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C72 Cardiology and Cardiac Surgery Toronto Notes 2023

Table 20. Commonly Used Cardiac Therapeutics

Drug Class Examples Mechanism of Action Indications Contraindications Side Effects

NITRATES

Relax vascular smooth

muscle,producing venous and dinitrate plushydralatine)

arteriolar dilation

CAD. MI.CNf (isosorbide Concurrent use of cyclic

guanosine monophosphate weakness,postural

phosphodiesterase inhibitors, hypotension

angle closure glaucoma,

increased intracranial

pressure

nitroglycerin Headache,dimness.

LIPID LOWERING AGENTS

Stalins atorvaslalin (Lipitor ).

pravastatin (Pravachol:

i.

rosuvastalin (Crestor'

).

simvastatin (Zocor 3).lovastatin which catalyzes the ratelimiting step in cholesterol

synthesis

Inhibits gut absorption ol

cholesterol

Inhibit hydroxy

9-methylglutaryl -CoA (HMGCoA) reductase,an enzyme

Dyslipidemia (1"

prevention

ot CAD).CAD,post- Ml|2“

prevention of CV events)

liver or muscledisease Myalgia,rhabdomyolysis,

abdominal pain

(Meracor 5

)

Cholesterol absorption

inhibitor

eietimibe (Ezetrol 3 ) Decreases low-density

lipoprotein but does not reduce

mortality

Primarily in familial

hypercholesterolemia

Hypercholesterolemia

liver or renal impairment Myalgia,rhabdomyolysis.

abdominal pain

Miscellaneous fibrates. bile acid sequestrates,

nicotinic acid

evolocumab

alirocumab

Gt side effects common

PCSK9 inhibitor Monoclonal antibody that

inhibits PCSKETs inhibitory

action on the recycling of LDL

receptors,thereby increasing

the number olIDlreceptors

on the surface of liver celts

Hypersensitivity reaction

to drug

Mild reactions to site ol

injection,nasopharyngitis

Antiarrhythmics

!i

2 slow Ctf'

influx

a D

-

Na'influx 5 3

3 K-efflux

_ threshold

a Na influx §

s

TIME

Figure 55. Representative cardiac action potential

Table 21. Antiarrhythmic' Drugs (Vaughan-Williams Classification)

Class Agent Indications Side Effects Mechanism of Action

quinidine

procainamide

disopyramide

SVT.VT Torsades de Pointes (all la),diarrhea

Lupus-like syndrome

Anticholinergic effects

Moderate Nr channel blockade

Slows phase 0 upstroke

Prolongs repolarization. slowing

conduction

Mild Na '

channel blockade

Shortens phase 3repolarization

Upstroke

la

Confusion,stupor,seizures

Gl upset,tremor

Exacerbation olVT (allIc)

Negative inotropy (all tc)

Bradycardia and heart block (all Ic)

Bronchospasm.negative inotropy,

bradycardia,AV block,impotence,

fatigue

Amiodarone:photosensitivity,

pulmonary toxicity,hcpalotoxlcity.

thyroid disease,increased INR

Amiodarone and sotalol:Torsades de

Pointes,bradycardia,heart block,

p-blockerside elfects

Bradycardia. AV block

Hypotension

lb lidocaine

mexiletine

propafenone

llecainide

encatnide

VI

Ic SVT.VT

AFib

SVT.AEib p blocker

Decreases phase 4

depolarization

Blocks K* channel

Piofongs phase 3 repolarization.

which prolongs refractory period

propranolol

meloprolol.etc.

III amiodarone" SV1.VI

solalol AFib

SVI. V1

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IV verapamil SV1 CCB

diltiazem AFib Slows phase 4 spontaneous

depolarization,slowing AV node

conduction + 'All antiarrhythmics have potential to beproarrhythmic

"Amiodarone has class I,II.III.andIV properties

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C73Cardiology and Cardiac Surgery Toronto Notes 2023

Table 22. Actions of a and p Adrenergic Receptors

a RECEPTORS p RECEPTORS

Target System

Cardiovascular

at a2 31 32

Constriction olvascular

smooth muscle

Constriction of skin,

skeletal muscle.and

splanchnic vessels

Increase myocardial

contractility

Decrease HR

Same as o1

Peripherally act to

modulate vessel tone

Vasoconstrict and dilate;

oppose o1vasoconstrictor Accelerate ectopic

activity

Increased myocardial

contractility

Accelerate SA node

conduction

Decreasedvascular

smooth muscle tone

pacemakers

Respiratory

Dermal

Bronchodilation

Pilomotor smooth muscle

contraction

Apocrine constriction

Radial muscle contraction

Inhibition of myenteric

plexus

Anal sphincter contraction

Pregnant uterine

contraction

Penile and seminal vesicle

ejaculation

Urinary bladder

contraction

Stimulate liver

gluconeogenesis and

glycogenolysis at the liver

Ocular

Gastrointestinal

Ciliary muscle relaxation

Smooth muscle wall

relaxation

Stimulation ol renalrenin

release

Genitourinary Bladder wallrelaxation

Uterine relaxation

Metabolic Same as ol

Fat cell lipolysis

Gluconeogenesis

Fat cell lipolysis

Fat cell lipolysis

Glycogenolysis

Adapted from the Family Practice Notebook (vrww.tpnotebook.com NEU194.htm)

Table 23. Commonly Used Drugs that Act on a and p Adrenergic Receptors

RECEPTORS p RECEPTORS

Mechanism ol u1andn2 o2 31 31 and 32 32

Action

Agonist

a1

Clonidine

Methyldopa

Vohimbine

Mirlatapine

Phenylephrine

Methoxamine

Praiosin

Phenoxybentamine

Epinephrine

Norepinephrine

Phentolamine

Norepinephrine

Dobutamine

Meloptolol

Acebutolol

Alptenolol

Atenolol

Esmolol

Isoproterenol

Epinephrine

Propranolol

Timolol

Nadolol

Pindolol

Carvedilol

Albuterol

Terbutaline

Antagonist Buloiamine

Adapted from the Family Practice Notebook (Yrww.tpnotebook.corn/NEU194.htm)

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C7-1Cardiology and Cardiac Surgery Toronto Notes 2023

Landmark Cardiac Trials

Trial Name Reference Clinical Trial Details

ISCHEMIC HEART DISEASE

HEJM 1992;326:10-16 Tillc:A Comparison ol Angioplasty with Medical Therapy in lire Treat men!of Single-Vessel Coronary Arlery Disease

Purpose:Compaic the effects of percutaneous transluminal coronary angioplasty (PICA) on angina and exercise tolerance in patients

with stable single-vessel disease

Methods:Patients with exercise-induced myocardial ischemia and epicardial arlery stenosis were randomized to PICA or medical

therapy,and repeat exercise testing performed at 6 mo.

Results: PICA was successful in 80% of patients,reducing mean % stenosis from 76% to 36%. At 6 mo, 64% PICA patients were anginafree. compared with 46% of medically heated patients.PTCA-treated patientshad longer exercise durations (2.1vs. 0.5 min.P- 0.0001)

than medically treated patients.

Conclusions:PICA offers earlier and better relief of angina than medical therapyin patients with single-vessel disease.

