mortality 248 (11.0) 201 (10.2) 334 (15.4) < Extended Follow Up n=4370 Tight Control n=1,389 Usual Control n=1,423 Not Controlled n=1,558 Outcome # of Events (Event Rate %) p value All Cause Mortality 270 (19.4) 259 (18.2) 370 (23.7) ; 95% CI, ; P = 0.04 (in JAMA 2010)

14 Results: Outcomes Tight Control Group (n=2,255) Reference Other significant variables in Cox regression model: age, race, PAD, MI, CHF, US residency, renal impairment, LVH, TIA/stroke

15 J-curve revisited: an analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT) trial in CAD patients Systolic pressure and primary cardiovascular outcome CI: upper 146 CV: lower 84 Bangalore S et al. Eur Heart J 2010;eurheartj.ehq328

16 Patients on AHT and BP < 130/80 mmhg in the National Diabetes Register of Sweden % Medicinkliniker, debut < 30 år Medicinkliniker, debut 30 år Primärvården ,4 40,6 36, ,3 26,6 27,9 22,6 19,9 21,8 16,4 17,1 41,7 31,8 25,6 44,9 45,4 36,7 39,2 28,7 31,2 49,1 42,

17 SWEDEN: 5-year rates of CHD by SBP across mmhg, fully adjusted in a Cox model based on data from 12,677 DM2 pat with treated HT Each spline represents event rates as a cubic function of SBP. Cederholm J, et al. J Hypertens 2010, October

18 Hazard ratios by tertiles of change in systolic BP from baseline to follow-up Baseline SBP change during Patients / Hazard ratio * P Events SBP mmhg 5 years of follow-up Events (95% CI) value CHD Tertile 1 (decrease) 501 / ( ) Tertiles 2-3 (increase) 1017 / Tertile / ( ) 0.02 Tertiles / >140 Tertile / ( ) <0.001 Tertiles / Stroke Tertile / ( ) 0.3 Tertiles / Tertile / ( ) 0.03 Tertiles / >140 Tertile / ( ) Tertiles / * Fully adjusted Nilsson P, et al. ESH XX Meeting (abstract) Cederholm J, et al. J Hypertens 2010, October

19 Diabetes är associerad med ökad kardiovaskulär risk och en multipel risk faktor kontroll strategi behövs (Steno-2) Blodtryckskontroll kan förebygga mikro- och makrovaskulära komplikationer i varierande grad vid diabetes (HOT, UKPDS, ADVANCE, ACCORD) Ett SBT mål som är well below 140 mmhg rekommenderas av ESH och behandlingsvinster sågs i ADVANCE vid SBT mindre än 135 mmg, men inte under 120 mmhg (ACCORD). Nyttan av BT-sänkning under 130 mmhg gäller bara stroke, men allvarliga biverkningar ökar Denna strategi stöds av observationella data (ONTARGET, INVEST, TNT, NDR-BP) PN 2011