Transcript Atypical features of angina pain
Ischemic Heart Disease (IHD): Angina Pectoris
Angina pectoris is the collection of symptoms resulting from myocardial ischemia as a result of atherosclerosis of coronary arteries
IHD
is also called coronary artery disease ( CAD ) or coronary heart disease ( CHD ) CHD includes together with angina, acute coronary syndrome (
ACS
) ACS comprises unstable angina (USA), acute myocardial infarction (MI), acute HF, and sudden death 1
Features of Angina Pain
Location:
Over the sternum or near to it, Small area of chest (≤3 cm), entire right/left side, leg pain
Radiation
to left shoulder/arm, jaw, tongue, teeth
Duration:
Ranges from seconds to hours
Descriptors:
pricking, gas Sharp, sticking, stabbing, knifelike,
Triggers:
Exercise, heavy meals, body position, cold weather
Nitroglycerin relief:
after 45 seconds-5 min
ECG:
ST-depression, T-wave inversion 2
Causes of Angina Pectoris
Typical angina results from advanced
coronary atherosclerosis
in at least one moderately sized epicardial coronary artery In general,
obstructions in diameter of 60% or greater
are likely to be associated with angina, whereas lesions of less than 50% ordinarily do not cause ischemia Severe angina (chest pain caused by little exertion) is usually associated with coronary obstructions of 80% to 100% Patients are often characterized as having one-, two-, or three-vessel disease, as determined by coronary arteriography 3
Causes of Angina Pectoris
A
, Several high-grade narrowing of a right coronary artery.
B
, Severe (>90%) stenosis (
arrows
) of a left anterior descending coronary artery 4
Coronary Stenosis
Coronary artery obstructions are capable of changing caliber, Constriction or narrowing of a preexisting lesion can be a factor in precipitating angina and myocardial ischemia
Nitrates Eccentric
5
Concentric
Risk Factors for Coronary Artey Disease
Modifiable CAD Risk Factors Causative Risk Factors (directly associated with CAD development)
o o o o o Cigarette smoking Hypertension Kidney disease Diabetes mellitus (Type-1 & 2) Elevated LDL & Reduced HDL
Predisposing Risk factors (Direct Impact on Causative RF Development) Non-modifiable CAD Risk Factors
Obesity (BMI? 25 kg/m Physical inactivity Socioeconomic factors 2 )
Age:
Males > 45 years Females > 55 years Male Gender Family history of coronary artery disease 6
Non-standard CAD Risk Factor
Non-standard CAD Risk Factor Lipoprotein(a) Homocysteine
Significance
Lp(a) is a cholesterol-rich plasma lipoprotein with a structure very similar to low density lipoprotein Increased levels of Lp(a) are associated with high risk for atherothrombotic cardiovascular disease. Homocysteine is sulphur containing amino acid and is derived from dietary methionine. Hyperhomocysteinemia is a risk factor for development of cardiovascular disease. It is associated with other cardiovascular risk factors like male gender, old age, smoking, high blood pressure, elevated cholesterol and lack of exercise. 7
AHA/ACC Guidelines for the Secondary Prevention for Patients with Coronary and Other Atherosclerotic Vascular Disease Risk Factor
Smoking Blood Pressure Lipid Metabolism Diabetes Physical activity Body Weight Influenza vaccination
Intervention & Goal
Complete cessation <140/90 mm Hg & <130/80 mm Hg in diabetics & kidney disease LDL-C <100 mg/dL, If triglycerides >200 mg/dL, non –HDL-C should be <130 mg/dL Hemoglobin A 1C <7% At least 30 min of moderate intensity aerobic activity (e.g., brisk walking) for minimum of 5 days/wk BMI between 18.5
–24.9 kg/m 2 Waist circumference men <40 in, women <35 in Patients with CAD should have an annual influenza vaccination 8
Myocardial Oxygen Supply & Demand
Oxygen Supply
•
Coronary Blood Flow
•
Oxygen Extraction & Saturation Oxygen Demand
•
Cardiac Contractility/Rate
•
Ventricular Wall Tension (Systolic & Diastolic )
9
Treatment Overview
Medical management should be
individualized
Risk factor modification is indispensible for prevention & treatment of CHD
Goal of therapy:
