Preventing Cardiovascular Disease Stroke Primary Prevention Guidelines John Potter Professor Ageing & Stroke Medicine University of East Anglia
Preventing Cardiovascular Disease Stroke Primary Prevention Guidelines People operate with beliefs and biases. To the extent you can eliminate both and replace them with data, you gain a clear advantage. - Michael Lewis, Moneyball: The Art of Winning an Unfair Game Human nature being what it is, we tend to say we are following Guidelines when in reality we re not - Rita Marker
Leading Causes of Death by Age and Cause UK 2013 45-64 years 65-84 years 85+ years All Ages
Deaths/year/ 100,000 Deaths/year/ 100,000 Deaths/year/ 100,000 Deaths/year/ 100,000 UK Deaths from CVD 1950-2010 35-69 Years 70+Years 2010 Deaths Male 29% 43% <2007 74% <1955 2010 Deaths Male 33% 46% <2007 76% <1955 Female 18% 45%<2007 82% <1955 Female 28% 48%<2007 81% <1955 UK Deaths from Stroke 1950-2010 2010 Deaths Male 4% 42% <2007 84% <1955 2010 Deaths Male 7% 44% <2007 82% <1955 Female 4% 44%<2007 87% <1955 Female 8% 44%<2007 83% <1955
http://www.jbs3risk.com/
Incidence 1000 patient years Prevalence 1000 patient years Changes in UK Stroke Incidence & Prevalence Incidence Prevalence Men 2.4% Women 2.2% Lee BMJ 2011
Primary CVD Prevention - GP Research Database BHS 3 QOF JBS2 Lee BMJ 2011
Stroke Primary Prevention The Untreatables - Age, Sex, Ethnicity, low Birthweight, Migraine, Genetic The Unattainables Lifestyle Mods - Obesity, Diet, Exercise, Smoking, Alcohol Medications - Oral contraceptive/hrt, Drugs, Infections - CMV Surgical - Asymptomatic Carotid Stenosis, IC Aneurysm screening
What s new in the Guidelines for Hypertension Management? Criteria for the measurement (Office, Home or Ambulatory) and diagnosis of hypertension What levels to start treatment especially the Old Old and those with TOD New Anti-hypertensive treatment regimens
The evidence that Diagnosis or Treatment changes based on ABPM v Office values improves BP control or Outcomes for Young or Old?
Masked Hypertension? Stage 1 CBP 140-159/90-99 ABPM 135/85 Stage 2 CBP 160-179/100-109 ABPM 150/95 Use Daytime ABPM (or Self BPM over 1 week) for Diagnosis Potential not to treat ABPM levels up to 149/94 mmhg
JBS3/NICE / BHS Threshold & Treatment BP Levels for Hypertension by Different Methods of Measurement Setting Clinic BP (>80 yrs) Aims! Diabetes/Stroke (JBS3 2014) SBP mmhg > 140 (160) 140 and/or DBP mmhg > 90 (100) 90 Target SBP mmhg <140 (<150) 130-135 <140 (130) Target DBP mmhg <90 (<90) 80-85 <90 (80) Home/Self (>80 yrs) Diabetes/Stroke (JBS3 2014) > 135 > 85 <135 (<150) 125 < 85 (<85) 75 Daytime ABPM (>80 yrs) BHS 2004 Diabetes/Stroke (JBS3 2014) > 135 (150) (>130) >85 (95) (>85) <135 (<145) <130 120 <85 (<85) <80 75 24 hour ABPM (JBS32014) Night >125 >120 >80 >75 Values in parenthesis for 80+ age group
First and Second line Treatment changes The Shrinking Alphabet? Removal since 2004 Guidelines Diuretic - Thiazide changed to Non-Thiazide Plus Lifestyle changes NICE - 1 st line agent CCB (not Diuretic) for older HT s as BP variability, Diabetes, Cost effectiveness & better outcome combined with ACEI (Contrast to AHA 2013!)
The important recent changes in Hypertension Management Use of ABPM (SBPM) for Diagnosis of HT Stage 1 - Start drug treatment dependent on CV Risk level (?20% over 10 years) or presence of CVD/Diabetes Stage 2 Start drug treatment Target BP same for those with TOD and no TOD, office BP<140/90 mmhg, 80+ age group <150/90 mmhg Offer 80+age group same treatment as those 55-80 years CCB as 1 st line agent in 55+ age group If Diuretic added use low-dose Thiazide-like e.g. Chlortalidone, Indapamide not Thiazide Single pill combinations preferred
What s new in the Guidelines for Lipid Management? Changes from previous Guidelines? Treat at 20% CV risk. Which lipid fractions best predict risk ie Total Cholesterol & Non-HDL-c (TC HDL-c) v LDL-c v Apo s. What levels to start treatment and benefits, especially the Old Old and those with TOD. What to use and what dose? Treatment Goals Treat to Target, Lower the Better, Give and Forget?
Lipid Management - What do we/others do now? NICE (2014) - Statins for Primary Prevention if 10 year CV risk 10% for those aged 40-74 (85+) years (No target TC/HDL, was<4/2 mmol/l) AHA (2013) - Primary Prevention if 10 year CV risk 7.5% for those aged 40-75 years or LDL-C >4.9 mmol/l LDL-C 4.9 mmol/l 4.9 mmol/l.9 mmol/l High Intensity Statins eg Atorvastatin 80 mg 50% LDL Moderate Intensity Statins eg Atorvastatin 20 mg = 30-50% LDL Target No Recommendations LDL-C 1.8-4.8 mmol/l?
