Researchers at the VA Boston Healthcare System, Brigham and Women’s Hospital, and Harvard Medical School conducted a randomized controlled trial of pharmacogenetic testing related to statins, such as atorvastatin and simvastatin, which are used by millions of Americans to lower the risk of heart attack and stroke. However, in rare cases, patients might experience muscle damage from statins, which can sometimes be serious and life-threatening.

Pharmacogenetic testing can identify whether a patient carries a genetic variant in the SLCO1B1 gene that puts them at a higher risk of such statin-associated muscle injury. Although this test might help patients avoid adverse drug effects, it might also have the unintended consequence of causing patients not to do enough to lower their risk of cardiovascular disease.

The scientists published the results of their study, entitled “Effect of Pharmacogenetic Testing for Statin Myopathy Risk vs Usual Care on Blood Cholesterol,” in JAMA Network Open.

“Nonadherence to statin guidelines is common. The solute carrier organic anion transporter family member 1B1 (SLCO1B1) genotype is associated with simvastatin myopathy risk and is proposed for clinical implementation. The unintended harms of using pharmacogenetic information to guide pharmacotherapy remain a concern for some stakeholders,” write the investigators. “[The purpose of the study was to] determine the impact of delivering SLCO1B1 pharmacogenetic results to physicians on the effectiveness of atherosclerotic cardiovascular disease (ASCVD) prevention (measured by low-density lipoprotein cholesterol [LDL-C] levels) and concordance with prescribing guidelines for statin safety and effectiveness.”

“This randomized clinical trial was performed from December 2015 to July 2019 at 8 primary care practices in the Veterans Affairs Boston Healthcare System. Participants included statin-naive patients with elevated ASCVD risk. Data analysis was performed from October 2019 to September 2020.

“The primary outcome was the 1-year change in LDL-C level. The secondary outcomes were 1-year concordance with American College of Cardiology–American Heart Association and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for statin therapy and statin-associated muscle symptoms (SAMS).

Among 408 patients (mean [SD] age, 64.1 [7.8] years; 25 women [6.1%]), 193 were randomized to the intervention group and 215 were randomized to the control group. Overall, 120 participants (29%) had a SLCO1B1 genotype indicating increased simvastatin myopathy risk. Physicians offered statin therapy to 65 participants (33.7%) in the intervention group and 69 participants (32.1%) in the control group.

“Compared with patients whose physicians did not know their SLCO1B1 results at baseline, patients whose physicians received the results had noninferior reductions in LDL-C at 12 months (mean [SE] change in LDL-C, −1.1 [1.2] mg/dL in the intervention group and −2.2 [1.3] mg/dL in the control group; difference, −1.1 mg/dL; 90% CI, −4.1 to 1.8 mg/dL; P < .001 for noninferiority margin of 10 mg/dL). The proportion of patients with American College of Cardiology–American Heart Association guideline-concordant statin prescriptions in the intervention group was noninferior to that in the control group (12 patients [6.2%] vs 14 patients [6.5%]; difference, −0.003; 90% CI, −0.038 to 0.032; P < .001 for noninferiority margin of 15%). All patients in both groups were concordant with CPIC guidelines for safe statin prescribing.”

“Physicians documented 2 and 3 cases of SAMS in the intervention and control groups, respectively, none of which was associated with a CPIC guideline–discordant prescription. Among patients with a decreased or poor SLCO1B1 transporter function genotype, simvastatin was prescribed to 1 patient in the control group but none in the intervention group.”

“Clinical testing and reporting of SLCO1B1 results for statin myopathy risk did not result in poorer ASCVD prevention in a routine primary care setting and may have been associated with physicians avoiding simvastatin prescriptions for patients at genetic risk for SAMS. Such an absence of harm should reassure stakeholders contemplating the clinical use of available pharmacogenetic results.”

“This study provides reassurance that patients and providers can use pharmacogenetic testing in a way that maximizes its benefits while avoiding harmful unintended consequences,” said corresponding author Jason Vassy, MD, a clinician investigator at the Brigham, primary care physician at the VA Boston Healthcare System, and assistant professor at Harvard Medical School. “Our findings do not support the idea that all patients should have pharmacogenetic testing before starting a statin, but they do provide rigorous, real-world evidence that the harms of such testing are minimal.”

Vassy and colleagues enrolled 400 patients at the VA Boston Healthcare System who were not currently prescribed a statin but had cardiovascular disease risk factors that might make them candidates for statin treatment now or in the near future. The researchers conducted a controlled study in which statin pharmacogenetic results were given to a random half of the participants and their primary care providers at the beginning of the study, while the other half received their results after one year.

After one year, the cholesterol levels in the group who received their pharmacogenetic results were not higher than those in the group who did not receive their results, and they were not less likely to receive medical care meeting recommended guidelines. In some cases, physicians may have used the results to choose an alternate, but equally effective, medication for the patient. Overall, the study results suggest that pharmacogenetic testing did not cause patients and their primary care providers to be less proactive in lowering their risk of cardiovascular disease.

The authors note that fewer than expected participants were prescribed statin therapy in general, potentially a reflection of patient reluctance and physician prescribing patterns. Less than 16 percent of physicians documented talking to their patients about their SLCO1B1 in the intervention arm of the trial.

Vassy said the team’s findings should allay stakeholders’ concerns about the potential unintended consequences of pharmacogenetic results, a conclusion that he claims will become increasingly relevant as more and more patients undergo genetic testing as a part of their health care.