Remodelling elective hospital services in the COVID-19 era - designing the new normal.

The provision of elective clinical services has decreased during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic to enable hospitals to focus on acute illness. Any end to the pandemic through widespread vaccination, effective treatment or development of herd immunity may be years away. Until then, hospitals will need to resume treating other diseases while also attempting to eradicate transmission of COVID-19 within the healthcare setting. In this article we suggest six major themes which could affect the design and delivery of elective clinical services: hospital avoidance, separation of high- and low-risk groups, screening, maintenance of adequate infection control, and new ways of working.

Proximal occlusion versus distal filter for cerebral protection during carotid stenting: updated meta-analysis of randomised and observational MRI studies.

AIMS: Proximal occlusion (PO) and distal filter (DF) serve for cerebral embolic protection during carotid artery stenting (CAS). New cerebral lesions at diffusion-weighted magnetic resonance imaging (DW-MRI) represent a surrogate endpoint for embolisation, though their clinical impact is controversial. We performed a meta-analysis of randomised and observational DW-MRI studies comparing PO and DF during CAS. METHODS AND RESULTS: We searched electronic scientific databases. The primary endpoint was the incidence of new cerebral lesions at DW-MRI; secondary endpoints were the incidence of new ipsilateral and new contralateral cerebral lesions at DW-MRI and death/cerebrovascular events (CVE). A total of 392 patients (seven studies) received CAS. At DW-MRI after 48 hours 178 patients (48.3%) presented new cerebral lesions. The use of PO versus DF reduced neither the risk of new cerebral lesions (OR [95% confidence interval] 0.65 [0.28-1.52], p=0.32) nor the risk of death/CVE (0.59 [0.22-1.60], p=0.30). Diabetes, baseline stenosis and symptoms significantly modified the risk estimates for new cerebral lesions. CONCLUSIONS: In this meta-analysis, one half of patients receiving protected CAS developed new embolic cerebral lesions at DW-MRI, although the overwhelming majority were asymptomatic. Cerebral protection with PO versus DF neither reduced cerebral embolisation nor impacted on clinical outcomes.

Long-term outcomes of biodegradable versus durable polymer drug-eluting stents in patients with acute ST-segment elevation myocardial infarction: a pooled analysis of individual patient data from three randomised trials.

AIMS: Arterial plaque rupture and thrombus characterise ST-elevation myocardial infarction (STEMI) and may aggravate delayed arterial healing following durable polymer drug-eluting stent (DP-DES) implantation. Biodegradable polymer (BP) may improve biocompatibility. We compared long-term outcomes in STEMI patients receiving BP-DES vs. durable polymer sirolimus-eluting stents (DP-SES). METHODS AND RESULTS: We pooled individual patient-level data from three randomised clinical trials (ISAR-TEST-3, ISAR-TEST-4 and LEADERS) comparing outcomes from BP-DES with DP-SES at four years. The primary endpoint (MACE) comprised cardiac death, MI, or target lesion revascularisation (TLR). Secondary endpoints were TLR, cardiac death or MI, and definite or probable stent thrombosis. Of 497 patients with STEMI, 291 received BP-DES and 206 DP-SES. At four years, MACE was significantly reduced following treatment with BP-DES (hazard ratio [HR] 0.59, 95% CI: 0.39-0.90; p=0.01) driven by reduced TLR (HR 0.54, 95% CI: 0.30-0.98; p=0.04). Trends towards reduction were seen for cardiac death or MI (HR 0.63, 95% CI: 0.37-1.05; p=0.07) and definite or probable stent thrombosis (3.6% vs. 7.1%; HR 0.49, 95% CI: 0.22-1.11; p=0.09). CONCLUSIONS: In STEMI, BP-DES demonstrated superior clinical outcomes to DP-SES at four years. Trends towards reduced cardiac death or myocardial infarction and reduced stent thrombosis require corroboration in specifically powered trials.

