Update on CVD. Dr Youssef Beaini

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Update on CVD Dr Youssef Beaini Clinical Lead Cardiovascular Disease for Bradford Districts CCG, Bradford City CCG and Airedale, Wharfedale and

1 Update on CVD Dr Youssef Beaini Clinical Lead Cardiovascular Disease for Bradford Districts CCG, Bradford City CCG and Airedale, Wharfedale and Craven CCG CVD advisor to the Yorkshire and Humber Strategic Clinical Network GPwSI Cardiology GP Partner at The Ridge Medical Practice, Bradford

2 We will cover New NICE guidance in AF New NICE guidance in lipid management Know your numbers: BP and lipids Power of lifestyle interventions Acute coronary syndromes Post cardiac rehab care

3 Atrial Fibrillation

5 Prevalence AF by practice 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% B83014 B83700 B83604 B83062 B83045 B83009 B83659 B83069 B83039 B83010 B83030 B83002 B83641 B83032 B83029 B83653 B83019 B83026 B83647 B83034 B83033 B83055 B83627 B83660 B83043 B83614 B83661 B83015 B83044 B83006 B83049 B83054 B83626 Y01118 B83056 B83052 B83040 B83613 B83031 B83658 B83631

6 Expected Prevalence AF by practice 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 3.5% B83014 B83700 B83604 B83062 B83045 B83009 B83659 B83069 B83039 B83010 B83030 B83002 B83641 B83032 B83029 B83653 B83019 B83026 B83647 B83034 B83033 B83055 B83627 B83660 B83043 B83614 B83661 B83015 B83044 B83006 B83049 B83054 B83626 Y01118 B83056 B83052 B83040 B83613 B83031 B83658 B83631

7 ESC advice on screening

8 AF screening NICE DON T advocate national screening program DO advocate opportunistic screening in anyone with : Breathlessness Palpitations Syncope/dizziness Chest discomfort Stroke/TIA This is being debated in the UK further

9 PAF vs AF (paroxysmal vs permanent AF)

10 Annual risk of stroke (%) The risk of stroke with paroxysmal AF is comparable to that with permanent AF 1,2 Observed rate of ischaemic stroke 1 14 Intermittent AF Sustained AF 0 Low Moderate High Stroke risk category 1. Hart RG et al. J Am Coll Cardiol 2000;35:183 7; 2. Flaker GC et al. Am Heart J 2005;149:657 63

11 Effectiveness of warfarin vs aspirin

12 Warfarin better Placebo better AFASAK SPAF BAATAF CAFA SPINAF EAFT All trials RRR 64% *, ARR 2.7% (95% CI: 49 74%) RRR (%) Random effects model; Error bars = 95% CI; * p>0.2 for homogeneity; Relative risk reduction (RRR) for all strokes (ischaemic and haemorrhagic) 100 Compared to a 19% RRR, 0.7% ARR for aspirin Hart RG et al. Ann Intern Med 2007;146:

13 Summary of NICE AF guidance Use new CHADSVASc scoring system to assess anticoagulation (instead of CHADS2 score) Use HASBLED scoring system to assess for bleeding risk For CHADSVASc = 0, no anticoagulation required For CHADSVASc 1, anticoagulant (warfarin or NOAC) NO ASPIRIN for AF (aspirin still good for IHD/MI/PAD. Clopidogrel is used for stroke now rather than aspirin)

14 Atrial Fibrillation Stratification of stroke risk: CHADS 2 score Score CHF or LV dysfunction 1 Hypertension 1 Age >75 years 1 Diabetes 1 Stroke/TIA Adjusted Stroke Rate (per 100 pt years) CHADS 2 score Gage BF et al. JAMA 2001;285:

15 CHA 2 DS 2 VASc Discussed C 1 H A 1-2 DS Vascular, +1 Female over 65

16 CHA 2 DS 2 VASc Congestive heart failure/left ventricular systolic dysfunction Score 1 Hypertension 1 Age 75 2 Diabetes 1 Stroke / TIA 2 Vascular disease 1 Age Sex (female) 1 Lip G et al. Chest 2010; 137 (2):

17 CHA 2 DS 2 VASc Score Percent AF population Adjusted risk of clots

18 C statistics based on Cox regression models in a large real world cohort with long-term follow up based on categorisation of patients into risk groups 1 year 5 year 10 year CHADS CHA 2 DS 2 VASc C statistic >8 is very good Confidence intervals did not overlap between CHADS 2 and CHA 2 DS 2 VASc Olesen J et al. BMJ 2011;342:d124

