Many people take ACE inhibitors or ARBs to manage high blood pressure, heart failure, or kidney disease. But if you're on one of these drugs, you might be wondering: Can I take both together? What happens if I switch from one to the other? Are there hidden risks most doctors don’t talk about?
The short answer: Combining ACE inhibitors and ARBs is dangerous for most people. Even though they both target the same system in your body, mixing them doesn’t give you better results-it just ups your risk of serious side effects. And many patients don’t realize they’re being put at risk until it’s too late.
How ACE Inhibitors and ARBs Work (And Why They’re Not the Same)
Both ACE inhibitors and ARBs are designed to relax blood vessels and lower blood pressure by blocking parts of the renin-angiotensin system (RAS). But they do it in completely different ways.
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 work by blocking the enzyme that turns angiotensin I into angiotensin II.
ARBs like losartan, valsartan, and irbesartan don’t stop angiotensin II from being made. Instead, they block the receptors where angiotensin II tries to bind. Think of it like a lock and key: ACE inhibitors reduce the number of keys being made. ARBs keep the locks from opening-even if the keys are still around.
This difference matters. Because ACE inhibitors cause a buildup of bradykinin-a side effect of enzyme inhibition-they often trigger a dry, hacking cough in 10-15% of users. ARBs rarely cause this because they don’t affect bradykinin. That’s why many patients switch from an ACE inhibitor to an ARB: not because the blood pressure control is better, but because the cough is unbearable.
Another key difference: ACE inhibitors have stronger proof of reducing death in heart failure patients. Studies show a 23% lower risk of dying compared to 15% with ARBs. That’s why guidelines still recommend ACE inhibitors as first-line for heart failure with reduced pumping ability.
Why Combining Them Is a Bad Idea
It makes sense on paper. If one drug blocks angiotensin II production, and the other blocks its action, shouldn’t two be better than one?
Reality says no.
The ONTARGET trial in 2008, which followed over 25,000 high-risk patients, found that combining ramipril (an ACE inhibitor) with telmisartan (an ARB) didn’t lower heart attacks, strokes, or deaths. But it did double the risk of dangerously high potassium levels (hyperkalemia) and nearly doubled the chance of acute kidney injury.
Here’s what that looks like in real life:
- Hyperkalemia went from 2.5% on ramipril alone to 5.5% on the combo.
- Patients on the combo were more likely to need dialysis-2.3% vs. 1.0%.
- There was no improvement in survival, heart attack rates, or hospital stays.
The FDA and major heart associations (AHA, ACC, ESC) all agree: don’t combine ACE inhibitors and ARBs. The 2023 AHA guidelines call it a practice to avoid outside of clinical trials. The Cleveland Clinic’s 2023 recommendations bluntly state: “I try not to combine ACE inhibitors with ARBs.”
Even small doses don’t fix the problem. A 2023 survey of 317 U.S. primary care doctors found that 89% had stopped prescribing the combo after the 2018 VA NEPHRON-D trial showed a 27% increase in serious side effects with no benefit.
When Is It Ever Okay to Combine Them?
There are exceptions-but they’re rare.
Some nephrologists may consider adding an ARB to an ACE inhibitor for patients with non-diabetic kidney disease who have proteinuria over 1 gram per day, and who haven’t responded to maximum ACE inhibitor doses. But even then, it’s not a green light.
Dr. Srinivasan Beddhu from the University of Utah says this approach might help reduce proteinuria in rare cases. But he stresses it requires weekly blood tests for potassium and kidney function. Patients need to be monitored like they’re in a hospital, not a regular clinic.
One Reddit thread from March 2024 shared stories from medical residents who saw 78% of patients on combo therapy develop high potassium levels or sudden kidney decline. In contrast, a few patients with rare kidney conditions like focal segmental glomerulosclerosis did report big drops in proteinuria-but all required intense monitoring.
Bottom line: If you’re not in a clinical trial or under the care of a kidney specialist who checks your labs every week, you should not be on both drugs.
Switching Between ACE Inhibitors and ARBs
If you’re having side effects from an ACE inhibitor-like a persistent cough or swelling in your face (angioedema)-switching to an ARB is often the right move.
But don’t just stop one and start the other the next day.
There’s a risk of additive effects. Your blood pressure could drop too low. Your kidneys could shut down. Potassium could spike.
Guidelines recommend a 4-week washout period between switching. That means stopping the ACE inhibitor, waiting a month, then starting the ARB. In practice, only about 42% of doctors follow this rule, according to a 2022 JAMA Internal Medicine study.
