PCI

Short Aspirin Therapy Noninferior to DAPT for 1 Year After PCI for ACS

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Stopping aspirin within 1 month of implanting a drug-eluting stent (DES) for acute coronary syndrome (ACS) followed by ticagrelor monotherapy was shown to be noninferior to 12 months of dual antiplatelet therapy (DAPT) in net adverse cardiovascular and bleeding events in the T-PASS trial.

“Less than one month of DAPT followed by ticagrelor monotherapy met a noninferiority threshold and provided evidence of superiority to 12 months of ticagrelor-based DAPT for a 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily due to a significant reduction in bleeding events,” senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Seoul, Korea, told attendees here at the Transcatheter Cardiovascular Therapeutics 2023 congress.

“This study provides evidence that stopping aspirin within 1 month after implantation of drug-eluting stents for ticagrelor monotherapy is a reasonable alternative to 12-month DAPT as for adverse cardiovascular and bleeding events,” Hong concluded.

The study was published in Circulation ahead of print to coincide with the presentation.

Three Months to 1 Month

Previous trials (TICO and TWILIGHT) have shown that ticagrelor monotherapy after 3 months of DAPT can be safe and effectively prevent ischemic events after percutaneous coronary intervention (PCI) in ACS or high-risk PCI patients.

The current study aimed to investigate whether ticagrelor monotherapy after less than 1 month of DAPT was noninferior to 12 months of ticagrelor-based DAPT for preventing adverse cardiovascular and bleeding events in patients with ACS undergoing PCI with a DES implant.

T-PASS, carried out at 24 centers in Korea, enrolled ACS patients aged 19 years or older who received an ultrathin, bioresorbable polymer sirolimus-eluting stent (Orsiro, Biotronik). They were randomized 1:1 to ticagrelor monotherapy after < 1 month of DAPT (n = 1426) or to ticagrelor-based DAPT for 12 months (n = 1424).

The primary outcome measure was net adverse clinical events (NACE) at 12 months, consisting of major bleeding plus major adverse cardiovascular events. All patients were included in the intention-to-treat analysis.

The study could enroll patients aged 19 to 80 years. It excluded anyone with active bleeding, at increased risk for bleeding, with anemia (hemoglobin ≤ 8 g/dL), platelets < 100,000/μL, need for oral anticoagulation therapy, current or potential pregnancy, or a life expectancy less than 1 year.

Baseline characteristics of the two groups were well balanced. The extended monotherapy and DAPT arms had an average age of 61 ± 10 years, were 84% and 83% male and had diabetes mellitus in 30% and 29%, respectively, with 74% of each group admitted via the emergency room. ST-elevation myocardial infarction occurred in 40% and 41% of patients in each group, respectively.

Results showed that stopping aspirin early was noninferior and possibly superior to 12 months of DAPT.

For the 12-month clinical outcome, fewer patients in the < 1-month DAPT followed by ticagrelor monotherapy arm reached the primary clinical endpoint of NACE vs the ticagrelor-based 12-month DAPT arm, both in terms of noninferiority (P < .001) and superiority (P = .002). Similar results were found for the 1-month landmark analyses.

T-PASS: Primary Outcome

Endpoint< 1-Month DAPT Followed by Ticagrelor Monotherapy (Cumulative Incidence, %)Ticagrelor-Based 12-Month DAPT (Cumulative Incidence, %)Hazard Ratio (95% Confidence Interval)P (Noninferiority)P (Superiority)
12-month clinical outcome2.85.20.54 (0.37 – 0.80)< .001.002
1-month landmark analyses2.04.10.48 (0.31 – 0.75)< .001.001

For both the 12-month clinical outcome and the 1-month landmark analyses, the curves for the two arms began to diverge at about 150 days, with the one for ticagrelor monotherapy essentially flattening out just after that and the one for the 12-month DAPT therapy continuing to rise out to the 1-year point.

In the < 1-month DAPT arm, aspirin was stopped at a median of 16 days. Panelist Adnan Kastrati, MD, Deutsches Herzzentrum München, Technische Universität, Munich, Germany, asked Hong about the criteria for the point at which aspirin was stopped in the < 1-month arm.

Hong replied, “Actually, we recommend less than one month, so therefore in some patients, it was the operator’s decision,” depending on risk factors for stopping or continuing aspirin. He said that in some patients it may be reasonable to stop aspirin even in 7 to 10 days. Fewer than 10% of patients in the < 1-month arm continued on aspirin past 30 days, but a few continued on it to the 1-year point.