Lipid Management JBS3 (NICE) All 40+ should have lipids checked, no upper age limit set (individualise >75 years, 85 +) Use non-fasting samples for TC & HDL-C (Non-HDL-C will replace LDL-C), treatment benefits from LDL <2mmol/l Lifestyle support Cholesterol lowering drugs (Statins) for: High 10 year risk (NICE to decide level, probably @10% level) High lifetime risk (to include younger people), upper age limit? High risk conditions eg Diabetes, CKD stage 3-5, FH +ve Established CVD Primary Prevention - Atorvastatin 20mg Secondary Prevention - Atorvastatin 80mg?Targets (40% reduction Non-HDL-C or <2.5 mmol/l LDL-C <1.8 mmol/l)
Statins in 1 o Prevention Statins Compared to Control/Placebo: Stroke 22% (NNT for 5 years 155) but small increase in Cerebral Haemorrhage Fatal/Non-Fatal CHD 27% (NNT 88) Total CVD Events 25% (NNT 49) All deaths 14% (NNT 138) Type 2 Diabetes 18% (NNH 99) Other potential benefits - Dementia & MCI (26%) Adverse events overall No difference including Cancer risk
What s new in the Guidelines for Anti-platelet and Anti-coagulant therapy?
Aspirin in Primary Prevention BHS 4 (2004). primary prevention in people with hypertension over the age of 50 years who have a 10-year CVD risk 20% and in whom BP is controlled to the audit standard (A). JBS2 (2005) -. evidence supports daily doses of aspirin in the range of 75 150 mg for the long term prevention of serious vascular events in high risk people.. Benefits - Outcome Odds Ratio (95% CI) 1 0 Prevention Trials (5) All CHD Events 0.72 (0.60 0.87) CHD death 0.87 (0.70 1.09) Total stroke 1.02 (0.85 1.23) All-cause mortality 0.93 (0.84 1.02) Harms Haemorrhagic stroke 1.4 (0.9 2.0) Major gastrointestinal bleeding event 1.7 (1.4 2.1) Outcome Estimated 10-Year Risk for 1000 treated patients CHD Events at Baseline 2% 6% 10% Effect on all-cause mortality No change No change No change CHD events avoided, n 3 (1 4) 8 (4 12) 14 (6 20) Ischaemic strokes avoided, n 0 0 0 Haemorrhagic strokes precipitated, n 1 (0 2) 1 (0 2) 1 (0 2) Major gastrointestinal bleeding events n 3 (2 4) 3 (2 4) 3 (2 4)
Aspirin and Primary Prevention Risks v Benefits Old Studies Prior Stroke/TIA 2000 n = 100,000 F/U 6 years 4000 events Meta-Analysis Odds Ratio Major CV Events 0.87 (0.80-0.93) Major CHD events 0.85 (0.69-1.02) Any Stroke 0.92 (0.83-1.02) Vascular Death 0.96 (0.80-1.14) Any Death 0.93 (0.87-1.00)
Aspirin and Primary Prevention Benefits v Risks Cancers 0-2.9 years 3-4.9 >5 Major Vascular Events 0-2.9 years 3-4.9 >5 Major Extracranial Bleeds 0-2.9 years 3-4.9 >5 GI Bleeding Risk NNH = Number Needed to Harm Odds Ratio Major Bleed 1.6 (1.4-1.8) with low dose Aspirin Men Moderate CV risk Benefit 1-3/1000/yr v 1-2/1000/yr Major Bleeds Benefit of Aspirin v Other Measures? NO Aspirin in Primary Prevention
New Anticoagulants v Warfarin for Event/Risk Factor Stroke/Systemic Embolic events <75 years 75 years Atrial Fibrillation RR (95% CI) 0.81 (0.73-0.91) 0.85 (0.73-0.99) 0.78 (0.68-0.88) Cerebral Infarct (High Dose) 0.92 (0.83-1.02) Cerebral Infarct (Low Dose) 1.28 (1.02-1.6) PICH 0.49 (0.38-0.64) Cranial Bleeding (SAH, PICH, Sub-dural etc) 0.48 (0.39-0.59) All Cause Mortality 0.90 (0.85-0.95) GI Bleed 1.25 (1.01-1.55) Major Bleed (High Dose) 0.86 (0.70-1.00) Ruff Lancet 2014
JBS3 Risk Calculator - 10 Year & Lifetime CV Risk Framingham based Framingham score, JBS2/BHS, New Zealand, Framingham General CV Risk Score Non-Framingham - ASSIGN, Heart Score, QRISK2, UKPDS Risks factors included- Age, Sex, BP, Lipids, Smoking? + FH, Diabetes, Rh Arthritis, LVH, Post Code, Race Only UKPDS suitable for Diabetics Most Risk Calculators only allowed 5-10 year risk assessment Good for Population Risk,? Individual Risk Prediction JBS3 Risk Calculator Intervention Assumptions BP 20mmHg reduction = 50% CVD reduction LDL-c 1 mmol/l reduction = 22% CVD reduction Smoking Weight? effect
JBS3 Risk Calculator - 10 Year & Lifetime CV Risk
JBS2/BHS 26%
Not to be used in TIA patients
Take Home Messages Cardiovascular disease is still a major cause of morbidity and mortality in UK, prevention remains key. Many new and important Guideline based changes in CV management are being introduced. Need for intensive risk factor modification in those at high risk. Hypertension - new initiatives in diagnosis, treatment & targets. Lipids Non-fasting, LDL levels not needed, consider higher strength statins at 10% CV risk in all ages, use statins for 1 0 & 2 0 prevention, target 40% reduction. Aspirin -No for Primary prevention. Oral Anti-Coagulants - new OAC should be routinely considered. CV Risk Calculators - Differ in level of Risk assessment. JBS3 gives 10 year and Lifetime risk level. Potential different risk levels for BP and Lipid drug intervention. Guidelines are for Guidance, not a substitute for informed clinical judgement and pragmatic reasoning.