2014 AHA/ACC Guideline for

the Management of Patients With

NonST-Elevation Acute Coronary Syndromes:
Executive Summary
 Nitro-glycerine Injection

Nitro-glycerine Injection is indicated for treatment of peri-operative hypertension; for

control of congestive heart failure in the setting of acute myocardial infarction; for
treatment of angina pectoris in patients who have not responded to sublingual nitro-
glycerine and -blockers; and for induction of intraoperative hypotension.

Nitro-glycerine Injection is contraindicated in patients who are allergic to it + patients

with pericardial tamponade, restrictive cardiomyopathy, or constrictive pericarditis
(where cardiac output is dependent upon venous return). Amplification of the
vasodilatory effects of nitro-glycerine by sildenafil can result in severe hypotension.

Hypotension induced by nitro-glycerine may be accompanied by paradoxical bradycardia

and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

Nitro-glycerine infusions should be administered only via a pump that can maintain a
constant infusion rate.

5 mcg/min continuous IV infusion via non-absorptive tubing; increase by 5 mcg/min

every 3 to 5 minutes as needed up to 20 mcg/min.
 Anti-Ischemic Medications
Nitrates: Recommendations
Class I
1. Patients with NSTE-ACS with continuing ischemic pain should receive
sublingual nitroglycerin tablet every 5 minutes for up to 3 doses, after which an
assessment should be made about the need for intravenous nitroglycerin if not
contraindicated. (Level of Evidence: C)
2. Intravenous nitroglycerin is indicated for patients with NSTE-ACS for the
treatment of persistent ischemia, HF, or hypertension. (Level of Evidence: B)
Class III: Harm
1. Nitrates should not be administered to patients with NSTE-ACS who recently
received a phosphodiesterase inhibitor, especially within 24 hours of sildenafil
or vardenafil, or within 48 hours of tadalafil. (Level of Evidence: B)
2. Nitrates should not be administered also to patients with hypotension or
administered with caution to patients with right ventricular infarction.
Mechanisms of action of nitrates:
1] Nitrates are endothelium-independent peripheral and coronary vasodilators.
2] Nitrates decrease cardiac preload and reduce ventricular wall tension By
dilating the capacitance vessels.
3] Nitrates result in afterload reduction and further decrease in MVO2.
4] Nitrates also dilate normal and atherosclerotic coronary arteries and increase
coronary collateral flow.
5] Nitrates may also inhibit platelet aggregation.
 Analgesic Therapy: Recommendations
Class IIb
1. In the absence of contraindications, it may be reasonable to administer
morphine sulfate intravenously to patients with NSTE-ACS if there is
continued ischemic chest pain despite treatment with maximally tolerated anti-
ischemic medications. (Level of Evidence: B)

Class III: Harm

1. Nonsteroidal anti-inflammatory drugs (NSAIDs) (except aspirin) should not
be initiated and should be discontinued during hospitalization for NSTE-ACS
because of the increased risk of MACE associated with their use. (Level of
Evidence: B)

Although constipation, nausea, and/or vomiting occur in >20% of patients,

hypotension and respiratory depression are the most serious complications of
excessive use of morphine. Naloxone (0.4 mg to 2.0 mg IV) may be administered
for morphine overdose with respiratory or circulatory depression.
Beta-Adrenergic Blockers: Recommendations
Class I
Oral BBs therapy should be initiated within the first 24 hours in patients
who do not have any of the following:

1) signs of HF, 2) evidence of low-output state, 3) increased risk for

cardiogenic shock, or 4) other contraindications to BBs (e.g., PR interval
>0.24 second, second- or third-degree heart block without a cardiac
pacemaker, active asthma, or reactive airway disease). (Level of Evidence:
A)

2) In patients with concomitant NSTE-ACS, stabilized HF, and reduced systolic

function, it is recommended to continue beta-blocker therapy with 1 of the 3
drugs proven to reduce mortality in patients with HF: sustained-release
metoprolol succinate, carvedilol, or bisoprolol. (Level of Evidence: C)
 Beta-Adrenergic Blockers (Continue)
Actions of BBs in NSTEMI:
BBs decrease heart rate, contractility, and BP, resulting in decreased MVO2. Although
early administration does not reduce short-term mortality, BBs decrease
myocardial ischemia, reinfarction, and the frequency of complex ventricular
dysrhythmias, and they increase long-term survival.