Title:Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE):A

Randomised.Double-blind. Placebo-controlled Trial

Purpose:Assess efficacy and safety of ASA versus placebo in patientswith moderate risk of a first CV event.

Methods:Patients with moderate CV risk were randomized to receive ECASA or placebo tablets,once daily.The primary endpoint was a

composite of time to CV death,MI. UA. stroke,or TIA.

Results: The primary endpoint occurred in 4.29% of ASA- treated patients versus 4.48% of placebo-treated patients (hazard ratio 0.96;

95% Cl 0.81 to 1.13:P'0.6). The overall incidence of adverse events was similar between groups (82.01% in ASA group versus 81.72% in

placebo group).

Conclusions: Among patients at moderate risk of CHD.the use of ASA was not beneficial. ASA was not associated with a reduction in

adverse CV events.

Tide:Prevention of Coronary andStroke Events with Atorvaslatin in Hypertensive Patients who have Average or Lower than Average

Cholesterol Concentrations,In the Anglo Scandinavian Cardiac Outcomes Trial- Lipid Lowering Arm (ASCOT lla): A Multicenlre

Randomised Controlled Trial

Purpose:Assess benefits ol cholesterol lowering In primary prevention ol CHD in hypertensive patients.

Methods:Hypertensive patients aged 40 79 were randomized to atorvastatin 10 mg or placebo. The primary endpoint wasnon- fatal Ml

and fatal CHD after 5- yr follow-up.

Results:100 primary events occurred in the atorvaslatin group compared to 154 events in the placebo group at a median lollowup of

3.3 yr (hazaid ratio 0.64;95% Cl 0.50 lo 0.83;P'0.0005). Fatal and non-fatal stroke,total CV events and total coronary events were

also lowered in the atorvastatin group.

Conclusions:In hypertensive patients with risk factors for CHD and average cholesterol levels,atorvastatin reduced non- fatal Ml, fatal

CHD.fatal/non- fatal stroke,coronary events but not all-cause mortality.

Title:A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease

Purpose:Determine optimal treatment for patients withI2DM and stable ischemic heart disease.

Methods:Patients withT2DM and heart disease were randomized to promptrevascularization with intensive medical therapy, or

intensive medical therapy alone.Primary endpoints weremortality.Ml.orstroke

Results:5-yr survival did not differ significantly between groups (88.3% in revas.cularizalion group vs.87.8% in the medical therapy

group:P'0.97).In the PCI group,there were no significant differences inprimary endpoints,while in the CABG group, rates of CV events

were significantly lower with revascularization than medical therapy (22.4% vs.30.5%:P'0.01).

Conclusions:There wasno significant difference in the rates of death and major CV events between promptrevascularization and

medical therapy.

Title:A Randomised. Blinded. Trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE)

Purpose:Assess the relative efficacy of clopidogrel and ASA in reducingrisk of clinical thrombotic events.

Methods:Patients with atherosclerotic vascular disease were randomized toclopidogrel 75 mg once daily or ASA 325 mg once daily.

Pnmaiy endpoints were a composite ol ischemic stroke. Ml. or vascular death.

Results:Patients treated with clopidogrel had a 5.32% annual risk of stroke. Ml or death,compared with 5.83% ol ASA palients

(p'0.043). There were no ma|0idifferences In terms of safety.

Conclusions:In atherosclerotic vascular disease, clopidogrelreduced the rales of stroke. Ml. or vascular death compared lo ASA.

Title:Ihe Effect of Piavaslatin on Coronary Events after Myocardial Infarchon in Patients with Average Cholesterol levels

Purpose: Determine the elleds of cholesterol lowering in palients with coronary disease and average cholesterollevels.

Methods:Patients with Ml who had plasma cholesterol levels <240 mg were administered either 40 mg pravastatin or placebo. The

primary endpoint was a fatal coronary event or fatal Ml.

Results: The primary endpoint occuired in 10.2% of the pravastatin- treated patients and 13.2% of placebo- treated patients (95% Cl 9%

to 36%:P-0.003). There were no significant differences in overallmortality or mortality from nonvascular causes.Pravastatin lowered

the rate ol coronary events more among men than women.

Conclusions:Pravastatin reduced Ml and stroke in patients with previous Ml and average cholesterol.

Title:Optimal Medical Therapy with or without PCI for Stable Coronary Disease

Purpose:Compare initial strategy of PCI plus intensive pharmacological therapy andlifestyle intervention against optimal medical

therapy alone,in patients with stable coronary disease.

Methods: 2287 patients with myocardial ischemia and significant CAD were randomized to PCI with optimal medical therapy,or optimal

medical therapy alone.The primary outcome was all-cause mortality and non-fatal Ml.

Results:There were 211 primary events in the PCI group and 202in the optimal medical therapy group (hazard ratio for PCI,1.05; 95%

Cl 0.87 tol.27:P'

0.62).There were no significant differences between groups in the composite of death.Ml, stroke,or hospitalizations

for ACS.

Conclusions:Compared with optimal medical therapy alone.PCI plus medical therapy didnot reduce all-cause mortality and non-fatal

Ml.and it did not reduce the incidence of major CV events.

Title:Effects of Clopidogrel in Addition to Aspirin in Patients with Acute Coronary Syndromes without Si-Segment Elevation

Purpose:Evaluate efficacy and safely of clopidogrel with ASA in patients with ACS without ST- elevation.

Methods:12562 palients who presented within 24 h ol symptom onset were randomizedlo clopidogrel or placebo in addition to ASA lor

3-12 mo. The primary endpoint was a composite ol CV mortality,non- fatal Ml. or stroke.

Results: The primary endpoint occuired in 9.3% ol clopidogrel patients and 11.4% ol patients in the placebo group |RR 0.80:95% Cl

0.72 lo 0.90; P'

0.001). Ihcrc were significantly more patients with bleeding in the clopidogrel group than Ihe placebo group (3.7% vs.

2.7%:RR 1.38:P'0.001).

Conclusions:Clopidogrel plus ASA reduced death from CV causes, non- falal Ml. or stroke but increased bleeding complications.

ACME

ARRIVE Lancet 2018:392:1036-46

ASCOTLLA lancet 2003:361:1149 58

BARI 2D HEJM 2009:360:2503 15

CAPRIE Lancet 1996:348:1329 39

CARE HEJM 1996:335:1001 09

COURAGE HEJM 2007:356:1503-16

CURE HEJM 2001:345:494 502

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C75Cardiology and Cardiac Surgery Toronto Notes 2023

Trial Name Reference Clinical Trial Details

EUROPA Lancet 2003;362:782-88 Title:Efficacy of Perindoprilin Reduction of Cardiovascular Events Among Patients withStable Coronary Artery Disease:Randomised.

Double-blind.Placebo-controlled,Multicentre Trial (The EUROPA Study)

Purpose:Assess whether ACEI reduced CV risk in a low-risk population with stable coronary disease.

Methods:Alter a run-in of 4 vrk,in which all pabents received perindopril,12218 patients were randomired to perindopril 8 mg 00 or

matching placebo.The primary endpoint was CV death.Ml.or cardiac arrest

Results:8% of perindopril patients experienced a primary endpoint,compared with10% of placebo pabents.These benefits were

consistent inall subgroups and secondary endpoints.