There was no difference between the < 1-month DAPT followed by ticagrelor monotherapy arm and the 12-month DAPT arm in terms of major adverse cardiac and cerebrovascular events at 1 year (1.8% vs 2.2%, respectively; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.50 – 1.41; log-rank, P = .51).

However, the 12-month DAPT arm showed a significantly greater incidence of major bleeding at 1 year: 3.4% vs 1.2% for < 1-month aspirin arm (HR, 0.35; 95% CI, 0.20 – 0.61; log-rank, P < .001).

Hong said that a limitation of the study was that it was open-label and not placebo-controlled. However, an independent clinical event adjudication committee assessed all clinical outcomes.

Lead discussant Marco Valgimigli, MD, PhD, Cardiocentro Ticino Foundation, Lugano, Switzerland, noted that T-PASS is the fifth study to investigate ticagrelor monotherapy versus a DAPT, giving randomized data on almost 22,000 patients.

“T-PASS showed very consistently with the prior four studies that by dropping aspirin and continuation with ticagrelor therapy compared with the standard DAPT regimen is associated with no penalty…and in fact leading to a very significant and clinically very convincing risk reduction, and I would like to underline major bleeding risk reduction,” he said, pointing out that this study comes from the same research group that carried out the TICO trial.

Routine Functional Testing or Standard Care in High-Risk Patients after PCI

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Abstract

BACKGROUND

There are limited data from randomized trials to guide a specific follow-up surveillance approach after myocardial revascularization. Whether a follow-up strategy that includes routine functional testing improves clinical outcomes among high-risk patients who have undergone percutaneous coronary intervention (PCI) is uncertain.

METHODS

We randomly assigned 1706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI or to standard care alone. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Key secondary outcomes included invasive coronary angiography and repeat revascularization.

RESULTS

The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan–Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan–Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval [CI], 0.61 to 1.35; P=0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, −0.01 to 5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, −0.22 to 4.68).

CONCLUSIONS

Among high-risk patients who had undergone PCI, a follow-up strategy of routine functional testing, as compared with standard care alone, did not improve clinical outcomes at 2 years.

Discussion

In this multicenter, pragmatic, randomized trial of routine functional testing as compared with standard care for guiding follow-up strategies in patients with high-risk anatomical or clinical characteristics who had undergone PCI, we found no significant between-group difference in the primary composite outcome of death, myocardial infarction, or hospitalization for unstable angina at 2 years. The routine stress-testing strategy appeared to be associated with more frequent invasive coronary angiography and repeat revascularization after 1 year, which did not result in a significant reduction in major cardiovascular events or mortality.

Previous observational studies have shown that elective stress testing after either PCI or CABG was common, but the diagnostic yield for subsequent coronary angiography and repeat revascularization was low.5-8,23,24 Although abnormal findings on stress imaging were related to higher risks of death and major cardiac events,25 the use of stress testing was not associated with a reduction in death or myocardial infarction, but it was associated with a higher incidence of repeat revascularization.6,23 The Aggressive Diagnosis of Restenosis (ADORE) I and II trials assessed the effect of stress testing after PCI,10,11 and the results showed that routine functional testing was associated with improved exercise endurance without significant differences in clinical outcomes. Unfortunately, these trials are not relevant to current practice because they were conducted when PCI was performed with bare-metal stents or with early-generation drug-eluting stents, and the trials were considerably underpowered (348 patients in the ADORE-I trial and 84 patients in the ADORE-II trial). In our large-scale, randomized trial involving high-risk patients who had undergone PCI, we found that routine functional testing, as compared with standard care, did not reduce the incidence of the primary or key secondary outcomes. In this clinical context, this trial can provide reliable evidence regarding the prognostic role of active surveillance with routine functional testing and offer definitive insights regarding the most appropriate follow-up strategy in high-risk patients who undergo PCI.

The key findings of the POST-PCI trial should be interpreted in the context of the results of the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA).26 The ISCHEMIA trial showed that an initial invasive strategy, as compared with an initial conservative strategy, did not reduce the risk of ischemic cardiovascular events or death among patients with stable coronary artery disease and moderate-to-severe ischemia on stress testing. Both the ISCHEMIA and POST-PCI trials show the benefits of a “less is more” concept (i.e., if more invasive strategies or testing are performed less frequently, it will result in better patient outcomes). Although the characteristics of the patients in both trials were quite different, a more invasive therapeutic approach (in the ISCHEMIA trial) as well as a more aggressive follow-up approach (in the POST-PCI trial) did not provide an additional treatment effect beyond a conservative strategy on the basis of guideline-directed medical therapy.