reduction of the number, severity, & duration of anginal attacks
Six drug classes are used alone/ in combinations: o o
Nitrates β-blockers
o
Calcium channel blockers
o
Antiplatelets, Anticoagulants
o
ACE inhibitors
10
Diagnostic Procedures
• Exercise tolerance test: ECG signs of ischemia, angina HR-SBP product is usually used • Myocardial imaging, echocardiographic or nuclear, preferred to exercise tolerance Pharmacologic stress (e.g, dobutamine or adenosine injection) can be used Cardiac catheterization & subsequent angiography can detect coronary artery spasm 11
Anti-Ischemic Drug Therapy
NITRATES
Treatment of all anginal syndromes Mechanism & Properties: Inhibition of thromboxane synthase Venodilation is more than arterial because the latter needs higher plasma nitrate level NO production→ + vascular SM –SH groups →
S nitrothiols
→
Activation of
Guanylate cyclase
→ Increased intracellular cGMP
Venous dilation
→
lowered preload
→reduction of ventricular filling pressure → decreased myocardial 12 O 2 consumption → anginal pain relief
NITRATES
Coronary artery vasodilation
→ increased coronary blood flow
increased oxygen supply
Angiographic studies showed that coronary arteries with eccentric atherosclelerotic lesion will dilate in response to nitrates Another antianginal agent (ß-blocker or CCB) must provide the antianginal effect during the nitrate-free perio d 13
Short-Acting Nitrates Sublingual Nitroglycerin (NTG)
Dose: mostly 0.4 mg, relief of pain, objective hemodynamic effect (10 mm Hg drop, ↑HR) Onset: 1-3 min, duration:10-30 Prevention of attack: To be taken 5-10 min before the exertion that possibly precipitate angina Instructions to Patient: o Sit immediately, place NTG tablet under tongue o o o o Max three tablets over 15 min If pain persists >30 min →suspected MI NTG tablets are volatile →a tablet left outside loses activity in min An open bottle →use for 6-12 months 14
Nitroglycerin Lingual Spray
NTG lingual spray, 0.4 mg/metered dose is an alternative for SL NTG Each canister has
200 metered dose/3 years shelf-life
Spray a single dose under or onto the tongue NTG lingual spray should not be inhaled Max dose: three sprays over 15 min 15
Long-Acting Nitrates
o NTG: SR capsule, Topical ointment, transdermal patches o
Isosorbide Dinitrate (ISDN):
oral, SR, SL, and chewable o
Isosorbide Mononitrate (ISMN):
release tablets SR tab, rapid Long-acting nitrates are the
prevention corner stone therapy of all types angina
CCB can be an alternative especially if angina patient has improperly controlled HTN 16
Side Effects to Nitrates
Hypotension
Headache : tolerance develops after few weeks
Dizziness
Syncope/fainting
necessitates dosage reduction o o Severe hypotension & bradycardia caused cardiac arrest in patients experiencing MI NTG-induced vaso vagal response → NTG syncope → leg elevation, atropine, fluids
Met-Hbemia
doses used is important when large IV NTG 17
Nitrate Tolerance
Tolerance is unlikely to occur with NTG (SL, oral spray), and SL isosorbide dinitrate Tolerance is likely with long-acting oral nitrates (ISMN) & transdermal patches 12 hour NTG transdermal patches’ intermittent therapy minimize tolerance
Intravenous NTG
used in unstable angina (USA) & severe HF is associated with tolerance
12 hour intermittent intravenous NTG
limit nitrate tolerance 18
Nitrate Tolerance Minimization
Nitrate-free interval of 10-12 hours
tolerance to therapeutic activity minimize Lowest effective nitrate dose lower tolerance ß-blocker or CCB is given to provide anginal protection during nitrate-free period Long-acting nitrates have no evidence of causing tolerance to SL nitrates’ use 19
MECHANISM OF Nitrate Tolerance
• • • • Depletion of vascular –SH groups, plasma volume expansion, neurohormonal activation Nitrates increases superoxide anion (O 2 ) + NO →
peroxynitrite
producing: Decreased endothelial NO production Increased sympathetic & RAA systems Increased vasoconstrictor responsiveness Peroxynitrite-dependent assumption stimulates the question: dose nitrate have long-term detrimental effects?