Risk factors for shock include: 1] patients >70 years of age, 2] heart rate >110 beats
per minute, 3] systolic BP <120 mm Hg, and 4] late presentation. Early BBs,
particularly if given intravenously, can increase the likelihood of shock in patients
with risk factors.

In patients with LV dysfunction (LVEF <0.40) with or without pulmonary

congestion, beta blockers are strongly recommended before discharge.

BBs should be used prudently with ACE inhibitors or (ARBs) in patients with
HF.
RAAS blocking agents should be cautiously added in patients with decompensated
HF.
In patients with chronic obstructive lung disease or a history of asthma, BBs are not
contraindicated in the absence of active bronchospasm. Beta-1 selective BBs
(Nebivelol, Bisoprolol, Atenolol, and Metoprolol) are preferred and should be
initiated at a low dosage.
Calcium Channel Blockers: Recommendations
Class I
1. A nondihydropyridine calcium channel blocker (CCB) (e.g., verapamil or
diltiazem) should be given as initial therapy in patients with NSTE-ACS in: a]
continuing or frequently recurring ischemia, b] a contraindication to BBs, c] in
the absence of 1. clinically significant LV dysfunction, 2. increased risk for
cardiogenic shock, 3. PR interval > 0.24 second, or second- or third degree
atrioventricular block without a cardiac pacemaker. (Level of Evidence: B)
2. Oral nondihydropyridine CCBs are recommended in patients with NSTE-ACS who
have recurrent ischemia in the absence of contraindications, after appropriate use
of beta blockers and nitrates. (Level of Evidence: C)
3. CCBs are recommended for ischemic symptoms when beta blockers are not
successful, are contraindicated, or cause unacceptable side effects. (Level of
Evidence: C)
4. Long-acting CCBs and nitrates are recommended in patients with coronary artery
spasm. (Level of Evidence: C)

Class III: Harm

1. Immediate-release nifedipine should not be administered to patients with NSTE-
ACS in the absence of BB therapy. (Level of Evidence: B)
 Calcium Channel Blockers: Continue
CCBs include dihydropyridines and nondihydropyridines.
The dihydropyridines (nifedipine and amlodipine) produce the most marked
peripheral vasodilation and have little direct effect on contractility,
atrioventricular conduction, and heart rate.
The nondihydropyridines (diltiazem and verapamil) have significant negative
inotropic actions and negative chronotropic and dromotropic effects = [affects the
conduction speed in the AV node]. They cause similar coronary vasodilation and
are preferred in vasospastic angina. They also alleviate ischemia due to
obstructive CAD by decreasing heart rate and BP. Verapamil and diltiazem
decreased reinfarction in patients without LV dysfunction in some studies.

Immediate-release nifedipine causes a dose-related increase in mortality

in patients with CAD and in ACS and is not recommended for routine use in
patients with ACS.

Long-acting preparations may be useful in older patients with systolic

hypertension
 Ranolazine (Ranexa)
Ranolazine is an antianginal medication with minimal effects on heart rate and
BP.

It inhibits the late inward sodium current and reduces the deleterious effects of
intracellular sodium and calcium overload that accompany myocardial ischemia.

Ranolazine is currently indicated for treatment of chronic angina.

 Inhibitors of Renin-Angiotensin-
Aldosterone System: Recommendations
Class I
1. ACE inhibitors should be started and continued indefinitely 1] in all patients
with LVEF < 0.40 and 2] in those with hypertension, diabetes mellitus, or stable
CKD (Section 7.6), unless contraindicated. (Level of Evidence: A)

2. ARBs are recommended in patients with HF or MI with LVEF < 0.40 who are
ACE inhibitor intolerant. (Level of Evidence: A)

3. Aldosterone blockade is recommended in patients postMI without significant

renal dysfunction (creatinine >2.5 mg/dL in men or >2.0 mg/dL in women) or
hyperkalemia (K >5.0 mEq/L) who are receiving therapeutic doses of ACE
inhibitor and beta blocker and have a LVEF 0.40 or less, diabetes mellitus, or
HF. (Level of Evidence: A)

NB: ACE inhibitors reduce mortality in patients with recent MI, primarily
those with LV dysfunction (LVEF <0.40) with or without pulmonary congestion.
In patients with normal LV function (including patients with diabetes mellitus),
total mortality and MACE (including HF) are reduced.
N/A, not applicable
 Clopidogrel
Administration of clopidogrel with aspirin was superior to administration of
aspirin alone in reducing the incidence of cardiovascular death and nonfatal
MI or stroke both acutely and over 12 months.

