Optimal medical treatment for polyvascular patient

Transcription

1 Optimal medical treatment for polyvascular patient Dr. M. Sprynger 21 st of April 2018 Moderators: Prof. Dr. T. De Backer and Dr. P. Borgoens

2 Optimal medical treatment for polyvascular patient Plenary session April 21, 2018 Muriel SPRYNGER, MD, FESC Cardiology-Angiology CHU Liège

3 Atherosclerosis Presentations of Peripheral Arterial Diseases (PADs) Aorta disease Territories Cerebrovascular diseases: - Carotid artery disease - Vertebral artery disease Presentations Stroke, Transient Ischaemic Attack ( TIA), acute monocular blindness Coronary Artery Disease (CAD) Upper-Extremity Artery Disease (UEAD) Subclavian steal syndrome, pain on exertion, digital symptoms, acute ischaemia Mesenteric artery disease Chronic Mesenteric Ischaemia (CMI) Acute Mesenteric Ischaemia (AMI) Peripheral Arterial Diseases (PADs) Renal Artery Disease (RAD) Lower-Extremity Artery Disease (LEAD) Hypertension, renal failure Typical claudication, atypical symptoms, Chronic Limb-Threatening Ischaemia (CLTI), Acute Limb Ischaemia (ALI) ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with ESVS (European Heart Journal 2017; doi: /eurheartj/ehx095) 41

4 General prevention PADs patients management Address general CV risk prevention Address specific localizationrelated symptoms

5 Atherosclerosis Is a Progressive Disease Leading to Atherothrombosis and Ischaemia CAD PAD Normal artery Fatty streak Fibrous plaque Atherosclerotic plaque Plaque disruption and thrombosis Flow-limiting stenosis Symptoms with exercise, e.g. stable angina and intermittent claudication Atherothrombosis MI Stroke CV death Limb ischaemia 1. Insull W Jr, Am J Med 2009;122(1 Suppl):S3 S14; 2. Bradberry JC et al, J Am Pharm Assoc 2004;44:S37 S45

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8 General CV prevention Best Medical Therapy Non pharmacological therapy Pharmacological measures Smoking cessation Healthy diet Weight loss Regular physical exercise Anti-HTN drugs Statins Optimal glucose control in diabetic pts Antithrombotic drugs

9 Healthy diet and physical activity Diet Physical activity Diet influences CVD risk: effect on RFs (cholesterol, BP, body weight, DM) other Impact of diet: specific nutrients specific foods/food groups specific dietary patterns, i.e. Mediterranean diet Physical activity reduces, in a dose-response fashion, by % all-cause and CVD mortality in healthy individuals with RFs and cardiac patients Positive effect on RFs Recommendations Healthy diet and physical activity are recommended for all patients with PADs. Clas s I Lev el C

10 Smoking cessation Smoking cessation reduces CV events and mortality (especially in pts with cerebrovascular disease and lower extremity artery disease) Recommendations Smoking cessation is recommended in all patients with PADs. Clas s I Lev el B Stopping smoking is the most cost-effective strategy for CVD prevention. Passive smoking should be assessed and prevented (increases CVD risk by an estimated 30%)

11 Anti-hypertensive drugs Lowering BP (SBP) reduces CV events Recommendations In patients with PADs and hypertension, it is recommended to control blood pressure at <140/90 mmhg. ACEIs or ARBs should be considered as first line therapy in patients with PADs and hypertension. Clas s I IIa Lev el A B In old and frail patients these levels should be achieved only if well tolerated without orthostatic hypotension Caution to avoid SBP decrease < mmhg in LEAD pts ACEIs or ARBs are recommended even in pts with chronic limb-threatening ischemia (decreased CV events and mortality without any effect on limb outcome) BB are not contraindicated in pts with LEAD

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13 2017 ACC/AHA guidelines

14 2017 ACC/AHA guidelines Strict conditions of BP measurement CKD and DM = high risk