Conclusions:With stable CAD and no CH F,perindopril reduced CV death,Ml. and totalmortality.

Title:Twelve-Year Follow-up of Survival in the Randomized European Coronary Surgery Study

Purpose:Evaluate survival rates in men with good LVEF after CA8G or medical therapy.

Methods:767 men were randomized to early CABG or medical therapy.

Results:At the proddedS yr follow-up period,there was a significantly higher survival rate in the surgical group than in the medical

treatment group (92.4% vs.83.1%,P‘

0.0001).

Conclusions: CABG resulted in higher survival than medical therapy at 5-yr follow-up but not at12- yr follow-up.

Title:Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease

Purpose:Assess long-term outcomes after PCI with contemporary drug-eluting stents,as compared with CABG.inpatients with left

main CAD.

Methods:1905 patients with left main CAD of low/intermediate anatomical complexity were randomized to PCI or CA8G.The primary

outcome was a composite of death,stroke or Ml.

Results: At 5 yr,the primary outcome occurred in 22.0% of PCI pabents and19.2% of CABG patients (2.8% difference:95% Cl -0.9 to

6.5:P‘0.13).Rates of CV death and Ml were not significantly different between groups.All cerebrovascular events were less frequent

after PCI than CABG (3.3% vs. 5.2%;95% Cl - 3.8 to 0).

Conclusions:Among patients with left main CAD. there was no significant difference between PCI and CABG in terms of the composite

outcome of death.stroke,or Ml at 5 yr.

Title:MRC /BHF Heart Protection Study of Cholesterol lowering with Simvastatin in 20,536 High-risk Individuals:A Randomised

Placebo-controlled Trial

Purpose:Assess effect of IDl-lowerlng with simvastatin on vascular disease,in patients of normal LDL-C.

Methods:20536 adults with coronary disease or DM were randomized to simvastatin 40 mg daily or placebo.Primary outcomes were

mortality,and fatal or non-fatal vascular events .

Results:Alt-cause mortality was significantly reduced (12.9% in simvastatin patients vs.14.7%in placebo).There were significant

reductions in the first event rate for non- fatal Ml (8.7% vs.11.8%;P<0.0001). There were no significant effects on cancer incidence or

hospitalization for a non- vascular cause.

Conclusions:In high-risk patients with ranging LDL-C values,simvastatin reduced all

-cause mortality,coronary deaths,and ma)or

vascular events.

Title:Ezetimibe Added toStatin Therapy after Acute Coronary Syndromes

Purpose:Assess the effects of adding ezetimibe to statin therapy in reducing the rate of CV events.

Methods:18144 patients who were hospitalized with ACS were randomized to combination (simvastatin 40 mg plus ezetimibe 10 mg),

simvastatin 40 mg alone, or placebo. Primary endpoint was a composite of CV death,non- fatal Ml. UA.or non- fatal stroke.

Results:The Kaplan Meier event rates for the primary endpoint were 32.7% in the combination group and 34.7% in the statin

monotherapy group (P-'

O.OOI).Rales of pie-specified muscle,gallbladder, and hepatic adverse effects were similar.

Conclusions:Ezetimibe added to statin reduces mortality in ACS patients.

Title:Rosuvastalin to Prevent Vascular Events in Men and Women with Elevated C Reactive Protein

Purpose:Evaluate the effects olStalin treatment on CV events in patients withelevated CRP without hyperlipidemia .

Methods:17802 apparently healthy patients with IDL levels«130 mg/dland CRP levels >2.0 mg were randomized to rosuvastalin 20

mg daily or placebo. The primary endpoint was a composite of Ml.stroke, revascularization,hospitalization for UA. or CV death.

Results: The rales of the primary endpoint were 0.77 and 1.36 per 100 person-years in the statin and placebo groups respectively

(hazard ratio 0.56; 95% Cl 0.46 to 0.69:P- 0.00001). The rosuvastalin group did not have a significant increase in myopathy or cancer,

but a higher rate of diabetes.

Conclusions: With low to normal IDL and elevated high CRP.treatment with rosuvastalin significantly reduced major CV events.

Title:Ten - Year Follow-Up Survival of the Medicine.Angioplasty,or Surgery Study (MASS II)

Purpose:Compare 10 yr follow -up of PCI.CABG.and medical treatment in patients with mullivessel coronary disease,UA,and

preserved ventricular function.

Methods:611 patients were randomized to CABG,PCI,or medical treatment.The primary endpoints were overall mortality.0 wave Ml,

or refractory angina requiring revascularization.

Results: 10- yr survival was 74.9% with CABG. 75.1% with PCI,and 13.3% with medical treatment (P‘0.089) 10 yr rates olMl were

10.3% with CABG.13.3% with PCI. and 20.7% with medical treatment|P«0.010). 10-yr freedom from angina was 64% with CABG.59%

with PCI.and 43% with medical treatment|P«0.001).

Conclusions: Compared to medical therapy, CABG resulted in greater relief of angina symptoms and lower rates of subsequent Ml.

additional revascularization,and cardiac death. Compared to PCI. CABG resultedIn decreased need for further revascularization,a

tower incidence olMl,and lower risk of combined events.

Title:Alirocuinab and Cardiovascular Outcomes after Acute Coronary Syndrome

Purpose: Determine whether alirocumab would Improve CV events after ACS inpatients receiving high-intensity statin thcrap.y

Methods:18924 patients receiving high intensity statins for ACS 1-12 prior were randomized to alirocumab SO at 75 mg or placebo,

every 2 wk. The primary endpoint was a composite oldeath from CH0. non fatal Ml.fatal or non latal stroke,or UA

Results: The primary endpoint occurred in9.5% of patients in the alirocumab group and in 11.1% of patients in the.placebo group

(hazard ratio 0.85; 95% Cl 0.78 to 0.93; P- 0.001). The incidence of adverse events was simitar in the two groups.

Conclusions: Among patients with ACS In the preceding 1-12 mo,use of alirocumab significanUy reduces all- cause mortality and Ml

Title:Five-Year Outcomes after On Pump and Olf-Pump Coronary Artery Bypass

Purpose: Reporting of 5 - yr outcomes in patients included In the Veterans Trial olon-pump vs. off pump CABG.

Mcthods:2203 patients were randomly assigned to undergo either on- pump or off -pump CABG. The primary 5-yr outcomes were all

cause mortality and a composite of major CV events or non- fatal Ml.

Results:5- yr mortality was15.2% in the oil-pump group,compared with11.9% in the on- pump group|RR 1.28:95% Cl 1.03 to1.58:

P‘0.02).Iherale of major CV events in the oil pump group was 31.0% compared to 27.1% in the on-pump group|RR 1.14;95% Cl 1.00 to

1.30; P-0.046).

Conclusions:Off - pump CABG led to lower rates of 5 -yr survival and event free survival when compared to on- pump CABG.