Although the sample size was determined on the basis of data from a previous pragmatic trial,21 the observed number of primary-outcome events was lower than expected. This discrepancy might be explained in part by differences between clinical or lesion characteristics, interventional practice, or race or ethnic group. Also, it may be due to advances in PCI methods and improvements in cardiovascular care over the past decade, which include improved stent technology, more effective periprocedural and adjunctive pharmacologic treatment after stenting, and high levels of adherence to recommended medical therapy. These explanations are congruent with a recent trial that used contemporary PCI devices.27 Strategy trials have also shown lower-than-expected event rates.26,28 In addition, an increased use of intravascular imaging (in 74% of patients) and fractional flow reserve (in 36% of patients) during PCI might have reduced the incidence of major cardiovascular events.29,30 Nevertheless, an extremely large study sample (>90,000 patients) would be required to detect a clinically relevant difference in the primary outcome (details are provided in Section I in the Supplementary Appendix).

Several limitations of the trial should be considered. First, it was not possible to mask the follow-up strategy from the patients and investigators, and the possibility of ascertainment bias cannot be excluded. Second, a 30% relative lower risk of a primary-outcome event with active surveillance with stress testing than with standard care may be too ambitious with contemporary medical therapy. However, given that referent data were scant at the time the trial was designed, the relative effect size was determined on the basis of previous available trials with a similar concept or design.28,31 Third, some nonadherence of stress testing in the functional-testing group was observed owing to several medical reasons; this could be interpreted in the context of the pragmatic trial design and enhances its generalizability to real-world settings. Fourth, routine stress testing included three different types of methods with diagnostic accuracy varying across the tests. Therefore, applying these different tests might result in inconsistent judgment of a patient’s ischemic burden and affect clinical responses. Fifth, our trial did not address quality of life, cost-effectiveness, or radiation exposure, which could be crucial components of decision making and warrants further investigation. Finally, women were underrepresented in the trial, and the direct application of trial findings to “all-comer” populations of patients who have undergone PCI may be limited (Table S6).

In this trial involving high-risk patients who had undergone PCI, routine functional testing, as compared with standard care, did not result in a lower risk of ischemic cardiovascular events or death from any cause at 2 years.

SOURCE: NEJM

Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction

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bstract

BACKGROUND

Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.

METHODS

We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores.

RESULTS

A total of 700 patients underwent randomization — 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P=0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, −1.6 percentage points; 95% CI, −3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, −1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months.

CONCLUSIONS

Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure.

Discussion

We performed a randomized comparison of the efficacy and safety of a strategy of PCI plus optimal medical therapy, as compared with strategy of optimal medical therapy alone, among patients with severe left ventricular systolic dysfunction, extensive coronary artery disease, and demonstrable viable myocardium. The incidence of death from any cause or hospitalization for heart failure (the primary outcome) did not differ significantly between the trial groups. An apparent early benefit of PCI was observed with respect to quality of life, but the between-group difference diminished over time owing to the progressive improvement in scores in the optimal-medical-therapy group. Cardiac function appeared to improve in both groups over the course of follow-up, but this change was not affected by the trial-group assignment.

With the stipulation of a minimum number of dysfunctional segments that were viable and amenable to revascularization, our trial was designed to enroll an enriched cohort of patients who were most likely to show reverse remodeling after revascularization. However, PCI failed to produce recovery of global left ventricular function that was incremental to the improvement with optimal medical therapy alone. These findings challenge the paradigm of myocardial hibernation, which is classically defined according to improvement in left ventricular volumes and function after revascularization. Our observations mirror those in the STICH trial, in which revascularization by CABG did not affect left ventricular function, a finding that was consistent across the whole trial cohort, including the subgroup who underwent discretionary viability testing.16 We have not yet determined the concordance between the coronary arteries revascularized by PCI and the viable myocardial segments; hence, we cannot determine whether viability tests predict changes in segmental contractile function after medical therapy or revascularization or whether such changes are linked to clinical outcomes.17

In our trial, the incidences of death from any cause and the composite of death or hospitalization for heart failure were similar to the annualized rates observed in the medical-therapy groups of STICH and contemporary trials involving patients with left ventricular systolic dysfunction (Fig. S9), despite enrollment of a population with a more adverse risk profile. We enrolled older patients (mean age, 70 years) with a greater burden of coronary disease and included patients with left main coronary disease, a group that has traditionally been excluded from trials of revascularization as compared with medical therapy.18,19 The percentage of patients with ICD or cardiac resynchronization devices in our trial may be one reason why the clinical outcomes were similar despite higher baseline risk, and the serial improvement in left ventricular systolic function and reduction in NT-proBNP concentrations in both groups in our trial are objective markers of effective medical and device therapy.

