Do the adverse events associated with drug-eluting stents change over time?

The authors assessed the 5-year outcomes of two types of drug-eluting stents.

A drug-eluting stent is a scaffold that is inserted into a narrowed or diseased artery that slowly releases a drug in order to block cell division and growth. This prevents the development of fibrosis (thickening or scarring of the artery tissue) which could block the stented artery.

Many of the first studies of drug-eluting stents involved 9-12 month outcomes, but very few studies assess longer term outcomes. For example, the first-generation zotarolimus-eluting stent was initially believed to be less safe than the second-generation sirolimus(Rapamune)-eluting stent, but some studies suggested a reversal in this trend with time. Both zotarolimus and sirolimus are immunosuppressant drugs (used to reduce the activity of the immune system) used to coat stents in coronary artery disease.

The authors of this study presented clinical outcomes at up to 5 years for zotarolimus-eluting stents and sirolimus-eluting stents.

2,332 patients were randomly allocated to receive either zotarolimus-eluting stents (1,162 patients) or sirolimus-eluting stents (1,170).

At 5-year follow-up, clinical outcomes did not significantly differ between groups. Patients using the zotarolimus-eluting stents had higher rates of adverse events during the first year; however patients using the sirolimus-eluting stents experienced higher rates of adverse events between the end of the first year and the fifth year.

For example, at 1-year follow-up, the zotarolimus group had 2.13 times the odds of experiencing a major cardiovascular event compared to the sirolimus group. By 1-5 years of follow-up, compared to the sirolimus group, the zotarolimus group was 22% less likely to experience a major cardiovascular event.

At 1-year, the zotarolimus group had 3.6 times the odds of experiencing a heart attack compared to those in the sirolimus group. By 1-5 years of follow-up, compared to the sirolimus group, the zotarolimus group was 22% less likely to experience a heart attack, but this was not deemed to be statistically significant.

At 1-year, the zotarolimus group had 3.34 times the odds of having a definite stent thrombosis (when a previously placed stent becomes blocked by a blood clot) compared to the sirolimus group. By 1-5 years of follow-up, compared to the sirolimus group, the zotarolimus group was 95% less likely to experience a definite stent thrombosis.

At 1-year, the zotarolimus group had 2.48 times the odds of having to undergo target vessel revascularization (treatment to restore blood flow to the target vessel following a recurrence of symptoms) compared to the sirolimus group. By 1-5 years of follow-up, compared to the sirolimus group, the zotarolimus group was 45% less likely to require target vessel revascularization.

The authors concluded that the superiority of the sirolimus-eluting stent compared with the zotarolimus-eluting stent at 1-year of follow-up was lost at 5-years of follow-up. This result was caused by a reduced risk of adverse events between 1 and 5 years’ follow-up in patients allocated to treatment with zotarolimus-eluting stent.