European Coronary Surgery NEJM 1988;319:332-37

Study

EXCEL NEJM 2019;381:1820- 30

HPS lancet 2002;360:7-22

IMPROVE-!! NEJM 2015:372:2387 97

JUPITER NEJM 2008;359:2195- 207

MASS It Circulation 2010;122:949- 57

ODYSSEY OUTCOMES NEJM 2018;379:2097-107

R00BY NEJM 2017;377:623-32

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C76Cardiology and Cardiac Surgery Toronto Notes 2023

Trial Name Reference Clinical TrialDetails

SYNTAX NEJM 2009;360:961-72 Title:Percutaneous Coronary Intervention versus Coronary-Artery Bypass Grafting for SevereCoronary Artery Disease

Purpose:Compare PCI and CABG for treating patents withpreviously untreated three-vessel or left mam CAD.

Methods:1800 patents with three- vessel or left main coronary disease were randomised to CABG or PCI(1:1rabo).The primary

outcomes were a major adverse cardiacor cerebrovascular event.

Results:Rates of primary outcomes at12 mo weresignificantly higher inthe PCI group (17.8 a vs.12.4V P-0.002J.At 12 mo.rales of

death and Ml weresimilar between groups and stroke was significantly more likely with CABG.

Conclusions:CABG had a lower rate olmajor cardiac or cerebrovascular events,however therate of stoke was increased with CABG

whereas the rate ofrepeat revascularizaton was increased withPCI.

Title:Intensive lipidlowering withAlorvastatm m Patents withStable Coronary Disease

Purpose:Assess the efficacy and safety of IDl-tnvermg below 100 mgdlin patients withstable CH0.

Methods:10001patents with stable CH0 and101‘

130 mg dlwere randomised to doubleblind therapy of atorvastatn10 mg or 80 mg

daily.The primary endpoint was the occurrence of a first major CV event.

Results:A primary endpoint occurred in 8.7% of patents treated with atorvastatn 80 mg.as compared with10.9% inpatients receiving

atorvastatin 10 mg.There wasno difference inoverall mortality between groups.

Conclusions:lipid-lowering therapy with atorvastatin 80 rcgdinpatents with stableCH0 provides clinical benefit beyond

atorvastatin10 mg.

'

d.

TNT NEJM 2005:352:1425 35

MYOCARDIAL INFARCTION

BHAI JAMA 1982:247:1707 14 Title:A Randomised Trial of Propranololin Patients with Acute MyocardialInfarcton

Purpose:Study the effects on mortality of administering propranololhydrxhlocide inpatents who eiperienced at least one M.

Methods:3387 patents were randomised toeither propranolol or placebo for 21d post infarction.The primary outcome was all-cause

mortality.

Results:Total mortality during the average 25-mo follow-up was 7.2%idthe propranolol group and9.2% in the placebo group.

Conclusions:In acute Ml.propranololreduced all-cause mortality.CV death,andsudden death from atheroscleroticheart disease.

Title:Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction

Purpose:Assess the efficacy and safety of low-dose colchicine after Ml.

Methods:Patients were randomised toreceive 0.S mgcolchicine once daily or placebo.The primary endpoint was a composite of CV

death,resuscitated cardiac arrest.Ml.stroke,or UA leading to revascalanzation.

Results:The primary endpoint occurred in 5.5% of colchicine-treatedpatents and 7.1% intheplacebo group (hasard rabo 0.77;95% Cl

0.61to 0.96:P~0.02).The hasard ratios were 0.84 for CV death.0.83 for resuscitated cardiac arrest 0.91for Ml.0.26 for stoke,and

0.50 for UA.

Conclusions:Inpatents with recent ML colchicine lowered the risk of subsequent CV events as compared to placebo.

Title:Complete Revasculansaton with Multrressel PCI for Myocardial Infarcton

Purpose:To assess whether PCI of noncolprit lesions reduced rates of CV death or Ml inSIEMIpatents.

Methods:Patients with STEMI and successful PCI of culpritlesions wererandomised to complete revascularisation with PCI or no

further revascularisaton.The primary outcome was a composite of CV death or Ml.

Results:At 3 yr.the primary outcome occurred in7.8% of patents inthe complete-revasculansat on group,compared with10.5% in

the culprit-lesion PCI only group (hasard ratio 0.74:95% Q0.60to 0.91:P'0-0041.The benefit was observed regardless of the intended

timing of nonculpritlesion PCI.

Conclusions:Inpatents with STEMI and mulbvessel CAD.complete revascularisaton by PCI further reduced the risk of CV death orMl

as compared to culprit-1esion- onlyPCI.

Title:Twelve or 30 Months of DualAntplatelet Therapy after Dmg-ElubngStents

Purpose:Study the effects of dual antplatelet therapy beyond1yt.to prevent thrombotic complications after drug-eluting stents.

Methods:After 12 mo treatmentwith dopidogrel or prasugrel.patents were randomised to contnumg this therapy or receiving

placebo.The primary endpoints werestent thrombosis andmajor adverse CV events from12-30 mo.

Results:Continued treatment reduced the rates of stent thrombosis (0.4% vs.1.4%:95% Q0.17 to 0.48:P'O.OOIj.and major CV and

cerebrovascular events(4.3%vs.5.9%:95% Cl0.59 to 0.85:P

‘

0.001).The rate of moderate-severe bleeding was increased in the

contnued treatment group (2.5% vs.1.65%:P~0.001|.

Conclusions:Dual antiplatelet therapy beyond1yr confersadditional benefit

Title:Comparison of Fondaparinuiand Enoiaparin m Acute Coronary Syndromes

Purpose:Assess whether fondaparinui wouldreduce bleeding risk while retaining Lheanb-tschemic benefits of enoiaparin.

Methods:20078 patents were randomized toreceive either fondaparinui2.5mg daily,or enoiapann1mg kg twice daily.The primary

outcomes were death.Ml.refractory ischemia at 9 d.or bleedrng.

Results:The primary outcome rates were similar between the two groups (hasard rabo1.01: 95% Cl 0.90 to1.13).The rate of 9- d major

bleeding was lower in the fondaparinui group than the enoiaparin group (2.2% vs.4.1%:hazard ratio 0.52;P‘

0.001).

Conclusions:Compared to enoiaparin.fondaparinuireducedmortality rates.ma>or bleeds at 9 d.andMlat 30 and180 rt

Title:long-Term Use of TicagrelorinPatents with Prior Myocardial Infarcton

Purpose:Investigate the safety andefficacy of bcagreloc after an ACS.

Methods:21162 patients who hada prior Ml were randomised to ticagrelor 90 mg SID.or placebo. The primary endpoints were a

composite of CV death.Ml.or stoke.The primary safety endpoint was thrombolysis in Mlandmajor bleeding.

Results:Kaplan-Meier event rates showed that ticagrelor reduced event rates at 3yt.at 7.77% for the beatment group and 9.04% in the

placebo group (hasard rabo 0.85:95% Cl 0.75 to 0.96:P'0.008).Rates of major bleeding were higher with ticagrelor than with placebo

(P‘

0.001).

Conclusions:Ticagrelor on top olASA reduces CV events in patients withahistory of Ml.

Title:Ticagrelor vs.Clopidogrel inPatients with AcuteCoronary Syndromes

Purpose:Evaluate the efficacy of ticagrelor vs.dopidogrelin patients with an ACS.

Methods:18624 patients admitted to hospital with ACS.with or without ST-eleiaton.were randomized to ticagrelor (180 mg loading.

90 mg twice daily after) or clopidogrel(300-600 mg loading;75 mg daily after).The primary endpoint was a composite of vascular

death.Ml.orstok.

