NEW YORK, June 9: A comprehensive 23-year medical study has raised concerns over the long-term safety of lisinopril, a widely prescribed blood pressure medication. The research shows a 19% higher risk of stroke-related death among lisinopril users compared to those taking other antihypertensive drugs, prompting fresh scrutiny over how blood pressure is managed in the long term.

The long-term study tracked more than 33,000 patients and compared lisinopril to two other common medications: amlodipine and chlorthalidone. While the overall cardiovascular mortality rates were found to be similar across all three drugs, lisinopril was associated with a significantly higher stroke death rate.

According to the study, the adjusted hazard ratio for stroke mortality with lisinopril was 1.19, indicating 119 stroke-related deaths in the lisinopril group for every 100 in the amlodipine group.

“These findings don’t suggest lisinopril is inherently dangerous,” said Dr. Sarah Chen, lead researcher at Johns Hopkins. “But they do indicate we need to adopt a more personalized approach to prescribing antihypertensive medications.”

The study’s unusually long duration — nearly 25 years — distinguishes it from most pharmaceutical trials, which typically last just 2–5 years. This extended follow-up allowed researchers to identify long-term trends not visible in shorter studies.

One suspected mechanism behind the elevated risk is hyperkalemia — a buildup of potassium in the blood. Lisinopril, an ACE inhibitor, blocks the angiotensin-converting enzyme, which can lead to elevated potassium levels. In some patients, this increases the risk of arrhythmias that may trigger strokes.

Unlike other ACE inhibitors, lisinopril is not a prodrug and is entirely processed by the kidneys. This makes patients with even mild kidney impairment more susceptible to drug accumulation, which could increase both its benefits and its risks.

Another factor is the elevation of bradykinin, a peptide that causes blood vessel dilation. While this helps lower blood pressure, excessive bradykinin may lead to inflammation in brain vessels, potentially contributing to stroke risk. This same inflammatory process is believed to cause the common “ACE inhibitor cough” experienced by many users.

Not all patients are affected equally. According to the study:

Patients currently taking lisinopril are advised not to stop their medication without medical advice. The absolute increase in stroke risk remains relatively small — estimated at 2–3 additional deaths per 1,000 patients over two decades.

However, patients — particularly those over 65 without diabetes or kidney disease — are encouraged to discuss these findings with their healthcare providers. Alternative medications such as amlodipine or chlorthalidone may offer a better safety profile for certain individuals.

Doctors may also consider monitoring potassium levels quarterly, especially for patients continuing on lisinopril. The study also warns against combining lisinopril with potassium supplements or salt substitutes, which can amplify the risk of hyperkalemia.

This study underscores the growing importance of personalized medicine in managing chronic conditions like hypertension. Researchers suggest that in the future, genetic testing might help predict how individual patients respond to specific drugs, including ACE inhibitors like lisinopril.

“Medication is not one-size-fits-all,” said Dr. Chen. “As we learn more about genetic and physiological differences, we can better match the right drug to the right patient.”

The findings do not call for an immediate halt in lisinopril use but emphasize the need for individualized treatment plans. Patients and physicians are urged to weigh risks and benefits carefully and to consider long-term implications when choosing antihypertensive therapies.

As always, regular communication with a healthcare provider is key to ensuring safe and effective treatment.