Robert C. Stoler

The "final" 5-year follow-up from the ENDEAVOR IV trial comparing a zotarolimus-eluting stent with a paclitaxel-eluting stent.

OBJECTIVES This study sought to report the final 5-year outcomes of the ENDEAVOR IV (A Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions) trial comparing the Endeavor zotarolimus-eluting stent (E-ZES) (Medtronic, Santa Rosa, California) with the Taxus paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Massachusetts) in patients with single de novo coronary lesions. BACKGROUND Primary results of the ENDEAVOR IV trial demonstrated similar clinical outcomes with E-ZES and PES. Concerns with regard to late adverse clinical events with drug-eluting stents highlight the need for long-term follow-up with these devices. METHODS Late outcomes after the use of E-ZES and PES were examined in the multicenter randomized ENDEAVOR IV trial in cumulative and landmark analyses. Assessed outcomes were related to device efficacy and patient safety. RESULTS At 5 years, clinical data were available for 722 (93.4%) E-ZES patients and 718 (92.6%) PES patients. Overall rates of target lesion revascularization (7.7% vs. 8.6%, p = 0.70) and target vessel failure were similar (17.2% vs. 21.1%, p = 0.061) with E-ZES compared with PES. The incidence of cardiac death or myocardial infarction (MI) was lower with E-ZES (6.4% vs. 9.1%, p = 0.048), primarily driven by a lower rate of target vessel MI with E-ZES (2.6% vs. 6.0%, p = 0.002). Although overall definite/probable stent thrombosis rates were similar between stents (1.3% vs. 2%, p = 0.42), rates of very late stent thrombosis (0.4% vs. 1.8%, p = 0.012) and late MI events (1.3% vs. 3.5%, p = 0.008) were significantly lower with E-ZES compared with PES. CONCLUSIONS These data demonstrate the durable efficacy and safety of E-ZES compared with PES for the treatment of de novo coronary lesions. Significant improvements in late safety outcomes were observed with E-ZES but should be considered hypothesis-generating, given the limited statistical power of the trial. (The ENDEAVOR IV Clinical Trial: A Trial of a Coronary Stent System in Coronary Artery Lesions; NCT00217269).

Health status after transcatheter aortic valve replacement in patients at extreme surgical risk: Results from the CoreValve U.S. Trial

OBJECTIVES The purpose of this study was to characterize health status outcomes after transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis among patients at extreme surgical risk and to identify pre-procedural patient characteristics associated with a poor outcome. BACKGROUND For many patients considering TAVR, improvement in quality of life may be of even greater importance than prolonged survival. METHODS Patients with severe, symptomatic aortic stenosis who were considered to be at prohibitive risk for surgical aortic valve replacement were enrolled in the single-arm CoreValve U.S. Extreme Risk Study. Health status was assessed at baseline and at 1, 6, and 12 months after TAVR using the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Short Form-12, and the EuroQol-5D. The overall summary scale of the KCCQ (range 0 to 100; higher scores = better health) was the primary health status outcome. A poor outcome after TAVR was defined as death, a KCCQ overall summary score (OS) <45, or a decline in KCCQ-OS of 10 points at 6-month follow-up. RESULTS A total of 471 patients underwent TAVR via the transfemoral approach, of whom 436 (93%) completed the baseline health status survey. All health status measures demonstrated considerable impairment at baseline. After TAVR, there was substantial improvement in both disease-specific and generic health status measures, with an increase in the KCCQ-OS of 23.9 points (95% confidence interval [CI]: 20.3 to 27.5 points) at 1 month, 27.4 points (95% CI: 24.2 to 30.6 points) at 6 months, 27.4 points (95% CI: 24.1 to 30.8 points) at 12 months, along with substantial increases in Short Form-12 scores and EuroQol-5D utilities (all p < 0.003 compared with baseline). Nonetheless, 39% of patients had a poor outcome after TAVR. Baseline factors independently associated with poor outcome included wheelchair dependency, lower mean aortic valve gradient, prior coronary artery bypass grafting, oxygen dependency, very high predicted mortality with surgical aortic valve replacement, and low serum albumin. CONCLUSIONS Among patients with severe aortic stenosis, TAVR with a self-expanding bioprosthesis resulted in substantial improvements in both disease-specific and generic health-related quality of life, but there remained a large minority of patients who died or had very poor quality of life despite TAVR. Predictive models based on a combination of clinical factors as well as disability and frailty may provide insight into the optimal patient population for whom TAVR is beneficial. (Safety and Efficacy Study of the Medtronic CoreValve® System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Analysis of Stroke Occurring in the SYNTAX Trial Comparing Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention in the Treatment of Complex Coronary Artery Disease

