Five commonly prescribed drugs may be associated with a lower risk for aneurysmal subarachnoid hemorrhage (aSAH), a drug-wide association study suggested.
The blood pressure drug lisinopril; the cholesterol drug simvastatin; the diabetes drug metformin; and the drug tamsulosin, prescribed for an enlarged prostate, were all associated with decreased aSAH risk, investigators found.
Conversely, four other drugs were associated with an increased risk for this severely morbid, often deadly, condition.
"The motivation for this study was the fact that we can currently prevent bleeding from intracranial aneurysms only by invasive treatment of those aneurysms with inherent complication risks," study investigator Ynte Ruigrok, MD, PhD, associate professor of neurology and neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands, told Medscape Medical News. "Drugs to reduce or eliminate this risk are not yet available. This study is a first step in identifying such drugs."
The findings were published online on June 5 in Neurology.
Surprising Results
For the study, the researchers used the Secure Anonymized Information Linkage databank in Wales to identify 4879 patients with aSAH between January 2000 and December 2019 and 43,911 patients without aSAH matched on age, sex, and year of database entry. Clustering resulted in 2023 unique drugs, of which 205 were commonly prescribed.
After adjusting for other factors such as high blood pressure, alcohol abuse, smoking, and a total number of health conditions, the results yielded two surprises, Ruigrok observed.
The first was a significant decrease in aSAH risk for current use of lisinopril compared with nonuse (odds ratio [OR], 0.63; 95% CI, 0.44-0.90) and a nonsignificant decrease with current use of amlodipine (OR, 0.82; 95% CI, 0.65-1.04).
"Hypertension is a major risk factor for occurrence and bleeding from aneurysms. If there is indeed a specific blood pressure-lowering drug that not only has a blood pressure-lowering effect but also has additional protection against aSAH, then perhaps that drug should become the drug of choice in aneurysm patients in the future," he said.
Notably, recent use of both drugs, defined as between 1 year and 3 months before the index date, was associated with an increased risk for aSAH. This trend was not found for other antihypertensives and was significant for amlodipine but not lisinopril.
The reasons are unclear, but "we trust the findings on lisinopril more," Ruigrok said. "The findings on amlodipine may be due to confounding by indication, specifically caused by hypertension. Therefore, it is important to validate our findings in an independent research cohort, and we are in the process of doing so."
The study's second surprise was the antidiabetic drug metformin and cholesterol-lowering drug simvastatin were also associated with reduced aSAH risk, Ruigrok noted.
"We already knew from previous studies that diabetes and high cholesterol are protective factors for aSAH," he said. "Our results suggest that perhaps not the conditions themselves are protective for aSAH but rather the drugs used to treat these conditions with are."
The risk for a ruptured brain aneurysm among current users was 42% lower with metformin (OR, 0.58; 95% CI, 0.43-0.78), 22% lower with simvastatin (OR, 0.78; 95% CI, 0.64-0.96), and 45% lower with tamsulosin (OR, 0.55; 95% CI, 0.32-0.93).
An increased risk for aSAH was found only in current users of warfarin (OR, 1.35; 95% CI, 1.02-1.79), venlafaxine (OR, 1.67; 95% CI, 1.01-2.75), prochlorperazine (OR, 2.15; 95% CI, 1.45-3.18), and co-codamol (OR, 1.31; 95% CI, 1.10-1.56).
Other drugs within the classes of vitamin K antagonists, serotonin reuptake inhibitors, conventional antipsychotics, and compound analgesics did not show an association with aSAH.
The study was limited by the use of drug prescriptions, and patients may not take their drugs or use them incorrectly, noted the researchers, led by Jos P. Kanning, MSc, also with University Medical Center Utrecht.
The study was supported by the European Research Council. The authors reported no relevant financial relationships.