Statins often negatively interact with other CV drugs

NEW ORLEANS — Many CV medications have interactions with statins, so clinicians must understand the magnitude of these relationships to ensure no harm to their patients, an expert said at the National Lipid Association Scientific Sessions.

As a result, some patients who require a high-intensity statin may not be suited for it, and “clinical practice may dictate combinations that are not ideal,” Barbara S. Wiggins, PharmD, FCCP, FAHA, FNLA, AACP, BCPS (AQ Cardiology), CLS, said.

Barbara S. Wiggins

Wiggins, clinical specialist – cardiology at Medical University of South Carolina and adjunct professor at South Carolina College of Pharmacy, Charleston, discussed the degrees of interaction between statins and other CV drugs, with minor interactions defined as area under the curve 1.2-1.9, moderate interactions defined as AUC greater than 2 to 4.9 and severe interactions defined as AUC 5 or more.

“Even at the moderate level, that’s going to cause some alarms,” Wiggins said. “That’s when we need to [ask]: ‘How severe is this? What are the implications of combining these drugs? Should I make a change in the drug or the dose?’ Once you get to the severe level, it’s more of a red flag, in which this drug combination may not be of any value in any situation.”

Some fibrates are known to interact with statins, and this may be because fibrates such as gemfibrozil inhibit glucuronidation, a process by which statins such as atorvastatin, lovastatin and simvastatin eliminate their active hydroxyl acid metabolites, Wiggins said, adding that “there are several mechanisms involved in this interaction.” She noted that fenofibrate does not have this issue.

The calcium-channel blockers amlodipine, diltiazem and verapamil have all been shown to increase the AUC of lovastatin and simvastatin, according to Wiggins. Amlodipine increases the AUC of both statins by 1.76-fold, while diltiazem increases the AUC of lovastatin by 3.6-fold and simvastatin by 3.7-fold, and verapamil increases the AUC of simvastatin by 2.5-fold, she said.

Antiarrhythmic drugs amiodarone and dronedarone (Multaq, Sanofi Aventis) also have interactions with lovastatin and simvastatin, she said.

Ranolazine (Ranexa, Gilead Sciences) has a minor interaction with simvastatin, while ticagrelor (Brilinta, AstraZeneca) has moderate interactions with lovastatin and simvastatin, she said.

Immunosuppressive agents cyclosporine, everolimus, sirolimus and tacrolimus increase the AUC of various statins by anywhere from twofold to 15-fold, according to Wiggins.

Little is known about how statins interact with two new HF drugs, ivabradine (Corlanor, Amgen) and sacubitril/valsartan (Entresto, Novartis), she said.

“We want to do the best for our patients and put them on optimal medical therapy,” she said. “If they have [atherosclerotic] CVD or are at high risk for it, we want to give them a high-intensity statin. However, there are some patients with either complex lipid abnormalities or other disease states that necessitate certain medication combinations. Additionally, tolerability and cost issues may limit alternative options. We have to make a decision about whether we can still utilize a given combination at a reduced dose, enabling use of both medications a patient might need while minimizing the adverse effects overall.” – by Erik Swain

Reference:

Wiggins BS. Evaluating the Landscape of Statin Drug Interactions with Select Cardiovascular Medications: What You Need to Know. Presented at: National Lipid Association Scientific Sessions; May 19-22, 2016; New Orleans.
Disclosure: Wiggins reports no relevant financial disclosures.