Best Medical Therapy for asymptomatic carotid disease

Transcription

1 Best Medical Therapy for asymptomatic carotid disease Richard Bulbulia Consultant Vascular Surgeon and Co-PI ACST-2 MRC Population Health Research Unit CTSU, Nuffield Department of Population Health University of Oxford

2 Italian ACST-2 Collaborators Meeting Martedi 0730 (!) Sala Europa

3 3 choices for asymptomatic carotid stenosis

4 3 choices for asymptomatic carotid stenosis ACST-2

5 Carotid Guidelines 2017

6 Use Triple Medical Therapy to Prevent MI & Stroke 1. Anti-platelet agents 2. Anti-hypertensive agents 3. Statins to lower LDL-C

7 Anti-platelet Therapy 75 mg aspirin (or 75 mg clopidogrel if aspirin intolerant)

8 Anti-platelet agents Intensive anti-thrombotic therapy in acute disease Mono-therapy (aspirin) favoured for secondary prevention Aspirin not recommended for primary prevention bleeding risks outweigh any potential benefits aspirin has not been shown to prevent stroke in primary prevention Asymptomatic carotid patients = primary prevention? Annual risk of CV event >3% per annum, so a carotid stenosis can be considered a CHD risk equivalent

9 Effects of antiplatelet therapy on MI and Stroke in high-risk patients Category APT CTRL Reduction Prior MI 13.5% 17.0% 25%±4 Acute MI 10.4% 14.2% 30%±4 Prior stroke/tia 17.8% 21.4% 22%±4 Acute stroke 8.2% 9.1% 11%±3 Other high risk 8.0% 10.2% 26%±3 All except acute stroke 11.7% 14.8% 25%±2 All trials 10.7% 13.2% 22%± (p<0.0001) ATTC

10 CAPRIE: Clopidogrel v Aspirin (secondary prevention) Clopidogrel: ARR = 0.5%; RRR 8.7% (P=0.043)

11 Anti-hypertensive Therapy Aim for BP < 140/80

12 How important is blood pressure to vascular death? 20 mmhg drop in systolic BP halves vascular mortality at Prospective Studies Collaboration (1 million adults) PSC, Lancet 2002; 360: 1903

13 LDL-C Lowering Intensive statin therapy mg atorvastatin or mg rosuvastatin (Irrespective of baseline lipid profile)

14 How important are blood lipids? Good statin regimen reduces LDL cholesterol by 2 mmol/l and vascular risk by 40% (Non-vascular mortality is unaffected) CTT, Lancet; online Nov 9, 2010

15 Proportional effects on MAJOR VASCULAR EVENTS per mmol/l reduction in LDL cholesterol No. of events (% pa) Statin/more statin Control/less statin Relative risk (CI) Nonfatal MI CHD death Any major coronary event 3485 (1.0) 1887 (0.5) 5105 (1.4) 4593 (1.3) 2281 (0.6) 6512 (1.9) 0.73 ( ) 0.80 ( ) 0.76 ( ) CABG PTCA Unspecified Any coronary revascularisation 1453 (0.4) 1767 (0.5) 2133 (0.6) 5353 (1.5) 1857 (0.5) 2283 (0.7) 2667 (0.8) 6807 (2.0) 0.75 ( ) 0.72 ( ) 0.76 ( ) 0.75 ( ) Ischaemic stroke Haemorrhagic stroke Unknown stroke Any stroke 1427 (0.4) 257 (0.1) 618 (0.2) 2302 (0.6) 1751 (0.5) 220 (0.1) 709 (0.2) 2680 (0.8) 0.79 ( ) 1.12 ( ) 0.88 ( ) 0.84 ( ) Any major vascular event (3.2) (4.0) 0.78 ( ) 99% or 95% CI CTTC: Lancet 2010; Statin/more statin better Control/less statin better

16 Proportional effects on MAJOR VASCULAR EVENTS per mmol/l reduction in LDL cholesterol No. of events (% pa) Statin/more statin Control/less statin Relative risk (CI) Nonfatal MI CHD death Any major coronary event CABG PTCA Unspecified Any coronary revascularisation Ischaemic stroke Haemorrhagic stroke Unknown stroke Any stroke 3485 (1.0) 1887 (0.5) 5105 (1.4) 2133 (0.6) 5353 (1.5) 1427 (0.4) 257 (0.1) 618 (0.2) 2302 (0.6) 4593 (1.3) 2281 (0.6) 6512 (1.9) 21% reduction 1453 (0.4) in 1857 ischaemic (0.5) stroke 1767 (0.5) 2283 (0.7) per mmol/l reduction in LDL-C 2667 (0.8) 6807 (2.0) 1751 (0.5) 220 (0.1) 709 (0.2) 2680 (0.8) 0.73 ( ) 0.80 ( ) 0.76 ( ) 0.75 ( ) 0.72 ( ) 0.76 ( ) 0.75 ( ) 0.79 ( ) 1.12 ( ) 0.88 ( ) 0.84 ( ) Any major vascular event (3.2) (4.0) 0.78 ( ) 99% or 95% CI CTTC: Lancet 2010; Statin/more statin better Control/less statin better

17 Statins and carotid-related stroke MRC/BHF Heart Protection Study (HPS) Allocation to statin halved rate of CEA 42 [0.4%] statin vs 82 [0.8%] placebo; P=0.0003

18 Effects of intensive statin therapy on stroke Lower LDL-C is better Residual risk of stroke persists despite intensive medical therapy

19 New developments Anti-thrombotic therapy COMPASS (2.5 mg rivaroxaban + aspirin v aspirin alone) Risk of stroke halved Blood pressure lowering therapy SPRINT (low v very low BP targets) 121 mmhg v 136 mmhg SBP (15mmHg) for 3 years 25% reduction in MVE Doubling of SAE due to study intervention: 220 [4.7%] v 118 [2.5%], largely driven by acute renal failure Lipid-lowering therapy: PCSK-9 Inhibition FOURIER (Evolocumab) 23% reduction in risk of stroke

20 Triple medical therapy effective Aspirin reduces CV risk by around 20%, but effect on stroke unclear

21 Triple medical therapy effective Aspirin reduces CV risk by around 20%, but effect on stroke unclear? Aim for lower SBP to prevent CV events (but at a cost) 120/80?

22 Triple medical therapy effective Aspirin reduces CV risk by around 20%, but effect on stroke unclear? Aim for SBP ~120 mmhg to prevent CV events (but at a cost) Intensive LDL lowering safe and effective

23 Triple medical therapy effective, but residual risk remains Aspirin reduces CV risk by around 20%, but effect on stroke unclear? Aim for SBP ~120 mmhg to prevent CV events (but at a cost) Intensive LDL lowering safe and effective Carotid intervention halves any residual risk VA, ACAS & ACST-1 IPD (restricted triple medical therapy)