Appeal type: Formulary Exception
Decision: Upheld

Diagnosis: Cardiac/Circulatory Problems/Hypertension/High Blood Pressure.
Treatment: Prescription Drugs/Edarbyclor.
The health plan denied the requested non-formulary drug Edarbyclor.
The health plan's determination is upheld.

The patient is a woman with a history of hypertension, type 2 diabetes, transient ischemic attack, thrombophilia, ascending aortic aneurysm, and obesity. At a physician visit, on Amlodipine, every other day Furosemide, and Metoprolol, her blood pressure was 122/80 millimeters of mercury (mmHg). However, she complained of lower extremity edema. The Amlodipine and Metoprolol were discontinued and Olmesartan 20 mg (milligrams) daily was prescribed (the maximum daily recommended dose is 40 mg). Her blood pressures on this regimen were frequently in the 140s-150s/the 90s-107 mmHg. At some point, the Olmesartan was discontinued and Edarbyclor 40/12.5 mg daily was prescribed. During subsequent visits, the patient's blood pressure ranged from 100-110/72-80 mmHg.
The medical necessity for the non-formulary drug, Edarbyclor is at issue.

I uphold, on the whole, the health plan's determination that Edarbyclor is not medically necessary in this instance.

The above list of formulary drugs consists of several angiotensin receptor blockers (ARBs), either alone or in combination with Hydrochlorothiazide (HCTZ), a thiazide diuretic. Edarbyclor is a combination of Azilsartan (an ARB) and Chlorthalidone (a thiazide diuretic).
Previously, this woman's blood pressure was poorly controlled on a submaximal dose of Olmesartan (20 mg daily). She achieved good control on Edarbyclor 40/12.5 mg daily (Azilsartan 40 mg/Chlorthalidone 12.5 mg). However, it is unclear if the improvement in her blood pressure resulting from the switch from Olmesartan to Azilsartan, from the addition of Chlorthalidone, or both. In the reports by White, et al, and Bakris, et al, while Azilsartan 80 mg reduced blood pressure more than Olmesartan 40 mg, the reductions seen with Azilsartan 40 mg versus Olmesartan 40 mg were not statistically different. Olmesartan-HCTZ is a formulary option. While Chlorthalidone has been shown to reduce blood pressure more than HCTZ, it is quite possible that a combination of Olmesartan 40 mg (the patient's prior dose was 20 mg) and HCTZ would be effective in treating this woman's hypertension. Another option would be Telmisartan-HCTZ. In the report by Naruse et al, Azilsartan and Telmisartan were similarly efficacious in reducing blood pressure in hypertensive patients with type 2 diabetes.
While the data regarding the comparative efficacy of Azilsartan versus the remaining ARBs are limited, there are reports that Azilsartan is more efficacious than Valsartan and Candesartan. For this reason, either of those combined with HCTZ would not be the preferred alternatives in this case. Likewise, in some studies, Losartan is less effective than other ARBs and would, thus, not be a good choice for this woman. However, Irbesartan-HCTZ would be an option.
In summary, while Azilsartan has been shown to be more effective than some other ARBs, its efficacy is similar to others. Moreover, while this woman had an inadequate response to Olmesartan (an ARB) the dose she tried was submaximal and she did not take it with a thiazide diuretic. It cannot be determined that all of the formulary alternatives (especially Olmesartan 40 mg/HCTZ and Telmisartan/HCTZ) would be ineffective in this case. The expected adverse effects are similar between different ARBs and thiazides (except for more hypokalemia with Chlorthalidone). Accordingly, one would not expect this woman to have more side effects with the formulary drugs than with Edarbyclor.