Harold L. Dauerman

Twelve or 30 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents

BACKGROUND Dual antiplatelet therapy is recommended after coronary stenting to prevent thrombotic complications, yet the benefits and risks of treatment beyond 1 year are uncertain. METHODS Patients were enrolled after they had undergone a coronary stent procedure in which a drug-eluting stent was placed. After 12 months of treatment with a thienopyridine drug (clopidogrel or prasugrel) and aspirin, patients were randomly assigned to continue receiving thienopyridine treatment or to receive placebo for another 18 months; all patients continued receiving aspirin. The coprimary efficacy end points were stent thrombosis and major adverse cardiovascular and cerebrovascular events (a composite of death, myocardial infarction, or stroke) during the period from 12 to 30 months. The primary safety end point was moderate or severe bleeding. RESULTS A total of 9961 patients were randomly assigned to continue thienopyridine treatment or to receive placebo. Continued treatment with thienopyridine, as compared with placebo, reduced the rates of stent thrombosis (0.4% vs. 1.4%; hazard ratio, 0.29 [95% confidence interval {CI}, 0.17 to 0.48]; P<0.001) and major adverse cardiovascular and cerebrovascular events (4.3% vs. 5.9%; hazard ratio, 0.71 [95% CI, 0.59 to 0.85]; P<0.001). The rate of myocardial infarction was lower with thienopyridine treatment than with placebo (2.1% vs. 4.1%; hazard ratio, 0.47; P<0.001). The rate of death from any cause was 2.0% in the group that continued thienopyridine therapy and 1.5% in the placebo group (hazard ratio, 1.36 [95% CI, 1.00 to 1.85]; P=0.05). The rate of moderate or severe bleeding was increased with continued thienopyridine treatment (2.5% vs. 1.6%, P=0.001). An elevated risk of stent thrombosis and myocardial infarction was observed in both groups during the 3 months after discontinuation of thienopyridine treatment. CONCLUSIONS Dual antiplatelet therapy beyond 1 year after placement of a drug-eluting stent, as compared with aspirin therapy alone, significantly reduced the risks of stent thrombosis and major adverse cardiovascular and cerebrovascular events but was associated with an increased risk of bleeding. (Funded by a consortium of eight device and drug manufacturers and others; DAPT ClinicalTrials.gov number, NCT00977938.).

Platelet functions beyond hemostasis

Summary.  Although their central role is in the prevention of bleeding, platelets probably contribute to diverse processes that extend beyond hemostasis and thrombosis. For example, platelets can recruit leukocytes and progenitor cells to sites of vascular injury and inflammation; they release proinflammatory and anti‐inflammatory and angiogenic factors and microparticles into the circulation; and they spur thrombin generation. Data from animal models suggest that these functions may contribute to atherosclerosis, sepsis, hepatitis, vascular restenosis, acute lung injury, and transplant rejection. This article represents an integrated summary of presentations given at the Fourth Annual Platelet Colloquium in January 2009. The process of and factors mediating platelet–platelet and platelet–leukocyte interactions in inflammatory and immune responses are discussed, with the roles of P‐selectin, chemokines and Src family kinases being highlighted. Also discussed are specific disorders characterized by local or systemic platelet activation, including coronary artery restenosis after percutaneous intervention, alloantibody‐mediated transplant rejection, wound healing, and heparin‐induced thrombocytopenia.

In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography.

OBJECTIVES The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT). BACKGROUND Plaque erosion and calcified nodule have not been systematically investigated in vivo. METHODS A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. RESULTS The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 μm vs. 60.4 ± 16.6 μm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). CONCLUSIONS Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non-ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Vascular closure devices: the second decade.

Vascular closure devices (VCDs) introduce a novel means for improving patient comfort and accelerating ambulation after invasive cardiovascular procedures performed via femoral arterial access. Vascular closure devices have provided simple, rapid, and reliable hemostasis in a variety of clinical settings. Despite more than a decade of development, however, VCD utilization has neither been routine in the U.S. nor around the world. Their limited adoption reflects concerns of higher costs for cardiac procedures and a lack of data confirming a significant reduction in vascular complications compared with manual compression. Recent data, however, suggest that VCD are improving, complication rates associated with their use may be decreasing, and their utilization may improve the process of care after femoral artery access. Challenges in the second decade of VCD experience will include performing definitive randomized trials, evaluating outcomes in higher-risk patients, and developing more ideal closure devices.

Comparing long-term survival of patients with multivessel coronary disease after CABG or PCI: Analysis of BARI-like patients in Northern New England

Background—Randomized trials comparing coronary artery bypass graft surgery (CABG) with percutaneous coronary interventions (PCIs) for patients with multivessel coronary disease (MVD) report similar long-term survival for CABG and PCI. These studies used a highly selected population of patients and providers, and their results may not be generalizable to actual care. Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice. Methods and Results—From our northern New England registries of consecutive coronary revascularizations, we identified 10 198 CABG and 4295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001. Vital status was obtained by linkage to the National Death Index. Proportional-hazards regression was used to calculate hazard ratios (HRs) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics. CABG patients were older; had more comorbidities, more 3-vessel disease, and lower ejection fractions; and were more completely revascularized. Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI (HR, 0.60; P<0.01) but not for patients with 2-vessel disease (HR, 0.98; P=0.77). The survival advantage of CABG for 3-vessel disease patients was present in all patient populations, including women, diabetics, and the elderly and in the era of high stent utilization. Conclusions—In contemporary practice, survival for patients with 3-vessel coronary disease is better after CABG than PCI, an observation that patients and physicians should carefully consider when deciding on a revascularization strategy.

