So with a high stroke risk your doctor should be throwing the kitchen sink at prevention. Is your doctor doing any of these?
Like maybe a 307% stroke risk reduction from these 11 possibilities?
https://www.medpagetoday.com/Neurology/Strokes/68005?
IRIS secondary analysis suggests greater CV benefit in high- vs. low-risk patients
Insulin-resistant
stroke patients with higher risk for recurrent stroke or myocardial
infarction (MI) may experience a greater benefit from the
insulin-sensitizing drug pioglitazone (Actos) than patients with lower
risk, a secondary analysis of the IRIS trial showed.
The 5-year risk for recurrent stroke or MI among IRIS participants who were at higher baseline risk was 14.7% in the pioglitazone group, compared with 19.6% in the placebo group (absolute risk difference, -4.9%, 95% CI -8.6% to 1.2%), according to Walter Kernan, MD, of the Yale School of Medicine and colleagues, writing in JAMA Neurology.
In lower-risk patients, the 5-year stroke or MI risk was 6% in the pioglitazone group versus 7.9% for placebo (absolute risk difference, 1.9%, 95% CI -4.4% to 0.6%).
Pioglitazone also increased the risk of bone fracture among higher-risk patients, the researchers noted.
Kernan said the fact that the absolute risk difference confidence intervals cross 1 "indicates that we were not powered to detect a difference in absolute risk difference." However, he said the "difference in magnitude between the absolute risk difference in the high risk group (-4.9%) and the low risk group (-1.9%) is clinically important."
He added that the study "part of a growing body of research that shows not all patients benefit similarly from any given therapy. The magnitude of benefit for patients at high risk was very high. The absolute risk reduction over 5 years for these patients was 4.9%. That's a pretty large reduction risk, compared to other novel emerging therapies for cardiovascular disease."
In 2016, the Insulin Resistance Intervention after Stroke (IRIS) trial, a study of 3,876 recent stroke or transient ischemic attack (TIA) patients who were insulin resistant, reported that pioglitazone reduced recurrent stroke or MI by about one-fourth compared with placebo (pioglitazone 9% versus placebo 11.8%; HR 0.76, 95% CI 0.62-0.93).
The trial excluded patients with diabetes, heart failure, or bladder cancer, as pioglitazone has been associated with an increased risk of bladder cancer, with the FDA reaffirming a potential link late last year. Other type 2 diabetes drugs in the thiazolidinedione class -- notably rosiglitazone (Avandia) -- have been plagued by concerns about adverse cardiovascular effects, though the FDA has rolled back prescribing restrictions on that drug.
IRIS participants had an average age of 63.1 years and included 1,338 women and 2,538 men. Eligible participants had a qualifying ischemic stroke or TIA within 180 days of entering the study. Stroke was the index event for 87.1% of these patients.
For this secondary analysis, investigators studied the entire IRIS population, combining data from pioglitazone and placebo groups to isolate patients who had a distinct risk for stroke or MI. To identify patients who might most benefit from treatment, they conducted a multivariable risk analysis to stratify patients according to their baseline risk of major outcome events.
Age, history of prior stroke, coronary artery disease, current smoking, hypertension history, and aphasia emerged as the baseline factors most strongly associated with recurrent stroke and MI. Each factor independently increased the relative risk of stroke or MI by about two-thirds.
In terms of numbers needed to be treated, 21 high-risk patients would need to be treated for approximately 5 years to prevent 1 stroke or MI, compared with 53 low-risk patients, they reported.
Hazard ratios were similar for patients above or below the median risk (0.77 versus 0.75, P=0.92), which the authors observed was a rule, not an exception, in treatment research. "This pattern illustrates the important added meaning of data on absolute risk reduction," they wrote. "Patients who experience the same relative risk reduction with a therapy may experience a very different absolute benefit depending on underlying risk."
Patients at high baseline risk also experienced a higher rate of bone fracture (16.9% for pioglitazone, compared to 10.1% for placebo) and higher absolute risk increment of fracture compared with patients at low baseline risk (6.8% for high-risk patients versus 3.2% for low-risk patients). Factors associated with fracture risk were older age, prior stroke, and aphasia.
A major limitation of this secondary analysis was that it was unplanned and not built into the design of the original IRIS trial, the authors noted.
That's why, Kernan said, it will be important that investigators who are designing clinical trials "start building in an ancillary analysis to stratify people into high risk and low risk for the outcome they're interested in, and see if the treatment works differently in the high risk and low risk groups."
In an accompanying editorial, Graeme Hankey, MD, of the University of Western Australia, called this investigation a "thoughtful and thorough analysis" that will help clinicians discriminate patients who are most likely to benefit and least likely to be harmed by pioglitazone.
"Although very elderly individuals (≥80 years of age) have arguably the highest risk of stroke and MI, and the most to gain from pioglitazone therapy, they also have the highest risk of bone fracture," Hankey noted. "The relative importance that these patients attribute to their risks of stroke and MI versus bone fracture will likely determine their preference for long-term pioglitazone therapy."
The 5-year risk for recurrent stroke or MI among IRIS participants who were at higher baseline risk was 14.7% in the pioglitazone group, compared with 19.6% in the placebo group (absolute risk difference, -4.9%, 95% CI -8.6% to 1.2%), according to Walter Kernan, MD, of the Yale School of Medicine and colleagues, writing in JAMA Neurology.
In lower-risk patients, the 5-year stroke or MI risk was 6% in the pioglitazone group versus 7.9% for placebo (absolute risk difference, 1.9%, 95% CI -4.4% to 0.6%).
