1. Swindon/Bath GP Registrar DRC 16 th Nov 2005 Jan Knobloch

2. Hypertension- ‘modern drugs halve stroke risk’ ASCOT

3. Aims Background BHS guidelines 2004 NICE guidelines 2004 ASCOT 09/2005 Expected changes Critics Summary How to get World Cup tickets?

4. Background 140/85 in non-diabetic, 130/80 in diabetics <10% of hypertensive patients, QOF standard <150/90, prevalence estimated 42% (age 35-64), GPs have prime responsibility Hypertension most important preventable cause of premature death in developed countries (stroke/CHD) ↑mortality with increasing systolic and diastolic blood pressures (syst./diast. BP independent risk factors) Reduction of strokes by 1/3 and coronary events by 1/6 if decrease of diast. BP of 5-6mmHg and syst. BP of 10mmHg Typical list 6 patients with secondary hypertension (mostly primary renal disease, Conn’s syndrome?!) Urindip for prot.+blood, U+E’s, BM/lipids fastened and ECG, assess risk of CVD (BNF) Specialist referral: ie, urgent treatment needed, possible underlying cause, young age, therapeutic problems, hypertension in pregnancy

5. Lifestyle measures Maintain normal weight (BMI 20-25) Salt Intake <100 mmol/day (<6g NaCl) Limit alcohol consumption to < 3u/day for men and < 2u/day for women Regular physical exercise for > 30 mins (at least 3x/week) Five portions/day of fresh fruit and vegetables, more fish Reduce intake of total and saturated fat

6. Tresholds for intervention-BHS guidelines 2004 <130/85: reassess in 5 yrs 130-139/85-89: reassess yrly 140-159/90-99: treat if target organ damage, established CVD or diabetes or 10 yrs CVD risk of > 20%, if not monitor yrly 160-179/100-109: see above, confirm over 3-4 weeks then treat, if not, observe for 4-12 weeks and treat if persists >180/110: unless malignant, confirm over 1-2 weeks then treat >220/120: treat immediately, if malignant admit for immediate treatment

7. BHS guidelines 2004 ie., (A)-Perindopril 2mg/30-£10.95, (B)-Atenolol 50mg/28-£1.02, (C)-Amlodipine 5mg/28-£8.89, (D)-Bendrofluazide 2.5mg/20-74p

8. NICE guidelines 2004 Largely consistent with BHS guidelines, but First line: thiazide-type diuretic (age < 55 β-blocker) Second line: add β-blocker, unless at risk of new-onset diabetes (ACE-I), third line Ca- channel blocker Guidelines based on evidence of cost effectiveness as well as clinical effectiveness

9. ASCOT-BPLA Anglo-Scandinavian Cardiac Outcomes Trial- Blood Pressure Lowering Arm Multi-centre prospective randomized primary prevention trial Effect of amlodipine+/- perindopril (n=9639) vs atenolol+/- BFZ (n=9618) on ‘non-fatal MI and fatal CHD’ in moderate risk hypertensive patients without previous heart disease 19.257 patients (age 40-79) with hypertension > 3 additional risk factors (ie age > 55, male, smoking, type 2 diabetes, prev. stroke) Treatment algorithm (Step 1 amlodipine 5mg, atenolol 50mg), target value <140/90 (130/80 in diabetics) Trial halted early after median 5.5 yrs due to all-cause mortality reduction benefit (11%) Reduction (10%) in primary endpoint not statistically significant but significant for 6 of the 7 secondary endpoints (MI 15%, CVA 23%, also 30% less new onset diabetes)

10. ASCOT-continue Lower BP with amlodipine regimen (throughout the trial of 2.7/1.9 mmHg) could account for results (stroke) But also beneficial effect on bodyweight, serum HDL cholesterol (CHD), triglyerides, creatinine, potassium and fasting blood glucose participants representative of hypertensives seen in daily practice (moderate to high risk) Only 32% of diabetic and 60% non-diabetic achieved BP goals

11. Expected Changes Joint BHS/NICE guidelines (poss. ACE-I+Calcium channel blocker first line, thiazides adjunctive and initial treatment with β-blocker questionable) If well controlled continue current treatment If not controlled on β-blocker+thiazide, add A or C according BHS, then ↓ β-blocker if no CHD Untreated Patient: A(B)CD, B with established CHD Add statin irrespective of baseline cholesterol (10yrs CVD risk 20%, new NICE)

12. Critical comments- ’hyped up?’ Quoted reductions relative, one less cardiovascular death for every 125 patients treated over 5.5 yrs Trial does not reach primary endpoint (failed to answer the question it was set to answer?) Patients with previous MI/angina excluded, but stroke patients enrolled (β-blocker disadvantaged?) 2-3mmHg BP reduction important at population level, but individual level? Similar proportion of patients in both groups had stopped medication due to adverse reactions, chosen agents representative for their group? 78% of patients required two or more, 8% four or more agents by the end of the study Cost effectiveness analysis of ASCOT clearly needed Pfizer as funding source

13. Summary Patients whose blood pressure is well controlled on a β- blocker (with or without diuretics) should continue, for new patients use the BHS ABCD model, but only use β- blocker in patients with established CHD (statin/aspirin?) Offer a tailored regimen to the patients situation Major benefits from BP reduction overall irrespective of which regimen is used ASCOT gives no reason not to start with thiazide diuretic ASCOT adds to what we know, it does not revoke or invalidate everything predating it

14. References Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo- Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial Lancet, 366, Sept.10., 895-906 NICE: Management of hypertension in adults in primary care, clinical guidelines 18, Aug. 2004 British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary BMJ 2004;328:634-40