19 HASBLED Score Hypertension (systolic blood pressure >160 mmhg) 1 Abnormal renal and liver function (1 point each) 1 or 2 Stroke 1 Bleeding 1 Labile INRs 1 Elderly (age >65) 1 Drugs or alcohol (1 point each) 1 or 2 Maximum 9 points

20 ESC guidelines 2012 bleeding risk assessment using HAS-BLED HAS-BLED score: allows clinicians to make informed assessment of bleeding risk makes clinicians think of the correctable risk factors for bleeding has been validated in several independent cohorts correlates well with ICH risk High HAS-BLED score per se should not be used to exclude patients from OAC therapy ESC = European Society of Cardiology; ICH = intracranial haemorrhage; OAC = oral anticoagulation 2012 focused update of the ESC Guidelines for the management of atrial fibrillation.

21 What might a patient with a high HASBLED score look like (=5)? Uncontrolled hypertension + Severe renal impairment + History of bleeding + Heavy drinker + 65 years = approx 1% of patients

22 When NOT to Anticoagulate? CHADS VASc = 0 Age <65 No previous stroke, TIA or embolic event No diabetes, hypertension or vascular disease No valvular heart disease or heart failure Do these AF patients exist? They do, but not many!

25 Question Which of the following statins does NOT interact with warfarin? Simvastatin Atorvastatin Pravastatin Rosuvastatin

26 Case #1 75 year old female Diabetic (T2DM) COPD Diagnosed opportunistically 4 years ago attending diabetes clinic

27 Case #1 Managed with aspirin Stroke in June 2010 right sided pure motor weakness, no cortical or sensory signs Warfarin initiated Local ambulance service takes her to warfarin clinic TTR <50% over 6/12. No easy correctable factors

28 Case #1 What do you think we should you do? Does this thing called TTR matter?

Retrospective analysis of 5 year stroke data from St Mary s Hospital Stroke Register (2003 2008) n=1297 total ischaemic strokes

29 Retrospective analysis of 5 year stroke data from St Mary s Hospital Stroke Register ( ) n=1297 total ischaemic strokes Pre-existing AF or PAF High risk stratification according to NICE 2006 criteria No contraindications to anticoagulation Bhargava et al (ESC 2010)

30 Question Of those patients known to be at high risk and not contraindicated to warfarin, how many were receiving warfarin? >90% 75% - 90% 50% - 74% 25% - 49% <25%

31 Results High risk patients with no contra-indication to warfarin: n=131 No anti-thrombotic agents Warfarin 27% 27% 46% Anti-platelets

32 Results Warfarin treated patients (n=35/131): Sub-therapeutic INR (<2.0): 69% (n=24/35) Overall only 8% (11/131) of eligible patients had therapeutic INR at time of stroke

33 Question In terms of TTR, when would you consider a patient to be uncontrolled on warfarin? <70% <60% <50% <40% NICE advise that <65% is low. Certainly <50% is significantly low

34 Cumulative survival Time in Therapeutic Range (TTR) matters... a lot! % Warfarin group 61 70% 51 60% 41 50% 31 40% <30% Non warfarin Survival to stroke (days) Morgan CL et al. Thrombosis Research 2009;124:37 41

35 Question You are comfortable that the patient is adhering to their warfarin treatment. She admits to having a glass of sherry every now and again, you also discover that she is taking Gingko given a family history of dementia. What is the most likely cause of her labile INRs / poor TTR? Metformin Antibiotics Sherry Ginkgo biloba (esp macrolides) or (acute alcohol can be P450 inhibitor)

36 Question In terms of her AF management, what do you think her GP should do? Stop warfarin and start aspirin Stop warfarin and start aspirin + clopidogrel Stop warfarin and NOT start either aspirin or clopidogrel Continue with warfarin NOAC

37 More detail on NOACs

How does Pradaxa compare to warfarin? Time to first stroke / SSE Cumulative hazard rates 0.05 0.04 0.03 RR 0.90 (95% CI: 0.74 1.10) p<0.001 (NI) p=0.30 (Sup) RRR 35% ARR 0.60% 0.02 0.01 RR 0.