OBJECTIVES This study sought to analyze stroke rates in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trials randomized and registry cohorts of patients being treated with coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) for treatment of complex coronary artery disease. BACKGROUND The SYNTAX trial compared PCI to CABG in patients with de novo 3-vessel and/or left main coronary disease. METHODS The SYNTAX randomized trial was conducted at 85 U.S. and European sites (n = 1,800). All strokes (up to 4 years) were independently adjudicated by a clinical events committee that included a neurologist. An additional 1,077 (of which 644 were followed for 5 years) and 198 patients were included in the CABG and PCI registries, respectively. RESULTS In the randomized cohort, 31 CABG and 19 PCI patients experienced 33 and 20 strokes post-randomization at 4-year follow-up, respectively (p = 0.062). Three strokes occurred pre-procedurally but following randomization in CABG-treated patients. After CABG, a large proportion of strokes occurred acutely (0 to 30 days: 9 of 33), whereas in the PCI arm, most strokes occurred >30 days after the procedure (18 of 20). Stroke resulted in death in 3 patients in both the PCI and CABG groups. Of the patients who developed stroke, 68% (21 of 31) in the CABG group had residual deficits at discharge; in the PCI group, 47% (9 of 19) had residual deficits. In a multivariate analysis, treatment with CABG was not significantly associated with increased stroke rates (odds ratio: 1.67, 95% confidence interval: 0.93 to 3.01, p = 0.089). The incidence and outcomes of stroke were similar in the randomized trial and registries. CONCLUSIONS There is a higher risk of periprocedural stroke in patients undergoing CABG versus PCI; however, the risk converges over the first 4 years of follow-up. (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries; NCT00114972).

Predictors of low clopidogrel adherence following percutaneous coronary intervention.

Few data are available on factors associated with low adherence or early clopidogrel discontinuation after percutaneous coronary intervention (PCI). Patients (n = 284) were evaluated before hospital discharge after PCI to identify factors associated with low adherence to clopidogrel 30 days later. Adherence to daily medications before PCI was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (score <6), medium (score 6 to <8), or high (score 8). Low adherence to clopidogrel was defined as MMAS-8 score <6 (n = 21) or having discontinued clopidogrel (n = 11), which was ascertained during a 30-day interview after PCI. At 30 days after PCI, 11% of patients had low adherence to clopidogrel. Odds ratios (95% confidence intervals [CIs]) for low adherence to clopidogrel were 3.78 (1.09 to 13.1), 3.06 (1.36 to 6.87), 2.46 (0.97 to 6.27), and 3.36 (0.99 to 11.4) for patients who before PCI reported taking smaller doses of medication because of cost, had difficulty filling prescriptions, had difficulty reaching their primary physician, and were not comfortable asking their doctor for instructions, respectively. Odds ratios (95% CIs) for low clopidogrel adherence after PCI in patients with medium and low versus high adherence to daily medications before PCI were 6.13 (1.34 to 28.2) and 10.9 (2.46 to 48.7), respectively. The c-statistic associated with MMAS-8 scores before PCI for discriminating low clopidogrel adherence at 30 days after PCI was 0.733 (95% CI 0.650 to 0.852). In conclusion, adherence to daily medications before PCI may be a useful indicator for identifying patients who will have low clopidogrel adherence after PCI.

Safety and efficacy of staple-mediated femoral arteriotomy closure: results from a randomized multicenter study.

Mechanical closure of percutaneous femoral arteriotomies following catheter based procedures remains problematic.