Randomized comparison of biolimus-eluting stents with biodegradable polymer versus everolimus-eluting stents with permanent polymer coatings assessed by optical coherence tomography.

We sought to compare the healing patterns of biolimus-eluting stents with biodegradable polymer (BP-BES, Nobori) versus everolimus-eluting stents with permanent polymer (PP-EES, Xience) using intravascular optical coherence tomography (OCT). A total of 34 patients undergoing treatment of de novo coronary lesions were randomly assigned to receive BP-BES (n = 15) or PP-EES (n = 19). Stent tissue coverage and apposition as well as the incidence of peri-strut low intensity area (PLIA) were assessed by OCT at 6-8 months. Generalized linear mixed models were used to account for clustered data. OCT imaging was available for 17 lesions with 2,805 struts in the BP-BES group and 22 lesions with 3,890 struts in the PP-EES group. BP-BES as compared to PP-EES showed similar rates of uncovered struts (479 vs. 588, odds ratio (OR) 1.54 (95 % CI 0.63-3.79), P = 0.34) and malapposed struts (46 vs. 32 struts, OR 1.64 [95 % CI 0.21-12.5], P = 0.64). Three lesions with BP-BES (17.6 %) versus 5 lesions with PP-EES (22.7 %) had >30 % uncovered struts (P = 0.78). The proportion of patients with PLIA was similar in both groups (BP-BES 41.2 % vs. PP-EES 36.4 %, OR 1.11 [95 % CI 0.43-2.87], P = 0.83). New generation BP-BES as compared to PP-EES showed similar stent coverage and apposition as assessed by OCT at 6-8 months. In addition, PLIA-possible markers of delayed arterial healing-were observed with similar frequency in both groups.

Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography.

OBJECTIVE: Systematic investigation of restenosis after percutaneous coronary intervention (PCI) with bare metal stents (BMS) or first or second generation drug eluting stents (DES) in large scale, broadly inclusive patient populations undergoing follow-up angiography represents a gap in our scientific knowledge. We investigated the incidence of angiographically proven restenosis and its predictors in patients undergoing PCI with stents. METHODS: All patients undergoing successful implantation of coronary stents for de novo lesions from 1998 to 2009 and follow-up angiography at 6-8 months at two centres in Munich, Germany were eligible for inclusion. Patients with cardiogenic shock, dialysis dependent renal insufficiency or previous cardiac transplantation were excluded. Data were prospectively collected. The incidence of restenosis, defined as diameter stenosis ≥50% in the in-segment area at follow-up angiography, and its predictors were evaluated. RESULTS: A total of 12 094 patients met inclusion criteria. Angiographic follow-up was available for 10 004 patients (77.5%) with 15 004 treated lesions. Binary restenosis was detected in 2643 (26.4%) patients. Use of first generation DES versus BMS (OR 0.35, 95% CI 0.31 to 0.39) and second generation DES versus first generation DES (OR 0.67, 95% CI 0.58 to 0.77) were independent predictors of lower rates of restenosis. At multivariate analysis, smaller vessel size (OR 1.59, 95% CI 1.52 to 1.68, for each 0.5 mm decrease), total stented length (OR 1.27, 95% CI 1.21 to 1.33, for each 10 mm increase), complex lesion morphology (OR 1.35, 95% 1.21 to 1.51), presence of diabetes mellitus (OR 1.32, 95% 1.19 to 1.46), and history of bypass surgery (OR 1.38, 95% CI 1.20 to 1.58) were independently associated with restenosis and were similar across the spectrum of stent devices. CONCLUSIONS: In this large cohort of patients with angiographic surveillance we demonstrated the impact of device  development on antirestenotic efficacy, with sequentially improved efficacy from BMS to first generation DES to second generation DES. Predictors of restenosis were small vessel size, increased stented length, complex lesion morphology, diabetes mellitus, and prior bypass surgery.

Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients.

