Table 1. First-Line Agents for Vasospastic Angina

Class/Agent


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Doses Studied

Advantages

Disadvantages

Non-DHP CCB

Diltiazem IR

120mg/d 240mg/d

    — Safe, effective for symptom control

    — Decreases angina frequency

    — Negative chronotropic effects can cause bradycardia and atrioventricular conduction delay

    — Use with caution in elderly, chronic kidney disease, and history of heart failure with reduced ejection fraction

DHP CCB

Nifedipine ER

Nifedipine IR

40–160mg/d

63.2 + 6.4mg

    — Decreases amount of weekly sublingual nitroglycerin tablets used

    — Decreases number of weekly angina attacks

Nifedipine IR:

    — Orthostatic hyptension, pedal edema, nausea, anorexia, dizziness

    — Can worsen cardiac outcomes by inducing reflex sympathetic activation

    — Long-term efficacy to be determined

Non-DHP/DHP CCB

Verapamil IR

Nifedipine IR

120–600mg/d

 30–80mg/d

    — Well tolerated, lacks serious adverse events

    — Relieves angina

    — Associated with significantly less recurrence of angina in smokers

DHP: dihydropyridine; CCB: calcium channel blocker

Source: Harris JR et al. J Cardiovasc Pharmacol Ther. 2016;1-13.

Table 2. Second-Line Agents for Vasospastic Angina

Class

Doses Studied

Advantages

Disadvantages

Nitrates

Sublingual nifedipine 10mg + nitroglycerin intracoronary infusion 200mcg

Verapamil 120–-600mg/d or nifedipine 30–80mg/d + ISDN 20–80mg/d

Nitroglycerin and isosorbide mono-/dinitrate (any dose)

    — Reduce ventricular filling pressures through venodilation

    — Decrease myocardial oxygen demand

    — Rapid-acting agents have onset as soon as 1 minute

    — LANs suppress acute angina attacks, prevent recurrent attacks

    — In combination with CCBs, may have additive effect by vasodilating arteries synergistically

    — Repeat LAN dosing leads to waning effect (tolerance, tachyphylaxis)

    — Use with short-acting DHP CCB can cause reflex tachycardia, hypotension, flushing, headache

    — Contraindicated within 24 hours of PDE5 inhibitors sildenafil/vardenafil; within 48 hours of tadalafil

    — Long-term prognostic benefit remains unknown

Statins

Benidipine 4mg (titrated to a maximum dose of 12mg/d) + pravastatin 10–20mg/d (titrated to LDL < 100mg/dL) for 6 months

 Fluvastatin 30mg/d + CCB (diltiazem ER 100–200mg/d or nifedipine ER 20–40mg/d) or CCB alone

    — Help improve endothelial function, mitigating vasoconstriction

    — May reduce incidence of vasospastic angina; appears to be related to LDL reduction, HDL increase

    — Adding a statin to CCB may further reduce incidence of vasospastic angina

    — Larger studies needed to confirm safety

Alpha1-adrenergic receptor antagonists

    Prazosin 4mg every 8 hours 

    Prazosin 8–30mg/d + low-dose LAN or nifedipine IR

    Prazosin 9–15mg/d

    — Combination therapy with a CCB or LAN significantly decreases frequency, intensity of angina symptoms

    — Use when high-dose non-DHP CCBs + LAN do not ameliorate symptoms

— Prazosin monotherapy does not significantly decrease use of sublingual nitroglycerin, number or length of ischemic episodes, or ST-segment changes

— CNS depression, hypotension, tachycardia

CCB: calcium-channel blocker; CNS: central nervous system; HDL: high-density lipoprotein; ISDN: isosorbide dinitrate; LAN: long-acting nitrate; LDL: low-density lipoprotein

Source: Harris JR et al. J Cardiovasc Pharmacol Ther. 2016;1-13.

Table 3. Alternative Agents for Vasospastic Angina

Class/Agent

Doses Studied

Advantages

Disadvantages

Sodium ion channel inhibitor

Ranolazine

Titrated to 1,000mg twice daily

Improves physical function, angina stability, quality of life

    — Data only available from small trials, case reports

    — Contraindicated in hepatic cirrhosis, renal disease, with or at risk of QTc interval prolongation, history of malignancy, and with concurrent use of strong CYP3A4 inducers or inhibitors

Non-selective endothelin receptor antagonist

Bosentan

125mg twice daily

Reverses angina refractory to diltiazem, isosorbide mononitrate

    — Strict REMS due to adverse events: hepatotoxicity, teratogenicity, peripheral edema, hematologic changes

    — Approach cautiously; use last line

Selective inhibitor of phosphodiesterase-3

Cilostazol

Titrated to 100mg twice daily + amlodipine 5mg/day

Reduces weekly incidence of chest pain

    — Use caution in patients with heart failure and CAD, renal or hepatic dysfunction, thrombocytopenia, active pathological bleeding

    — Discontinue 4 days prior to surgery

    — Headache, diarrhea, palpitation, dizziness, paresthesia, peripheral edema, gastrointestinal symptoms

    — Potential drug-drug interactions with CYP3A4 and 2C19 agents

CAD: coronary artery disease; REMS: Risk Evaluation and Mitigation Strategy

Source: Harris JR et al. J Cardiovasc Pharmacol Ther. 2016;1-13.