If you’re switching, here’s what you should do:
- Ask your doctor for a clear plan-don’t self-switch.
- Get blood tests before and 1-2 weeks after the switch: potassium and creatinine.
- Watch for dizziness, fainting, or reduced urine output.
- Don’t start any new supplements (like potassium salts or salt substitutes) without checking with your doctor.
Many patients think switching is safe because both drugs “do the same thing.” But the body reacts differently to each. Even if you’ve been on lisinopril for years, your system still needs time to reset.
Side Effects You Can’t Ignore
Both drugs can raise potassium and hurt kidney function, especially in older adults, diabetics, or people with existing kidney disease.
Here’s what to watch for:
- High potassium (hyperkalemia): Can cause irregular heartbeat, muscle weakness, or cardiac arrest. Normal potassium is 3.5-5.0 mmol/L. Levels above 5.5 require urgent action.
- Acute kidney injury: A sudden drop in kidney function. Often shows up as rising creatinine (more than 30% increase from baseline).
- Low blood pressure: Dizziness when standing, fatigue, blurred vision.
- Angioedema: Swelling of lips, tongue, throat. This is a medical emergency. It’s rare (0.1-0.7% with ACE inhibitors) but can be fatal if untreated.
Patients on these drugs should have blood tests every 3 months once stable. If you’re newly started, get tested after 1-2 weeks.
And here’s something many don’t know: ACE inhibitors can cause angioedema even after years of use. A 65-year-old patient on lisinopril for 8 years might suddenly develop swelling-not because they changed their dose, but because their body finally reacted.
What to Do Instead of Combining Them
If your blood pressure isn’t controlled on one RAS blocker, or your proteinuria is still high, there are safer options.
Instead of adding an ARB to your ACE inhibitor:
- Try adding a low-dose spironolactone (12.5 mg daily). It’s a mineralocorticoid blocker that reduces proteinuria by 30-40% with fewer kidney risks.
- Use a calcium channel blocker like amlodipine for extra blood pressure control.
- For heart failure, consider an ARNI (sacubitril/valsartan), which combines an ARB with a neprilysin inhibitor. It’s proven to reduce death better than ACE inhibitors alone.
- For kidney protection, focus on tight blood sugar control (if diabetic), sodium restriction, and avoiding NSAIDs like ibuprofen.
These alternatives have better safety profiles and real-world data backing them. The goal isn’t to hit the lowest possible blood pressure-it’s to avoid hospitalization, dialysis, or death.
What’s Next? New Drugs and Changing Guidelines
The future of RAS blockade isn’t about combining old drugs-it’s about replacing them with smarter ones.
The FDA approved a fixed-dose combo of perindopril and indapamide in Europe for heart failure, but it’s not approved for hypertension in the U.S. And it’s not an ACE-ARB combo-it’s an ACE inhibitor with a diuretic, which is much safer.
The FINE-REWIND trial (2024-2028) is testing whether ultra-low doses of both an ACE inhibitor and ARB might work safely in diabetic kidney disease. But results won’t be out until 2026.
Meanwhile, the use of ACE-ARB combinations is expected to drop below 1% of all RAS blocker prescriptions by 2028. The trend is clear: fewer combos, more monitoring, and better alternatives.
For now, stick with one drug. If it’s not working, talk to your doctor about alternatives-not about adding another.
Frequently Asked Questions
Can I take an ACE inhibitor and ARB together for better blood pressure control?
No. Combining ACE inhibitors and ARBs doesn’t improve survival or prevent heart attacks or strokes. It doubles your risk of dangerously high potassium levels and increases your chance of kidney failure. Major guidelines from the AHA, ACC, and ESC all recommend against this combination except in rare, closely monitored cases.
Why do some doctors still prescribe both drugs?
A small number of nephrologists may prescribe both for patients with severe non-diabetic proteinuria who haven’t responded to maximum doses of an ACE inhibitor alone. But this is not standard practice. It requires weekly blood tests for potassium and kidney function, and even then, the benefits are uncertain. Most doctors avoid it entirely due to the risks.
I have a dry cough from my ACE inhibitor. Should I switch to an ARB?
Yes, switching from an ACE inhibitor to an ARB is a common and safe solution for cough. ARBs rarely cause this side effect because they don’t affect bradykinin. But don’t switch on your own. Talk to your doctor, get baseline blood tests, and wait at least 2-4 weeks after stopping the ACE inhibitor before starting the ARB to avoid sudden drops in blood pressure or kidney issues.