An initial loading dose of 300 mg to 600 mg is recommended. A 600-mg loading

dose results in a greater, more rapid, and more reliable platelet inhibition
compared with a 300-mg loading dose.

When possible, discontinue clopidogrel at least 5 days before surgery

Prasugrel
In patients with NSTE-ACS and defined coronary anatomy undergoing
planned PCI, a 60-mg loading dose of prasugrel followed by 10 mg daily was
compared with a 300-mg loading dose and 75 mg daily of clopidogrel. The
composite primary endpoint (cardiovascular death, nonfatal MI, and stroke)
was reduced in patients treated with prasugrel (hazard ratio [HR]: 0.81;
p=0.001).
 Ticagrelor
Ticagrelor is an oral, reversibly binding P2Y12 inhibitor with a relatively short plasma
half-life (12 hours). Compared with clopidogrel, ticagrelor has a more rapid and
consistent onset of action and, because it is reversible, it has a faster recovery of
platelet function. The loading dose of ticagrelor for patients treated either invasively
or with an ischemia-guided strategy is 180 mg followed by a maintenance dose of 90
mg twice daily.

In patients with NSTE-ACS treated with ticagrelor compared with clopidogrel, there
was a reduction in the composite outcome of death from vascular causes, MI, or
stroke (reduction: 11.7% to 9.8%; HR: 0.84; p<0.001). The mortality rate was also
lower in those patients treated with ticagrelor. The overall major bleeding was not
increased with ticagrelor. Side effects unique to ticagrelor include dyspnea and
bradycardia.

The short half-life requires twice-daily administration, which could potentially result
in adverse events in noncompliant patients, particularly after stent implantation.

When possible, ticagrelor should be discontinued at least 5 days before surgery.

 2016 ACC/AHA Guideline
Focused Update on Duration of
Dual Antiplatelet Therapy in Patients
With Coronary Artery Disease
Factors Associated With Appropriate Selection of Early Invasive
Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS
Drug Target Dose/regimen Supporting data
Irreversibly
Meta-analysis of
ASA inhibits the COX- 75325 mg daily
195 clinical trials
1 enzyme
CURE
(clopidogrel +
ASA)
Clopidogrel: 75
Irreversibly bind mg daily TRITON-TIMI 38
Thienopyridines to the ADP (prasugrel +
receptor P2Y12 Prasugrel: ASA)1
10 mg daily
TRILOGY ACS
(prasugrel vs
clopidogrel)
Reversibly binds
Ticagrelor (non- to P2Y12, non- 90 mg twice PLATO (ticagrelor
thienopyridine) competitively daily + ASA)
with ADP
 Duration of DAPT in Patients With ACS (NSTE-ACS and STEMI) Treated With
Medical Therapy Alone (Without Revascularization or Fibrinolytic Therapy):

COR LOE Recommendations

In patients with ACS who are managed with medical therapy alone (without
I B-R revascularization or fibrinolytic therapy) and treated with DAPT, P2Y12 inhibitor
therapy (clopidogrel or ticagrelor) should be continued for at least 12 months.

In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100

I B-NR
mg) is recommended .

In patients with NSTEACS who are managed with medical therapy alone (without
revascularization or fibrinolytic therapy) and treated with DAPT, it is reasonable to
IIa B-R
use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor
therapy.

In patients with ACS treated with medical therapy alone (without revascularization
or fibrinolytic therapy) who have tolerated DAPT without bleeding complication
IIb A SR and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy,
oral anticoagulant use), continuation of DAPT for longer than 12 months may be
reasonable.
Duration of DAPT in Patients With STEMI Treated With Fibrinolytic Therapy:
Recommendations

COR LOE Recommendations

In patients with STEMI treated with DAPT in conjunction
with fibrinolytic therapy, P2Y12 inhibitor therapy
I AC-EO (clopidogrel) should be continued for a minimum of 14
days (Level of Evidence: A) and ideally at least 12 months
(Level of Evidence: C-EO).
In patients treated with DAPT, a daily aspirin dose of 81
I B-NR
mg (range, 75 mg to 100 mg) is recommended.
 Duration of DAPT in Patients With ACS Treated With PCI: Recommendations