Results:The primary endpoint occurredin 9.8% of patents receivingticagrelor.compared with 11.7% of patients receiving clopidogrel

(hazard ratio 0.84:95% Cl 0.77 to 0.92:P‘

0.001).The rate of death was also reduced with ticagrelor (4.5% vs.5.9%:P

‘

0.001).There

were nosignificant differences in therates ofmajor b'eedmg.

Conclusions:In ACS patents with either STEMI or KSTEMI.regardless of reperfusion strategy,ticagrelor reduced mortality.Ml.and

stroke without increased bleeding compared to clopidogrel.

C0LC0T NEJM 2019:381:2497-505

COMPLETE NEJM 2019:381:1411-21

DAPT NEJM 2014:371:2155-66

OASIS-5 NEJM 2006:354:1464-76

PEGASUS- IIMI 54 NEJM 2015:372:1791-800

PLATO NEJM 2009:361:1045 57

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Trial Name Reference Clinical Trial Details

PROVE IT — TIMI 22 NEJM 2004;350:1495-504 Title:Intensive vs.Moderate Lipid LoweringwithStatins alter Scute Coronary Syndromes

Purpose:Determine the optimal LDL-C level in patients undergoing statin therapy (or reduction in risk of CV events.

Methods:4162 patients hospitalized with ACS in the preceding10 d were assigned to pravastatin 40 mg daily or atorvastalin 80 mg

daily. The primary end point was a composite of all- cause mortality Ml,US.revascularization, and stroke.

Results:Event rales were 26.3% in the pravastatin group and 22.4% in the atorvastalin group (P*0.005; 95% Cl 5 lo 26%).Ihe study

established the superiority olIhe more intensive regimen.

Conclusions:In patients hospitalized lor ACS.high dose atorvastalin reducedall- cause mortality.Ml.unstable angina,

revascularization,and stroke compared with pravastatin.

Title:Prasugrel vs.Clopidogrel in Patients with Acute Coronary Syndromes

Purpose:Compare clopidogrel and prasugrel in preventing thrombotic complications of ACS and PCI.

Methods:13608 patients with ACS and scheduled PCI were randomized to prasugrel (60 mg loading.10 mg maintenance) or clopidogrel

(300 mg loading. 75 mg maintenance).Ihe primary endpoint was CV death,non-fatal Ml. or non-latal stroke.The safety endpoint was

major bleeding.

Results:Iheprimary endpoint occurred in12.1% olclopidogrel patients and 9.9% ol prasugrel patients (hazard ratio 0.81;95% Cl 0.73

to 0.90:P<0.00t).Major bleeding was observed in 2.4% olprasugrel patients and1.8% ol clopidogrel patients (hazard ratio 1.32; 95%

Cl 1.0310I.68:P-0.03.)

Conclusions:In ACS patients scheduled for PCI.prasugrelreduced ischemic events but increased major bleeding compared lo

clopidogrel.

TRITON TIMI 38 NEJM 2007:357:2001-15

TRANSCATHETER AORTIC VALVE REPLACEMENT

NEJM 2016;374:1609-20 Title:Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients

Purpose:Evaluate survival rales between TAVR and surgical aortic valve replacement,inintermediaterisk patients.

Methods:2032intermediate risk patients were randomized lo 1AVR or surgicalreplacement. The primary endpoint was all-cause

mortality or disabling stroke al 2 yr.

Results: The rales ol primar y outcomes were similar between TAVR and surgicalreplacement groups (P'0.001).Al 2 yr.Ihe KaplanMeier event rates were 19.3% in the TAVR group and 21.1% in the surgical group (hazard ralio 0.89:95% Cl 0.73 lo1.09;P-0.25).

Surgery resulted in fewer major vascular complications and less paravaIvular aortic regurgitation.

Conclusions:In intermediate-risk patients with AS.TAVR and SAVR resulted in similar rales of all- cause mortality and disabling stroke.

Title:Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve inLow-Risk Patients

Purpose:Compare major outcomes in low-risk patients between TAVR andsurgical aortic-valve replacement.

Methods:1000 patients withsevere aortic stenosisand low surgical risk were randomized to TAVR or surgical aortic valve replacement.

Ihe primary endpoint was a composite of death,stroke, or rehospitalization at 1yr.

Results: The Kaplan- Meier event rales were significantly lower In Ihe TAVR group thanIhe surgery group (8.5% vs.15.1%;95% Cl 10,8

lo -2.5:P'

0.001) At 30 d. TAVR resulted inlower stroke rates and new-onset atrial fibrillation. There were no significant dtflercnces in

major vascular complications,new pacemaker insertion, or paravalvular regurgitation.

Conclusions:Among low-surgicalrisk patients withsevere AS.the rate olthe composite of death,stroke,or rehospitalization was

significantly lower with TAVR compared to surgical aortic-valve replacement.

PARTNER II

PARTNER III NEJM 2019:380:1695-705

HEART FAILURE

C0APT NEJM 2018:3792307-18 Title:Transcatheter Mitral-Valve Repair inPatients with Heart Failure

Purpose:Assess improvement in outcomes in patients with MR due loIV dysfunction, from transcatheter mitral valve repair.

Methods:Patients with HE and secondary mitral regurgitation were randomized lo transcatheter mitral-valve repair plus medical

therapy,or tomedical therapy alone. The primary endpoint was hospitalization lor HE al 24 mo.

Results: The primary cndpoml was 35.8% in the intervention group, compared to 67.9% in the control group (hazard ratio 0.53; 95%

Cl 0.40 lo 0.70;P<0.001|.Death Irom any cause occurred at 29.1% In the intervention group compared with 46.1% inIhe control group

(hazard ralio 0.62:95%Cl 0.46 to 0.82:P'

0.001).

Conclusions:Among patients with HE and secondary MR who remained symptomatic despite medical therapy,transcatheter mitralvalve repairresultedina lowerrate of hospitalization for HE and tower mortality than medical therapy alone.

Title:Effects of Candesartan on Mortality and Morbidity in Patients with Chronic Heart Failure:The Charm-Overall Programme

Purpose:Determine whether ACEI use could reduce mortality and morbidity in patients with CHE.

Methods:Patients with LVEF <40% not receiving ACEIs were randomized to candesartan or placebo.Ihe primary outcome was all-cause

mortality.CV death,or hospital admission for CNF.

Results: Mortality was 23% in Ihe candesartan gioup and 25%Inthe placebo group (hazard ratio 0.91:95% Cl 0.83 lo 1.00: P'0.055),

with (ewer CV deaths (18% vs..20%;P-0.012).

Conclusions:Candesartan reduced overall mortality.CV death,and CHE hospitalizations.

Title:Ihe Cardiac Insufficiency Bisoprolol Study It (CI8ISII):A Randomised Trial

Purpose:Investigate the efficacy of bisoprolol in decreasing all-cause mortality in CHE.

Methods:2647 patients with LVEF <35%receiving standard therapy were randomized to bisoprolol or placebo.Ihe primary outcome

was all-cause mortality.