Although the differences in the baseline characteristics of the patients enrolled in the STICH and REVIVED trials hamper direct comparison, the beneficial effect of CABG observed in the STICH trial was not seen with PCI in our trial.3 Incomplete revascularization by PCI has historically been a confounder in comparisons between PCI and CABG among patients with stable coronary disease.20 This factor is unlikely to be a consideration in the REVIVED trial, because the median percentage of completeness of revascularization was 71% in the PCI group, as measured by a coronary anatomical index, and the percentage of functional completeness of revascularization would be even higher, given that the protocol recommended revascularization for only coronary disease subtending viable myocardium.

Our trial has some limitations. First, we cannot rule out the possibility that the open-label design affected patient-reported outcomes. Any effect on the primary outcome was mitigated by ensuring that all hospitalizations for heart failure were adjudicated in a blinded fashion by an independent events committee, and the determination of death was robust to such bias; the left ventricular ejection fraction was assessed in a blinded fashion at the core laboratory. Second, most patients had little or no angina at enrollment, so the findings cannot be extrapolated to patients with angina that limits their quality of life or patients presenting with acute coronary syndromes. Third, there were 37 fewer primary-outcome events than what we estimated for the trial to have at least 85% power to address the primary hypothesis. Although this lower number of events had some effect on the prospective statistical power (263 events would provide the trial with 82% power if the other variables in our power calculation remained constant), the hazard ratio of 0.99 and the 95% confidence intervals observed with respect to the primary outcome suggest that the risk of a type II error was low.

In our trial involving patients with severe left ventricular systolic dysfunction, extensive coronary disease, and dysfunctional but viable myocardium who received optimal medical therapy, the addition of revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure, incremental improvement in the left ventricular ejection fraction, or a sustained difference in quality of life at a median of 3.4 years.

SOURCE: NEJM

That “Bump” in Creatinine Post-PCI Might “Bump Off” Your Patient: Can We Prevent This?∗

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Introduction

Acute kidney injury complicates about 10% to 15% of percutaneous coronary interventions (PCIs). Although some cases are caused by renal hypoperfusion in the setting of shock or heart failure, injury from nephrotoxic drugs, or cholesterol embolism, the great majority are caused by a direct toxic effect of contrast media. The mechanisms leading to contrast-associated acute kidney injury (CA-AKI) have been reviewed.1,2 Numerous studies have identified the risk factors for CA-AKI including dehydration, advanced age, hemodynamic compromise at the time of PCI, contrast dose, and most importantly, pre-existing chronic kidney disease (CKD).2

There remains controversy regarding the consequences of CA-AKI, especially with small and transient rises in creatinine post-PCI. Many consider these creatinine “bumps” benign. Although it is true that, in most cases, renal function returns to baseline, and the progression to dialysis rare (<0.5%), Maioli et al3 showed that about 20% of patients with baseline CKD who develop CA-AKI have persistent renal dysfunction. Importantly, persistent renal dysfunction was associated with higher mortality at 5 years compared with those without or with transient CA-AKI. Additional studies have related CA-AKI to higher mortality and cardiac events.4,5 However, there is nuance to this. For example, Guillon et al5 found a 2-fold increase in 6-month mortality for patients with CA-AKI defined as an absolute increase over baseline creatinine >0.3 mg/dL, but not for patients with lesser degrees of CA-AKI (creatinine >25% over baseline, but not exceeding 0.5 mg/dL absolute increase). The mechanism(s) leading to these deaths and cardiac events are unclear. It has been suggested that CA-AKI may simply be a marker and not a cause of adverse events. This notion is supported by the observation that CA-AKI was not an independent predictor of mortality or myocardial infarction (MI) after adjustment for cofounding variables.6