COR LOE Recommendations

In patients with ACS treated with DAPT after BMS or DES implantation, P2Y12 inhibitor
I B-R
therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months
In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is
I B-NR
recommended.
In patients with ACS treated with DAPT after coronary stent implantation, it is
IIa B-R reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12
inhibitor therapy.
In patients with ACS treated with DAPT after coronary stent implantation, who are not
at high risk for bleeding complications and who do not have a history of stroke or TIA, it
IIa B-R
is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor
therapy .
In patients with ACS treated with coronary stent implantation who have tolerated DAPT
without bleeding complication and who are not at high bleeding risk (e.g., prior
IIb A SR
bleeding on DAPT, coagulopathy, oral anticoagulant use) continuation of DAPT for
longer than 12 months may be reasonable.

In patients with ACS treated with DAPT after DES implantation who develop a high risk
of bleeding (e.g., treatment with oral anticoagulant therapy), are at high risk of severe
IIb C-LD
bleeding complication (e.g., major intracranial surgery), or develop significant overt
bleeding, discontinuation of P2Y12 therapy after 6 months may be reasonable.
III:
B-R Prasugrel should not be administered to patients with a prior history of stroke or TIA
Harm
 Duration of DAPT in Patients With ACS Treated With CABG: Recommendation

COR LOE Recommendation

In patients with ACS being treated with DAPT who undergo
I C-LD CABG, P2Y12 inhibitor therapy should be resumed after
CABG to complete 12 months of DAPT therapy after ACS
 Perioperative ManagementTiming of Elective Noncardiac Surgery in Patients
Treated With PCI and DAPT: Recommendations

COR LOE Recommendations

Elective noncardiac surgery should be delayed 30 days after BMS implantation and
I B-NR
optimally 6 months after DES implantation.
In patients treated with DAPT after coronary stent implantation who must undergo
surgical procedures that mandate the discontinuation of P2Y12 inhibitor therapy, it is
I C-EO
recommended that aspirin be continued if possible and the P2Y12 platelet receptor
inhibitor be restarted as soon as possible after surgery.
When noncardiac surgery is required in patients currently taking a P2Y12 inhibitor, a
IIa C-EO consensus decision among treating clinicians as to the relative risks of surgery and
discontinuation or continuation of antiplatelet therapy can be useful.
Elective noncardiac surgery after DES implantation in patients for whom P2Y12
inhibitor therapy will need to be discontinued may be considered after 3 months if
IIb C-EO
the risk of further delay of surgery is greater than the expected risks of stent
thrombosis.
Elective noncardiac surgery should not be performed within 30 days after BMS
III: Harm B-NR implantation or within 3 months after DES implantation in patients in whom DAPT
will need to be discontinued perioperatively.
Recommendations on the Management of Patients Treated With Triple Therapy

Assess ischemic and bleeding risks using validated risk predictors (e.g.,
CHA2DS2-VASc, HAS-BLED)
Keep triple therapy duration as short as possible; dual therapy only (oral
anticoagulant and clopidogrel) may be considered in select patients
Consider a target INR of 2.02.5 when warfarin is used
Clopidogrel is the P2Y12 inhibitor of choice
Use low-dose (100 mg daily) aspirin
PPIs should be used in patients with a history of gastrointestinal bleeding and
are reasonable to use in patients with increased risk of gastrointestinal
bleeding

CHA2DS2-VASc indicates congestive heart failure, hypertension, age 75 years

(doubled), diabetes mellitus, prior stroke or transient ischemic attack or
thromboembolism (doubled), vascular disease, age 6574 years, sex category;
HAS-BLED, hypertension, abnormal renal/liver function, stroke, bleeding
history or predisposition, labile INR, elderly, drugs/alcohol concomitantly.
 If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa
activity (either UFH or bivalirudin) should be administered because of the risk of catheter
thrombosis (class I). (Level of Evidence: B)

UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour
(maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic
anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is
performed (class I). (Level of Evidence: B)
Dosing of Parenteral Anticoagulants During PCI
 Risk Reduction Strategies for Secondary Prevention
CLASS I
1. Patients with NSTE-ACS should be referred to comprehensive CV rehabilitation program either before hospital discharge
or during the first outpatient visit. (Level of Evidence: B)
2. Pneumococcal vaccine is recommended for patients 65 years and in high-risk patients with CVD. (Level of Evidence: B)
3. Patients should be educated about appropriate cholesterol & BP management, smoking cessation, and lifestyle
management. (Level of Evidence: C)
4. Patients who have undergone PCI or CABG derive benefit from risk factor modification and should receive counselling
that revascularization does not obviate the need for lifestyle changes. (Level of Evidence: C)
5. Before hospital discharge, the patients need for treatment of chronic musculoskeletal discomfort should be
assessed, and a stepped-care approach should be used for selection of treatments. Pain treatment before
consideration of NSAIDs should begin with acetaminophen, nonacetylated salicylates, tramadol, or small doses of narcotics.
(Level of Evidence: C)
CLASS IIa
1. It is reasonable to use nonselective NSAIDs, such as naproxen, if initial therapy with acetaminophen, nonacetylated
salicylates, tramadol, or small doses of narcotics is insufficient. (Level of Evidence: C)
CLASS IIb
1. NSAIDs with increasing degrees of relative cyclooxygenase-2 selectivity may be considered for pain relief only for situations in
which intolerable discomfort persists despite use of acetaminophen, nonacetylated salicylates, tramadol, small doses of narcotics,
or nonselective NSAIDs. In all cases, use lowest effective doses for shortest possible time is encouraged. (Level of Evidence: C)
CLASS III: NO BENEFIT
1. Antioxidant vitamin supplements (e.g., vitamins E, C, or beta carotene) should not be used for secondary prevention in patients
with NSTE-ACS. (Level of Evidence: A)
2. Folic acid, with or without vitamins B6 and B12, should not be used for secondary prevention in patients with NSTE-ACS. (Level
of Evidence: A)
CLASS III: HARM
1. Hormone therapy with estrogen plus progestin, or estrogen alone, should not be given as new drugs for secondary prevention
of coronary events to postmenopausal women after NSTE-ACS and should not be continued in previous users unless the benefits
outweigh the estimated risks. (Level of Evidence: A)
2. NSAIDs with increasing degrees of relative cyclooxygenase-2 selectivity should not be administered to patients with NSTE-ACS
and chronic musculoskeletal discomfort when therapy with acetaminophen, nonacetylated salicylates, tramadol, small doses of
narcotics, or nonselective NSAIDs provide acceptable pain relief. (Level of Evidence: B)
 Summary of Recommendations for Special Patient Groups with
NSTE-ACS - In Older Patients
CLASS I
1. Older patients** with NSTE-ACS should be treated with GDMT, an early invasive strategy,
and revascularization as appropriate. (Level of Evidence: A)
2. Pharmacotherapy in older patients** with NSTE-ACS should be individualized and dose
adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in
pharmacokinetics/dynamics, volume of distribution, comorbidities, drug interactions, and
increased drug sensitivity. (Level of Evidence: A)

CLASS IIa
1. Bivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older patients** with
NSTE-ACS, both initially and at PCI, given similar efficacy but less bleeding risk. (Level of
Evidence: B)
2. It is reasonable to choose CABG over PCI in older patients** with NSTE-ACS who are
appropriate candidates, particularly those with diabetes mellitus or complex 3-vessel CAD (e.g.,
SYNTAX score >22), with or without involvement of the proximal left anterior descending
artery, to reduce cardiovascular disease events and readmission and to improve survival. (Level
of Evidence: B)

GDMT = [guideline-directed medical therapy] promotes medication adherence, timely

follow-up with the healthcare team, appropriate dietary and physical activities, and compliance
with interventions for secondary prevention.
Summary of Recommendations for Special Patient Groups
with NSTEMI
Summary of Recommendations for Special Patient Groups with NSTEMI [ continued]

*Provocative testing during invasive CA (e.g. ergonovine, acetylcholine, methylergonovine) is relatively safe,
especially when performed in a controlled manner by experienced operators. However, sustained spasm, serious
arrhythmias, and even death can also occur but very infrequently. Therefore, provocative tests should be avoided
in patients with significant LM disease, advanced 3-vessel disease, presence of high-grade obstructive lesions,
significant valvular stenosis, significant LV systolic dysfunction, and advanced HF.
CFR (also called absolute CFR) equals the ratio of maximum stress flow to rest flow
for a given arterial distribution with or without a stenosis or diffuse narrowing.

