Drug -Eluting Stents in Coronary Heart Disease

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; ALCARAZ, A.; GLUJOVSKY, D.; LOPEZ, A.; REY-ARES, L.; BARDACH, A.; CIAPPONI, A; URTASUN, M; KLEIN, K

Documento de Evaluación de Tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

Coronary stents increased the safety and efficacy of percutaneous angioplasty for the treatment of coronary disease by reducing acute occlusion and restenosis of the treated vascular segment. However, intra-stent restenosis (ISR), as a consequence of its associated fibroproliferative response, led to the development of drug-eluting stent (DES).TechnologyDESs are coated with drugs that inhibit cell proliferation and its placement technique is not different from that of conventional stents (CS).PurposeTo assess the available evidence on the efficacy, safety and coverage policies of the use of drug-eluting stents in coronary disease.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to including systematic reviews, randomized controlled clinical trials, health technology and economic assessments, clinical practice guidelines and coverage policies from other health systems.ResultsThe usefulness of DES on new lesions in acute and stable chronic ischemic heart disease was assessed in intra-stent restenosis and in the diabetic population.Acute Coronary SyndromeTwo systematic reviews (SRs) and one randomized clinical trial (RCT) (totaling 14,071 patients) comparing DES with CS during ST-segment elevation myocardial infarction (STEMI) were identified. The DES group showed lower need for revascularization of the culprit vessel (8.4% vs. 17.3%; OR: 0.44 95% CI: 0.35 to 0.54), with no differences in overall mortality, cardiac mortality and intra-stent thrombosis. One of the SR with 6,769 patients showed a lower incidence of DES-related myocardial re-infarction (ReMI) (3.8% vs. 4.32% ; RR: 0.76 95% CI: 0.58 to 0.98)Chronic Stable AnginaThree SRs (totaling 52,881) compared DES with CS and/or medical management of chronic stable angina, showing a lower need for revascularization of the culprit vessel (HR 0.45; 95% CI: 0.37- 0.54) with no differences in general mortality or ReMI in the DES group.Chronic Stable Angina and Acute Coronary Syndrome in CombinationTwo SRs (71,638 patients) making a comparison among the different DES and versus CS were identified; no differences in overall mortality or intra-stent thrombosis were found. The lower need for revascularization of the culprit vessel was related to DES, being the sirolimus-eluting stent the most efficacious one at short term (4.11% vs. 15.76%; OR: 0.31 95% CI: 0.22 to 0.42).One RCT (2,314 patients) comparing sirolimus-eluting stent with CS showed a reduction for the combination of cardiac mortality events and non-fatal acute myocardial infarction (AMI) (2.6% vs. 4.8%; HR: 0.54 95% CI: 0.31 to 0.93).Multiple Vessel Coronary DiseaseTwo SRs and one RCT (totaling 38,097 patients) comparing DES with myocardial revascularization surgery (MRS) in multiple coronary vessel disease were found. DES was associated to a higher need for revascularization of the culprit vessel (14.6% vs. 6.8%; OR: 2.09 95% CI: 1.72- 2.55), with no differences in the incidence of stroke or AMI. One of the SRs (15,193 patients) showed a 38% increase in DES-related overall mortality (HR: 1.38, 95% CI: 1.20-1.59).One SR comparing DES with CS in multiple coronary vessel disease (n= 5,794) was found and showed a lower need for revascularization of the culprit vessel (OR: 0.58; 95%, CI: 0.45- 0.75) with no differences in general mortality or AMI in the DES group.Left Main Coronary Artery DiseaseOne SR and RCT (totaling 10,129) comparing the use of DES with MRS for left main coronary artery disease treatment were found. They showed a higher incidence of DES-related revascularization, with no differences in overall mortality or AMI between both groups in most of the studies.One SR (10,342 patients) compared DES with CS and it showed an overall mortality decrease (OR: 0.70 95% CI: 0.53-0.92), AMI (OR: 0.49 95% CI: 0.26-0.92) and revascularization of the culprit vessel (OR: 0.46, 95% CI: 0.30-0.69) in the DES group.Total Chronic OcclusionThree SRs (11,428 patients) comparing the use of DES versus CS were identified and showed