In this issue of JACC: Cardiovascular Interventions, Mohebi et al7 used data from the ADAPT-DES trial (Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents), to investigate the determinants and outcomes of patients with CA-AKI. They included 7,412 patients with creatinine measured before and within 3 days after PCI, and defined CA-AKI as an absolute increase in creatinine >0.5 mg/dL or 25% increase over baseline. They created 4 subgroups based on the presence or absence of pre-existing CKD and the presence or absence of CA-AKI; a fifth group of 125 patients were on dialysis at entry. The rate of AKI was 6.5%, and most of these were small “bumps” in creatinine, with the median change in creatinine of only 0.3 mg/dL. Similar to other studies, multivariate analysis confirmed that patients developing CA-AKI were older, sicker, and more likely to be female, and have diabetes and pre-existing CKD. Several procedural variables were associated with CA-AKI including use of intra-aortic balloon pump, hypotension at the time of PCI, PCI for ST-segment elevation MI, radial access, and greater number of stents (a surrogate for contrast volume). At 2 years, CA-AKI was associated with a 2-fold increase in cardiac death and an increased risk of MI, stent thrombosis, and bleeding. The highest risk of death, MI, stent thrombosis, and bleeding occurred in the subgroup of patients with baseline CKD who developed CA-AKI.

The study is important because it reflects the contemporary practice of PCI in a large cohort and establishes the current risk factors for development of CA-AKI. The study clearly demonstrates higher rates of adverse events, including death, even with small “bumps” in creatinine. The study leaves several important questions unanswered. I would like to know the relationship between contrast volume and development of CA-AKI and staged versus “ad hoc” PCI. Importantly, I would like to know what happened to the patients’ renal function over time (persistent or transient?) and how that related to outcomes. This study does not inform us as to why CA-AKI is associated with worse outcomes. Although the investigators provide plausible explanations, including progression to end-stage renal disease, acceleration of atherosclerosis, and higher bleeding risk, these are hypothesis-generating, and in fact, we do not know whether the increased rate of death and cardiac events is caused by CA-AKI or is a marker of patients at increased risk. Future studies are needed to answer these questions.

Assuming that CA-AKI is the cause and not a marker of increased mortality, what, then, can we do to prevent CA-AKI? Many therapies have been proposed, and nearly all of them fail when tested in rigorous, randomized controlled trials, except for high-dose statins, but this is of limited additional efficacy because most patients undergoing PCI are already on statins.2 The 2 methods that consistently reduce risk of CA-AKI are hydration and limiting contrast volume. However, even hydration has been questioned since 1 randomized controlled trial showed no benefit over routine practices.8 It seems then that the primary focus to prevent CA-AKI should be on reducing contrast exposure.

We overuse contrast. In patients at high risk for CA-AKI, there are numerous steps that can reduce contrast dose. These have been elegantly described elsewhere.9-11 Many of these steps are simple. Avoid “ad hoc” PCI and patiently allow adequate time between contrast exposures when staging PCI. Carefully review prior images to identify fluoroscopic landmarks such as vessel calcification or prior stents that can be useful as a roadmap. Learn to engage coronaries without injecting contrast. Avoid guide catheters with side holes and consider subselection with a guide catheter extender. When injections are needed, use no more than 1 to 2 mL, and record the image on cineangiography at a high frame rate. Use a biplane system if available. Incorporate intravascular ultrasound before PCI to map out the artery, and plan the procedure and use it to assess the results after PCI instead of angiography; this can greatly limit contrast.12 Clever devices to prevent overinjection of contrast, augment urinary flow rates, or extract contrast from the coronary sinus are interesting, but their routine role is unclear at present.11

Does radial access reduce CA-AKI? Prior studies have suggested lower risk with radial as compared with femoral access, but the present investigation found otherwise. What is the dose limit for patients at high risk? Similar to radiation use, our goal should be to use “as low as reasonably achievable.” Several dosing algorithms have been proposed. A large study13 found a <2% rate of CA-AKI and <0.1% rate of need for dialysis if the contrast dose to calculated creatine clearance ratio was <2; ideally, we can achieve a ratio of <1 with the miserly use of contrast.9-11

In conclusion, future studies are needed to define whether CA-AKI is a cause or marker of worse outcomes, and we need to understand the mechanisms of these adverse events. In the meantime, we can do a better job at reducing high-risk patients’ exposure to contrast in order to reduce creatinine “bumps” post-PCI and avoid “bumping off” our patients.

Long-Term Clinical Impact of Contrast-Associated Acute Kidney Injury Following PCI: An ADAPT-DES Substudy

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Abstract

Objectives

This study sought to determine correlates and consequences of contrast-associated acute kidney injury (CA-AKI) on clinical outcomes in patients with or without pre-existing chronic kidney disease (CKD).