OBJECTIVES: This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. BACKGROUND: In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. METHODS: A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES. RESULTS: The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p < 0.001). G2-DES were associated with a similar risk of stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p < 0.001), but not with G2-DES compared with BMS (OR: 1.01; 95% CI: 0.32 to 3.25; p = 0.98). CONCLUSIONS: In a large cohort of unselected patients undergoing coronary stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS.

Long-term outcomes of biodegradable polymer versus durable polymer drug-eluting stents in patients with diabetes a pooled analysis of individual patient data from 3 randomized trials.

BACKGROUND: There is ongoing debate on the optimal drug-eluting stent (DES) in diabetic patients with coronary artery disease. Biodegradable polymer drug-eluting stents (BP-DES) may potentially improve clinical outcomes in these high-risk patients. We sought to compare long-term outcomes in patients with diabetes treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). METHODS: We pooled individual patient-level data from 3 randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4 and LEADERS) comparing biodegradable polymer DES with durable polymer SES. Clinical outcomes out to 4 years were assessed. The primary end point was the composite of cardiac death, myocardial infarction and target-lesion revascularization. Secondary end points were target lesion revascularization and definite or probable stent thrombosis. RESULTS: Of 1094 patients with diabetes included in the present analysis, 657 received biodegradable polymer DES and 437 durable polymer SES. At 4 years, the incidence of the primary end point was similar with BP-DES versus SES (hazard ratio = 0.95, 95% CI = 0.74-1.21, P = 0.67). Target lesion revascularization was also comparable between the groups (hazard ratio = 0.89, 95% CI = 0.65-1.22, P = 0.47). Definite or probable stent thrombosis was significantly reduced among patients treated with BP-DES (hazard ratio = 0.52, 95% CI = 0.28-0.96, P = 0.04), a difference driven by significantly lower stent thrombosis rates with BP-DES between 1 and 4 years (hazard ratio = 0.15, 95% CI = 0.03-0.70, P = 0.02). CONCLUSIONS: In patients with diabetes, biodegradable polymer DES, compared to durable polymer SES, were associated with comparable overall clinical outcomes during follow-up to 4 years. Rates of stent thrombosis were significantly lower with BP-DES.

Paclitaxel-coated balloon or primary bare nitinol stent for revascularization of femoropopliteal artery: a meta-analysis of randomized trials versus uncoated balloon and an adjusted indirect comparison.

BACKGROUND: The performance of paclitaxel-coated balloon (PCB) or primary bare nitinol stent (BNS) versus uncoated balloon angioplasty (UCB) for femoropopliteal artery disease and the relative efficacy and safety of PCB versus BNS are still debated. METHODS: A meta-analysis of trials in which patients were randomly assigned to PCB versus UCB or BNS versus UCB was performed, as well as an indirect comparison of PCB versus BNS, with UCB common comparator. The primary endpoint was target lesion revascularization (TLR); secondary endpoints were restenosis, death and amputation. RESULTS: In total, 1464 patients were assigned to revascularization with PCB versus UCB (n = 441) or BNS versus UCB (n = 1023). Treatment with PCB versus UCB reduced the risk of TLR (odds ratio [95% confidence interval] = 0.29 [0.15-0.56], p < 0.001) and restenosis (0.31 [0.19-0.51], p < 0.001) without affecting mortality (1.05 [0.41-2.71], p = 0.92) or amputation (0.68 [0.04-10.31], p = 0.78). BNS versus UCB therapy reduced the risk of TLR (0.46 [0.27-0.80], p = 0.006) and restenosis (0.51 [0.34-0.77], p = 0.02) without affecting mortality (2.08 [0.93-4.66], p = 0.07) or amputation (0.84 [0.30-2.35], p = 0.74). The indirect comparison found no difference with PCB versus BNS in the risk of TLR (0.63 [0.26-1.48] p = 0.29), restenosis (0.60 [0.32-1.15], p = 0.13) death (0.50 [0.05-4.82], p = 0.55) or amputation (0.80 [0.04-15.63], p = 0.66). CONCLUSIONS: In atherosclerotic disease of femoropopliteal artery, both PCB and BNS therapy have superior antirestenotic efficacy to UCB, without safety issues. At indirect comparison, PCB and BNS may have comparable antirestenotic efficacy and safety.