20
ISOSORBIDE DINITRATE & MONONITRATE (ISDN & ISMN)
ISDN oral formulation is used usually three times a day especially in severe angina Usually ISDN is taken at
7 AM, Noon &
allow 12 hr nitrate-free period
5 PM
to ISDN can be given
twice/day
severity angina in moderate
Isosorbide mononitrate (ISMN)
can be given
once or twice/day
(
early morning & 7 hrs later
) ISMN has better patient compliance 21
ß
-ADRENERGIC BLOCKERS
Decreased myocardial oxygen consumption
by
lowering adrenergic-related HR, BP & contractility
ß 2 adrenergic receptors contractility & HR were shown to be present in the heart by 10-40%, possibly augment cardiac In chronic angina: ß-blockers should be given before nitrates & CCBs ß-blockers are
more effective
than the other two agents in lowering incidence of anginal episodes The three classes are similar in mortality reduction They lower
CV morbidity/mortality
in HTN, HF, or MI patients 22
ß
-ADRENERGIC BLOCKERS THERAPEUTIC ENDPOINT
Anginal attacks frequency & NTG consumption
are indices for therapeutic efficiency of antianginals Reduction in
resting HR
ß-blockers’ dose is best monitored to adjust Dose can be increased till
HR is 55 b/min
, even 50 b/min is acceptable for asymptomatic patients ß-blockers with ISA do not lower resting HR Exercise testing is the best, though least practical: Reduction of exercise ST-depression HR-SBP product usually decreases (lowered wall tension & HR) 23
β-Adrenergic Blockers
Dosing
β-blocker
pharmacodynamic actions are longer than their plasma half-lives
Usually taken
once to twice daily
for angina Atenolol t 1/2 is 10 hours but clinical evidence support the effectiveness of once daily regimen
Propranolol
is of short 2-3 hrs t 1/2 , yet
its BP/HR lowering effects are pronounced for 12 hours
Clinical evidence support the effectiveness of
twice daily regimen of propranolol
24
β-Adrenergic Blockers
Cardio-selective & Contraindications
• • Cardio selective ß-blockers
did NOT
produce adverse respiratory effects in moderate respiratory diseases (Meta-analysis) Cardio selective ß-blockers low inhibition of ß 2 induced peripheral vasodilation ( α-vasoconstrictn) • Atenolol/acebutalol/metoprolol preferred in peripheral vascular disease & Raynaude’s disease DIABETES is NOT a contraindication for ß-blockers Lower mortality in diabetics after MI CAD is more severe in diabetics & has worse prognosis over that developed in non-diabbetics 25
β-Adrenergic Blockers
ISA ß-blockers
→less effect on lipid/glucose ISA ß-blockers→ less bradycardia →less effective in angina or worsen angina (better avoided)
ß-blockers abrupt withdrawal
can be serious in
severe atherosclerosis/USA
→severe CV effects like acute MI & sudden cardiac death
ß-blockers withdrawal schedule can be a two weeks four-steps on 2-3 days schedule
26
CALCIUM CHANNEL BLOCKERS
Amlodipine & felodipine
(DHPs) are the only CCBs that can be used in HF patients Nifedipine IR, diltiazem & verapamil should be avoided in HF patients INDICATIONS: Vasospastic & classical exertional angina CCBs by
arterial dilation
→decrease myocardial O 2 demand CCBs cause
coronary dilation Coronary
→ increase myocardial O 2 supply Vasospasm can occur at atherosclerotic site, CCB can cause dilation 27
CALCIUM CHANNEL BLOCKERS
NIFEDIPINE:
10%
nifedipine patients experience angina worsening because of powerful dilation→ reflex increase in HR → increase O 2 demand → can cause acute MI This is frequent with IR preparations
IR nifedipine no longer used for any disease
SR nifedipine is used
Side Effects:
hypotension, dizziness (15%), facial flushing & headache & nausea
Peripheral edema with DHPs
28 Constipation with verapamil
CALCIUM CHANNEL BLOCKERS contraindications
Severe hypotension Severe aortic stenosis Extreme bradycardia Moderate to severe HF Cardiogenic shock Sick sinus syndrome Second/third degree A-V block 29
COMBINATION THERAPY
ß-blockers-nitrate-CCB
triple therapy
is an option to maximize benefit & lower side effects
Disadvantages:
Cost, possible additive side effects (HF worsening by ß-blocker-CCB) Excessive vasodilation-bradycardia in triple therapy can be minimized using CCB with less potent vasodilating properties Initial therapy in chronic angina: ß-blocker Then Nitrate or CCB is added according to patient status (No fixed guidelines) 30