Results:All-cause mortality was significantly lower withbisoprolol than placebo (11.8% vs.17.3%,hazard ratio 0.66:95% Cl 0.54 to

0.81: P'

0.0001).Treatment effects were independent of etiology or severity of HE/

Conclusions:Bisoprolol reduced all-cause mortality.CV death, all-cause hospitalization,and CHE hospitalization/

Title:Comparison of Carvcdilol and Meloprolol on Clinical Outcomes inPatients withChronic Heart Failure in the Carvedilol or

Meloprolol European Trial (Cornel):Randomised Controlled Trial

Purpose:Compare outcomes of chronic HFrEF patients on carvedilol or meloprolol.

Methods:1511patients with CHE were randomized to carvedilol 25 mg twice daily,and1518 randomized to metoprolol 50 mg twice

daily.The primary endpoints were all-cause mortality,and the composite of all-cause mortality or all-cause admissio.n

Results: The all

-cause mortality was 34% for carvedilol patients and 40% for metoprolol patients (hazard ratio 0.83:95% Cl 0.74 lo

0.93:P'0.0017).Incidence of side effects and withdrawal did not differ significantly between groups.

Conclusions:Carvedilol was associated with a reduction inall-cause mortality compared withmeloprolol.

Title: Effect ol Carvedilol on Survival in Severe Chronic Heart Failure

Purpose:Assess Ihe effects ol fl-blockade on hospitalization and mortality inpatients with severe HE.

Methods 2289 patients with HE symptoms at rest and an EE <25% were randomized to carvedilol or placebo.Primar y endpoints were

rates of hospitalization and mortality.

Results:There was a 35% reduction in mortalityrisk in patients treated with carvedilol than placebo (95% Cl19% to 48%;P-0.0018).

Conclusions:Carvedilol in addition to standard treatment significantly reducedIhe risk of death or hospitalization in patients with

severe CHE.

CHARM Lancet 2003:362:759 66

CIBISII Lancet 1999:353:9-13

COMET Lancet 2003:362:7-13

COPERNICUS NEJM 2001:344:1651 58

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Trial Name Reference Clinical Trial Details

DAPi Hf NEJM 2019:381:1995-2008 Title:Dapagliflozin inPatients with Heart failure and Reduced Ejection Fraction

Purpose:Assess the efficacy of theSGLT2 inhibitor dapagliflorin in patients with HFrEF,independent of T2DM status.

Methods:4744 patients withHf andEf <40% were randomized to receive dapag'iflozin10 mg once daily,or placebo,in addition to

recommended therapy.The primary outcome was worsening Hf or CV death.

Results:The primary outcome occurred in16.3% of dapagliflorin-treated patents and 21.2% of placebo patients (hazard ratio 0.74:

95% Cl 0.65 to 0.85;P<0.001).A worsening of HF occurred at10.0% in the dapaghflozin group and 13.7% in the placebo group (hazard

ratio 0.70:95% Cl 0.59 to 0.83).findings in patients with DM were comparable to those in patients without DM.

Condusions:In patients withHfrEf.the risk of worsening HF or death from CV causes was lower among those who received

dapagliflorin than those whoreceived placebo.

Title:Empaglillozinin Heart Failure with a Preserved EjectionFraction

Purpose:Assess the efficacy of the S6LT2 inhibitor empagliflozin inpatents with HFmrEF and HFpEf. irrespective of diabetes status.

Methods: 5988 patients with symptomatic Hf and an EF >40% were randomized to receive empagliflozin10 mg once daily,or placebo,

in addition to usual therapy.The primary outcome was a composite of CV mortality or hospitalization for HF.

Results:Empagliflozin was assocated with a lower risk of CV mortality or hospitakzation for HF (13.8% vs.17.1%:HR 0.79:95% Cl 0.69

to 0.90;P<0.001),which wasmainly related to fewer HF hospitalization events in the empagliflozin group.Ihe effects of empagliflozin

appeared consistent in patients with or without diabetes.

Conclusions:In pabents with HFmrEF and HFpEF.empagliflozin was associated with a lower risk of the CV mortality or hospitalization

for HF.and this effect was primarily driven by fewer HF hospitalizations.

Title:Cardiovascular and Renal Outcomes with Empagliflozinin Heart Failure

Purpose:Assess the efficacy of the$GU2 inhibitor empagliflozin inpatients with HFrEF.irrespective of diabetes status.

Methods: 3730 patients with symptomatic HF and an EF <40% were randomized to receive empagliflozin 10 mg once daily. or placebo,

in addition to usual therapy.The primary outcome was a composite of CV mortality or hospitalization for worsening HF.

Results:Empagliflozin was associated with a lower risk of CV mortality or hospitaization for HF (19.4% vs.24.7%:HR 0.75:95% Cl 0.65

to 0.86;P<0.001).The effect of empagliflozin on the primary outcomewas consistent inpatients regardless of diabetes status.

Conclusions:In patients with HFrEF.empagliflozin was associated with a lower risk of CV mortality or hospitalization for HF.

independent of diabetes status.

Title:Irbesartan in Pabents with Heart Failure and Preserved Ejecbon Fracbon

Purpose:Study the effects of irbesartan in patients with HF and EF »45%.

Methods: 4128 patients withHF and EF »45% were randomized to irbesartan 300 mg daily,or matching placebo.Iheprimary outcome

was a composite of all-cause mortality or CV hospitalization.

Results:Ihe primary outcome occurred in 742 patients inIhe irbesartan group and 763 placebo patients (hazard ratio 0.95:95% Cl

0.86 to1.05:P-0.35). Overall,rates of death were 52.6 and 52.3 per 1000 patient-yr.respectively.

Conclusions:In pabents withCHF and normal LVEF.treatment with ARB (ubesattan) did not improve mortality or CV morbidity

compared to placebo.

Title:Angiotensin-Neprilysin Inhibition vs.Enalapril in Heart Failure

Purpose:Compare survival inHFrEF pabents treated with enalaprilor an angiotensin-neprilysin inhibitor.

Methods:8442 patients withHF and EF <40% were randomized to LC2696 200mg twice daily,or enalapril10mg twice daily.The

primary endpoint was a composite of CV death and HF hospitalization.

Results:The primary outcome occurred in 21.8% of LC 2696-treated patients and 26.5% of enalapril patients (hazardrabo 0.80c 95%

Cl 0.73 to 0.87;P<0.001).13_3% and16.5% of patients treated with LC2696 and enalapril.respectively,died of CV causes (hazardratio

0.80; 95% Cl 0.71to 0.89;P<0.001J

Conclusions:Novel drug (IC2696) containing valsartan and a neprilysiu inhibitor (prevents degradation of natriuretic pepbdes) reduces

hospitalization and mortality.

Title:Ihe Effect of Spironolactone on Morbidity and Mortality m Patients withSevere Heart Failure

Purpose:Assess the efficacy of spironolactone onmorbidity and mortality in patients withsevere HF.

Methods: 1663 patients withsevere HF and LVEF <35% who were being treated with ACEI.loop diuretic and digonn.wererandomized

to spironolactone 25 mg daily or placebo.The primary endpoint was all-cause mortality.

Results:There was a mortality rate of 46% in the placebo group,compared to 35% in the spironolactone group (RR 0.70:95% Cl 0.60

to 0.82:P<0.001).The freguency of hospitalization for worsening HF was 35% less in the intervention group (RR 0.65195% 00.54 to

0.77,P<0.001).