Differential relative efficacy between drug-eluting stents in patients with bare metal and drug-eluting stent restenosis; evidence in support of drug resistance: insights from the ISAR-DESIRE and ISAR-DESIRE 2 trials.

AIMS: In drug-eluting stent (DES) restenosis, the contribution of drug hyporesponsiveness is poorly defined. We sought to evaluate if, in the setting of treatment for in-stent restenosis, the relative efficacy of sirolimus-eluting stents (SES) and of paclitaxel-eluting stents (PES) depends on the underlying substrate in which the stents are implanted, i.e., on whether the restenosis occurs within bare metal stents or within SES. METHODS AND RESULTS: We pooled data from the ISAR-DESIRE and ISAR-DESIRE 2 randomised trials and analysed outcomes in SES-treated and PES-treated patients. In all, 650 patients were included. Angiographic follow-up was available for 87% of patients. In SES-treated patients, both late loss (LL) and percentage diameter stenosis (%DS) were lower in patients treated for bare metal stent restenosis compared with SES restenosis (0.21±0.59 mm versus 0.41±0.66 mm, p=0.007; 27.6±19.4% versus 34.0±20.9%, p=0.015, respectively). In PES-treated patients, LL and %DS were similar in patients treated for bare metal stent restenosis compared with SES restenosis (0.48±0.59 mm versus 0.39±0.71, p=0.47; 33.5±22.2% versus 32.7±18.6%, p=0.75, respectively). Similarly, in terms of overall clinical efficacy, in SES-treated patients clinical outcomes were better in patients with bare metal stent restenosis compared with SES restenosis while in PES-treated patients outcomes were similar in both groups. At multivariate analyses the use of SES to treat restenosis within SES was predictive of both higher LL and %DS. CONCLUSIONS: The efficacy of sirolimus-eluting but not paclitaxel-eluting stents is significantly reduced when used for treatment of SES restenosis as compared to bare metal stent restenosis. The lower antirestenotic efficacy following SES implantation in patients with SES restenosis may support a role for drug resistance in restenosis within these stents.

Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials.

AIMS: The aim of this study was to evaluate benefits and risks of extending dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in the drug-eluting stent era. METHODS AND RESULTS: We searched electronic databases (Medline, EMBASE, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, chapters in books, and proceedings of advisory panels for the US Food and Drug Administration, for randomized controlled trials investigating the clinical impact of extending DAPT duration in patients undergoing PCI. The primary endpoint was all-cause death. The secondary endpoints were myocardial infarction (MI), stent thrombosis (ST), cerebrovascular accidents (CVAs), and thrombolysis in myocardial infarction (TIMI) major bleeding. We included four trials that randomized 8231 patients (50.2%, extended DAPT duration vs. 49.8%, control duration). A total of 8158 patients (99.1%) were available for final analyses. The median DAPT duration was 16.8 vs. 6.2 months for the extended DAPT and control groups, respectively. At follow-up (median 16.8 months) extending DAPT duration did not reduce all-cause death [odds ratio (95% confidence interval) = 1.15 (0.85-1.54), P = 0.36], MI [0.95 (0.66-1.36), P = 0.77], ST [0.88 (0.43-1.81), P = 0.73], or CVAs [1.51 (0.92-2.47), P = 0.10]. Conversely, extended DAPT duration clearly increased the risk of TIMI major bleeding [2.64 (1.31-5.30), P = 0.006]. CONCLUSIONS: The extension of DAPT duration after percutaneous coronary interventions may increase the risk of bleeding without reducing ischaemic events. These results need corroboration from large ongoing trials.

Two zotarolimus-eluting stent generations: a meta-analysis of 12 randomised trials versus other limus-eluting stents and an adjusted indirect comparison.