Relative coronary flow reserve (relative CFR) equals the ratio of maximum stress
flow in the diseased artery to maximum flow in the absence of disease in either the
same or adjacent arterial distribution.

FFR [fractional flow reserve] as now used clinically equals the ratio of coronary
pressure to aortic pressure at pharmacologically induced maximal coronary flow.

For a single discrete stenosis in the absence of diffuse disease, the FFR pressure
ratio also equals relative CFR by flow or flow velocity measurements
 10 points to remember for the latest 2015 NSTEMI
guidelines per ESC
The following are 10 points to remember about the evaluation and treatment of patients without persistent
ST-segment elevation:
(1) ECG changes: may include transient ST-segment elevation lasting <20 minutes, persistent or transient ST-
segment depression, T-wave inversion, flat T waves, pseudo normalization of T waves, or no ECG changes)

2) In NSTE-ACS, the Global Registry of Acute Coronary Events (GRACE) risk score provides the most accurate
stratification of risk both on admission and at discharge. A GRACE score >140 signifies high risk.

3) In patients at risk of developing cardiogenic shock (i.e., age >70 years, heart rate >110 bpm, systolic blood
pressure <120 mm Hg), the observed shock or death rate was significantly increased in patients receiving beta-
blockers within 24 hours of hospital admission.

X 4) As the optimal timing of ticagrelor or clopidogrel administration in NSTE-ACS patients scheduled for an
invasive strategy has not been adequately investigated, no recommendation for or against pretreatment with
these agents can be formulated. Based on the ACCOAST (the Comparison of Prasugrel at the Time of
Percutaneous Coronary Intervention or as Pre-treatment at the Time of Diagnosis in Patients with Non-ST
Elevation Myocardial Infarction) trial, pre-treatment with prasugrel is not recommended.

XA P2Y12 inhibitor is recommended in addition to aspirin, for 12 months following NSTE-ACS unless there
are contraindications. Clopidogrel (300-600 mg loading dose, 75 mg daily dose) is recommended for patients
who cannot receive ticagrelor or prasugrel or who require oral anticoagulation (Class I, Level of Evidence B).
Prasugrel is contraindicated in patients with prior stroke/transient ischemic attack; and there is no apparent
benefit with prasugrel in patients >75 years of age or with low bodyweight (60 kg). Previous intracranial
hemorrhage is a contraindication to the use of ticagrelor.
XCangrelor is an intravenous adenosine triphosphate (ATP) analogue that binds reversibly and with high
affinity to the platelet P2Y12 receptor, and has a high affinity to the platelet P2Y12 receptor and has a
short plasma half-life (<10 minutes). Cangrelor may be considered in P2Y12 inhibitor-nave patients
undergoing percutaneous coronary intervention (PCI) (Class IIb, Level of Evidence A).

5) In patients on an oral anticoagulant, the following are suggested strategies to reduce bleeding risk
related to PCI:
In patients on vitamin K antagonists, avoid administration of unfractionated heparin if international
normalized ratio is >2.5 (Class I, Level of Evidence C)
In patients on novel oral anticoagulants (NOACs), regardless of the timing of the administration of the
NOAC, low-dose parenteral anticoagulation should be used (Class I, Level of Evidence C).
Glycoprotein IIb/IIIa inhibitors should be used only for bailout of periprocedural complications.

6) If a patient is at high bleeding risk (HAS-BLED 3), triple therapy with oral anticoagulant (OAC), aspirin
(75-100 mg/day), and clopidogrel 75 mg/day should be considered for a duration of 1 month, followed by
OAC and aspirin 75-100 mg/day or clopidogrel (75 mg/day) continued up to 12 months. The use of
ticagrelor or prasugrel as part of triple therapy is not recommended (Class III, Level of Evidence C).

7) Radial over femoral access is recommended for coronary angiography and PCI (Class I, Level of Evidence
A).

8) In NSTE-ACS, fractional flow reserve (FFR) may be overestimated (underestimating the relevance of a
coronary stenosis); accordingly, the value of FFR-guided PCI has not been properly addressed.