Background

The incidence and impact of CA-AKI on clinical outcomes during contemporary percutaneous coronary intervention (PCI) are not fully defined.

Methods

The ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study was a prospective, multicenter registry of 8,582 patients treated with ≥1 drug-eluting stent(s). CA-AKI was defined as a post-PCI increase in serum creatinine of >0.5 mg/dL or a relative increase of ≥25% compared with pre-PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. The primary endpoint was the 2-year rate of net adverse clinical events (NACE): All-cause mortality, myocardial infarction (MI), definite or probable stent thrombosis, or major bleeding.

Results

Of 7287 (85%) patients with evaluable data, 476 (6.5%) developed CA-AKI. In a multivariable model, older age, female sex, Caucasian race, congestive heart failure, diabetes, hypertension, CKD, presentation with ST-segment elevation MI, Killip class II to IV, radial access, intra-aortic balloon pump use, hypotension, and number of stents were independent predictors of CA-AKI. The 2-year NACE rate was higher in patients with CA-AKI (adjusted hazard ratio [HR]: 1.88; 95% CI: 1.42-2.49), as was each component of NACE (all-cause mortality, HR: 1.77; 95% CI: 1.22-2.55; MI, HR: 1.67; 95% CI: 1.18-2.36; definite/probable stent thrombosis, HR: 1.71; 95% CI: 1.10-2.65; and major bleeding, HR: 1.38; 95% CI: 1.06-1.80). Compared with the CA-AKI–/CKD– group, the CA-AKI+/CKD– (HR: 1.83; 95% CI: 1.33-2.52), CA-AKI–/CKD+ (HR: 1.56; 95% CI: 1.15-2.13), CA-AKI+/CKD+ (HR: 3.29; 95% CI: 1.92-5.67), and maintenance dialysis (HR: 2.67; 95% CI: 1.65-4.31) groups were at higher risk of NACE.

Conclusions

CA-AKI was relatively common after contemporary PCI and was associated with increased 2-year rates of NACE. Patients with pre-existing CKD were at particularly high risk for NACE after CA-AKI.

PERCUTANEOUS CORONARY INTERVENTION (PCI): A THERAPEUTIC MYTH?

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Professor of Cardiovascular Science, Cardiovascular and Cell Sciences Research Institute,St George’s, University of London, UK

PCI IN PATIENTS WITH STABLE ISCHAEMIC HEART DISEASE – A THERAPEUTIC MYTH?

Contrary to expectations, large randomised studies have demonstrated percutaneous coronary intervention (PCI) not to reduce mortality or the incidence of acute myocardial infarctions in patients with stable coronary artery disease. Symptom relief is therefore considered to be the primary goal of PCI in patients with chronic stable angina. Very recently, however, the ORBITA study, a double blind multicentre randomised trial of PCI versus a placebo procedure for angina relief carried out in the UK and published in The Lancet, (1) showed that in patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time significantly compared with a placebo procedure.

ORBITA enrolled patients with ≥70% single-vessel coronary artery stenosis who received 6 weeks of medication optimisation followed by pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires and stress echocardiography. Patients were randomised to undergo PCI or a placebo procedure.  After 6 weeks of follow-up, the assessments carried out before randomisation were repeated at the final assessment. The authors assessed the difference in exercise time increment between groups.

230 patients with ischaemic symptoms were included in the study with 200 patients randomised as follows: 105 patients were assigned to PCI and 95 assigned to placebo procedure. Mean area coronary stenosis was 84·4% (SD 10·2), fractional flow reserve 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22).

The main result of the study, as reported by the authors, was that “no significant difference was observed in the primary endpoint of exercise time increment. There were no deaths and serious adverse events included the following:  pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group”.

The results of this study may change practice in relation to management of chronic stable angina. Contrary to current belief, jointly shared by Interventional cardiologists and patients with stable angina alike (12), PCI does not appear to be better than a placebo intervention for the management of symptomatic patients with stable angina. As discussed in the manuscript (1), “in the absence of blinding, the effect size of PCI on symptomatic endpoints can be overestimated because of the addition of the placebo effect to the true physiological effect of intervention”.14 It is worth noting that as indicated by the authors, “in all previous trials, both investigators and patients were aware of the treatment allocation” and this could have markedly affected the results.

Findings in the ORBITA study, particularly if further confirmed by larger studies, will have major implications for the future of coronary intervention worldwide. Comments from the interventional community regarding the ORBITA study findings are eagerly awaited.