Contrast-Induced Acute Kidney Injury

Case Presentation : A 63-year-old man with prior mitral valve repair, hyperlipidemia, hypertension, and mild chronic renal insufficiency (creatinine 1 year earlier, 1.2 mg/dL) presents to the emergency department with progressive dyspnea on exertion and new anterior T-wave inversions. Subsequent laboratory testing confirms a myocardial infarction (troponin I, 11.0 ng/mL) and worsening renal insufficiency in the setting of recently being started on chlorthalidone for hypertension (creatinine, 2.7 mg/dL). Diuretics are discontinued; intravenous fluids are infused; and therapy for an acute coronary syndrome, including aspirin, clopidogrel, nitrates, and intravenous unfractionated heparin, is initiated. After 48 hours, creatinine improves to 1.8 mg/dL (estimated glomerular filtration rate, 46 mL/min), and the patient undergoes cardiac catheterization with iopamidol (Isovue, Bracco Diagnostics Inc, Princeton, NJ) contrast after receiving 1 hour of prophylactic sodium bicarbonate infusion. A complex bifurcation lesion of the left anterior descending artery/first diagonal branch is identified (Figure 1A). What is this patients risk of contrast-induced acute kidney injury (CI-AKI), and which measures may modify that risk significantly? This Clinician Update reviews the recent literature on the acute kidney injury that follows the administration of iodinated contrast medium. Figure 1. A, A complex culprit lesion in the left anterior descending artery (LAD) and first diagonal branch (D1). B, After 250 cm3 iopamidol contrast dye, successful drug-eluting stent placement in the LAD-D1 bifurcation lesion. Patients at risk for CI-AKI have comorbidities that will exacerbate the primary pathogenesis of the injury: contrast-induced vasoconstriction leading to diminished blood flow to the renal medulla. These comorbidities include diabetes mellitus, congestive heart failure, acute hypotension (requiring pressors or intra-aortic balloon pump), ST-elevation myocardial infarction, and volume depletion. Patients with chronic kidney disease are also at risk for contrast-induced acute kidney injury because compensatory mechanisms to maintain filtration function are diminished, and a smaller number of nephrons must excrete …

Bleeding avoidance strategies. Consensus and controversy.

Bleeding complications after coronary intervention are associated with prolonged hospitalization, increased hospital costs, patient dissatisfaction, morbidity, and 1-year mortality. Bleeding avoidance strategies is a term incorporating multiple modalities that aim to reduce bleeding and vascular complications after cardiovascular catheterization. Recent improvements in the rates of bleeding complications after invasive cardiovascular procedures suggest that the clinical community has successfully embraced specific strategies and improved patient care in this area. There remains controversy regarding the efficacy, safety, and/or practicality of 3 key bleeding avoidance strategies for cardiac catheterization and coronary intervention: procedural (radial artery approach, safezone arteriotomy), pharmacological (multiple agents), and technological (vascular closure devices) approaches to improved access. In this paper, we address areas of consensus with respect to selected modalities in order to define the role of each strategy in current practice. Furthermore, we focus on areas of controversy for selected modalities in order to define key areas warranting cautious clinical approaches and the need for future randomized clinical trials in this area.

Clinical study: myocardial infarctionTwenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term case fatality rates from initial q-wave and non-q-wave myocardial infarction: a multi-hospital, community-wide perspective☆

OBJECTIVES The goal of this study was to examine long-term trends in the incidence, in-hospital and long-term mortality patterns in patients with an initial non-Q-wave myocardial infarction (NQWMI) as compared with those with an initial Q-wave myocardial infarction (QWMI). BACKGROUND Limited data are available describing trends in the incidence and mortality from an initial QWMI and NQWMI from a multi-hospital community-wide perspective. METHODS Our study was an observational study of 5,832 metropolitan Worcester, Massachusetts residents (1990 census = 437,000) hospitalized with validated initial acute MI in all greater Worcester hospitals during 11 annual periods between 1975 and 1997. RESULTS The incidence of QWMI progressively decreased between 1975/78 (incidence rate = 171/100,000 population) and 1997 (101/100,000 population). In contrast, the incidence of NQWMI progressively increased between 1975/78 (62/100,000 population) and 1997 (131/100,000 population). Hospital death rates were 19.5% for patients with QWMI and 12.5% for those with NQWMI. After controlling for various covariates, patients with QWMI remained at significantly increased risk for hospital mortality (adjusted odds ratio = 1.63; 95% confidence interval: 1.35, 1.97). While the hospital mortality of QWMI has progressively declined over time (1975/78 = 24%; 1997 = 14%), the in-hospital mortality for NQWMI has remained the same (1975/78 = 12%; 1997 = 12%). These trends remained after adjusting for potentially confounding prognostic factors. The multivariable adjusted two-year mortality after hospital discharge declined over time for patients with QWMI and NQWMI. CONCLUSIONS Despite impressive declines in the incidence, in-hospital and long-term mortality associated with QWMI, NQWMI is increasing in frequency and has the same in-hospital mortality now as it did 22 years ago.

State-of-the-Art PaperVascular Closure Devices: The Second Decade

Vascular closure devices (VCDs) introduce a novel means for improving patient comfort and accelerating ambulation after invasive cardiovascular procedures performed via femoral arterial access. Vascular closure devices have provided simple, rapid, and reliable hemostasis in a variety of clinical settings. Despite more than a decade of development, however, VCD utilization has neither been routine in the U.S. nor around the world. