Tradeoff between bleeding and stent thrombosis in different dual antiplatelet therapy regimes: Importance of case fatality rates and effective treatment durations.

BACKGROUND: The tradeoff between stent thrombosis (ST) and major bleeding (MB) of 12- versus 6-month dual antiplatelet therapy (DAPT) after coronary stent implantation has not been clearly defined. METHODS: Definite/probable ST and MB (TIMI major and Bleeding Academic Research Consortium (BARC) ≥ 3) were compared in 2 subsequent trials with similar inclusion criteria but different DAPT duration, that is, BASKET (6 months; n = 557) and BASKET-PROVE (12 months; n = 2,314), between months 0 to 6 (DAPT in both trials), 7 to 12 (DAPT in BASKET-PROVE only), and 13 to 24 (aspirin in both trials) using propensity score-adjusted, time-stratified Cox proportional hazard models. RESULTS: Overall, event rates were low with fewer ST but similar MB in prolonged DAPT. Analysis of the 3 periods showed a uniform pattern for ST (interaction DAPT/period; P = .145) but an inconsistent pattern for MB (interaction DAPT/period; P < .001 for TIMI major and P = .046 for BARC ≥ 3), with more MB occurring during months 7 to 12 with prolonged DAPT. Considering observed case fatality rates of 31% with ST and 11% with MB, the extrapolated prevention of 27 ST deaths and the excess of 5 MB deaths resulted in an expected benefit of 22 survivors/10,000 patients treated over 2 years with prolonged DAPT. CONCLUSION: Despite overall low event rates, prolonged DAPT was associated with more MB during months 7 to 12 according to the interaction DAPT/period. Given the higher observed case fatality rates of ST versus MB, 12- versus 6-month DAPT was associated with an extrapolated reduction in mortality. Effective treatment periods and case fatality rates seem important in the analysis of different DAPT durations, specifically with regard to ongoing trials.

Stent thrombosis after coronary stent implantation: a protective effect of high-dose statin therapy?

OBJECTIVES: To assess independent predictors of stent thrombosis (ST) in an all-comer trial. METHODS: This is an observational case-control study based on a retrospective analysis of the Basel Stent Kosten Effektivitäts Trial (BASKET) (n = 826). Patients with ST were compared to controls with regard to baseline parameters. Multivariate models were performed to identify independent predictors of ST. RESULTS: At 36 months, there were 53 (6.4%) patients with ST, 17 (32%) of whom had early ST and 36 (68%) of whom had late/very late ST. Patients with ST were at a higher cardiovascular risk but received lower doses of statins than the controls (n = 212). Stents in ST patients were longer, had more overlap and were not as well expanded, with significantly more remaining stenoses than the stents in the controls. Multivariable analysis revealed interventions in saphenous vein grafts, malapposed stents, an overlap >3 mm, complex coronary anatomy and treatment with low-dose/no statins as risk factors for ST, while interventions in saphenous vein grafts, underexpanded or malapposed stents, a history of myocardial infarction and treatment with low-dose/no statins were risk factors for late ST. CONCLUSIONS: The use of statins might have a protective effect against ST. This observation is new, hypothesis-generating and should be evaluated in an adequately powered randomized trial.

Stent thrombosis up to 3 years after stenting for ST-segment elevation myocardial infarction versus for stable angina--comparison of the effects of drug-eluting versus bare-metal stents.

BACKGROUND: The long-term safety of drug-eluting stents (DES) for the treatment of ST-segment elevation myocardial infarction (STEMI) is unclear and may differ from that in stable angina (stable) patients as noted in autopsy studies. METHODS: To assess this problem, 210 consecutive STEMI and 323 stable patients, randomized 2:1 to DES versus bare-metal stents (BMS), were followed up for 3 years for definite/probable stent thrombosis (ST) and cardiac death/myocardial infarction. Events occurring during the initial 6 months were separated from later events. RESULTS: The 3-year rate of ST was 8.1% in STEMI vs 3.4% in stable patients (P = .02), with corresponding rates of 9.4% vs 2.9% (P = .01) for DES and of 5.6% vs 4.3% (P = .71) for BMS patients, respectively. This difference appeared only after 6 months: 4.6% in STEMI vs 1.7% in stable patients (P = .05) and in DES-treated patients (6.2% vs 2.0%, P = .05). Results of ST were paralleled by findings of clinical events, although here differences were less pronounced, but also seen only late after stenting. Thus, in STEMI patients, late events occurred more frequently after DES vs BMS implantation (11.6% vs 3.0%, P = .04), compared to results in stable patients (DES 6.4%, BMS 1.9%, P = .08). CONCLUSIONS: In this pilot study, we observed an increased rate of late ST and a trend to more related clinical events in patients after stenting for STEMI vs for stable angina, particularly if treated with DES. This may explain outcome differences between results of pivotal trials in stable patients vs those of "real-world" patients.