References

  1. Al-Lamee R et al. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. Lancet 2018; 391: 31–40
  2. Kaptchuk TJ, Goldman P, Stone DA, Stason WB. Do medical devices have enhanced placebo effects? J Clin Epidemiol 2000; 53: 786−92
  3. Rothberg MB, Sivalingam SK, Kleppel R, Schweiger M, Hu B, Sepucha KR. Informed decision making for percutaneous coronary intervention for stable coronary disease. JAMA Intern Med 2015; 175: 1199−206.
  4. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995; 273: 408−12.

Longer Infusion Gives Bivalirudin the Upper Hand in PCI

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Continued bivalirudin (Angiomax) infusion after primary percutaneous coronary intervention (PCI) may overcome its disadvantage in acute stent thrombosis rates compared with heparin while keeping the lower bleeding risk, according to a meta-analysis.

Bivalirudin use during PCI was tied to a doubling of acute stent thrombosis cases compared with heparin (risk ratio [RR] 2.36, 95% CI 1.46-3.02), found Rahman Shah, MD, of the University of Tennessee School of Medicine in Memphis, and colleagues.

 However, continuing with a full bivalirudin dose for 3 to 4 hours after PCI negated this effect (RR 0.90, 95% CI 0.32-2.54), the investigators reported online in JACC: Cardiovascular Interventions. There was no difference in acute stent thrombosis rates between patients who got heparin and full-dose bivalirudin in mixed-treatment models (odds ratio 0.97, 95% CI 0.36-2.21).

Post-procedural infusion of a low dose of bivalirudin failed to ameliorate the stent thrombosis disadvantage of the antithrombotic (RR 3.61, 95% CI 1.17-11.13).

At 30 days post-PCI, bivalirudin recipients had 47% lower odds of major bleedingcompared with their heparin counterparts. Those who got full-dose bivalirudin infusions were also less likely to have major bleeding (RR 0.29, 95% CI 0.16-0.53).

“While bivalirudin is associated with a greater risk of acute stent thrombosis than heparin post-primary PCI, this limitation may be mitigated by continuing full-dose bivalirudin (not reduced-dose bivalirudin) 3 to 4 hours postoperatively. The decrease in bleeding risk with bivalirudin compared to heparin is not compromised by this strategy,” Shah’s group concluded.

Marco Valgimigli, MD, PhD, and Giuseppe Gargiulo, MD, both of Bern University Hospital in Switzerland, called the results “potentially practice changing” and consistent with recommendations for bivalirudin in the U.S.

In an accompanying editorial, they recommended caution when interpreting the findings, however, due to the meta-analysis’ nonrandomized and unadjusted nature.

Shah’s investigation included five randomized controlled trials and 16,294 patients withacute coronary syndrome who underwent primary PCI.

Radial Access Safer in Ad Hoc PCI

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Randomized trial shows similar efficacy, less bleeding

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Transradial access was as good as going through the groin for outcomes in ad hoc percutaneous coronary intervention reflecting real-world practice, and modestly reduced bleeding, a randomized trial from China showed.

The primary endpoint of major adverse cardiac or cerebrovascular event (MACCE)-free rate at 12 months came out 95.8% for radial compared to 95.5% for femoral access, which easily met the non-inferiority criterion (P≤0.001), Shigeru Saito, MD, of Shonan Kamakura General Hospital in Kanagawa, Japan, and colleagues found.

Transradial access came out superior for the secondary endpoint of freedom from major bleeding complications by the BARC DefinitionType 3 or 5 at one week (99.9% versus 99.0%,P<0.001 for superiority), Saito reported here at the opening late-breaking clinical trial session of theTranscatheter Cardiovascular Therapeutics meeting.

While the finding of less bleeding was not surprising, it was definitive, Saito suggested.

“After this result, everybody must follow the transradial approach as a first approach,” he told reporters at a press conference.

The DRAGON (Determination of the Radial versus Groin Coronary Angioplasty) trial included 2,042 patients getting ad hoc PCI at 25 hospitals in China randomized 2:1 to transradial versus transfemoral access.

In China, transradial accounts for about 95% of procedures, noted Run-Lin Gao, MD, of China’s National Center for Cardiovascular Diseases, who commented at the press conference.

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So the findings might represent a best-case scenario of experienced radial operators, added press conference moderator and TCT co-director Roxana Mehran, MD, of Mount Sinai Hospital in New York City. While U.S. practice is increasingly moving toward radial access, it has still only reached about a quarter of procedures, she noted.