15 Lipid-lowering drugs Recommendations Clas s Level Statins are recommended in all patients with PADs. I A In patients with PADs, it is recommended to reduce LDL-C to <1.8 mmol/l (70 mg/dl) or decrease it by 50% if baseline values are mmol/l ( mg/dl). I C Lower extremity arterial disease 17% lower risk of CV events (4yr FU) Lower 1-yr mortality and CV events in most advanced LEAD stages Kumbhani DJ et al EHJ, 2014 Westin GG et al JACC, 2014

16 Lipid-lowering drugs Statin therapy : 17% decrease in adverse CV events rates in LEAD patients (REACH registry). Lower 1-year rates of mortality and major CV adverse events even in the most advanced stages of disease (Westin et al., JACC 2014). Increased walking distance. Combination treatment with ezetimibe in selected patients : beneficial (Murphy et al., JACC 2016). Ibezafibrate : no benefit over placebo to reduce coronary and cerebrovascular events in patients with LEAD. Evolocumab (monoclonal antibody inhibiting the PCSK9) : additional benefits of to reduce CV events in patients with atherosclerotic disease over statins alone.(fourier trial, Sabatine, NEJM 2017).The results were consistent in the subgroup of 1505 patients with LEAD alone.

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19 Antithrombotic therapy in patients with asymptomatic Lower Extremity Artery Disease Recommendations Lower extremity artery disease Because of a lack of proved benefit, antiplatelet therapy is not routinely indicated in patients with isolated asymptomatic LEAD. Randomized trials are negative (POPADAD, AAA) There are safety issues Inappropriate use is frequent Its benefit on top of statin must be evaluated Cla ss III Lev el A ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with ESVS (European Heart Journal 2017; doi: /eurheartj/ehx095) 57

20 Masked LEAD Severe LEAD without symptoms 1/3 of asymptomatic patients Incapacity to walk enough (heart failure, COPD ) Reduced pain sensitivity At risk for toe necrosis after a trivial wound!!!

21 Time delay Antiplatelet therapy in patients with lower extremity artery disease Management of antiplatelet therapy in patients with LEAD not requiring anticoagulation Asymptomatic Symptomatic Revascularization Percutaneous Surgery A Aspirin mg/day 0 1 mo. 1 year No SAPT b Class III A SAPT c A or C Class I A DAPT A + C Class IIa C SAPT c A or C Class IIa C SAPT c A or C Class IIb B VKA d O Class IIb B C O Clopidogrel 75 mg/day Oral Anticoagulation b SAPT should be considered if CAD/CAS c DAPT may be considered if ACS/PCI<1 year or complex PCI d Evidence is weak and bleeding doubles as compared to SAPT. Long term ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with ESVS (European Heart Journal 2017; doi: /eurheartj/ehx095)

22 Time delay Antithrombotic therapy in patients with LEAD requiring oral anticoagulation LEAD in patients requiring long-term oral anticoagulation (A)symptomatic Surgery Percutaneous intervention Bleeding risk low b Bleeding risk high b A C Aspirin mg/day Clopidogrel 75 mg/day 0 1 mo. OAC a Monotherapy O Class I DAT O A or C Class IIa O A or C DAT Class IIb O OAC a Monotherapy OAC a Monotherapy O Class IIa O Oral Anticoagulation a DAT may be considered in high ischaemic rick patients (ST, ALI on OAC, CAD) b Compared to the risk for stroke/clti due to stent/graft occlusion.. 1 year Class IIb Long term ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with ESVS (European Heart Journal 2017; doi: /eurheartj/ehx095) 60