38 How does Pradaxa compare to warfarin? Time to first stroke / SSE Cumulative hazard rates RR 0.90 (95% CI: ) p<0.001 (NI) p=0.30 (Sup) RRR 35% ARR 0.60% RR 0.65 (95% CI: ) p<0.001 (NI) p<0.001 (Sup) Years ARR, absolute risk reduction; RR, relative risk; CI, confidence interval; NI, non-inferior; Sup, superior Connolly SJ et al. N Engl J Med 2009;361:

Cumulative event rate (%) 6 5 4 3 2 1 Primary Efficacy Outcome Stroke and non-cns Embolism Event Rate Rivaroxaban Warfarin 1.71 2.16 Warfarin Rivaroxaban HR (95% CI): 0.79 (0.66, 0.

39 Cumulative event rate (%) Primary Efficacy Outcome Stroke and non-cns Embolism Event Rate Rivaroxaban Warfarin Warfarin Rivaroxaban HR (95% CI): 0.79 (0.66, 0.96) P-value Non-Inferiority: < No. at risk: Rivaroxaban Warfarin Event Rates are per 100 patient-years Based on Protocol Compliant on Treatment Population Days from Randomization

Apixaban - Primary Outcome Stroke (ischemic or hemorrhagic) or systemic embolism P (non-inferiority)<0.001 21% RRR Apixaban 212 patients, 1.

40 Apixaban - Primary Outcome Stroke (ischemic or hemorrhagic) or systemic embolism P (non-inferiority)< % RRR Apixaban 212 patients, 1.27% per year Warfarin 265 patients, 1.60% per year HR 0.79 (95% CI, ); P (superiority)=0.011 No. at Risk Apixaban Warfarin

41 January 2013 L.GB c Advantages of NOACs Rivaroxaban was non-inferior to warfarin in reducing the rate of stroke, with a comparable rate of major bleeding in the ROCKET-AF trial Apixaban use resulted in modest reductions (better) in the rates of stroke and major bleeding compared to warfarin in the ARISTOTLE trial All three NOACs reduced the risk of intracranial bleeding compared to warfarin in clinical trials No need for routine anticoagulant monitoring Dosing regimens are uncomplicated and a more stable level of anticoagulation is achieved with full concordance Fewer potential interactions with other medications, alcohol and diet

42 January 2013 L.GB c Disadvantages of NOACs New, so far less real world experience than with warfarin No antidote Some NOACs have higher rates of bleeding than warfarin in certain circumstances Expensive drug cost

43 NOAC MURs NOACs quickly out of the system if dose missed, so MURs can be very useful to check adherence and reinforce education. This is an anticoagulant, not like aspirin, doesn t protect you from stroke if you don t take it. Your risk of a stroke will go up by nearly x4 if you don t take it!

44 NOAC monitoring Blood tests at least yearly (FBC, renal and liver function) These drugs will build up if kidney function is impaired, so remind patients to report any conditions that might significantly affect kidney function, such as gastroenteritis.

45 When to consider NOACs

46 Examples where an NOAC might be a preferable choice Poorly controlled INR when previously had warfarin despite good adherence. Cannot adhere to blood tests: need for NHS transport (e.g. chair or bed bound); busy life style; dementia but still supported to take medication, and would find difficulty attending; needle phobia. Requires a monitored dosage system (e.g. Dosette box) rivaroxaban or apixaban are options, dabigatran is not stable outside packaging. Has food or drug interactions that are okay with a NOAC. Binge drinking which is likely to adversely affect warfarin control but which is slightly safer with a NOAC True allergy to warfarin.

47 Lipids, Statins and the Daily Mail

48 Statins have one of the largest evidence bases now Lipid lowering with statins reduces CV risk regardless of starting levels. Clinical benefit is related to the absolute reduction in LDL For secondary prevention, intensive therapy (atorvastatin 80) is safe and arrests atherosclerosis, reduces the risk of heart attacks, stroke, TIA and reduces hospitalisations for heart failure. In acute coronary syndromes (ACS), high-dose statins provide a rapid early reduction in risk which may be related to anti-inflammatory effects (separate to LDL lowering effects).

