Antithrombotics for Elderly CAD Patients: One Size Doesn’t Fit All

While available data can help clinicians make therapeutic decisions for their elderly patients with CAD, more research specific to older patient populations is needed, particularly with regard to emerging antithrombotic strategies, a new review concludes.

The document, published in JACC: Cardiovascular Interventions, reviews data from pivotal randomized controlled trials as well as registries. It also delves into some newer strategies for lowering bleeding complications and for managing special populations, including older patients with atrial fibrillation (AF) who require PCI.

“An important thing that we address in this review article is the concept that one size does not fit all with regard to our elderly patients,” study co-author Dominick J. Angiolillo, MD, PhD (University of Florida College of Medicine, Jacksonville), told TCTMD. “Obviously, the elderly patients who qualify to be enrolled in clinical trials may not be the same as those that we see in real-world clinical practice. Additionally, when we look at the elderly overall as a cohort, there remain a lot of unanswered questions simply because in the vast majority of trials that we conduct, the elderly only represent a subgroup.”

In reviewing factors affecting pharmacokinetic and pharmacodynamic profiles of antithrombotic therapies in older CAD patient groups, Angiolillo with co-author Piera Capranzano, MD, PhD (University of Catania, Italy), note the importance of considering age-related changes that affect absorption, distribution, metabolism, and excretion. Polypharmacy, which is common among elderly patients, can affect adherence and drug availability, and may lead to altered drug steady state, they add.

Among the newer bleeding reduction strategies discussed in the paper is shortened dual antiplatelet therapy (DAPT) duration, which has been shown in various subgroup analyses and a patient-level meta-analysis to possibly be more beneficial in elderly patients than in younger patients after new-generation DES implantation.

We see many elderly patients routinely, but when you look at the literature you realize that we need more data specific to them to aid us in our clinical judgment. Dominick J. Angiolillo

Another strategy is P2Y12 de-escalation based on the observation that the greatest anti-ischemic benefits are seen within 30 days after an acute event, while bleeding accrues during longer-term treatment, Capranzano and Angiolillo write. In The HOST-REDUCEPOLYTECH-ACS trial for example, de-escalation from prasugrel 10 mg to 5 mg at 1 month after ACS versus 12 months of prasugrel 10 mg resulted in reduced bleeding and led to lower net clinical events, regardless of patient age.

“Despite the encouraging outcomes with de-escalation, this strategy has raised concerns when the transition in therapy occurs toward clopidogrel in light of the considerable number of patients who may have [high platelet reactivity],” Capranzano and Angiolillo note. As a result, some have suggested de-escalating P2Y12 inhibiting therapy only after excluding patients with high platelet reactivity (HPR) via platelet-function testing or genetic testing. As the POPular GENETICS trial showed, cytochrome P450 2C19 genotype–guided P2Y12 inhibitor selection was associated with less minor bleeding and similar ischemic outcomes versus 12-month prasugrel or ticagrelor and was consistent across age groups.

Finally, dropping aspirin has been suggested as a bleeding avoidance strategy in the elderly. Across age groups, outcomes in RCTs have been more favorable with aspirin-free double antithrombotic strategies compared with triple antithrombotic therapy, with the only exception being data from the RE-DUAL PCI trial, which showed that double antithrombotic regimens containing dabigatran 110 mg were associated with increased thromboembolic events in older AF patients compared with triple antithrombotic therapy strategies that included a vitamin K antagonist.

Most studies of aspirin-free antiplatelet strategies in PCI patients without a concomitant indication for chronic oral anticoagulant therapy have shown that a P2Y12 inhibitor monotherapy strategy following  1- or 3-month DAPT is associated with less bleeding and similar risk of ischemic events compared with 12 months of DAPT, Capranzano and Angiolillo write. Furthermore, the literature suggest that the net clinical benefit of aspirin-free approaches is enhanced in elderly subgroups.

Practical Recommendations

Recognizing that elderly CAD patients are at increased risk for bleeding that can counterbalance ischemic benefits of antithrombotic strategies, Angiolillo and Capranzano say “all efforts should be made to maintain a favorable risk-benefit trade-off with the use of antithrombotic agents.” Key to this is a dynamic risk assessment. Other general measures, they add, may include use of proton pump inhibitors to reduce risk of GI bleeding, avoidance of NSAIDs, and risk factor control.

Another issue specific to the elderly is that risk scores have been shown to be only moderately accurate for predicting bleeding. Some data, Angiolillo and Capranzano note, “suggest that probably age as a continuum, instead of a cutoff criterion, in combination with multiple variables could be considered for risk stratification.” While more data are needed to clarify the effects of emerging antithrombotic strategies in elderly CAD patients, some ongoing trials may yield important evidence. MASTER-DAPT, for example, which includes an elderly cohort, is expected to provide important insights regarding the optimal duration of antiplatelet therapy after implantation of newer-generation stents in patients at high bleeding risk. OPT-BIRISK will include patients up to age 85 and will compare extended P2Y12 monotherapy versus DAPT after ACS in patients at high ischemic and bleeding risk.

Angiolillo said more concentrated efforts are needed to conduct trials specific to outcomes in elderly patients.

“There is an unmet need in our field as far as determining how we can conduct pragmatic trials so that we do not exclude some of the elderly that are commonly excluded from clinical trials based on their other medical conditions,” he added. “We see many elderly patients routinely, but when you look at the literature you realize that we need more data specific to them to aid us in our clinical judgment, especially because this is a population that is growing.”