a lower need for revascularization of the culprit vessel (10.20% vs. 23.19%; OR: 0.38, 95% CI: 0.24-0.60) with no differences in overall mortality, AMI and intra-stent thrombosis.Intra-sent RestenosisThree SRs and six RCTs (totaling 8,045 patients) that associated the use of DES to a lower need for revascularization of the culprit vessel (9.5% vs. 21.2%, OR: 0.35 95% CI: 0.25-0.49) were found and showed no differences in overall mortality, AMI or intra-stent thrombosis when compared versus other techniques such as balloon angioplasty or intravascular brachytherapy.Diabetic PatientsThree SRs (21,601 patients) comparing the use of DES versus MRS were identified and showed a lower need for revascularization of the culprit vessel (47.62% vs. 52.38 %; OR: 0.18, 95% CI: 0.11- 0.30) and a higher risk of stroke (OR: 2.1, 95% CI: 0.99- 4.68) associated to MRS, although with no differences in overall mortality or AMI.Three SRs (39,563 patients) comparing the use of DES versus CS were found which showed a significant reduction in the revascularization of the culprit vessel in all the DES assessed (RR: 0.38; 95% CI: 0.29-0.48 to RR: 0.63, 95% CI: 0.42-0.66) with no differences in overall mortality, AMI and intra-stent thrombosis.Clinical Practice Guidelines (CPG)CPGs from the American College of Cardiology together with the American Heart Association, the European Society of Cardiology and the Association for Cardio-Thoracic Surgery were identified; in all of them DES is considered as an alternative to CS in lesions of increased risk for restenosis and intra-stent thrombosis (vessels < 2.5 mm diameter, lesions > 20 mm long) if anti-platelet therapy can be complied with.Health Technology Assessments (HTA)One HTA from the Canadian Agency for Drugs and Health Technologies (CADHT) was identified; it highlights a decrease in revascularization of the culprit vessel (RR: 0.34, 95% CI: 0.26-0.44) and ReMI (RR: 0.73, 95% CI: 0.57-0.94) when using a DES in an acute coronary syndrome, in chronic occlusive lesions or in restenosis post-CS or balloon angioplasty.Coverage PoliciesCoverage policies from two US health sponsors were found, one of them endorsing the use of DES in new lesions with ≥ 50% stenosis, while the other one enhances its indication also in the presence of ISR. The National Institute for Health and Clinical Excellence (NICE) considers the indication of DES when the artery to undergo angioplasty is < 3 mm long, the lesion is > 15 mm long and the difference with CS is less than £ 300.CostsIn Argentina, the cost of DES is AR$ 7,000 to 12,000 (Argentine pesos, June, 2013) while CS is AR$1,000 to 2,500.ConclusionsThere is high quality evidence identifying DES as safe and efficacious for the treatment of stable chronic or acute coronary disease. The use of DES has been associated to a lower incidence of revascularization and myocardial infarction when compared with CS, with no differences in overall mortality or intra-stent thrombosis.In multiple vessel disease, moderate quality evidence showed the non superiority of DES versus the treatment of choice represented by MRS.In left main coronary artery lesions, moderate quality evidence showed a higher need for revascularization with the use of DES versus MRS, with no differences in the development of fatal and non fatal clinical events. However, DES was associated to a lower overall mortality, AMI and revascularization when compared with CS.High quality evidence associated the treatment of chronic occlusive coronary lesions and ISR using DES with a lower need for revascularization, no differences in the development of overall mortality, AMI or intra-stent thrombosis when compared with conventional treatment alternatives.In the diabetic population with left main coronary artery disease or multiple vessel disease, moderate quality evidence associated the use of DES to a higher need for revascularization but a lower incidence of stroke when compared with MRS (treatment of choice). High quality evidence associated a lower need for revascularization with the use of DES when compared with CS.The identified clinical practice guidelines, health technology assessments and coverage policies suggest the use of DES only in complex lesions if anti-platelet therapy can be implemented.