Advances in percutaneous coronary intervention and antiplatelet therapy in ischemic heart disease

Abstract

The present thesis has two principal aims: 1) to evaluate the clinical performance of a novel reservoir-based elution-technology and 2) to gain knowledge about optimizing dual antiplatelet therapy in patients with ischemic heart disease. To achieve these aims, we performed several clinical studies with different scientific designs ranging from a singlecenter prospective registry (chapter 2) to the design (chapter 3) of an international multicenter randomized trial (chapter 4) with independent data monitoring and event adjudication and from a nested case-control study (chapter 5) to a review of literature (chapter 6) and meta-analysis of randomized trials (chapter 7). Concerning the international multicenter randomized trial (chapter 4) we found that the 1-year clinical safety and efficacy of polymer-free amphilimus eluting stents are non-inferior to latest-generation permanent-polymer drug-eluting stents (e.g. target-lesion failure of 6.2 vs. 5.6%, p-non-inferiority = 0.0086), with low rates of stent thrombosis. In a 6-year survey (chapter 5) we found a 0.84% incidence of stent thrombosis within 1-year after stent implantation. We found angiographic hallmarks (>75%) in form of under expansion (40%), uncovered edge dissection (18%) and residual stenosis (17%) as well as a pharmacological substrate (~20%) and diabetes mellitus (~30%) to be related to stent thrombosis. In a meta-regression of randomized trials (chapter 7) including more than 19.000 patients, we demonstrated that a short (i.e. ~5 months) versus long duration of DAPT leads to a ~50% reduction of major bleeding. This large cohort was comprised of patients with ~45% stable angina, ~35% unstable angina, ~5% ST-segment elevation myocardial infarction, ~30% diabetes and ~50% complex lesions. Multiple risk scores have been introduced to resolve the impasse of stratifying individual patients’ risk of the two competing and opposing driving forces: thrombosis and bleeding. Using data from the ReCre8 trial, we reported on the discriminative capability of two risk scores (PARIS and CREDO) (chapter 8) that are comprised of separate models for post-discharge ischemic events and post-discharge major bleeding events. We found a marginal predictive capability for both PARIS and CREDO scores to predict postdischarge events in a contemporary all-comers population. The accuracy that we found (i.e. c-statistics ~0.57 to 0.67), fell below the level of what is considered to be adequate. However, an increased number of risk factors in a risk score is likely to reduce the clinical utility. It should not be forgotten that ~350 risk models have been investigated in cardiovascular disease but not more than a handful were resilient to independent testing. It is clear that no single coronary stent or DAPT regime will ever be suitable for all patients with ischemic heart disease. A more individual choice of stents and antiplatelet therapy will be necessary, taking into account clinical characteristics, lesion characteristics and other factors influencing stent as well as patients’ perspectives. Future advances in clinical outcomes after coronary stenting will rely on the combination of adequate engineering, that takes advantage of the absence of (or adequately chosen) polymers, on adequate patient-tailored antiplatelet regimens and on appropriate studies to evaluate stent technology yet to come.