Pharmacogenetics in Elderly CAD Patients: A Path Toward Personalized Cardiovascular Therapy

Heart disease continues to be the leading cause of death across the globe, and among its various forms, coronary artery disease (CAD) stands out as both the most common and the most dangerous. Older adults are particularly vulnerable, not just because their hearts and blood vessels naturally weaken over time, but also because CAD often brings along serious complications like heart attacks, strokes, and heart failure. Thanks to medical advancements, more people are surviving these conditions, but living with CAD often means dealing with multiple other health problems as well. As a result, many elderly patients end up taking five or more medications at once—a situation known as polypharmacy. While necessary, managing so many drugs at the same time comes with its own set of risks, including potential drug interactions, unexpected side effects, and even reduced effectiveness of certain treatments. One of the biggest challenges in treating elderly patients with CAD is that medications do not work the same way for everyone. The reason? Genetics. Each person processes drugs differently based on their genetic makeup, which determines how their body breaks down and responds to medications. This field of study, known as pharmacogenetics, looks at how genes affect drug response. For example, some people metabolize clopidogrel poorly, meaning it does not thin their blood as intended, leaving them at greater risk of dangerous blood clots. Others process statins too slowly, making them more prone to severe muscle pain and damage. Without a way to personalize prescriptions based on genetics, many elderly patients may be receiving medications that either do not work as they should or cause unnecessary harm. Even though experts recognize how genetics plays a role in medication effectiveness, it is still not common practice to test patients before prescribing drugs. Instead, most doctors follow standard dosing guidelines, which treat all patients the same, regardless of their genetic differences. Often, changes to a patient’s medication only happen after something goes wrong—either the treatment does not work, or the patient experiences side effects. While single-gene tests exist for certain medications like warfarin and clopidogrel, broader pharmacogenetic panel testing, which evaluates multiple genes at once, is not yet widely used in cardiology. Researchers have not yet fully explored whether using these panels could improve outcomes for elderly CAD patients dealing with polypharmacy.

A recent study published in the Journal of Pharmaceutics set out to answer this question. Led by Dr. Lisha Dong, Dr. Shizhao Zhang, Dr. Chao Lv, Dr. Qiao Xue, and Dr. Tong Yin from the Institute of Geriatrics at the Second Medical Center of Chinese PLA General Hospital, the study examined whether testing for genetic variations before prescribing medication could lead to better heart health, fewer drug-related side effects, and a more effective approach to managing multiple medications. The research team carried out a large-scale study, observing 892 elderly patients who had been diagnosed with cardiovascular disease and were prescribed at least five medications upon leaving the hospital. Since older adults often need multiple drugs to manage heart conditions and other related health issues, the goal was to see if a pharmacogenetic panel-based approach could improve treatment outcomes. To do this, each patient underwent genetic testing to identify 13 specific variants across 10 pharmacogenes. These genes are known to influence how the body processes commonly used heart medications like clopidogrel, warfarin, statins, beta-blockers, ACE inhibitors, and proton pump inhibitors. The researchers wanted to find out whether having certain genetic variants made a difference in major cardiovascular events, adverse drug reactions, and overall survival rates.

The results were striking. A staggering 80.3% of the elderly patients had at least one drug–gene pair that could potentially affect how their medications worked. This meant that for most patients, their genetic makeup suggested they might need changes to their prescribed drugs or dosages. One of the most frequently observed genetic variations was in the CYP2C19 enzyme, which plays a major role in breaking down both clopidogrel and proton pump inhibitors. Patients with certain CYP2C19 variants had trouble activating clopidogrel, leaving them at greater risk for serious clotting events like heart attacks and strokes. On the other hand, some patients had variations that made them break down proton pump inhibitors too quickly, potentially reducing their ability to protect the stomach from ulcers and other complications. To better understand how these genetic differences affected real-world health outcomes, the researchers followed patients for nearly four years, tracking their cardiovascular health. One of the most eye-opening discoveries was that patients with more drug–gene pairs had significantly fewer major cardiovascular events over time. In fact, for every additional drug–gene pair a patient had, their risk of experiencing a heart attack, stroke, or stent thrombosis dropped by 19.7%. This suggested that recognizing and adjusting prescriptions based on genetic information could have a major impact on preventing life-threatening heart complications.

However, there was a trade-off. While more drug-gene pairs were linked to better heart health, it also appeared to increase the likelihood of adverse drug reactions. Patients with certain genetic variations were more prone to side effects like bleeding, muscle pain from statins, and sudden drops in blood pressure. For instance, those with SLCO1B1 variants were more likely to experience muscle problems from statins, which can sometimes lead patients to stop taking the medication altogether, increasing their heart risk. Similarly, patients with CYP2C9 and VKORC1 variants, which influence how the body processes warfarin, were at higher risk of dangerous bleeding. Beyond cardiovascular outcomes and side effects, the researchers also looked at overall survival rates. Interestingly, patients who carried pharmacogenetic variants actually had a slightly lower risk of dying from any cause during the study period. The benefit was especially noticeable in those whose genetic makeup indicated reduced drug efficacy, which was in line with the therapeutic drug dosages for the elderly patients was lower than the younger patients. To determine whether the benefits of pharmacogenetic testing appeared right away or took time to develop, the researchers analyzed survival data across different follow-up periods. In the first year, there was no major difference in heart event rates between patients with and without drug–gene pairs. However, over time, the gap became more noticeable. By the four-year mark, those with pharmacogenetic guidance had significantly fewer major cardiovascular events.

In conclusion, the new work of Dr. Tong Yin and colleagues advanced our understanding on how to manage coronary artery disease in elderly patients who take multiple medications. It shows how **pharmacogenetic testing—analyzing a person’s genes to see how they process medications—**can make treatments safer and more effective. By proving that genetic differences play a big role in how drugs work, this research makes a strong case for bringing pharmacogenetics into everyday heart care. From a bigger-picture perspective, the study questions the traditional trial-and-error approach to prescribing heart medications. Right now, doctors follow general dosing guidelines, assuming most patients will respond the same way. However, this research shows that not all patients metabolize drugs the same, making a one-size-fits-all approach less effective, especially for older adults taking multiple medications. Instead, introducing pharmacogenetic testing early could allow doctors to make better choices from the start, reducing the need for later corrections due to medication failures or bad reactions.