23 Can we do better?

24 PAD Trials Investigating Intensified Antiplatelet Therapy in Patients with PAD Show Mixed Results CHARISMA (subgroup analysis) 1 TRA2 P-TIMI 50 (subgroup analysis) 2 EUCLID 3 PEGASUS (subgroup analysis) 4,5 Clopidogrel + aspirin vs aspirin in patients with prior MI, stroke or symptomatic PAD Vorapaxar + aspirin vs aspirin in patients with stable symptomatic PAD Ticagrelor vs clopidogrel in patients with PAD Ticagrelor + aspirin vs aspirin in patients with prior MI + PAD MACE 17% No reduction in risk of MACE No reduction in risk of MACE MACE 31% Hospitalization for ALI 42% No decrease in MALE* No decrease in MALE # No decrease in mortality No increase in severe bleeding Major bleeding 1.5 No decrease in mortality No increase in major bleeding Mortality 48% No increase in major bleeding *Hospitalization for ALI or lower limb revascularization (individual endpoints); #Composite of ALI or peripheral revascularization; No mortality benefit in the overall trial population 5 1. Bhatt DL et al, J Am Coll Cardiol 2007;49: ; 2. Bonaca MP et al, Circulation 2013;127: ; 3. Hiatt WR et al, N Engl J Med 2017;376:32 40; 4. Bonaca MP et al, J Am Coll Cardiol 2016;67: ; 5. Bonaca MP et al, N Engl J Med 2015;372:

25 Index Dual Pathway Approach Targeting Chronic Patients with CAD or PAD COMPASS Study Objective: To determine the efficacy and safety of rivaroxaban, vascular dose of rivaroxaban plus aspirin or aspirin alone for reducing the risk of MI, stroke and cardiovascular death in CAD or PAD Population Chronic CAD (91%) PAD (27%) N~27,395 1:1:1 R 30-day run-in, aspirin 100 mg Rivaroxaban 2.5 mg BID + aspirin 100 mg OD Rivaroxaban 5.0 mg BID Aspirin 100 mg OD 30-day washout period Factorial design ± pantoprazole* Average follow up: 23 months at early termination of study Final follow-up visit Final washout period visit Antithrombotic investigations* were stopped 1 year ahead of expectations in Feb 2017 due to overwhelming efficacy in the rivaroxaban 2.5 mg BID + aspirin arm *Patients who were not receiving a proton pump inhibitor (PPI) were randomised to pantoprazole or placebo (partial factorial design); the PPI pantoprazole component of the study is continuing; data will be communicated once complete Eikelboom JW et al. N Engl J Med 2017; DOI: /NEJMoa ; Bosch J et al. Can J Cardiol 2017;33: L.BE.MA

26 Eligibility for COMPASS CAD, PAD or both CAD : either MI within 20 years multi-vessel CAD history of stable or unstable angina previous multi-vessel PTCA or previous multi-vessel CABG. Multi-vessel coronary artery disease Patients also needed to : be aged at least 65 years have documented atherosclerosis or revascularisation in an additional vascular bed (carotid or peripheral) to have at least 2 of the following RF: current smoker or quit within 1 year of randomisation, T2DM, egfr < 60 ml/min, heart failure, or non-lacunar ischaemic stroke at least 1 month before randomisation

27 Inclusion and Exclusion Criteria Ensure That Patients with Chronic PAD are Enrolled CAD PAD Key inclusion criteria Previous peripheral artery revascularization Previous limb or foot amputation for arterial vascular disease Intermittent claudication plus: Low ABI (<0.90), or Significant peripheral artery stenosis ( 50%) Previous carotid revascularization, or asymptomatic carotid artery stenosis 50% CAD + low ABI (<0.90) Key exclusion criteria High risk of bleeding Stroke within 1 month History of haemorrhagic/lacunar stroke Severe heart failure (ejection fraction <30%) egfr <15 ml/min A need for dual antiplatelet therapy A need for non-aspirin antiplatelet therapy An indication for anticoagulation therapy Anand SS et al, Lancet 2017;doi: /S (17)

28 COMPASS Included over 7000 Patients with Symptomatic PAD or Concomitant CAD and PAD CAD PAD Number of patients All patients with PAD 7470 Symptomatic lower-extremity PAD 4129 Carotid disease 1919 CAD + asymptomatic PAD (ABI <0.90) 1422 PAD was defined according to patient presentation at enrolment In addition, a patient could be defined as a PAD patient based on medical history and/or measurement of ABI at baseline visit The latter category added patients with CAD and asymptomatic PAD patients into the overall PAD subgroup Median follow-up: 21 months Anand SS et al, Lancet 2017;doi: /S (17)