9) Among patients with diabetes mellitus, multivessel coronary artery disease, and acceptable surgical risk,
coronary artery bypass grafting is recommended over PCI.

10) High-intensity statin therapy should be initiated as early as possible (unless contraindicated) and
maintained long-term.
Summary of discrimination of various risk scores to
predict long term outcomes in populations with non
ST-segment elevation ACS.
 TIMI risk score
The TIMI risk score was developed to predict the occurrence of the primary end-point (all
cause mortality, myocardial infarction, or urgent revascularisation) at 14 days in patients
with NSTEMI assigned to treatment with unfractionated heparin.

The components of TIMI risk score for death, new or recurrent MI, or urgent
revascularization at 14 days13:
Age 65 years
At least three of: FH of CAD, HTn, hypercholesterolemia, diabetes, or current smoker
Significant coronary stenosis (for example, prior coronary stenosis 50%)
ST segment deviation on ECG
Severe anginal symptoms (for example, 2 anginal events in the last 24 hours)
Use of aspirin in the last seven days
Elevated serum cardiac markers (CK-MB and/or cardiac-specific troponin level)
 Risk scores to assess prognosis in patients with
NSTE-ACS
CK-MB is much less sensitive for detection of myocardial injury than troponin, and
substantially more tissue injury is required for its detection. With the availability of
cardiac troponin, CK-MB, myoglobin, and other diagnostic biomarkers are no longer
necessary.

TIMI Risk Score* for NSTE-ACS:

1] Age 65.
2] 3 Risk Factors for Coronary Artery Disease.
3] Known prior Coronary Artery Stenosis 50%.
4] Use of Aspirin for Past 7 Days or Longer.
5] Elevated Troponin.
6] 0.5 mm of ST Elevation on ECG.
7] 2 Episodes of Cardiac Chest Pain in Preceding 24 Hours.

Low risk: <3 risks. Moderate risk: 3-4 risks. High risk: 5-7 risks.
 2] Global Registry of Acute Coronary Events (GRACE) model
for In-Hospital Mortality for ACS
The GRACE risk model predicts in-hospital and post-discharge mortality or MI
 Ischaemic risk assessment

The GRACE risk score provides the most accurate stratification of risk both on admission
and at discharge. Variables used in the GRACE 2.0 risk calculation include 1] age, 2] SBP, 3] HR,
4] serum creatinine, 5] Killip class at presentation, 6] cardiac arrest at admission, 7] elevated
cardiac biomarkers and 8] ST deviation.

The TIMI risk score uses seven variables in an additive scoring system: 1] age 65 years, 2]
CAD risk factors, 3] known CAD, 4] aspirin use in the past 7 days, 5] severe angina (two or
more episodes within 24 h), 6] ST change 0.5 mm and 7] positive cardiac marker. It is simple
to use, but its discriminative accuracy is inferior to that of the GRACE risk score and the GRACE
2.0 risk calculation.
 Timing of Urgent CABG in Patients With NSTE-ACS in Relation
to Use of Antiplatelet Agents: Recommendations

Class I
1. Nonenteric-coated aspirin (81 mg to 325 mg daily) should be administered
preoperatively to patients undergoing CABG. (Level of Evidence: B)

2. In patients referred for elective CABG, clopidogrel and ticagrelor should be

discontinued for at least 5 days before surgery (Level of Evidence: B) and
prasugrel for at least 7 days before surgery. (Level of Evidence: C)

3. In patients referred for urgent CABG, clopidogrel and ticagrelor should be

discontinued for at least 24 hours to reduce major bleeding. (Level of Evidence: B)

4. In patients referred for CABG, short-acting intravenous GP IIb/IIIa inhibitors

(eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before
surgery and abciximab for at least 12 hours before to limit blood loss and
transfusion. (Level of Evidence: B)
NSTE-ACS in Older Patients: Recommendations
Class I
1. Older patients** with NSTE-ACS should be treated with Guideline-Directed
Medical Therapy (GDMT), an early invasive strategy, and revascularization as
appropriate. (Level of Evidence: A)
2. Pharmacotherapy in older patients with NSTE-ACS should be individualized and
dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related
changes in pharmacokinetics/dynamics, volume of distribution, comorbidities, drug
interactions, and increased drug sensitivity. (Level of Evidence: A)