COMBINATION THERAPY
Nitrates, as a second class, are preferred in patients with LV dysfunction CCBs, as a second class, are preferred whenever further BP control is needed
Two CCBs combination:
Nifedipine with verapamil or diltiazem lower dizziness & effects on cardiac conduction & contractility Two CCBs combination used when standard triple therapy (at max tolerable individual doses) is still ineffective 31
Ranolazine (FDA Approval 2006) Mechanism of Action
Unlike traditional antianginal agents, it does not have any appreciable effects on heart rate, arterial resistance vessels, the myocardial inotropicity, or coronary blood flow It does NOT affect blood pressure or heart rate Ranolazine does not affect myocardial oxygen supply or demand Early preclinical work showed that it inhibits fatty acid oxidation, however, at higher plasma level than those used therapeutically 32
Ranolazine (FDA Approval 2006) Mechanism of Action
It is now known that ranolazine's anti ischemic effects are modulated through inhibition of the
late sodium current (INa)
By inhibiting late sodium entry, and hence calcium overload during ischemia 33
Ranolazine (FDA Approval 2006) Mechanism of Action
Ranolazine effectively inhibits the consequences of ischemia as decreased microvascular perfusion, as well as increased myocardial oxygen demand This
novel mechanism of action
offers the possibility of complementary effects when added to more traditional antianginal agents which act through their hemodynamic actions 34
Vasculoprotective Drug Therapy
35
Rationale for CONVERTING ANGIOTENSIN ENZYME INHIBITORS
ACEIs reduced MI by 23% in HF patients
→
Are ACEIs beneficial in LV dysfunction-free CAD patients and post-acute MI patients?
The HOPE study:
9,297 patients with
chronic CAD
and
no HF
Ramipril reduced incidence of death, MI, stroke, need for revascularization, and angina worsening Benefit was
independent of BP lowering
effect Patients were on standard angina therapy 36
CONVERTING ANGIOTENSIN ENZYME INHIBITORS
EUROPA study : 12,218 PATIENTS, 4.2 YEARS
o Perindopril in
stable angina with no HF
o Reduction of combined incidence CV death, MI & cardiac arrest o Similar to HOPE study, is this beneficial effect class-related?
o Tissue binding & inhibition of ACE in myocardium & endothelium varies among different ACEIs
For ARBs, there is no clinical trials yet
37
Antiplatelet Therapy
Aspirin
Platelet activation produces coronary occlusion either by formation of a platelet plug or through release of vasoactive compounds from the platelets A single 100-mg aspirin dose virtually eliminates thromboxane A 2 production, whereas doses below 100 mg result in a dose-dependent reduction in thromboxane A 2 synthesis Determine the effect of aspirin doses on the TXA 2 to PGI 2 Selective inhibition of platelet-generated TXA 2 synthesis has been shown with 75 mg of controlled-release aspirin daily 38
Aspirin
It has been believed that higher doses of aspirin would produce a higher level of efficacy than low doses However, all available literature indicates that low dosages of aspirin (75 –325 mg/day) are as effective as higher dosages (625 –1,300 mg/day) in the treatment of angina Therefore, current guidelines recommend a daily dosage of
75 to 162 mg orally
for the prevention of MI and death in patients with CAD 39
Clopidogrel
Clopidogrel (Plavix), a thienopydridine, inhibits platelet function in vivo via noncompetitive antagonist of the platelet ADP receptor Clopidogrel at a dosage of 75 mg orally every day was demonstrated in one study to be slightly more effective than aspirin in the secondary prevention of MI and death in patients with various manifestations of atherosclerotic vascular disease
Clopidogrel historically was to serve as an alternative antiplatelet agent in patients with a true contraindication to aspirin
40
Clopidogrel
The magnitude of difference in benefit seen with clopidogrel was quite small and not sufficient to justify its broad scale use in the treatment of CAD Based on this study, the role of clopidogrel historically was to serve as
an alternative antiplatelet agent in patients with a true contraindication to aspirin
41
Aspirin/Clopidogrel Combination
The combination of aspirin and clopidogrel was compared with aspirin alone in patients with