Drug-eluting stents and glycoprotein IIb/IIIa inhibitors in vessels at low anatomic risk: a retrospective analysis of previously published data from the Basel Stent Kosten Effektivitäts Trial.

BACKGROUND: Drug-eluting stents (DESs) are associated with late stent thromboses, but the exact mechanism of action is unknown. OBJECTIVE: The goal of this article was to assess the clinical interaction of glycoprotein IIb/IIIa inhibitors (GPIs) with different stent and vessel types in unselected patients undergoing percutaneous coronary intervention (PCI). METHODS: This was a predefined retrospective analysis of the randomized controlled Basel Stent Kosten Effektivitats Trial (BASKET), which compared DES with bare-metal stents (BMSs) in patients undergoing PCI. Patients were compared for major adverse clinical events in relation to GPI use (abciximab and tirofiban) after 18 months. In a subgroup analysis prespecified in the study protocol, specific regard was given to angiographic groups at different risk levels for late events (high-risk vessels [ie, small vessels with a diameter <3.0 mm and saphenous vein grafts], and low-risk vessels [ie, large native vessels > or =3.0 mm]). Baseline differences between patients with or without GPI use were identified and incorporated into a multivariable Cox proportional hazards regression analysis if different at a <0.05 level. RESULTS: A total of 826 patients (650 males, 176 females) were enrolled in BASKET; 301 (36%) received GPI therapy. Of these 301 patients, 255 (85%) received abciximab and 46 (15%) received tirofiban. After 18 months, the rate of cardiac death and nonfatal myocardial infarction was higher in patients with GPI use than in those without GPI use (35/301 [12%] vs 32/525 [6%]; P = 0.005). In patients undergoing PCI in anatomically low-risk vessels and receiving GPI therapy, there was a higher rate of cardiac death and nonfatal myocardial infarction at 18 months with a DES versus a BMS (22/151 [15%] vs 3/66 [5%]; P = 0.033). In patients undergoing PCI in anatomically low-risk vessels and without GPI therapy, there was no significant difference for cardiac death and nonfatal myocardial infarction (DES vs BMS, 11/207 [5%] vs 6/134 [4%]). In the multivariable analysis, GPI use (hazard ratio = 2.93; 95% CI, 1.53-5.63; P = 0.001) and age (hazard ratio = 1.034 per year increase; 95% CI, 1.008-1.062; P = 0.012) remained the only significant independent predictors of outcome. Interaction of stent type and GPI use was significant (P = 0.006). CONCLUSIONS: This retrospective analysis of the BASKET data found that GPIs and DESs used in patients with large native vessels may have an adverse interaction in terms of late stent thromboses. However, large prospective studies are needed to confirm these findings.

Long-term outcomes after intracoronary Beta-irradiation for in-stent restenosis in bare-metal stents.

OBJECTIVE: We sought to characterize the long-term outcomes of patients undergoing intracoronary brachytherapy using Beta- irradiation (Beta-BT). BACKGROUND: Beta-BT is effective in reducing angiographic restenosis as well as target vessel revascularization (TVR) in patients with in-stent restenosis (ISR) after bare-metal stenting (BMS). METHODS: 81 consecutive patients undergoing Beta-BT for ISR (irradiated length 32 [32-54] mm) after BMS in native vessels (n = 79) or saphenous vein grafts (n = 2) between 2001 and 2003 were followed. Major cardiac events (MACE), including cardiac death, nonfatal myocardial infarction (MI), and TVR occurring > 1 year or > 1 year were assessed 5.2 (4.4-5.6) years after the index procedure. RESULTS: During the entire follow-up period, the total MACE rate was 49.4%. Within the first year and at > 1 year, MACE rates were 25.9% and 23.5%, cardiac death occurred in 2.4% and 6.2%, and nonfatal MI in 6.2% and 12.3% for annual cardiac death/MI rates of 8.7% at < 1 year and 4.1% thereafter. TVR was required in 19% at < 1 year and in 16% of patients later on. The only independent predictor of MACE occurring < 1 year was an irradiated vessel length > 32 mm (odds ratio [OR] 2.73, 95% confidence interval [CI] 1.10-6.78; p = 0.03). The best, albeit not statistically significant, predictor of MACE occurring at > 1 year was the presence of diabetes mellitus (OR 2.49, 95% CI 0.94-6.57; p = 0.07). CONCLUSIONS: Patients undergoing Beta-BT for ISR after BMS carry a substantial risk of MACE also beyond the first year, with annual cardiac death and nonfatal MI rates of 1.5% and 2.9% up to 5 years postprocedure.