Condusions:In severe CHF (class lll

'

IV) and LVEF <35%.spironolactone reduced all-cause mortality,sudden death,and death due to

progression of HF.

Title:Amiodarone or an Implantable Cardioverter-Defibrillator for Congestive Heart Failure

Purpose:Study prognosis differences in CHF patients healed with amiodaroneor ICO.

Methods: 2521patients withCHF and LVEF <35% were randomized to conventional therapy plus placebo, conventional therapy plus

amiodarone.or conventional therapy plus shock- only single-lead ICD. The primary endpoint was death from any cause.

Results: Mortality rates were 29% in placebo patients. 28% in the am odatone group,and 22%in Ihe ICD group (hazard ratio1.06:

97.5% Cl 0.86 to 1.30:P'0.53).ICD was associated with a decreased risk of death of 23% compared to placebo lhazard ratio 0.77:

97.5% Cl 0.62 to 0.96:P'

0.007).Results did not vary based onischemic or nonischemic causes of CHF.

Conclusions:In mild-to-moderate CHF.shock-only ICD significantly reduces risk of death:amiodarone had no benefit compared with

placebo in treabng patients withmild-to-moderate CHF.

Title:A Clinical Trial of the Angiotensm-Converting-Enzyme Inhibitor Trandolapril inPabents with Left Ventricular Dysfuncbon after

Myocardial Infarction

Purpose:Determine whetherthe mortality benefit of ACEI post- MI extends to allpabents, or only selected pabents.

Methods:On d 3-7 post-MI.1749 pabents were randomized to receive oral trandolapril or placebo.The primary endpoint was all-cause

mortality.

Results:The mortality rate was 34.7% in the trandolapril group,comparedwih42.3% in the placebo group (P‘0.001:RR 0.78:95% Cl

0.67 to 0.91). Trandolaprilreduced rates of sudden death [RR 0.75:95% Cl 0.59 to 0.98:P'

0.03) and CV death (RR 0.75:0.62 to 0.89:

P-0.001).

Conclusions:In pabents withIV dysfunction post-MI,long-term trandolaprilreduced the risk of death or progression tosevere CHF and

reduced risk of sudden death.

EUPEROR-Preserved NEJM 2021:385:1451-1461

EMPEROR Reduced NEJM 2020;383:1413-1424

I PRESERVE NEJM 2008:359:2456-67

PARADIGM HF NEJM 2014:371593-1004

RALES NEJM 1999:341:70917

SCD-HeF! NEJM 2005;352:225-37

TRACE NEJM1995:333:1670-76

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C79 Cardiology and Cardiac Surgery Toronto Notes 2023

Trial Name Reference Clinical Trial Details

ARRHYTHMIA

Title:A Comparison of Rate Control and Rhythm Control inPatients with Atrial Fibrillation

Purpose:Compare rate and rhythm control in patients with AFib and high risk of stroke or death.

Methods:4060patients with AFib were randomized to rhythm-control therapy with antiarrhythmic drugs,or rate-control therapy.

Results:The mortality rate was 23.8% in rhythm-controlled patients and 21.3% in rate-controlled patients (hazard ratio1.15:55% Cl

0.95 lo1.34:P -0.08).More patients were hospitalized in the rhythm-control group,with higher rates of adverse drug events.

Conclusions:No significant differencein mortality rates between rate or rhythm control of AFib.

Title:Apnaban vs.Warfarin inPatients with Atrial Fibrillation

Purpose:Assess the efficacy of apixaban for stroke prevention in patients with AF.in comparison with warfann.

Methods:18201patients with AFib and one additional RF for stroke were randomized to apixaban 5 mg twice daily or warfarin.The

primary outcome wasstroke or systemic embolism.

Results:The rate of primary outcome was1.27%per year in the apixaban group and1.60% per year in the warfarin group (hazardratio

0.79:95% Cl 0.66 to 0.95;P'

0.001).The rate of major bleeding was 2.13% per year with apixaban and3.09% per year with warfann

(hazard ratio 0.69;95% Cl 0.69 to 0.80:P'

0.001). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group and 0.47%

per year in the warfann group.

Conclusions:AFib patients treated with apixaban had a lower incidence of stroke,major bleeding and mortality compared to warfarin.

Title:Antithrombotic Therapy after Acute Coronary Syndrome or PCIin AtrialFibrillation

Purpose:Elucidate benefits of antithrombotic regimens for patients with AFib and either ACS or previousPCI.

Methods:Patients with AFib and a prior ACS or PCI were randomized to apixaban or a vitamin K antagonist,and to ASA or placebo for 6

mo.Theprimary outcome wasmajor or clinically relevant non-major bleeding.

Results:The primary outcome occurred in10.5% of apixaban patients and14.7% of vitamin K antagonist-patients (hazard ratio 0.69:

95% Cl1.59 to 2.25:P'

0.001).Patients in the apixaban group had a lower incidence of death or hospitalization compared to the vitamin

K antagonist group (23.5% vs. 27.4%:hazard ratio 0.83; 95% Cl 0.74 lo 0.93:P-0.002).

Conclusions:In patients with AFib and recent ACS or PCI.apixaban reduced bleeding compared to regimens that includeda vitamin K

antagonist.ASA. or both.

JAMA Cardiol.2020:5:1358-65 Title:Coronary Angiography after Cardiac Arrest without ST Segment Elevation: One-Year Outcomes of the COACT RandomizedClinical

AFFIRM NEJM 2002:347:1825-33

ARISTOTLE NEJM 2011:365:531-92

AUGUSTUS NEJM 2019:380:1509-24

COACT

Trial

Purpose:Compare1-yr clinical outcomes of immediate angiography and PCI versus delayed angiography in resuscitated cardiac arrest

patients without STEMI.

Methods:552 patients who had undergone cardiac arrest in the absence ot STEMI were randomized to immediate coronary

angiography,or angiography after recovery of neurological function.PCI was carried outas indicated by angiography,in keeping

with the time allotments between groups.The primary endpoints were survival.Ml.revascularization,hospitalization for HF.and the

composite of death and Ml.at1yr follow-up lime.

Results:Survival at1-yr follow-up were 61.4% and 64.0% in the immediate angiography and delayed angiography groups,respectively

(OR 0.90:95% Cl 0.63 to1.28:P'

0.51).Similar to 90-d outcomes,this represents a statistically insignificant difference.Mlrates were

0.8% and 0.4% in the immediate and delayed groups,respectively (OR 1.96:95%CI 0.18 to 21.8).The composite outcome of death,

revascularization,or Mloccurred at a rate of 42.9% and 40.6% in the immediate and delayed groups,respectively (OR 1.10:95% Cl0.77

to156).

Conclusions:Similar to the previous90-d follow-up,immediate angiography did not significantly improve1-yr clinical outcomes

compared to delayed angiography inresuscitated cardiac arrest patients without evidence of STEMI.

Title:Edoxaban vs.Warfarin in Patients with Atrial Fibrillation

Purpose:Compare thelong-term efficacy and safety of edoxaban and warfarininAFib patients.

Metbods:21105 patients with moderate-high risk AFib were randomized to two once-daily regimens of edoxaban or warfarin.The

primary endpoint was stroke or systemic embolism.

