p.70 抽出テキスト

CLINICAL STATEMENTS AND GUIDELINES

August 29, 2023 Circulation. 2023;148:e9–e119. DOI: 10.1161/CIR.0000000000001168

Virani et al 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Chronic Coronary Disease Guideline

transplant recipients with or without established cardiac allograft vasculopathy, early (<2 years) versus late (>2 years) initiation of statin was associated with significantly lower rates of cardiac allograft vasculopathy progression as measured by change in plaque volume and plaque index by intravascular ultrasound, as well as decreased risk of cardiac allograft vasculopathy–related events (allograft failure associated with cardiac allograft vasculopathy, MI, or PCI) and the composite of all-cause death and cardiac allograft vasculopathy–related events, over a median follow-up of 8.2 years.1 The choice and dose of statin in heart transplant recipients is not well established and will often depend on the other medications (particularly immunosuppressants) that the patient is concomitantly taking (Table 24).20 A recent retrospective analysis of 346 adult patients who underwent heart transplant between 2006 and 2018 found that moderate/high- versus low-intensity statin therapy was associated with a significant reduction in the primary composite of time to HF hospitalization, MI, revascularization, and all-cause death.21

2 Aspirin is frequently initiated early after heart trans-

plant for prevention of cardiac allograft vasculopathy. Although the proposed benefits of aspirin use have not been validated in RCTs, evidence from small retrospective single-center studies support early initiation of aspirin after heart transplant.2,22–24 In a retrospective observational study of 529 heart transplant recipients with or without established cardiac allograft vasculopathy, early (<1 year) versus late (>1 year) initiation of aspirin was associated with significantly lower rates of cardiac allograft vasculopathy progression as measured by change in plaque volume and plaque index by intravascular ultrasound, as well as decreased risk of all-cause death and cardiac allograft vasculopathy–related graft dysfunction, over a median follow-up of 6.7 years.2

3 Data showing improved outcomes with revascu-

larization versus medical therapy alone for cardiac allograft vasculopathy are lacking. However, because increasing severity of cardiac allograft vasculopathy is associated with worse outcomes, revascularization is reasonable in patients with suitable anatomy.3 PCI can be beneficial in patients with cardiac allograft vasculopathy who present with severe, proximal, discrete lesions.7 Observational studies showed PCI for cardiac allograft vasculopathy is not only feasible with high procedural success rates but also associated with reliable mid- to long-term angiographic outcomes, especially with the use of second-generation DES.4–6 PCI with everolimus-eluting stents for cardiac allograft vasculopathy was associated with in-stent restenosis rates of 3% to 5% at 6 to 12 months and 10% at 3 years, which are comparable to the use of everolimus-eluting stents in non–heart transplant CAD.4-6,25,26 Coronary physiology assessment measuring FFR and the index of microcirculatory resistance early after heart transplant has prognostic significance.27,28 However, the use of FFR to guide revascularization in patients with cardiac allograft vasculopathy (as opposed to those with non–heart transplant CAD) remains unknown. The use of CABG for severe cardiac allograft vasculopathy is limited by high early mortality rate (36% at 30 days) associated with surgical revascularization in this patient population.29

Table 24.  Drug-Drug Interactions With Statins and Immunosuppressants and Recommendations for Management Immunosuppressant Statin Effect Magnitude Recommendation Cyclosporine/ tacrolimus/everolimus/ sirolimus* Atorvastatin Increased statin exposure through multiple mechanisms.

Increased risk for muscle-related toxicity. Severe 6- to 15-fold increase in AUC of atorvastatin Limit dose of atorvastatin to 10 mg daily

Rosuvastatin Severe 7-fold increase in AUC of rosuvastatin Limit dose of rosuvastatin to 5 mg daily Pravastatin Severe 5- to 10-fold increase in AUC of pravastatin Limit dose of pravastatin to 40 mg daily Fluvastatin Moderate 2- to 4-fold increase in AUC of fluvastatin Limit dose of fluvastatin 40 mg daily Simvastatin Severe 6- to 8-fold increase in AUC of simvastatin Avoid combination Lovastatin Severe 5- to 20-fold increase in AUC of lovastatin Avoid combination Pitavastatin Severe 5-fold increase in AUC of pitavastatin Avoid combination

Magnitude of drug-drug interactions based on AUC increase: minor, >1.25 to <2; moderate, ≥2 to 4.9; and severe, ≥5. *Changes in magnitude of statin AUC are reported with cyclosporine. Limited data exist with tacrolimus, everolimus, and sirolimus. AUC indicates area under the curve. Adapted with permission from Wiggins BS, et al.30 Copyright 2016 American Heart Association, Inc.

Downloaded from http://ahajournals.org by on October 7, 2026