Assessing Patient-Reported Outcomes and Preferences for Same-Day Discharge After Percutaneous Coronary Intervention Results From a Pilot Randomized, Controlled Trial

Background—Same-day discharge after percutaneous coronary intervention (PCI) may be safe for some patients. Few data are available on patient-reported outcomes and preferences for same-day discharge after PCI. Methods and ResultsBetween March 2008 and March 2010, a total of 298 patients undergoing elective PCI via femoral access at 2 medical centers (Mount Sinai Hospital, New York, NY, and Baylor Medical Center, Dallas, TX) were randomized to same-day (n=150) or next-day (n=148) discharge. The primary outcome was high patient coping during the 7 days after discharge defined as scores <20 on the validated postdischarge coping difficulty scale. Safety outcomes, clopidogrel adherence, and patient preferences were secondary outcomes. Before discharge, patients randomized to same-day and next-day discharge were similar with respect to sociodemographic and clinical characteristics. High-coping ability, assessed 7 days after PCI, was present for 79% of patients randomized to same-day discharge and for 77% of patients randomized to next-day discharge. The difference in high coping ability, 2 (95% confidence interval, −7 to 11), did not cross the noninferiority threshold of −12% (P<0.001 that same-day discharge is not noninferior to next-day discharge). At 30 days after PCI, clopidogrel adherence, physician and emergency room visits, and hospitalization were similar in the 2 randomization groups. In addition, 80% and 68% of those randomized to same-day and next-day discharge, respectively, stated they would prefer same-day discharge if they were to have another PCI procedure. Conclusions—Same-day discharge after PCI was associated with patient-reported and clinical outcomes similar to those of next-day discharge and was preferred by most patients. Clinical Trial Registration—URL: http://www.clinicaltrials.gov/show/NCT01230606. Unique identifier: NCT01230606.

Postpartum multivessel spontaneous coronary artery dissection confirmed by coronary CT angiography

Spontaneous coronary artery dissection is a rare but potentially life-threatening event associated with the peripartum period. We present a case of postpartum multivessel spontaneous coronary artery dissection diagnosed by conventional angiography and monitored with computed tomographic coronary angiography. The patient was initially managed medically and later received a coronary stent.

Prevalence of and Risk Factors of Renal Artery Stenosis in Patients With Resistant Hypertension

Renal artery stenosis (RAS) is a common cause of secondary hypertension. Renal artery angiography is the gold standard for diagnosing RAS. The aim of this study is to report (1) the prevalence of RAS in patients with resistant hypertension and (2) the association of RAS with peripheral vascular disease (PVD) and diabetes mellitus (DM). We studied 285 consecutive patients (mean age: 72.5 years) with resistant hypertension (systolic blood pressure >140 mm Hg despite administration of at least 3 antihypertensive drugs) who underwent renal artery angiography at Baylor Heart and Vascular Hospital from January 2006 to December 2010. Sixty-nine cases of RAS were identified (incidence: 24.2%). The propensity-adjusted analysis (controlling for clinical and nonclinical risk factors) showed a strong and significant association between RAS and PVD (odds ratio 5.15, 95% confidence interval 2.68 to 9.89, p <0.0001). However, the association between RAS and DM, a previously defined risk factor for RAS, was not significant in this cohort (odds ratio 0.63, 95% confidence interval 0.34 to 1.19, p = 0.16). In conclusion, results from this study define the prevalence of RAS in patients with resistant hypertension. Patients with PVD were found to be 5 times more likely to experience RAS than patients without PVD, whereas DM did not confer any increased risk.

Thrombotic Complications Associated With Early and Late Nonadherence to Dual Antiplatelet Therapy

