Getting to the Heart of the Matter: A Review of Potential Drug Interactions With Cardiac Medications

Adverse drug reactions (ADRs) are among the leading causes of morbidity and mortality in the United States and worldwide.¹ More than 400,000 preventable ADRs occur annually, with drug-drug interactions (DDIs) accounting for more than 30%.² Incorrectly prescribed cardiovascular medications are responsible for almost 25% of all preventable ADRs.³ Older adults are particularly affected. It is estimated that close to 1/3 of older adults are taking six or more drugs.² As the population ages, this number is rising. One study found that 54% of elderly patients were taking more than five medications in 1998, vs. 67% in 2003, and 19% were taking more than 10 medications in 1998, vs. 28% in 2003.⁴ Since so many elderly patients are taking cardiovascular medications, the vulnerability of this population to DDIs is enormous.

A study of 812 patients in a cardiology department found a 30% incidence of potential DDIs.⁵ Another study of 400 patients with heart failure found 863 potential DDIs.⁶ Zhou et al reported that a cardiologist wrote a prescription containing both simvastatin (40 mg) and amlodipine (5 mg). This event inspired the authors’ review of DDIs between 4-dihydropyridine calcium channel blockers (DHP-CCBs) and statin drugs (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors).⁷ Two additional articles examine potential DDIs between clopidogrel and morphine⁸ and between novel anticoagulant drugs and other agents.⁹

Dihydropyridine Calcium Channel Blockers (DHP-CCB) and Statins

Coadministration of DHP-CCBs with statins is common in treating patients with comorbid hypercholesterolemia and hypertension.⁷ Statins are metabolized by cytochrome P450 (CYP3A4) in the liver. DHB-CCBs have an inhibitory effect on CYP3A4, thereby increasing statin blood levels and increasing risk of myopathies (a potential side effect of statins).⁷ Zhou et al reviewed 19 pharmacokinetic studies of DDIs between DHB-CCBs and statins. Their findings are summarized in Table 1.

Table 1

Combination	Potential Clinical Outcome	Recommendation
Pravastatin-nimodipine	Enhanced vasodilatory effect of nimodipine	Not recommended
Lovastatin-nicardipine	Enhanced vasodilatory effect of nicardipine	Not recommended
Isradipine-lovastatin	Decreased cholesterol-lowering efficacy	Not recommended
Amlodipine–simvastatin	Increased myopathy risk	Not recommended
Amlodipine-atorvastatin	Absence of clinical significance	Recommended, monitor therapy