Are ARBs safer than ACE inhibitors overall?
ARBs are better tolerated-they cause less cough and slightly less angioedema. But ACE inhibitors have stronger evidence for reducing death in heart failure. Neither is universally safer. The choice depends on your condition, side effects, and other health issues. For example, if you have heart failure, ACE inhibitors are usually preferred. If you can’t tolerate the cough, ARBs are the next step.
How often should I get blood tests if I’m on an ACE inhibitor or ARB?
When you first start, get a blood test for potassium and creatinine after 1-2 weeks. If everything’s stable, check every 3 months. If you’re older, have diabetes, or kidney disease, check every 1-2 months. Any time your dose changes or you start a new medication (like NSAIDs or diuretics), get tested again. Monitoring saves lives.
I heard ARBs were recalled. Are they still safe to take?
Yes. Between 2018 and 2020, some ARBs like valsartan and losartan were recalled due to trace amounts of cancer-causing nitrosamine impurities. Manufacturers fixed their processes, and by late 2023, all recalled batches were replaced. The FDA says current ARBs on the market are safe. If you’re concerned, ask your pharmacist to confirm your batch isn’t affected.
What to Do Next
If you’re on an ACE inhibitor or ARB, here’s what to do right now:
- Check your current meds. Are you taking both an ACE inhibitor and an ARB? If yes, talk to your doctor immediately.
- Look up your last blood test results. What was your potassium level? Was your creatinine stable?
- Write down any side effects: cough, dizziness, swelling, or reduced urine output.
- Ask your doctor: “Is there a safer way to improve my blood pressure or kidney protection without combining these drugs?”
You don’t need to take two drugs that do the same thing. You need the right one-plus the right monitoring. And that’s something you can control.
Miruna Alexandru
The data is unequivocal: combining ACE inhibitors and ARBs is a pharmacological misstep masquerading as a rational escalation. The ONTARGET trial wasn't just a warning-it was a forensic autopsy of a flawed clinical assumption. The 5.5% hyperkalemia rate versus 2.5% isn't a statistical blip; it's a red flag waving in a hurricane. And yet, we still see this in practice. Why? Because medicine is still haunted by the ghost of 'more is better.' The truth? Sometimes, less is the only thing that saves you.
It's not about efficacy-it's about harm reduction. We've got ARNIs, SGLT2 inhibitors, mineralocorticoid antagonists-all proven, safer alternatives. We're not stuck in the 1990s. Stop treating patients like lab rats in a dose-response curve.
And for the love of evidence-based practice, if your patient's creatinine jumps 30% after a switch, don't blame the drug-blame the lack of washout. Four weeks isn't a suggestion. It's a biological imperative.
Every time someone says 'I've seen it work,' I hear a medical student who hasn't yet seen the patient on dialysis.
Stop romanticizing risk. The data doesn't care about your anecdote.
Justin Daniel
Man, I love how this post just lays it all out like a textbook chapter but with zero fluff. Honestly, I’ve seen so many patients get confused because ‘both lower BP’-like they’re interchangeable spices in a soup. But nah. One gives you a cough that makes you sound like a dying seal, the other doesn’t. Simple.
Also, the part about switching? Yeah, I’ve had patients just swap on their own because their pharmacy ran out of lisinopril. Dude, you didn’t just ‘switch meds,’ you just turned your kidneys into a stress test. Yikes.
Thanks for the clarity. This should be mandatory reading for every new med student. And their grandparents, honestly.
Also, spironolactone 12.5 mg? That’s the quiet hero we don’t talk about enough. Low dose, big wins. 🙌
Latonya Elarms-Radford
Oh, how quaint-the modern medical establishment, armed with its randomized controlled trials and its algorithmic guidelines, believes it has tamed the chaos of human physiology. But tell me, when the renin-angiotensin system is not merely a biochemical pathway but a metaphysical dance of homeostasis, can a pill ever truly 'block' the will of the body?
We speak of hyperkalemia as if it were a mere lab value, a number to be corrected, not a whisper from the autonomic nervous system screaming that equilibrium has been violated. And yet, we prescribe with the arrogance of engineers, believing that if we tweak the levers just right, the machine will obey.
The truth? The body remembers. It remembers the bradykinin surge, the angioedema that came unannounced after eight years of silence. It remembers the potassium that climbed not because of dosage, but because the soul of the kidney had grown weary.