Effectiveness and safety of paclitaxel-eluting stents in patients with ST-segment elevation acute myocardial infarction.

AIMS: The efficacy of paclitaxel-eluting stents (PES) in patients with ST-segment elevation acute myocardial infarction (STEMI) has not been demonstrated yet. The aim of the present study was to evaluate the efficacy and safety of PES in patients with STEMI. METHODS AND RESULTS: A meta-analysis from three randomised trials that compared PES and bare-metal stents in patients with STEMI was performed. Overall, 925 patients were included: 459 allocated to PES, and 466 to bare-metal stents (BMS). The rates of major adverse events (i.e. death, reinfarction, and target vessel revascularisation at 6-12 month follow-up) was compared for patients with PES and BMS. Compared to patients with BMS, a significant reduction in the incidence of events (9.1% vs. 13.9%, p=0.02; OR 0.62; 95%, CI: 0.41-0.93), and target vessel revascularisation (4.7% vs. 8.3%, p=0.03; OR 0.54; 95%, CI 0.31-0.94) was found in patients with PES. The rates of death and reinfarction were similar in BMS and DES patients. CONCLUSIONS: The use of PES in patients with STEMI is associated with a significant reduction in MACE and need for new revascularisations.

Influence of revascularization on long-term outcome in patients > or =75 years of age with diabetes mellitus and angina pectoris.

Little is known about the effect of revascularization in patients > or =75 years of age with symptomatic coronary artery disease (CAD) and diabetes mellitus (DM) for whom periprocedural risk and overall mortality are increased. Therefore, we examined the 301 patients of the Trial of Invasive versus Medical therapy in the Elderly with symptomatic CAD (TIME) with special regard to diabetic status. Patients were randomized to an invasive versus optimized medical strategy. The median follow-up was 4.1 years (range 0.1 to 6.9). Patients with DM (n = 69) had a greater incidence of hypertension (73% vs 58%, p = 0.03), > or =2 risk factors (93% vs 46%, p <0.01), previous heart failure (22% vs 12%, p = 0.04), and previous myocardial infarction (59% vs 43%, p = 0.02), and a lower left ventricular ejection fraction (48% vs 54%, p = 0.02) than did patients without DM. Mortality was greater in patients with DM than in those without DM (41% vs 25%, p = 0.01; adjusted hazard ratio 1.86, p = 0.01). Revascularization improved the overall survival rate from 61% (no revascularization) to 79% (p <0.01; adjusted hazard ratio 1.68, p = 0.03), an effect similarly observed in patients with and without DM. The event-free survival rate was 11% in nonrevascularized patients with DM compared with 40% in nonrevascularized patients without DM and 41% and 53% in revascularized patients with and without DM, respectively (p <0.01). Angina severity and antianginal drug use were similar for patients with and without DM, but those with DM performed worse in daily activities and physical functioning. In conclusion, elderly diabetic patients with chronic angina have a worse outcome than those with DM but benefit similarly from revascularization regarding symptom relief and long-term outcome. However, physical functioning related to daily activities is reduced in those with DM and may need special attention.

Selective embolization of a pulmonary artery rupture caused by a Cournand catheter.

Pulmonary artery rupture is a rare but often fatal complication of right heart catheterization. We present a case of a ruptured pulmonary artery caused by a Cournand catheter in a high-risk patient with pulmonary hypertension on oral anticoagulation with successful emergency embolization with gelatine foam.