chronic stable angina
- substernal chest discomfort that is:
- typically relieved by NTG &/or rest (no more than 20 min)
- aggravated by exertion & emotion stress, cold, meals
unstable angina & high risk features
rest angina
new onset angina
increasing angina
high risk symptoms
rest angina
angina occurring at rest & usually lasting >20min
new onset angina
angina of class III (marked limitation of normal activity) in the past 2 months
increasing angina
stable angina that is now increasing in duration or frequency
high risk symptoms
pulmonary edema
rales
angina w/ hypotension
nocturnal angina
chronic stable angina goals of therapy
- morbidity: provide symptomatic relief from angina that limites exercise & QOL
- mortality: slow the progression of atherosclerosis leading to CV events & death
chronic stable angina & HTN
- these pts have established coronary artery disease-> compelling indication for ACEI/ARB & beta-blocker
non-pharmacological management of chronic stable angina
- typically reserved for those who have significant symptoms despite optimal medical management
- percutaneous coronary intervention (PCI): balloon angioplasty &/or stenting
- CABG- coronary bypass grafting
- external counterpulsation therapy (ECP/EECP): for those w/ refractory CSA & not candidates for PCI or CABG
Can you titrate anti-anginal/BP medications below the standard target BP (e.g,. 140/90) to reduce symptoms of chronic stable angina?
yes
CSA 4 main agents used
beta-blockers, CCB. nitrates & ranolazine
wht therapy may be adequate for symptoms that occur rarely or predictably
PRN nitrates
chronic antianginal therapy should be up-titrated if patients
experience daily episode or symptoms sig. impact QOL
majority of CSA therapy
decreased HR and/or BP
minimal HR
55bpm
minimal BP
100/65
critical side effects
orthostatic hypotension, +/-falls, syncope, severe fatigue
Which pharmacological effects would be helpful in reducing anginal episodes?
○ Beta-blocker to reduce inotropy, thereby reducing cardiac oxygen demand
○ Beta-blocker to reduce chronotropy, thereby reducing cardiac oxygen demand
○ DHP-CCB/nitrate to cause vasodilation, thereby increasing coronary blood flow
○ DHP-CCB/nitrate to cause vasodilation, thereby reducing afterload and cardiac workload
first line in the management of CSA
beta blockers
beta-1 selective
- preferred for unstable asthma/COPD, PVD, DM, sexual dysfunction
mixed alpha/beta blockers
(Carvedilol)
- may be used if additional BP control is needed
agents with intrinsic sympathomimetic activity
should be avoided
- increase HR
beta blocker dosing
titrate BB to HR of ~55bpm as BP & side effects allow
- add additional agents as necessary
BB in combo with nonDHP CCBs
avoided due to risk of bradycardia & Heart block
BB in combo with DHP CCBs
BB blunts reflex tachycardia that may occur w/ DHPs
- so good
BB in combo with nitrates
BB blunts reflex tachycardia that may occur w/ nitrates
- so good
BB in combo w/ ranolazine
no significant issues
monitoring of CSA therapy
- BP, HR, appearance of side effects
alt first line agents for those who are not candidates for beta blockers
non-DHP CCBs
consideration for selection of nonDHPs
- avoid in systolic HF (LV dysfunction/ <EF)
- may be reasonable agent in those with relative CI to BB (Asthma, unstable COPD, severe PVD)
- appropriate for those with prinzmetal angina
- select a formulation that allows for QD or BID doising
NonDHP dosing
titrate to a HR of ~55bpm as BP & side effects allow
- add additional agents as needed
nonDHP in combo with BB
avoided due to risk of bradycardia & heart block
nonDHP in combo with DHP
nonDHP blunt reflex tachycardia that may occur with DHP
nonDHP in combo with nitrates
nonDHP blunts reflex tachycardia that may occur withnitrates
nonDHP in combo with ranolazine
-CYP3A4 interaction->max of ranolazine 500mg PO BID
dont titrate up to max dose
second line agent for CSA
DHP
amlodipine, delodipine, nicardipine
- typically add on therapy
consideration in selection of a DHP
potential for reflex tachycardia & lack of effect on HR make monotherapy undesirable
dosing of DHPs
up-titrate DHP to relief of angina symptoms as BP & side effects allow
DHP in combo with nitrates
no issues as long as BB or nonDHP is ALSO used for reflex tachycardia
DHP in combo with ranolazine
no issues
monitoring of DHP
BP, relief of symptoms, side effect (peripheral edema-tk at night to prevent, reflex tachycardia)
- does not reduce HR
what should be made available to every pt for CSA?
short acting nitrates (SL NTG or translingual NTG)
nitrostat
0.4mg placed under tongue & allowed to dissolve Q5min, up to 3 doses
nitrolingual
one spray under the tongue or on the tongue Q5min, up to 3 doses
- must be primed
- do not rinse mouth
- keep at RT
third line agents for CSA
long acting nitrates
long acting nitrates should be reserved for
ass-on therapy (w/ BB or nonDHP to blunt reflex tachycardia)
long acting nitrates require
a nitrate-free interval of 8-12hrs/day (only partial antianginal coverage) due to tachyphylaxis
- Long-acting nitrates should be dosed in which fashion?
○ With a ~12 hour nitrate-free interval to avoid development of tolerance
○ Around the clock dosing will lead to tachyphylaxis (tolerance)
○ BID when you wake up, then 6 hours later (so you have your nitrate free interval)
long acting isosorbide mononitrate drugs
immediate (Ismo, monoket)
sustained (imdur)
long acting isosorbide dinitrate
sustained (isochron)
long acting NTG patch
nitrodur
monitoring for long acting nitrates
BP & relief of symtpoms, reflex tachycardia, decreased efficacy,, HA, orthostatic hypotension
CI nitrate use with sildenafil (viagra) & verdenafil (levitra) in
24 hours
CI nitrate use with tadalafi (cialis) in
48 hours
newest agent & third line add-on agent
(due to cost)
ranolazine (ranexa)
ranolazine has almost zero effect on
BP & HR
- potential add on for those with low BP or HR
safety or ranolazine
QT prolongation
- minimal risk of torsades when used alone
- do not use with FQ, macrolide, antiarrhythmics, antipsycotics
drug interactions with ranolazine
- substrate for CUP3A4, 2D6 & PGP
1. inc ranolazine: nonDHP-CCBs
2. digoxin may inc & require close monitoring
3. simvastatin levels usually DOUBLE with addition of ranolazine
ranolazine dosing
500mg PO BID titrated to 1000mg PO BID prn anginal symptoms
CI to ranolazine
- severe hepatic impairment, strong CYP3A4 inhibitor
side effects of ranolazine
constipation
nausea
dizziness