acute coronary syndromes without ST-segment elevation in the CURE study
for an average of
9 months
The combination of aspirin and clopidogrel significantly reduced CVS death, nonfatal MI, or stroke The results of the CURE study were confirmed in the
Clopidogrel for Results of Events During Observation (CREDO) trial
where patients with
ACS
who were treated with
percutaneous coronary stent intervention
received aspirin/clopidogrel for
1 year
Patients receiving both aspirin and clopidogrel for 1 year had a lower incidence of death, MI, and stroke in 42 comparison to patients who only received aspirin
Aspirin/Clopidogrel Combination in Chronic CAD
Given the beneficial effects seen in patients with recent ACS, and in patients with PCI plus stent placement Is dual therapy with aspirin plus clopidogrel would be superior to aspirin in the treatment of chronic stable CAD In the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (
CHARISMA
)
trial
, 15,063 patients with documented vascular disease (CAD, cerebrovascular, peripheral arterial disease), or no documented vascular disease but with multiple cardiovascular risk factors, were assigned to aspirin alone or aspirin plus clopidogrel for an average of 28 months duration 43
Aspirin/Clopidogrel Combination in Chronic CAD
Unlike the results from ACS studies, however, the combination of aspirin plus clopidogrel did NOTreduce the incidence of the primary endpoint (risk of death, MI, stroke, or coronary revascularization) as compared with aspirin alone In a secondary analysis of patients who entered the trial with documented vascular disease, dual therapy did produce statistically significant reductions in the primary endpoint as compared with aspirin 44
VARIANT ANGINA (CORONARY ARTERY SPASM)
ST-segment elevation
variant angina is the cardinal mark for It results from severe large coronary artery segmental spasm with transient total occlusion Transient arrhythmias & conduction disturbances may be observed during pain or no symptoms
↑ HR-SBP product
characterizing stable angina during pain does not occur with variant angina Angiography can show the vasospasm
Ergonovine test
can provoke the unpredictable coronry vasospasm by stimulating α-adrenergic & 45 5-HT receptors
VARIANT ANGINA therapy
CCBs are usually preferred over nitrates or ß blockers
All CCBs are equally effective but intrinsically long-acting or SR forms are preferred
CCB-Nitrate combination
should be tried when max CCB dose is still ineffective
Aspirin is indicated for variant angina
ß-blockers mostly worsen variant angina by unmasking α-vasoconstriction by ß 2 -blockade Cardioselective ß-blockers can worsen variant 46 angina
VARIANT ANGINA therapy Prognosis
50% of variant angina patients undergo full spontaneous recovery via unknown mechanism This occurs with isolated vasospasm without atherosclerosis (short-duration symptoms) Therapy can be stopped, after gradual tapering, if patients are free from pain, significant arrhythmias, or silent ischemic episodes for one year Risk factor modification may enhance variant angina remission 47
VARIANT ANGINA therapy Development of mi
Variant angina can proceed to MI or myocardial death especially in multi-vessel coronary spasm In a small group of hospitalized variant angina patients, 76% experienced morbid cardiac events (acute MI, sudden death, & CA bypass graft) within a month of angina onset Aggressive CCB+NTG infusion during the early stages improve prognosis 48
Acute Coronary syndrome (ACS)
49
50
UA/NSTEMI Goal of Therapy
Prevent total occlusion of the infarct-related artery (a) Glycoprotein (GP) IIb/IIIa inhibitors, other antiplatelet agents, and anticoagulants (b) Percutaneous coronary intervention (PCI) can be either or both: (1) Percutaneous transluminal coronary angioplasty, (i.e., “balloon”) (2) Stent implantation 51
Unstable Angina Initial Treatment “MONA” (MOrphiNe, OxygeN, NTG)
predisposing factors (HTN, infection, HF, arrhythmias) are indispensable Pharmacologic strategy aims to reduce ischemia & inhibit thrombotic process ß-blockers must be acutely administered to prevent the progression to MI & death initialy by IV route, then orally Nitrates both SL & then intravenously for pain relief & ischemia reduction CCBs can reduce ischemia bur should be reserved to ß-blockers resistant patients 52