51 Declaration of Interests I have no shares in statin companies and have never been paid by them for any statin-related work or presentations or research. So:

52 Cholesterol Treatment Trialist s (CTT) collaborators - meta-analyses of mortality and morbidity from all relevant large-scale randomised trials of statin therapy Data on 90,056 individuals from 14 trials were combined. Mean follow-up of 5 years Almost a half-million person years of observation A significant 12% reduction in all-cause mortality per 1mmol/l reduction in LDL-C, A 19% reduction in coronary mortality, A 24% reduction in the need for revascularisation A 17% reduction in stroke and A 21% reduction in any major vascular event. Importantly, a similar proportional benefit was observed in different age groups, across genders, at different levels of baseline lipids [including triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)] and equally among those with prior CAD and cardiovascular (CV) risk factors as in those without.

53 CTT Safety data The safety data presented in CTT come from randomised control trials some of which (e.g. HPS) have a run-in period and consider only patients who are able to tolerate statin therapy Risk of rhabdomyolysis was 3/100,000 person years, Myopathy was 11/100,000 person years, Peripheral neuropathy 12/100,000 person years Liver disease even rarer. The authors conclude that side effects are rare and likely to be more common when drugs which block the CYP3A4 pathway are co-administered.

54 Cochrane Collaboration and CTT collaboration 2013 Evidence now justified the use of statins in people of low cardiac risk Cochrane figures for NNT over 5yrs; NNT Low risk [<1% annually]- 167 NNT Intermediate risk [1-2% annually]-67

55 CTT reviews of side effects BMJ non-cardiovascular effects of statins statin trials Alternative systematic review- no significant increase in rhabdomyolysis vs placebo- 60% of cases of rhabdomyolysis occurred pts using drugs which interact eg fibrates Influenced by high dose simvastatin now no longer recommended CK rises reported but in both statins and placebo Myalgia [muscle pain without CK rise]- 21 studies no increased risk but broken down atorvastatin higher risk of myalgia [5% vs 1% approx] Recent studies show no effect on muscle performance of myalgia 2 recent studies found 80% and 90% of patients able to tolerate statins when rechallenged

56 Current views Observational study 18% of users had statin-related clinical events that may be interpreted as adverse reactions by patients or clinicians Basis of the anti-statin lobby vs the pro-statin lobby in clinical trials just as many people taking placebo had muscle and joint pains as taking statins Is the truth somewhere in between? But evidence very strong for CV risk reduction! So when patients are wary, I simply lay out the information and they can decide. But I do advise them to critically appraise their sources of information! Google/internet forums/ my mate down the street says vs informed discussion with clinician!

57 Cataracts?prevent proper epithelial cell development in the lens?avascular so relies on endogenous cholesterol synthesis to meet cholesterol demands No robust evidence No support from small trials Observational suggestion only

58 Others Dementia - suggestion of benefit in preventing alzheimers, no definite evidence DVT - no clear association Pancreatitis - suggestion of reduced incidence [decreased risk of gallstones] Erectile Dysfunction -?reduced synthesis of testosterone vs vascular protection - no clear-cut evidence Fatigue - no evidence [assessed in one large trial] Cancer - for those who can remember! No evidence COPD - statins reduce inflammatory markers therefore worsening COPD and PH- no definite evidence

59 NICE Guidance Lipid Modification and CV Risk assessment for the primary and secondary prevention of CVD NICE guidance June 2014

60 Recommendations Key Points Calculate CV risk with a calculator called Qrisk 2 [up to 84yrs!]. It highlights a few caveats Communication about risk assessment Cardio-protective diet [avoid marlin, shark and swordfish]- don t recommend plant stanols Lipids measurement- full lipid profile, risk assess, pick out Familial Hyperlipidaemia

61 Statins Atorvastatin 20mg for: Primary prevention for Qrisk2>10% risk Type 1 DM [over 40yrs, DM 10yrs, other CVD risk factors] Type 2 DM Qrisk2>10% CKD but increase dose if 40% chol reduction not achieved [specialist input if severe CKD 4/5] Atorvastatin 80mg for: Secondary prevention (prior vascular disease = stroke, TIA, IHD, MI, or PAD) Lower if interactions, very elderly [lower muscle mass], impaired renal function, patient preference Cost effectiveness clearly demonstrated

62 Follow up Measure lipids at 3 months and increase dose if 40% reduction not achieved: consider atorvastatin 80mg if not to target Review, emphasise lifestyle, compliance/adherence Annual med review- consider an annual non-fasting blood test to inform discussion Estimated that at least 100,000 patients locally will require input. The way NICE have advised to do this, it is quite labour intensive!

