When it comes to managing high blood pressure, heart failure, or kidney damage from diabetes, two drug classes are often the first choice: ACE inhibitors and ARBs. They both target the same system in your body-the renin-angiotensin system-but they do it in different ways. And while they might seem interchangeable, mixing them can be dangerous.
How ACE Inhibitors and ARBs Work
ACE inhibitors like lisinopril, enalapril, and ramipril stop your body from making angiotensin II, a chemical that tightens blood vessels and raises blood pressure. They do this by blocking the enzyme that converts angiotensin I into angiotensin II. Less angiotensin II means relaxed blood vessels, lower blood pressure, and less strain on the heart and kidneys.
ARBs-like losartan, valsartan, and irbesartan-work differently. Instead of stopping the production of angiotensin II, they block its receptors. Think of it like putting a lock on the door so angiotensin II can’t get in, even if it’s still being made. This means ARBs leave angiotensin II floating around, but it can’t do its job.
Both classes are effective at lowering blood pressure and protecting the kidneys in people with diabetes. But here’s the catch: ACE inhibitors can cause a dry, nagging cough in 10-15% of users because they build up a substance called bradykinin. ARBs don’t do that. That’s why doctors often switch patients from an ACE inhibitor to an ARB if the cough becomes unbearable.
Why You Shouldn’t Mix Them
It’s tempting to think that if one drug works well, two must work better. But with ACE inhibitors and ARBs, that’s not true. Combining them doesn’t give you extra protection-it just adds risk.
The ONTARGET trial, a massive study published in the New England Journal of Medicine in 2008, looked at over 25,000 high-risk patients. Half got ramipril (an ACE inhibitor), half got telmisartan (an ARB), and a third group got both. The results were clear: the combo group had no fewer heart attacks, strokes, or deaths. But they had twice the risk of high potassium (hyperkalemia) and more than double the chance of kidney failure requiring dialysis.
That’s not a small trade-off. A 2022 review of 12 clinical trials found that combination therapy increased the risk of acute kidney injury by 80%. In patients with diabetes, the VA NEPHRON-D trial showed a 27% spike in serious side effects-like sudden kidney drops or dangerous potassium levels-without a single improvement in survival or kidney function.
Because of this, the American Heart Association, the American College of Cardiology, and the European Society of Cardiology all agree: don’t combine ACE inhibitors and ARBs. The guidelines say it’s only acceptable in rare, research-approved cases-and even then, only with weekly blood tests and expert supervision.
Real-World Consequences
Doctors aren’t just following guidelines-they’re seeing the damage firsthand. Dr. Lisa Chen, a nephrologist at Massachusetts General Hospital, stopped combination therapy in 87% of her 215 diabetic kidney disease patients because of high potassium or sudden kidney decline. On medical forums, residents report seeing patients hospitalized for hyperkalemia after being put on both drugs.
It’s not just about kidney function. The combo increases the risk of low blood pressure, fainting, diarrhea, and even sudden cardiac events. One Reddit thread from March 2024 had 142 medical students sharing stories: 78% had seen a patient get sick from this combo during their rotations.
There are exceptions-but they’re rare. A few nephrologists, like Dr. Srinivasan Beddhu, say that in non-diabetic patients with very high protein loss in urine (over 1 gram per day), adding an ARB to a maximized ACE inhibitor dose might help. But even then, it’s not standard. These patients need blood tests every week, not every three months. And most doctors won’t even try it.
Switching Between ACE Inhibitors and ARBs
If you need to switch from one to the other-say, because of a cough or side effect-you can’t just swap them on the same day. Both drugs stay active in your body for hours. Taking them together, even briefly, can cause a dangerous spike in potassium or drop in kidney function.
The Cleveland Clinic recommends a 4-week washout period between switching. That means stopping the first drug, waiting a month, then starting the new one. But in practice, only 42% of doctors follow this rule. Many patients are switched too quickly, and that’s when problems start.
Instead of switching, sometimes the better move is to add something else. Mineralocorticoid receptor antagonists like spironolactone or eplerenone can help reduce proteinuria and lower blood pressure without the same risks as ARBs. They’re safer, especially when used at low doses (12.5-25 mg daily), and they’re backed by solid data.
Monitoring Is Non-Negotiable
Whether you’re on an ACE inhibitor or an ARB, you need regular blood tests. Both drugs can raise potassium and lower kidney function, especially in older adults, diabetics, or people with existing kidney disease.
The KDIGO guidelines recommend checking serum potassium and creatinine:
- 1-2 weeks after starting or changing the dose
- Then every 3 months if stable
If your potassium goes above 5.5 mmol/L or your creatinine rises by more than 30%, you need to stop or adjust the drug. A 0.3-0.5 mmol/L rise in potassium is common and usually harmless-but anything higher needs attention.