Unstable Angina Treatment Antiplatelets
Chewable aspirin (325 mg dose) should be administered to all patients as they prevented progression to MI & death
Aspirin
(81-325 mg/day) &
clopidogrel
(300 mg load, 75 mg PO) combination acutely & up to 1 year has been shown to decrease risk of CV death, MI & stroke in USA/NSTEMI patients Patients with USA/NSTEMI receiving aspirin & undergoing
PCI,
clopidogrel should be given prior to the procedure followed by 1-12 months treatment Patients undergoing CABG, clopidogrel should be discontinued for 5-7 days before procedure 53
Unstable Angina Treatment
•
Antithrombin
: UFH & LMWHs were found to be equivalent as regards improving clinical outcomes in USA/NSTEMI patients Enoxaparin, recommended by ACC/AHA, shown to be superior to UFH in preventing CV events GP IIb/IIa receptor antagonists , in addition to aspirin & UFH/LMWH, decreased composite risk death, MI, urgent revascularization in patients USA/NSTEMI:
Eptifibatide
and
tirofiban
Abciximab is NOT approved for UA/NSTEMI medical management unless PCI is planned within 54 24 hrs
Revascularization: Percutaneous Coronary Intervention
Percutaneous coronary intervention (PCI), also known as
angioplasty
, involves the percutaneous insertion of a balloon catheter into the femoral artery in a similar fashion to angiography Stents can be of the
bare metal (BMS)
variety, or contain a drug impregnated on the surface of the stent to prevent re-stenosis (
drug-eluting stent or DES
) 55
Revascularization: Percutaneous Coronary Intervention
Mechanical disruption of the atherosclerotic plaques and exposure of plaque contents to the bloodstream during PCI, can cause acute thrombotic events likee MI & death Potent
antiplatelet
and
antithrombotic
needed to prevent such reactions strategies are Initially, strategies involved the use of high-dose unfractionated heparin and aspirin Current strategies involve the administration of aspirin, clopidogrel, an antithrombin agent, as well as a glycoprotein (Gp) IIb/IIIa receptor antagonist in selected patients 56
Antiplatelets in Revascularization
In patients who are NOT on daily aspirin, 325 mg aspirin should be initiated 2 hrs before procrdure A
600 mg clopidogrel loading dose
on or before the procedure is recommended, producing antiplatelet action within 2 hours
GPIIb/IIIa receptor antagonists
improve outcomes in patients undergoing PCI as well as UA/NSTEMI patients medical management These agents, when administered IV during PCI and for 12 to 24 hours afterward, significantly decrease the risk of death, acute MI, or need for repeat PCI 57
Indications and Dosing of Glycoprotein IIb/IIIc Receptor Antagonists
Indication Abciximab Eptifibatide Tirofiban
Percutaneous transluminal coronary angioplasty (PCTA) Coronary stent placement Acute coronary syndrome (unstable angina and non –STEMI) 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min IV infusion × 12 hr 180 mcg/kg IV bolus, then 2.0 mcg/kg/min IV × 20–24 hr Repeat 180 mcg/kg IV bolus 10 mins after first bolus Not approved use 0.25 mg/kg IV bolus, then 0.125 mcg/kg/min IV infusion × 12 hr Same as above Not approved use 180 mcg/kg IV bolus, then 2.0 mcg/kg/min IV
× 20–24 hr
Not approved use 0.4 mcg/kg/min IV load × 30 mins, then 0.1 mcg/kg/min IV infusion
× 48–102 hr
58
Use of GpIIb/IIIa Antagonists in UA/NSTEMI
The Gp IIb/IIIa receptor antagonists currently are recommended as options in patients with USA/NSTEMI in one of the following groups: in whom catheterization and PCI is planned who have continuing ischemia despite treatment with aspirin, UFH/ LMWH/ fondaparinux/ bivalirudin, nitrates, β-blockers, and clopidogrel Patients have other high risk features, such as elevated troponin or ST-segment changes on the initial ECG 59
Antithrombin Therapy & Revascularization
Unfractionated heparin (
UFH
), LMWH enoxaparin and the direct thrombin inhibitir
bivalirudin
options for administration at the time of the are procedure They are discontinued after PCI procedure unless a compelling indication exists They are used in the following: ACS: Medical management PCI: Therapy initiated at time of procedure PCI: Continuation of prior therapy 60