63 Bradford s Healthy Hearts Recommendation Pragmatic approach to maximise efficacy in a high risk population, aid GP engagement and minimise patient inconvenience. Also, USA uses 40mg atorvastatin instead of 20mg in guidelines. 1. Primary prevention patients already identified at risk - 40mg Atorvastatin 2. Secondary prevention patients - 80mg Atorvastatin

64 If intolerant to statin Reduce dose Try a different statin (up to three different ones is reasonable) No use of fibrates, nicotinic acid, omega 3.

65 Lifestyle So important! As effective as one antihypertensive medication in hypertension, sometimes much more so. Losing 10-12lbs or 4-5kg lowers BP by 10/5mmHg. Losing 4-5% of body weight reduced cholesterol by 23%, from 6 to 4.6 mmol/l and LDL also reduced by 23%, from 3.9 to 3.0 mmol/l. This will equate to about a 20% reduction in risk of CV events and was equivalent to taking pravastatin 20mg, or nearly half as effective as taking atorvastatin 40mg. No lifestyle intervention will be successful if not realistic for that patient. Tablets are not instead of a healthy lifestyle! Both will reduce risk of stroke and heart attacks

66 Lifestyle 2 Make exercise targets realistic. Ideally 30 minutes at least 5 days a week, but Can divide into minute periods Work up gradually Do something that you enjoy Use stairs instead of lift, get off bus 2 stops early, park your car at the far end of the car park and walk! Pedometers sometimes help (gaining fashionablity e.g. standard clip on pedometer, wrist ones such as fitbit, Apple Watch!) (Second disclaimer I am not paid by Apple.)

67 Pedometers If I wear four, I will have done 4x steps, right?

68 Numbers needed to treat for different secondary interventions MeReC Bulletin 1999;10:(2) Interventions for secondary prevention of MI Number Needed to Treat (NNT) for five years to avoid one vascular death Mediterranean diet 9 Eating oily fish 19 Stopping smoking 21 Statins 26 Beta-blockers 30 Aspirin 37 Based on patients who have a baseline CHD risk of 3% per year

69 Adherence 1. Simply explain what medicine is for and why treat. Sounds simple but so effective and often poorly done by doctors. 10% of CV events due to poor adherence. 2. Check for side effects early and make a plan (usually best to speak to GP. If no recent cardiac event in past year, can take 6 week statin holiday if convinced of side effects. Better than patient stopping it unilaterally) 3. Encourage patient participation (know your numbers for BP and lipids) 4. Once daily dosing if possible 5. Pill boxes, dosette etc. You will be experts in this!

70 Know your numbers Helps patients feel more involved. Improves adherence: Total cholesterol < 4 LDL < 2 (moving to non-hdl in future) BP in pharmacy or GP surgery or hospital: <140/90 for under 80s <150/90 for over 80s BP at home: 5/5 less

71 The Challenge!

72 Acute Coronary Syndromes

73 Antiplatelets Aspirin for all post MI- indefinitely Clopidogrel monotherapy for aspirin sensitive. For 12 months post MI, stent or CABG: add second antiplatelet, Clopidogrel or Ticagrelor.

74 High dose statin Strong evidence for atorvastatin 80mg OD post-mi/post-acs with benefit in risk seen at just 30 days. Continue life long as per NICE 2014.

75 Post Cardiac Rehab Physical Psychological Social The early discharge period is the time at which the patient is the most vulnerable and psychological distress at this stage is a predictor of poor outcome and increased use of hospital services independent of the physical damage to the heart. Patients should be screened for anxiety and depression at this stage and should be treated with suitable non-cardiotoxic antidepressants if appropriate. Smoking cessation if not already done. Some of you may have services in-house. Massive risk reduction.

76 Post Cardiac Rehab In order to be effective, physical activity and changes in lifestyle need to be maintained for the long-term. Checking medication adherence is really useful at this stage.

77 We ve covered a fair amount there.

78 The secret to our local success in CVD: The Programme Board

79 Thank you for your attention Questions

Primary Prevention of Stroke

Primary Prevention of Stroke Dr Chris Ellis Cardiologist Green Lane CVS Service, Auckland City Hospital & Auckland Heart Group, Mercy Hospital, Auckland 67 Pages Long, 735 References 29 Sub-Headings for