OBJECTIVE: To evaluate efficacy and safety of two zotarolimus-eluting stent generations versus other limus-eluting stents (LES), and to compare Resolute zotarolimus-eluting stents (R-ZES) with Endeavor zotarolimus-eluting stents (E-ZES). BACKGROUND: The performance of zotarolimus-eluting stents versus other LES, and the possible improvements of R-ZES versus E-ZES still remain to be defined. METHODS: We undertook a meta-analysis of trials in which patients were randomly assigned to percutaneous coronary interventions (PCI) with R-ZES versus LES, or with E-ZES versus LES, as well as an indirect comparison of R-ZES versus E-ZES, with LES as common comparator. The primary efficacy endpoint was ischaemia-driven target vessel revascularisation (ID-TVR); the primary safety endpoints were myocardial infarction (MI), cardiac death and cumulative definite/probable stent thrombosis (ST). RESULTS: Overall, 13'709 patients were assigned to PCI with R-ZES versus LES (n=7185) or with E-ZES versus LES (n=6524). The risk of ID-TVR (OR (95% CI)=1.06 (0.90 to 1.25), p=0.47), MI (1.00 (0.81 to 1.25), p=0.97), cardiac death (0.99 (0.69 to 1.42), p=0.96) and ST (1.18 (0.68 to 2.03), p=0.56) did not differ between R-ZES and LES. Patients receiving E-ZES were more likely to undergo ID-TVR as compared with those receiving LES (1.95 (1.40 to 2.73), p<0.0001). The risk of MI (0.91 (0.54 to 1.54), p=0.73), cardiac death (1.02 (0.54 to 1.91), p=0.96) and ST (1.10 (0.50 to 2.44), p=0.81) was similar between E-ZES and LES. At indirect comparison, PCI with R-ZES versus E-ZES reduced the risk of ID-TVR (0.54 (0.37 to 0.78), p=0.001), without increasing MI (1.09 (0.62 to 1.93), p=0.74), cardiac death (0.97 (0.46 to 2.00), p=0.93) and ST (1.07 (0.40 to 2.80), p=0.88). CONCLUSIONS: The antirestenotic efficacy of Resolute zotarolimus-eluting stents is superior to Endeavor zotarolimus-eluting stents and similar to other limus-eluting stents. Endeavor zotarolimus-eluting stents increase the risk of reinterventions as compared with other limus-eluting stents. First and second-generation zotarolimus-eluting stents have similar thrombogenicity compared with other limus-eluting stents.

Everolimus-eluting versus sirolimus-eluting stents: an updated meta-analysis of randomized trials.

BACKGROUND: Everolimus-eluting stents (EES; Xience V) are among the most commonly used newer generation drug-eluting stents in clinical practice and have clearly proven superiority over paclitaxel-eluting stents. Nevertheless, the relative merits of EES against the previous gold-standard sirolimus-eluting stent (SES; Cypher) have been less extensively assessed. We aimed to compare the clinical outcomes of EES with SES in patients with coronary artery disease undergoing percutaneous coronary intervention. METHODS AND RESULTS: We identified eight eligible randomized trials comparing EES with SES including 11,167 patients. The primary endpoint was the incidence of major adverse cardiac events (MACE). Secondary endpoints were target lesion revascularization (TLR) and the composite of definite and probable stent thrombosis. The follow-up ranged from 9 to 36 months. No heterogeneity across the trials was observed regarding the selected endpoints. There was no difference in risk of MACE (HR 0.91 [0.79-1.04]; p = 0.15), TLR (HR 0.86 [0.72-1.04]; p = 0.12) and the composite of definite and probable stent thrombosis (HR 0.84 [0.54-1.29], p = 0.42). The risk of definite stent thrombosis was significantly lower in patients receiving EES (HR 0.49 [0.27 to 0.91]; p = 0.02). CONCLUSION: Using the largest available dataset of patients treated in randomized trials, the present meta-analysis demonstrated that the use of EES versus SES was associated with comparable incidence of overall clinical events. However, EES may be associated with a lower risk of definite stent thrombosis.