Class IIa
1. Bivalirudin, rather than a GP IIb/IIIa inhibitor plus UFH, is reasonable in older
patients with NSTE-ACS, both initially and at PCI, given similar efficacy but less
bleeding risk. (Level of Evidence: B)
2. It is reasonable to choose CABG over PCI in older patients**with NSTE-ACS
who are appropriate candidates, particularly those with diabetes mellitus or
complex 3-vessel CAD (e.g., SYNTAX score >22), with or without involvement of
the proximal LAD artery, to reduce cardiovascular disease events and readmission
and to improve survival (Level of Evidence: B)
 ACS With Angiographically Normal Coronary
Arteries: Recommendation
ACS associated with angiographically normal or nonobstructive (<50% stenosis)
coronary arteries (also referred to as syndrome X) may be related to coronary
endothelial dysfunction; plaque rupture that may be evident only with intracoronary
ultrasound; coronary vasospasm; and coronary artery dissection.
Myocarditis may present with electrocardiographic and biomarker findings similar
to ACS and can be distinguished by magnetic resonance imaging. Intracoronary
ultrasound and/or optical coherence tomography to assess the extent of
atherosclerosis and exclude obstructive lesions may be considered in patients with
possible ACS and angiographically normal coronary arteries. If ECGs during chest
pain are not available and coronary spasm cannot be ruled out, coronary
angiography and provocative testing with acetylcholine, adenosine, or methacholine
and 24-hour ambulatory ECG may be undertaken after a period of stabilization.
Endothelial dysfunction is more common in women than in men, and chest pain is
typical or atypical. In the absence of a culprit coronary lesion, prognosis of coronary
endothelial dysfunction and/or occult plaque rupture is favorable.
Risk factor reduction and medical therapy with nitrates, beta blockers, and CCBs
alone or in combination are considered for endothelial dysfunction. High doses of
arginine have also been given. Imipramine or aminophylline have been used in
patients with endothelial dysfunction for continued pain despite optimal medical
therapy. Cardiac magnetic resonance imaging (CMRI) is a powerful tool for
differential diagnosis between myocardial infarction (MI), acute myocarditis and
Tako-tsubo cardiomyopathy (TTC).
 Stress (Takotsubo) Cardiomyopathy:

Stress (Takotsubo) cardiomyopathy (also referred to as transient LV apical

ballooning or Takotsubo cardiomyopathy) mimics NSTE or STEMI. There is no
obstructive CAD, and the distribution of electrocardiographic changes and LV wall
motion abnormalities usually includes >1 coronary artery territory. Cardiac
troponin elevations are usually modest. The majority of cases occur in
postmenopausal women, and presentation is typically precipitated by emotional or
physical stress. Imaging by echocardiography, ventriculography, or magnetic
resonance imaging demonstrates characteristic hypokinesis or dyskinesis of the LV
apex with basilar increased contractility. Variants include hypokinesis of the mid or
base of the left ventricle , and right ventricular involvement is common. In the vast
majority of patients, electrocardiographic and LV wall motion abnormalities
normalize within 1 to 4 weeks, and recurrences are uncommon. The pathogenesis
has been attributed to excess catecholamine release, coronary spasm, or small
coronary vessel hypoperfusion.
 Stress (Takotsubo) Cardiomyopathy:
Recommendations
Class I
1. Stress (Takotsubo) cardiomyopathy should be considered in patients who
present with apparent ACS and nonobstructive CAD at angiography. (Level of
Evidence: C)
2. Imaging with ventriculography, echocardiography, or magnetic resonance
imaging should be performed to confirm or exclude the diagnosis of stress
(Takotsubo) cardiomyopathy. (Level of Evidence: B)
3. Patients should be treated with conventional agents (ACE inhibitors, beta
blockers, aspirin, and diuretics) as otherwise indicated if hemodynamically stable.
(Level of Evidence: C)
4. Anticoagulation should be administered in patients who develop LV thrombi.
(Level of Evidence: C)

Class IIa
1. It is reasonable to use catecholamines for patients with symptomatic
hypotension if outflow tract obstruction is not present. (Level of Evidence: C)
2. The use of IABP is reasonable for patients with refractory shock. (Level of
Evidence: C)
3. It is reasonable to use beta blockers and alpha-adrenergic agents in patients with
outflow tract obstruction. (Level of Evidence: C)