Behandling af hypertension IRF 31-01-08 Tage Lysbo Svendsen Ledende overlæge dr.med Holbæk Sygehus Formand for Dansk Hypertensionsselskab

Definitions and Classification of Blood Pressure Levels (mmHg) 85-89 and/or 130-139 High Normal 80-84 120-129 Normal <80 and <120 Optimal Diastolic Systolic Category 90-99 and/or 140-159 Grade 1 Hypertension 100-109 and/or 160-179 Grade 2 Hypertension Grade 3 Hypertension ≥180 and/or ≥110 <90 and ≥140 Isolated Systolic Hypertension

Stratification of CV risk in four categories Blood pressure (mmHg) Other risk factors, OD or disease Normal SBP 120-129 or DBP 80-84 High normal SBP 130-139 or DBP 85-89 Grade 1 HT SBP 140-159 or DBP 90-99 Grade 2 HT SBP 160-179 or DBP 100-109 Grade 3 HT SBP ≥180 or DBP ≥110 No other risk factors Average risk Low added risk Moderate added risk High added risk 1-2 risk factors Very high added risk 3 or more risk factors, MS, OD or diabetes Established CV or renal disease SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

Non farmakologisk behandling Motion Saltrestriktion Afmagring ved overvægt Reduktion af alkoholindtagelse DASH diet

Farmakologisk behandling Diuretika Betablokkere Calciumantagonist ACE/AII-antagonister Reninantagonister Alfa-blokkere Centralt virkende antihypertesiva Aldosteronantagonister

Betablokkere Beta1selektive(atenolol,metoprolol) Non- selektive(Propranolol) Alfa-betablokkere(carvedilol, labetalol) Uspecifik vasodilaterende (nebivolol)

Reduction in the Risk of Stroke1 8 Fatal and nonfatal stroke 7 Atenolol 6 5 Losartan 4 Proportion of patients with first event (%) 3 2 Slide 16: Reduction in the Risk of Stroke1 This graph shows the Kaplan-Meier curves for the individual endpoint of fatal and nonfatal stroke. The losartan and atenolol curves separated early in the study. The outcome was in favor of losartan, with a 24.9% reduction in relative risk of stroke compared with atenolol. The risk reduction was significant (p = 0.001).No significant differences in CV death (11.4%, p = 0.206) and MI (-7.3%, p = 0.491) vs. atenolol were observed. Reference: 1. Dalhöf B, Devereux RB, Kjeldsen SE et al, for the LIFE study group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): A randomised trial against atenolol. Lancet 2002;359: 995-1003. Adjusted risk reduction 24.9%, p = 0.0010 Unadjusted risk reduction 25.8%, p = 0.0006 1 6 12 18 24 30 36 42 48 54 60 66 Time (months) Number at risk Losartan (n) 4605 4528 4469 4408 4332 4273 4224 4166 4117 3974 1928 925 Atenolol (n) 4588 4490 4424 4372 4317 4245 4180 4119 4055 3894 1901 897 No significant difference in CV death and MI vs. atenolol. Risk reduction = relative risk vs. atenolol. 7 1. Dahlöf B et al. Lancet 2002;359:995-1003.

Ascot Atenolol (+diuretica) versus Amlodipin (+ace) 19. 257 pt. Signifikant reduktion i Apopleksi,Kardiovaskulærmortalitet,AMI på 11-24%

Thiazider Thiazider er lige så effektive til at sænke blodtrykket og til at reducere morbiditet og mortalitet som ACE-hæmmmere, A-II-antagonister, calciumantagonister og betablokkkere. I de doser der anvendes i dag er bivirkningsfrekvensen lav.

Calciumantagonister Dihydropyridin derivater (amlodipin, nifedipin og mf) Non – dihyropyridin (verapamil og diltiazem)

ACE/AII-antagonister ACE (Ramipril,enalpril,perindopril lisinopril og mf) AII-antag.(Losartan,irbesartan, candersartan og mf) Reninantagonister

Andre antihypertensiva Alfa- blokker (Prazosin,doxazosin terazosin) Centralt virkende (methyldopa,moxonidin)

Den ukomplicerede hypertensions patient Calciumantagonist f.eks amlodipin To stof behandling: 1)Ace- inhibitor f.eks enalpril, Tre stof behandling:Tiazid (eller ACE eller Beta blokker)

Possible combinations between some classes of antihypertensive drugs Thiazide diuretics β-blockers Angiotensin receptor antagonists α- blockers Calcium antagonists ACE inhibitors The preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials

Diabetes Mellitus AMI Hjerteinsufficiens Nyresygdom Angina Apopleksi Ace-inhib/a-II antag. Betablokker Ace- Inhib/ betablok Ace-inhib Betablok /calciumanta Ace-inh./A-II-anta

Antal patienter i monoterapi

Antal pt.i to-stof behandling

Antal pt. i tre-stof behandling

Pris fire-stof kombinationsbehandling Thiazid Centyl c Kcl 1,44 kr Betablok Atenolol mg100 0,71 kr Calciumanta. Amlodipin 10mg 0,63 kr Ace inhib. Enalpril mg 20 0,71 kr Fire-stof kombin. 3,49 kr

Pris fire-stof kombinationsbehandling Thiazid Centyl c Kcl 1,44 kr Beta Bisoprolol mg 10 3.15 kr Calciumant Myonil mg 240 10,70 kr Coversyl mg 8 6,40 kr A-II antag irbesartan 300mg 11,41 kr Fires-tof kombinationsbeh. 33,10 kr

Mest anvendte behandling 2006 Monoterapi Diureticum 104261 To-stof beh. Ace/AII+Diur. 115516 Tre.stofbeh Cal+ACE+D 49563

Sundhedsstyrelsen 2001 2004 2006 Alle patienter 508 163 628 982 716 326 41,0% Pt på 2 stof behandling 233 877 336 382 407460 74,2 % Pt på 3 stof behandling 57 307 106 728 144 277 151,7%