NEW YORK — Pharmacogenetic test results might not lead patients to avoid certain helpful treatments as feared, a new clinical trial focusing on statins has found.
Pharmacogenetic testing enables patients to learn whether they harbor any genetic variants that could affect their response to particular drugs, with an eye toward selecting more effective therapies. But there are also concerns that positive test results could lead patients to avoid drugs for their possible adverse effects and shy away from treatments from which they may still benefit.
Statins are prescribed to millions of adults in the US to help lower their cholesterol levels and reduce their risk of heart attack and stroke. But previous studies have tied a genetic variant in SLCO1B1 to an increased risk of simvastatin myopathy, muscle damage that can be severe and possibly life threatening that is associated with taking the statin simvastatin.
In a new randomized clinical trial, researchers from Harvard Medical School examined in a cohort of more than 400 patients whether knowing a patient's SLCO1B1 genotype affected their cholesterol levels a year later. The trial, which sought to model typical medical practice, found no difference between the groups of patients whose SLCO1B1 status was known versus unknown, as the researchers reported Thursday in JAMA Network Open.
"This study provides reassurance that patients and providers can use pharmacogenetic testing in a way that maximizes its benefits while avoiding harmful unintended consequences," lead author Jason Vassy, an assistant professor of medicine at Harvard, said in a statement.
For the Integrating Pharmacogenetics in Clinical Care (I-PICC) study, Vassy and his colleagues enrolled primary care physicians at eight Veterans Affairs Boston Healthcare practices into their study and evaluated nearly 21,000 of their patients for eligibility. To be in the study, patients had to be between 40 and 75 year old, never before taken a statin, and exhibit risk factors for atherosclerotic cardiovascular disease.
In all, 408 patients who met the criteria were randomized to either receive their SLCO1B1 genotype results directly after testing or a year later. About a third of patients in the study were offered statin therapy, and 13.5 percent of the intervention group and 11.1 percent of the control group were prescribed statins.
Overall, 120 participants, 45 in the intervention and 75 in the control group, had a SLCO1B1 genotype — T/C or C/C genotype — that indicated increased risk for simvastatin myopathy.
Within the intervention group, seven of the statin prescriptions were for simvastatin, all for patients with a normal T/T genotype. Patients in that group with T/C or C/C genotypes were all prescribed atorvastatin. At the same time, in the control group, approximately equal numbers of patients were prescribed atorvastatin, simvastatin, or rosuvastatin. In that group, one patient later known to have a T/C genotype was prescribed simvastatin.
Over the course of the one-year study, the mean LDL levels in the intervention group fell by 1.1 mg/dL from 106.2 mg/dL at baseline and in the control group by 2.2 mg/dL from 109 mg/dL at baseline. This, the researchers noted, was consistent with SLCO1B1 testing at baseline not leading to worse LDL-levels.
These findings suggested to the researchers that pharmacogenetic testing for SLCO1B1 genotype did not lead to worse measures of atherosclerotic cardiovascular disease prevention, and could assuage concerns about the unintended harms of testing.
"Our study offers empirical evidence that the clinical use of pharmacogenetic test results for SLCO1B1 does not worsen patient outcomes, which we hope will help inform the debate about utility and unintended harm for this kind of testing," Vassy added.