How do you safely treat a psychiatrically ill patient who is taking seven to nine potent cardiovascular medications? Our approach is to organize the effects of psychiatric drugs into a systematic, easy-to-use framework, which we remember by the mnemonic HALT. It reminds us to consider any drug’s effect on hypertension, arrhythmias, lipids and liver enzymes, and risk of thrombosis. Using HALT as a decision tool can help you avoid drug-drug interactions when selecting psychotropics for patients with a history of myocardial infarction (MI).
The multi-medication challenge
In psychiatry, medication guidelines and algorithms encourage us to start with monotherapy before we try more complex regimens.1-3 Cardiologists, however, jump directly to a multimedication, cardio-protective approach for today’s post-MI patient.4-5 The cardiac standard of care includes angiotensin-converting enzyme (ACE) inhibitors, cardioselective beta-blockers, lipid-lowering agents, and platelet and clotting inhibitors.
Adding even one psychotropic to such a complex daily regimen could risk an adverse reaction. But, unfortunately, no guidelines exist for the medical management of psychiatrically ill post-MI patients, and research is very limited:
- only one randomized, controlled trial has examined drug treatment of their depression
- no randomized, controlled trials have addressed bipolar mania or psychosis drug treatment.
Table
THREE TYPES OF ACUTE CORONARY SYNDROMES
| Type | Diagnostic features |
|---|---|
| ST elevation MI | ST elevation in two contiguous ECG leads or new left bundle-branch block |
| Non-ST elevation MI | Positive CPK-MB or positive troponin levels and ST depression on ECG |
| Unstable angina | ST depression or T-wave inversion with no enzyme release |
| MI: myocardial infarction | |
| CPK-MB: creatine phosphokinase of muscle band (an enzyme released by ischemic heart muscle) | |
Pathophysiology of acute coronary syndromes
Acute coronary syndromes present as three broad types: ST elevation MI, non-ST elevation MI, and unstable angina (Table ). ST elevation MI, non-ST elevation MI and—to a lesser extent—unstable angina result from plaque rupture within the coronary intima, with sudden occlusion of one or more coronary arteries or branches and ischemia to the affected myocardium. Multiple pathologic processes—such as hypertension, dyslipidemia, or inflammatory disease—may weaken or injure the vascular lumen, and the development of a thrombus at the plaque rupture site involves many steps and triggers.
Ischemic myocardial injury increases an acute MI survivor’s risk of arrhythmias, heart failure, and sudden death. Tachycardia related to psychological stress can trigger these cardiac events in patients with heart disease. The goal of post-MI medical therapy is to protect the heart from further hypertensive injuries, arrhythmias, dyslipidemias, and thrombus formation.
Typical post-MI medications
ACE inhibitors. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to angiotensin II. Angiotensin II—a vasoconstrictor—increases blood pressure, restricts blood flow to the kidney, and stimulates aldosterone secretion by the adrenal cortex. ACE inhibition results in lower plasma levels of angiotensin II, with decreased blood pressure, vasopressor activity, and aldosterone secretion; this last effect may increase serum potassium.
Two ACE inhibitors—lisinopril and ramipril—have been shown in clinical trials to protect against recurrent cardiac events.6,7 ACE inhibitors may have variable effects among different ethnic groups. For example, ACE inhibitors have shown a less robust blood pressure-lowering effect in black patients than in non-blacks in some clinical trials.8
Beta blockers. Beta-adrenergic receptor blocking agents compete with beta-adrenergic agonists for available receptor sites in the heart and lungs. Cardioselective or beta-1 adrenergic agents such as metoprolol affect primarily the receptors in the heart and can slow the sinus rate and decrease AV nodal conduction. Metoprolol reduces heart rate, cardiac output, and systolic blood pressure, and inhibits reflex and drug-induced tachycardia. These pharmacologic actions lower oxygen demand, thus reducing the risk of ischemia and arrhythmias.
Beta blockers are a mainstay in regimens prescribed for post-MI outpatient treatment.9 Although earlier studies suggested that these drugs might cause depression, a recent systematic review rebuts that conclusion.10
Lipid-lowering agents. First-line treatments of hyperlipidemia include HMG-CoA reductase inhibitors (or “statins”) and niacin (also known as nicotinic acid). These drugs have been shown to lower lipids (cholesterol and triglycerides), reduce low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) levels, and increase high-density lipoproteins (HDL).
HMG-CoA reductase inhibitors have been shown in large international trials to reduce mortality from cardiac events in post-MI patients.11 These agents—atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin—are associated with some side effect risks, including hepatotoxicity and rhabdomyolysis. Most are metabolized by cytochrome P450 3A4; the exception is fluvastatin, which is metabolized by CYP 2C9.
Niacin has been shown to decrease serum levels of apolipoprotein B-100—the major protein component of VLDL and LDL fractions—and of lipoprotein (a), an LDL variant independently associated with coronary risk.12 Niaspan—a long-acting formulation of niacin—is indicated to reduce recurrent nonfatal MI risk in patients with a history of MI and hypercholesterolemia. Niacin’s side effects include flushing, increased serum transaminase levels, slightly reduced platelet count, and (rarely) rhabdomyolysis.