29 PAD PAD Patients Rivaroxaban vascular dose 2.5 mg BID plus aspirin reduced the composite endpoint of stroke, MI or CV death by 28%. MALE by 46% Major amputations by 70% Despite an expected increase in major bleeding events with Rivaroxaban 2.5 mg BID plus aspirin, no significant increase was observed in fatal or critical organ bleeding *Defined as CV death, MI, stroke, MALE, major amputation, fatal bleeding or critical organ bleeding Anand SS et al, Lancet 2017;doi: /S (17)

30 Best medical therapy : CV risk factor management Including optimal pharmacological therapy as well as nonpharmacological measures such as smoking cessation, healthy diet, weight loss and regular physical exercise Statins Antiplatelet drugs in secondary prevention only Need for earlier and more efficient prevention and management strategies for the 40 million individuals of our continent affected by PADs A multisystemic disease requires a multidisciplinary team!

31 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) Endorsed by the European Stroke Organization (ESO) ESC Chairperson: Victor Aboyans (France). Co-Chairperson: Jean-Baptiste Ricco 1 (France). Authors/Task Force Members: Marie-Louise EL Bartelink (The Netherlands), Martin Björck 1 (Sweden), Marianne Brodmann (Austria), Tina Cohnert 1 (Austria), Jean-Philippe Collet (France), Martin Czerny (Germany), Marco De Carlo (Italy), Sebastian Debus 1 (Germany), Christine Espinola- Klein (Germany), Thomas Kahan (Sweden), Serge Kownator (France), Lucia Mazzolai (Switzerland), A. Ross Naylor 1 (UK), Marco Roffi (Switzerland), Joachim Röther 2 (Germany), Muriel Sprynger (Belgium), Michal Tendera (Poland), Gunnar Tepe (Germany), Maarit Venermo 1 (Finland), Charalambos Vlachopoulos (Greece), Ileana Desormais (France). 1 Representing the European Society for Vascular Surgery (ESVS) - 2 Representing the European Stroke Organisation (ESO) ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with ESVS (European Heart Journal 2017; doi: /eurheartj/ehx095) 69

32 And do not forget that women are at risk too!!!

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34 EUCLID

35 COMPASS Study (Lancet, 2017) Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial patients- 558 centres LEAD (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease) Carotid artery disease (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%) CAD + ABI < % with a history of CAD and 27.3% with a history of PAD Rivaroxaban (2 5 mg twice a day) plus aspirin (100 mg once a day) vs rivaroxaban twice a day (5 mg with aspirin placebo once a day) vs aspirin once a day (100 mg and rivaroxaban placebo twice a day) Primary outcome : CV death, MI or stroke Primary PAD outcome : major adverse limb events including major amputation.

36 COMPASS Study Riva + Asp vs Asp reduced the composite endpoint of CV death, MI, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0 72, 95% CI , p=0 0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR % CI , p=0 0037). Riva 5 mg twice a day vs Asp did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0 86, 95% CI , p=0 19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0 67, 95% CI , p=0 05). Median duration of treatment was 21 months. Riva + Aspirin increased major (mainly gi) bleeding compared with Asp (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1 61, 95% CI , p=0 0089). Although major bleeding was increased (3% vs 2%, HR 1 68, 95% CI ; p=0 0043), fatal or critical organ bleeding was not. + Pantoprazole?

37 Dual pathway inhibition with rivaroxaban 2.5 mg BID + aspirin 100 mg OD vs aspirin alone Significantly reduced the combined risk of stroke, CV death and MI by 24% Demonstrated 42% reduction in stroke and 22% reduction in CV death Resulted in low major bleeding rates (mainly gi) and, as expected, an increase (of 70%) compared to aspirin alone, with no significant increase in intracranial, critical organ or fatal bleeding Showed a substantial improvement in net clinical benefit of 20%, and 18% reduction in all-cause mortality + Pantoprazole? Index Eikelboom JW et al. N Engl J Med 2017; DOI: /NEJMoa