Pioglitazone also increased the risk of bone fracture among higher-risk patients, the researchers noted.
Kernan said the fact that the absolute risk difference confidence intervals cross 1 "indicates that we were not powered to detect a difference in absolute risk difference." However, he said the "difference in magnitude between the absolute risk difference in the high risk group (-4.9%) and the low risk group (-1.9%) is clinically important."
He added that the study "part of a growing body of research that shows not all patients benefit similarly from any given therapy. The magnitude of benefit for patients at high risk was very high. The absolute risk reduction over 5 years for these patients was 4.9%. That's a pretty large reduction risk, compared to other novel emerging therapies for cardiovascular disease."
In 2016, the Insulin Resistance Intervention after Stroke (IRIS) trial, a study of 3,876 recent stroke or transient ischemic attack (TIA) patients who were insulin resistant, reported that pioglitazone reduced recurrent stroke or MI by about one-fourth compared with placebo (pioglitazone 9% versus placebo 11.8%; HR 0.76, 95% CI 0.62-0.93).
The trial excluded patients with diabetes, heart failure, or bladder cancer, as pioglitazone has been associated with an increased risk of bladder cancer, with the FDA reaffirming a potential link late last year. Other type 2 diabetes drugs in the thiazolidinedione class -- notably rosiglitazone (Avandia) -- have been plagued by concerns about adverse cardiovascular effects, though the FDA has rolled back prescribing restrictions on that drug.
IRIS participants had an average age of 63.1 years and included 1,338 women and 2,538 men. Eligible participants had a qualifying ischemic stroke or TIA within 180 days of entering the study. Stroke was the index event for 87.1% of these patients.
For this secondary analysis, investigators studied the entire IRIS population, combining data from pioglitazone and placebo groups to isolate patients who had a distinct risk for stroke or MI. To identify patients who might most benefit from treatment, they conducted a multivariable risk analysis to stratify patients according to their baseline risk of major outcome events.
Age, history of prior stroke, coronary artery disease, current smoking, hypertension history, and aphasia emerged as the baseline factors most strongly associated with recurrent stroke and MI. Each factor independently increased the relative risk of stroke or MI by about two-thirds.
In terms of numbers needed to be treated, 21 high-risk patients would need to be treated for approximately 5 years to prevent 1 stroke or MI, compared with 53 low-risk patients, they reported.
Hazard ratios were similar for patients above or below the median risk (0.77 versus 0.75, P=0.92), which the authors observed was a rule, not an exception, in treatment research. "This pattern illustrates the important added meaning of data on absolute risk reduction," they wrote. "Patients who experience the same relative risk reduction with a therapy may experience a very different absolute benefit depending on underlying risk."
Patients at high baseline risk also experienced a higher rate of bone fracture (16.9% for pioglitazone, compared to 10.1% for placebo) and higher absolute risk increment of fracture compared with patients at low baseline risk (6.8% for high-risk patients versus 3.2% for low-risk patients). Factors associated with fracture risk were older age, prior stroke, and aphasia.
A major limitation of this secondary analysis was that it was unplanned and not built into the design of the original IRIS trial, the authors noted.
That's why, Kernan said, it will be important that investigators who are designing clinical trials "start building in an ancillary analysis to stratify people into high risk and low risk for the outcome they're interested in, and see if the treatment works differently in the high risk and low risk groups."
In an accompanying editorial, Graeme Hankey, MD, of the University of Western Australia, called this investigation a "thoughtful and thorough analysis" that will help clinicians discriminate patients who are most likely to benefit and least likely to be harmed by pioglitazone.
"Although very elderly individuals (≥80 years of age) have arguably the highest risk of stroke and MI, and the most to gain from pioglitazone therapy, they also have the highest risk of bone fracture," Hankey noted. "The relative importance that these patients attribute to their risks of stroke and MI versus bone fracture will likely determine their preference for long-term pioglitazone therapy."
This work was
supported by an award from the National Institute of Neurological
Disorders and Stroke/National Institutes of Health and from the
Patient-Centered Outcomes Research Institute.
One of the investigators reported receiving a consulting fee from Takeda Pharmaceuticals International for analyzing prostate cancer data in the IRIS trial. Another served as a consultant or committee member for AstraZeneca, Boehringer Ingelheim, Daichii Sankyo, Lexicson, Janssen, Merck, Poxel, Sanofi, vTv Pharmaceuticals, Novo Nordisk and Intarcia. No other disclosures were reported.
The editorialist reported no conflicts of interest.
One of the investigators reported receiving a consulting fee from Takeda Pharmaceuticals International for analyzing prostate cancer data in the IRIS trial. Another served as a consultant or committee member for AstraZeneca, Boehringer Ingelheim, Daichii Sankyo, Lexicson, Janssen, Merck, Poxel, Sanofi, vTv Pharmaceuticals, Novo Nordisk and Intarcia. No other disclosures were reported.
The editorialist reported no conflicts of interest.
Primary Source
JAMA Neurology
Source Reference: Kernan W, et al "Targeting pioglitazone hydrochloride therapy after stroke or transient ischemic attack according to pretreatment risk for stroke or myocardial infarction" JAMA Neurol 2017; DOI: 10.1001/jamaneurol.2017.2136.Secondary Source
JAMA Neurology
Source Reference: Hankey G "Which patients with ischemic stroke and insulin resistance may benefit from pioglitazone hydrochloride?" JAMA Neurol 2017; DOI: 10.1001/jamaneurol.2017.2142.
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