People on these drugs should also avoid salt substitutes (which are full of potassium), NSAIDs like ibuprofen, and certain herbal supplements like licorice root. These can make kidney and potassium problems worse.
What’s Next in Treatment?
The future of RAS blockade isn’t about combining ACE inhibitors and ARBs-it’s about moving past them. Drugs like sacubitril/valsartan (Entresto), an angiotensin receptor-neprilysin inhibitor (ARNI), have replaced ACE inhibitors in many heart failure patients because they reduce death and hospitalization more effectively.
Even newer drugs are being tested. The FINE-REWIND trial, running from 2024 to 2028, is looking at whether half-doses of both ACE inhibitors and ARBs might be safe for kidney protection in diabetics. Early results aren’t expected until late 2026.
For now, the message is clear: if you’re on one, stick with it. Don’t add the other. If you’re having side effects, talk to your doctor about switching-not stacking.
What to Do If You’re on Both
If you’re currently taking an ACE inhibitor and an ARB together, don’t stop suddenly. That can cause your blood pressure to spike. Instead:
- Call your doctor. Ask if the combo is still necessary.
- Request recent lab results: potassium, creatinine, eGFR.
- If you’re not being monitored every 3 months, ask why.
- Consider switching to one drug only-most people do just fine on either.
There’s no benefit to staying on both. Only risk.
fiona vaz
January 28, 2026 AT 16:23Really appreciate this breakdown. I’ve been on lisinopril for years and switched to losartan after the cough got unbearable. No more 3 a.m. hacking fits - life-changing. Just make sure your doc checks your potassium and kidney numbers regularly. Simple stuff, but so many people skip it.
Sue Latham
January 29, 2026 AT 05:21Ugh, I can’t believe people still get prescribed both. It’s like putting two turbochargers on a lawn mower and wondering why it explodes. The guidelines aren’t suggestions-they’re warnings written in blood. If your doctor’s still doing this, find a new one. 🙄
Lexi Karuzis
January 29, 2026 AT 05:57Wait… did you know that Big Pharma secretly funds the guidelines? They want you on BOTH drugs so you need MORE lab tests, MORE prescriptions, MORE co-pays. They’ve been pushing this combo since 2005-look up the AstraZeneca internal memos! And don’t get me started on how they bury the renal failure data…
My cousin died from hyperkalemia after his cardiologist ‘just wanted to be aggressive.’ They never even checked his potassium for 6 months. This isn’t medicine-it’s profit-driven negligence.
And why does everyone ignore the fact that ACE inhibitors cause angioedema too? Nobody talks about that. It’s like the medical establishment is in a cult. Wake up people!
Brittany Fiddes
January 29, 2026 AT 20:44Oh please, the Americans think they invented medicine. In the UK, we’ve known since the 90s that combining these is madness. We don’t need your $200 lab tests and your ‘guidelines’-we’ve got NICE, which actually means something. You lot are still arguing over whether salt is bad while we’ve moved on to real science.
And don’t even get me started on your ‘Cleveland Clinic.’ I’ve seen their billing codes. It’s a money machine. Stick to statins and stop the nonsense.
Mark Alan
January 30, 2026 AT 19:56Bro I was on both for 3 months after my heart attack 😭 My doc said ‘it’s fine’ but my potassium hit 6.1 and I almost died in the ER. Now I’m on losartan only and I feel like a new person. 🙏 Don’t be like me. Listen to the science, not the ‘maybe’ doctors.
Amber Daugs
February 1, 2026 AT 05:34It’s not just the combo-it’s the lack of accountability. Doctors are lazy. They don’t want to explain why they’re not prescribing the ‘better’ option. So they just stack drugs and call it ‘optimization.’ But patients pay the price with dialysis, ER visits, and lost jobs.
If you’re on both and your doctor doesn’t check your labs every 30 days, you’re being endangered. This isn’t just bad medicine-it’s morally wrong. And no, ‘I’ve always done it this way’ is not an excuse.
doug b
February 2, 2026 AT 18:42Good post. Real talk: if you’re on one of these, stick with it. If you’re having side effects, talk to your doc about switching-not adding. And get your blood work done. It’s not complicated. Your kidneys aren’t magic-they need monitoring.
Also, spironolactone is way underrated. Low dose, low risk, big benefit. Ask your doc about it. No need to gamble with both ACE and ARB.
Mel MJPS
February 3, 2026 AT 02:54My dad was on both after his diabetes diagnosis. I didn’t know any better until I read this. We got his labs done and his potassium was sky-high. He switched to just valsartan and now he’s fine. Thank you for explaining why this happens-it’s scary how common this is.
Katie Mccreary
February 3, 2026 AT 22:02Typical. Someone writes a 10-page essay on why you shouldn’t do something, but no one tells you what to do instead. Oh, spironolactone? Cool. But what if you’re already on it? What if you’re allergic to thiazides? What if you’re 80 and frail? The real answer: nothing’s safe. Just die quietly.