Results:The primary endpointrate was1.50% with warfarinand1.18% in the edoxaban group (hazard ratio 0.79:97.5% Cl 0.63 to 0.95:

P'

0.001).The annualized rate of major bleeding was 3.43% with warfarin and 2.75% with high-dose edoxaban (hazard ratio 0.80:95%

00.71to 0.91;P'

0.001).

Conclusions:AFib patients treated with edoxaban had similar rates of stroke and lower rates of major bleeding compared to warfarin.

TitleiAlcohol Abstinence in Drinkers with Atrial Fibrillation

Purpose:Study the effects of alcohol abstinenceon secondary prevention of atrial fibrillation.

Methods:Adults who consumed ^

standardized drinks/wk with AFib were randomized to abstinence or continuation of current

practices.The two primary endpoints were freedom from AFib rccurrenceand total AFib burden.

Results:Alter a 2-wk blanking period.AFib recurred in 53% of patients in the abstinence group and 73% of patients m the control group

(hazard ratio 0.55:95% Cl 0.36 to 0.84:P-0.005). The AFib burden after 6 mo was lower in the abstinence group than the control group.

Conclusions:Abstinence from alcohol reduced arrhythmia recuriences in regular drinkers with AFib.

Title:Oabigatran vs.Warfarin inPatients with Atrial Fibrillation

Purpose:Compare the reduction of stroke risk in AFib patients with warfarin versus dabigatran.

Methods:18113 patients with AFib and stroke risk were randomized to fixed doses of dabigatran (110 mg or 150 mg twice daily) or

warfarin.The primary outcome was systemic embolism.

Results:Rates of primary outcomes were 1.69% per year with vrarfarin,compared with1.53% per year with110 mg dabigatran(RR

0.91:95% Cl 0.74to1.11:P«0.001) and1.11% per year with150 mg dabigatran (RR 0.66:95% Cl 0.53 to 0.82:P'

0.001).The rate of

major bleeding was 3.36% in the warfarin group,compared to 2.71% in the dabigatran110 mg group and 3.TI% in the dabigaban150

mg group.

Conclusions:AFib patients heated with dabigatran had a lovrer incidence of stroke compared to warfarin,withsimilar rates of major

bleeding.

Trtle:Rivaroxaban vs.Warfarin in Nonvalvular Atrial Fibrillation

Purpose:Compare rivaroiaban with warfarin in reducing stroke risk inAFib patients.

Methods:14264patients with nonvalvular AFib were randomized to rivaroiaban 20 mg daily or dose-adjusted warfarin.The primary

endpoint was stroke or systemic embolism.

Results:The primary endpoint occurred in1.7% of patients in the rivaroxaban group and 2.2% of patients on warfarin(hazard ratio

0.79:95% Cl 0.66 to 0.96:P'

0.001).Major and non-major bleeding occurred in14.9% of patients in therivaroiaban group and14.5% of

warfarin patients|hazard ratio1.03; 95% Cl 0.96 to1.11;P“0.44|.

Conclusions:Inpatients with AFib. rivaroxaban is non-inferior to warfarin for stroke prevention without an excess of maior bleerhng.

ENGAGE AF-TIMI48 NEJM 2013:369:2093 104

ET 0H AFib NEJM 2020:382:20-23

RELY NEJM 2009:361:1139 51

ROCKET-AFib NEJM 2011:365:883-91

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C80 Cardiology and Cardiac Surgery Toronto Notes 2023

Trial Name Rctcrenee Clinical Trial Details

HYPERTENSION

HYVEI HUM 2008:368:188/ 98 Title:treatment ol Hypertension in Patients 80 Years ol Age or Older

Purpose:Assess anlihypcrlensive therapy lor stroke risk reduction,in patients -80 yr with hypertension.

Methods:3845 patients with sBP -160 mmHg and >80 yr were randomiied to mdapamide SR 2.5 mg or placebo.Penndopril 2 mg or 4

mg was added ilneeded lo achieve target BP 160/80 mmHg.the primaiy endpoint was fatal or non-fatal stroke.

Results:Active treatment was associated with a 30% reduction in fatal or non-fatal stroke (95% Cl -1lo 51;P*0.06),a 39% reduction in

death from stroke (95% Cl1to 62:P'0.05) and a 21% reduction in all-cause mortality|9S% Cl 4 to 36;P‘

0.02).

Conclusions:In hypertensive patients

-

80 yr,treatment with indapamide.with or without perindopril, showed a trend towards

reduced relative risk of fatal or non-fatal stroke.

Title:A Randomized Trial of Intensive vs.Standard Blood-Pressure Control

Purpose:Determine appropriate targets for sBP to reduce CV morbidity and mortality among patients without DM.

Methods:9361patients with an sBP130 mmHg or greater and increased CV risk,without diabetes, were randomized to s8P target <120

mmHg or <140 mmHg.The primary outcome was a composite of Ml.other ACS.stroke, HF,or CV death.

Results:There was a significant reduction in the rates of primary outcome in the intensive group compared to the conservative group

(1.65% vs.2.19%;hazard ratio 0.75;95% Cl 0.64 lo 0.89:P<0.001).All- cause mortality was significantly lowered in the intensive group

(hazard ratio 0.73;95% Cl 0.60 to 0.90;P'0.003).

Conclusions:In patients with high risk of CV events deluding DM. strict sBP contiol (<120 mmHg) is associated with fewer CV events

and lower all-cause mortality.

SPRINT NEJM 2015;373:2103-16

lancet 2004;363:2022-31 Title:Outcomes inHypertensive Patients at High Cardiovascular Risk Treated with Regimens Based on Valsartan or Amlodipine: The

Value Randomised Trial

Purpose:Determine whether valsartan would reduce cardiac morbidity more than amlodipine in hypertensive patients with high CV

VALUE

risk.

Methods:15245 patients with hypertension and high CV risk were randomized to valsartan or amlodipine.The primary endpoint was a

composite of cardiac morbidity and mortality.

Results:The primary composite endpoints occurred in 10.6% of patients in the valsartan group and10.4% of patients in the amlodipine

group (hazard ratio1.04; 95% Cl 0.94 to 1.15:P'0.49).

Conclusions:The valsartan group had a higher incidence of Ml than the amlodipine group.

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ACPAAlS/PCNA/SCAI/SIS Ouidcline for the diagnosisand managementof patients withstable ischemic heart disease.JACC 2012;60:e44- e164,

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ACCF/AHA 2009 focused update on the guidelines for the diagnosis and management of heart failure in adults.Circulation 2009:119:1977- 2016.

Adler Y.Charron P.Imaiio M.et al. ESC Scienlific Document Croup.2015 ESC Guidelineslor the diagnosis and managementof pericardial diseases:The task Force lor the Diagnosis and Management of Pericardial

Oiseascsof the European Society ol Cardiology (ESC) Endorsed by:The European Association for Cardio Thoracic Surgery (EACTS).European Heart Journal.Volume 36.Issue 42.7 November 2015.Pages

2921-2964.

Ahmed AH.Shankar KJ.Eftekhari H. et al.Silent myocardial ischemia:Current perspectives and future directions (Internet].Vol.12.Experimental andClinical Cardiology.Pulsus Group:2007 (cited 2021Jun 6|.p.

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