OBJECTIVES This study sought to assess the frequency and clinical impact of dual antiplatelet therapy (DAPT) nonadherence. BACKGROUND There are limited data on the impact of DAPT nonadherence during the first year after a second-generation drug-eluting stent placement. METHODS After successful Endeavor zotarolimus-eluting stent implantation, 2,265 patients were enrolled in a registry with limited exclusions and monitored during 12 months of prescribed DAPT. Predictors of any nonadherence (ANA) at 6 months were analyzed by multivariable analysis, and the association between ANA at 6 or 12 months with the endpoints of death, myocardial infarction, and stent thrombosis was assessed. RESULTS The study population included 30% female patients, 34% with diabetes and 36% with acute coronary syndromes. ANA occurred in 208 patients (9.6%) before 6 months and 378 patients (18.5%) before 1 year. Major bleeding (odds ratio [OR]: 12.83, 95% confidence interval [CI]: 7.55 to 21.80, p < 0.001) was the only predictor of ANA at 6 months. In time-dependent analyses, ANA before 6 months was associated with an increased risk of death or myocardial infarction (7.6% vs. 3.0%, p < 0.001) and a numerical increase in stent thrombosis (2.0% vs. 0.9%, p = 0.12). After adjustment for baseline differences, ANA within 6 months remained associated with death or MI (OR: 1.95, 95% CI: 1.02 to 3.75). ANA occurring after 6 months did not increase the risk of subsequent ischemic events. CONCLUSIONS DAPT ANA occurs frequently and is associated with increased risk for thrombotic complications if it occurs within the first 6 months. Major bleeding was a significant correlate of DAPT ANA within 6 months. (EDUCATE: The MEDTRONIC Endeavor Drug Eluting Stenting: Understanding Care, Antiplatelet Agents and Thrombotic Events; NCT01069003).

Effect of mechanically expanded vs self-expanding transcatheter aortic valve replacement on mortality and major adverse clinical events in high-risk patients with aortic stenosis: The REPRISE III randomized clinical trial

Importance Transcatheter aortic valve replacement (TAVR) is established for selected patients with severe aortic stenosis. However, limitations such as suboptimal deployment, conduction disturbances, and paravalvular leak occur. Objective To evaluate if a mechanically expanded valve (MEV) is noninferior to an approved self-expanding valve (SEV) in high-risk patients with aortic stenosis undergoing TAVR. Design, Setting, and Participants The REPRISE III trial was conducted in 912 patients with high or extreme risk and severe, symptomatic aortic stenosis at 55 centers in North America, Europe, and Australia between September 22, 2014, and December 24, 2015, with final follow-up on March 8, 2017. Interventions Participants were randomized in a 2:1 ratio to receive either an MEV (n = 607) or an SEV (n = 305). Main Outcomes and Measures The primary safety end point was the 30-day composite of all-cause mortality, stroke, life-threatening or major bleeding, stage 2/3 acute kidney injury, and major vascular complications tested for noninferiority (margin, 10.5%). The primary effectiveness end point was the 1-year composite of all-cause mortality, disabling stroke, and moderate or greater paravalvular leak tested for noninferiority (margin, 9.5%). If noninferiority criteria were met, the secondary end point of 1-year moderate or greater paravalvular leak was tested for superiority in the full analysis data set. Results Among 912 randomized patients (mean age, 82.8 [SD, 7.3] years; 463 [51%] women; predicted risk of mortality, 6.8%), 874 (96%) were evaluable at 1 year. The primary safety composite end point at 30 days occurred in 20.3% of MEV patients and 17.2% of SEV patients (difference, 3.1%; Farrington-Manning 97.5% CI, −∞ to 8.3%; P = .003 for noninferiority). At 1 year, the primary effectiveness composite end point occurred in 15.4% with the MEV and 25.5% with the SEV (difference, −10.1%; Farrington-Manning 97.5% CI, −∞ to −4.4%; P<.001 for noninferiority). The 1-year rates of moderate or severe paravalvular leak were 0.9% for the MEV and 6.8% for the SEV (difference, −6.1%; 95% CI, −9.6% to −2.6%; P < .001). The superiority analysis for primary effectiveness was statistically significant (difference, −10.2%; 95% CI, −16.3% to −4.0%; P < .001). The MEV had higher rates of new pacemaker implants (35.5% vs 19.6%; P < .001) and valve thrombosis (1.5% vs 0%) but lower rates of repeat procedures (0.2% vs 2.0%), valve-in-valve deployments (0% vs 3.7%), and valve malpositioning (0% vs 2.7%). Conclusions and Relevance Among high-risk patients with aortic stenosis, use of the MEV compared with the SEV did not result in inferior outcomes for the primary safety end point or the primary effectiveness end point. These findings suggest that the MEV may be a useful addition for TAVR in high-risk patients. Trial Registration ClinicalTrials.gov Identifier: NCT02202434