Clotting and platelet inhibitors. Anticoagulants such as warfarin sodium and platelet inhibitors such as clopidogrel are major components of drug therapy to prevent blood clots in post-MI patients.
Warfarin is indicated to reduce the risk of death, recurrent MI, and thromboembolic events such as stroke or systemic embolization after MI. It acts by inhibiting the synthesis of vitamin Kdependent clotting factors II, VII, IX, and X and anticoagulant proteins C and S.
Warfarin is metabolized by numerous CYP isoenzymes—principally 2C9, but also 2C19, 2C8, 2C18, 1A2, and 3A4—and interacts with many drugs that are metabolized by the same enzyme systems.12 Although some cardio-protective drugs and NSAIDs may lead to drug interactions due to CYP2C9, most common psychotropics do not inhibit this isoenzyme.
The protein-binding properties of some psychotropics—such as fluoxetine, sertraline, paroxetine, and risperidone—may increase warfarin levels in some patients. Thus, closer monitoring of warfarin levels is warranted when using these agents. Divalproex—because of its protein binding and potential for thrombocytopenia and liver injury—should be used with caution in patients receiving warfarin.
HALT: A DECISION TOOL FOR PRESCRIBING TO THE POST-MI PATIENT
H Can this agent cause or worsen hypertension?
A Can this agent increase the risk of arrhythmia?
L Can this agent adversely affect lipids? Can it affect medication serum levels due to liver enzyme inhibition or liver injury?
T Can this agent increase the risk of thrombosis or bleeding?
Clopidogrel is indicated for reducing the risk of MI, stroke, and vascular death in patients with atherosclerosis documented by recent stroke, recent MI, or established peripheral arterial disease.13 This drug selectively inhibits adenosine diphosphate (ADP) from binding to its platelet receptor and activates the ADP-mediated glycoprotein GPIIb/IIIa complex, which inhibits platelet aggregation. Clopidogrel can inhibit the CYP 2C9 isoenzyme. Thrombotic thrombocytopenic purpura has been reported rarely following use of clopidogrel, sometimes after brief exposure (< 2 weeks). The medical team must watch for GI bleeding, a potential side effect.
HALT: A decision framework
A decision tool based on the mnemonic HALT can help psychiatrists systematically and safely add antidepressants, antipsychotics, and mood-stabilizing agents to the complicated regimens of post-MI patients (Box). As HALT suggests, any selection strategy must address the agent’s impact on:
- Hypertension
- Arrhythmias
- Lipids and Liver enzymes
- Thrombosis risk.
The following section lists examples of medications that fit the HALT framework well and others that do not. The psychiatrist, cardiologist, and primary care physician should all be aware of the different agents the post-MI patient is taking and monitor for adherence and drug interactions.
Selecting an antidepressant
Most newer-generation antidepressants are safe and effective for patients with heart disease. Venlafaxine increases heart rate and blood pressure minimally. Fluoxetine, paroxetine, and bupropion tend to interact to some degree with drugs metabolized by CYP2D6, including beta blockers. Mirtazapine may increase appetite and cause weight gain, which can exacerbate hypertension and alter lipid levels. Even so, minimal drug interactions and end-organ effects should not preclude the use of any of these antidepressants when the drug is best suited for managing a patient’s depressive disorder.
Sertraline. Excellent articles and systematic reviews have addressed the importance of treating depression in patients with heart disease.14-16 However, only one recent randomized, double-blind, controlled trial has addressed antidepressant therapy for major depressive disorder in patients with acute MI or unstable angina.17 The trial included 369 patients (64% male; mean age 57) with MDD who received the selective serotonin reuptake inhibitor (SSRI) sertraline, 50 to 200 mg/d, or placebo for 24 weeks.
Compared with placebo, sertraline did not significantly affect left ventricular ejection fraction, ventricular premature complexes, QTc interval, or other cardiac measures. Depressive symptoms improved more with sertraline than with placebo in patients who had a history of at least one episode of major depressive disorder (MDD) or severe MDD (defined as a Hamilton Depression Scale score 18 and two or more prior episodes of MDD). The authors concluded that sertraline is safe and effective for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.
Using the HALT framework, sertraline does not exacerbate hypertension or increase heart rate, which can trigger arrhythmias. It does not cause weight gain or affect lipid levels and is a weak inhibitor of liver enzymes. Like other SSRIs, it may make platelets “less sticky” and reduce the risk of thrombogenesis.
Selecting an antipsychotic
Using the HALT framework reminds us that all atypical antipsychotics carry some cardiovascular risks in the post-MI population. Although none are known to directly increase heart rate, ziprasidone can increase the QT interval and pose a significant risk for arrhythmia. It therefore should be avoided in post-MI patients.18