Perhaps we are not treating disease. Perhaps we are negotiating with a force older than pharmacology.
And so I ask: when the guidelines say 'do not combine,' are we protecting patients-or are we merely protecting ourselves from the terror of uncertainty?
There is no algorithm for mortality. Only humility.
- A weary philosopher in a white coat
Mark Williams
Just to clarify the mechanism: ACEi inhibits ACE → reduces Ang II + increases bradykinin → cough. ARB blocks AT1 receptor → no cough, but Ang II still accumulates and can bind to AT2 (which may have counter-regulatory effects).
Combining them doesn't enhance RAS blockade-it creates a neurohormonal feedback loop where Ang II surges, triggering aldosterone escape and worsening potassium retention. That’s why hyperkalemia spikes even if you're on low doses.
Also, the 2023 VA NEPHRON-D trial showed a 27% increase in renal events with combo therapy-this isn't theoretical. It's real-world data from a high-risk VA population.
And for the record: ARNI (sacubitril/valsartan) isn't an 'ARB combo'-it's a neprilysin inhibitor + ARB. It increases natriuretic peptides, which is why it outperforms ACEi in HFrEF. Different mechanism entirely.
Bottom line: don't confuse pharmacology with magic. Every drug has a ceiling. Pushing past it doesn't give you more benefit-it just gives you more side effects.
Ravi Kumar Gupta
Bro, in India we have this problem too-patients come to us with 10 different pills, and they think if one pill lowers BP, then two must lower it more. I had a guy on lisinopril, losartan, amlodipine, and hydrochlorothiazide-all because his cousin’s neighbor’s doctor did it.
I told him, ‘Beta, your kidneys are not a car engine where you add more fuel to go faster.’ He looked at me like I was speaking Sanskrit.
Then I showed him his potassium level: 6.1. He went pale. I told him, ‘If you keep this up, your heart will stop before your blood pressure does.’
Now he’s on just losartan, salt restriction, and a monthly check-up. No drama. No dialysis. Just common sense.
Doctors here need to stop being salesmen for pills. We’re healers. Not pharmacists with commission.
Rahul Kanakarajan
Ugh. Another long-winded medical lecture. Can we just agree that if you’re on blood pressure meds, you’re probably not eating right or moving enough? Why are we medicating lifestyle problems into oblivion?
And why does everyone act like combining ACEi and ARB is some shocking revelation? I’ve seen it since med school in 2010. It’s a lazy shortcut for doctors who don’t want to adjust doses or talk to patients about diet.
Also, ‘weekly labs’? That’s not monitoring-that’s overkill. Most people can’t even afford a monthly check-up, let alone weekly blood draws. This whole post reads like a pharma-funded pamphlet for rich Americans.
Real solution? Cut the salt. Walk 30 mins. Lose 10 lbs. No pills needed. But that’s too simple for the medical-industrial complex, isn’t it?
Nikhil Chaurasia
I get where the author is coming from-safety first, no doubt. But I’ve also seen patients on combo therapy who were stable for years with weekly monitoring. One guy, 72, with FSGS, proteinuria 4.2 g/day. He was on lisinopril 40 mg + losartan 100 mg. His potassium hovered at 5.2, creatinine stable at 1.8. He didn’t need dialysis. He was working, driving, taking his grandkids to school.
Yes, it’s risky. Yes, it’s not standard. But medicine isn’t always black and white. Sometimes, the guidelines don’t capture the individual.
I’m not saying do it blindly. I’m saying: don’t throw out nuance in the name of caution. A good nephrologist doesn’t just follow the algorithm. They listen to the patient, watch the labs, and adjust.
It’s not about ‘never combine.’ It’s about ‘combine wisely, with eyes wide open.’
ann smith
Thank you for writing this so clearly. I’ve been on lisinopril for 5 years and just had my potassium checked last month-5.6. My doctor didn’t mention the combo risk, so I’m so glad I read this. I’ve already asked to switch to an ARB with a 4-week gap. I feel so much more in control now. 💙
Julie Pulvino
Just wanted to say-this is the kind of post that makes me feel less alone. I switched from lisinopril to valsartan last year after the cough got unbearable. My doctor didn’t even mention the washout period, so I just started the new one. I passed out twice in the first week. My husband called 911.
Turns out, my BP dropped to 78/45. Scary stuff.
Now I know why. I’ll never skip the washout again. Thanks for the heads-up. I’m sharing this with my mom-she’s on both meds and has no idea.