Still, Saito suggested that the findings could be “applied very easily to the U.S.,” despite differences between the two populations in things like body mass index.

Even in complex cases, there’s no reason not to take a transradial-first approach, agreedMarie-Claude Morice, MD, of Institut Cardiovasculaire Paris Sud in Massy, France.

Daniel I. Simon, MD, of University Hospitals’ Case Medical Center in Cleveland, Ohio, was a little more circumspect.

“There are two sort of diverging paths here,” he said at the press conference. “One is that interventions are getting more complex and… one of the things I’d hate to see is our trainees and fellows lose the techniques that you need from transfemoral catheterization to do some cases. Certainly the femoral will still be required for some procedures, but it certainly seems that you could make a very strong case in ST-segment elevation MI that this [transradial access] really should be the standard. That’s where I think the data is the most robust.”

FDA Approves Kengreal for Prevention in PCI

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Indication for thrombotic risk reduction given after initial setbacks

The FDA granted the antiplatelet agent cangrelor (Kengreal) approval for prevention of thrombotic events in adults getting percutaneous coronary intervention (PCI) without use of other antiplatelet agents.

The label specified use “as an adjunct to PCI for reducing the risk of periprocedural myocardial infarction, repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.”

That was a slight deviation from what the FDA advisory panel voted in favor of, which was use when “an oral P2Y12 platelet inhibitor prior to PCI is not feasible and when glycoprotein IIb/IIIa receptor antagonists are not anticipated to be used.”

The panel had expressed concern that approval of cangrelor as an alternative to preloading clopidogrel (Plavix) would further drive ad hoc PCI as a matter of convenience.

The drug had initially been turned down for a broad indication in prevention of thrombotic events associated with coronary stenting and for bridging patients whose existing antiplatelet regimen must be interrupted for surgery.

The second panel also had reservations about the single positive trial upon which approval could be based, the CHAMPION PHOENIX trial in which cangrelor reduced post-procedural cardiovascular events by 22% compared with clopidogrel (Plavix).

The FDA noted bleeding as the most serious risk with the drug, as with all antiplatelet agents. In the trial, serious bleeding was more common with cangrelor than clopidogrel, with rates of about one in 170 versus one in 275 patients.

The number needed to treat with cangrelor was 156 to prevent one MI, stent thrombosis, or revascularization. The number needed to harm was 461 to cause one additional GUSTO severe or moderate bleed or 198 to cause one additional TIMI major or minor bleed.

Drugmaker The Medicines Company said it expected cangrelor to be available for the U.S. market in July.

FDA Favorably Views Cangrelor in PCI for CAD Patients Ahead of Panel Meeting

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The injectable antiplatelet agent cangrelor (the Medicines Company, Parsippany, NJ) may be one step closer to approval for use as an adjunct to PCI for reducing thrombotic events in patients with CAD, should the panel vote in concert with the briefing documents released today by the Cardiovascular and Renal Drugs Advisory Committee of the US Food and Drug Administration (FDA)[1]

Although official vote by the committee won’t come until the end of Wednesday, FDA reviewers are recommending that cangrelor be approved “in patients in whom treatment with an oral P2Y12 platelet inhibitor prior to PCI is not feasible and when glycoprotein IIb/IIIa–receptor antagonists are not anticipated to be used.” This is in contrast to last year’s vote.
In February 2014, the advisory committee voted 7 to 2 that cangrelor should not be approved because the risk/benefit profile was not sufficient enough. In addition, although the large CHAMPION-PHOENIX trial showed positive results, the previous CHAMPION-PLATFORM and CHAMPION-PCI trials were negative and weighed into the decision making of some of the panel members.

After requesting and receiving further sensitivity analyses and a more simplified application letter, the reviewers now state that PHOENIX is sufficient enough as a stand-alone trial to warrant approval.

“The benefit of cangrelor compared with clopidogrel is small, but the risk is smaller,” write the reviewers. “Treating 171 patients prevents one clinically meaningful periprocedural MI. In comparison, treating 1106 patients causes one GUSTO severe bleed, a safety factor of ~6.5-fold. Using a less severe bleed to assess benefit risk, such as a GUSTO moderate or TIMI minor bleed, still favors the use of cangrelor.”
Last year, the advisory committee also recommended unanimously that cangrelor not be approved as a “bridging” therapy for patients with stents who stop oral P2Y12 inhibitors because of surgery. The Medicines Company is no longer seeking to market the medication for that indication.