Author: Elisa Riera, MD
Medscape Professional Network
The long-term management of coronary artery disease (CAD) remains debated, particularly regarding antiplatelet therapy, including the duration of dual antiplatelet therapy (DAPT), selection of maintenance monotherapy, and low-density lipoprotein cholesterol (LDL-C) targets. Three recent clinical trials have provided robust evidence that may influence current clinical practices.
DAPT remains the standard treatment for at least 12 months in patients without a considerable risk for bleeding. Strategies to reduce bleeding include the use of proton pump inhibitors for gastrointestinal protection, early transition to ticagrelor monotherapy following percutaneous coronary intervention (PCI) in stable patients, and early discontinuation of aspirin within 1-7 days with continuation of a P2Y12 inhibitor in individuals requiring anticoagulation.
The 3-year follow-up of the HOST-IDEA trial evaluated the optimal duration of DAPT following PCI with third-generation stents. A total of 2013 patients were randomly assigned to receive DAPT for 3-6 months or 12 months.
The primary composite endpoint of cardiovascular (CV) death, target vessel myocardial infarction, target lesion revascularization, stent thrombosis, and major bleeding occurred in 7.7% and 8.2% of the patients in the short and standard duration groups, respectively (hazard ratio [HR], 0.94; 95% CI, 0.69-1.29; P = .71). No significant differences were observed between the groups. These findings indicate that a shorter duration of DAPT provides clinical outcomes similar to those of the standard duration.
Monotherapy
The HOST-EXAM trial, with a 10-year follow-up, showed that clopidogrel was superior to aspirin for long-term maintenance following PCI. The study randomly assigned 5438 patients who had completed 6-18 months of DAPT without adverse events to receive clopidogrel 75 mg daily or aspirin 100 mg daily.
The primary composite endpoint, including all-cause death, nonfatal myocardial infarction, stroke, readmission for acute coronary syndrome, and major bleeding, occurred in 25.4% vs 28.5% of the clopidogrel group vs aspirin group, with an HR of 0.86 (95% CI, 0.77-0.96; P = .005). Clopidogrel reduced ischemic outcomes, including acute coronary syndrome, and caused less bleeding than aspirin.
Adherence to clopidogrel was higher, with fewer gastrointestinal discomforts and minor bleeding events reported. No differences in all-cause mortality were observed between the two groups.
Per-protocol analyses suggested a greater benefit with clopidogrel; intention-to-treat analyses showed 254 vs 285 events per 1000 patients with clopidogrel vs aspirin, corresponding to a number needed to treat of approximately 33 over 10 years.
LDL Targets
The most significant change in lipid management involves stricter LDL-C targets and earlier initiation of combination therapy. High-intensity statin therapy should be initiated in all patients with acute coronary syndrome, with the addition of ezetimibe at hospital discharge.
In patients receiving maximally tolerated statins with LDL-C levels ≥ 70 mg/dL, additional therapies are recommended. These include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as evolocumab and alirocumab, ezetimibe, inclisiran, and bempedoic acid.
The Ez-PAVE trial provided the first randomized evidence comparing LDL-C targets for secondary prevention. The study included 3048 patients with atherosclerotic CV disease who were assigned to LDL-C targets of < 55 mg/dL or < 70 mg/dL.
The median LDL-C levels during follow-up were 56 mg/dL vs 66 mg/dL in the intensive target group vs the standard target group. At 3 years, the primary composite endpoint, including CV death, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina, occurred in 6.6% of the intensive group and 9.7% of the standard group (HR, 0.67; 95% CI, 0.52-0.86; P = .002). The benefit was observed through a reduction in nonfatal myocardial infarction and revascularization.
At 3 years, 48.4% of the patients in the intensive group received high-intensity statins, 66.6% received ezetimibe, and 2.3% received PCSK9 inhibitors compared with 32.3%, 56.7%, and 0.9% in the standard group, respectively.
No differences were observed between the groups in terms of new-onset diabetes, glycemic control, statin-associated muscle symptoms, cancer diagnosis, or cataract surgery. Elevated creatinine levels were less frequent in the intensive target group.
Implication on Practice
These trials provide consistent evidence that challenges the established treatment strategies.
- In patients receiving third-generation stents, 3-6 months of DAPT provides similar clinical outcomes compared with 12 months, reducing exposure without compromising efficacy.
- Clopidogrel is superior to aspirin for long-term antiplatelet therapy after PCI, with sustained reductions in ischemic outcomes and bleeding risk, with benefits maintained for up to 10 years. Higher adherence was seen with clopidogrel.
- LDL-C targets of < 55 mg/dL are associated with lower rates of CV events than LDL-C targets of < 70 mg/dL and support the earlier use of lipid-lowering therapy, with no increase in adverse events.
Current EU guidelines, including the 2024 European Society of Cardiology recommendations, included an LDL-C target of < 55 mg/dL as a class I, level A recommendation and placed clopidogrel at the same level of recommendation as aspirin. These data reinforce the current recommendations and support reconsideration of aspirin use in secondary coronary prevention.