DHP CCB-Induced Peripheral Edema

Personally, I like using dihydropyridine calcium channel blockers (DHP CCB) in my clinic when managing blood pressure (given no comorbid disease states). Why? Because it's the only first-line agent that's easy to titrate and doesn't require lab follow-up, which is a HUGE plus especially for those who have difficulty getting to the lab. However, the main caveat of using a DHP CCB is the famous peripheral edema, more specifically, bilateral ankle swellings.

In pharmacy school, we learned that DHP CCB can cause dose-dependent peripheral edema in addition to constipation and, rarely, gingival hyperplasia (ya'll remember that?). But did you guys know that the risk of CCB-induced peripheral edema may be reduced if used with ACEs/ARBs? If you did, kudos to you. This is news to me and it blew my mind so I'm going to share it here :)

(slide credit: Dr. Aziz-ur-Rehman)

As seen above, the mechanism of action of peripheral edema is thought to be due to CCB's action on dilating arterioles (but not affecting venules) --> increasing arteriolar capillary pressure & permeability --> therefore, causing a "leak" into the intravascular space, AKA edema. Because CCB-induced peripheral edema is not associated with sodium & water retention, diuretic therapy isn't an effective treatment. This often time warrants to either decrease to previously "tolerated" dose or discontinue the therapy.

So where does ACEs/ARBs or RAAS therapy comes into play? The MOA of RAAS therapy targets vasodilation of the venules (venodilation), thus theoretically balancing the "imbalance" of the capillary pressure and preventing the "leakage." A study has shown that amlodipine 5mg+benazepril 20mg significantly lowered both SBP & DBP compared to amlodipine 10mg alone AND amlodipine 5mg + HCTZ 25mg, while also reducing the risk of peripheral edema. How cool is that?! Another meta-analysis showed that CCB+ACE combination showed a greater reduction in peripheral edema compared to CCB+ARB combination. I'll add the references to both on the bottom.

I plan on incorporating this into my practice especially if the patient is tolerating the edema without any decrease in quality of life (first, do no harm!) or has exhausted other options.

Please leave a comment on your thoughts :)

References:
1. Effect of renin-angiotensin system blockade on calcium channel blocker-associated peripheral edema. 2011 Am J Med.
2. Pilot study to evaluate a water displacement technique to compare effects of diuretics and ACE inhibitors to alleviate lower extremity edema due to dihydropyridine calcium antagonists. 2001 Am J Hypertension.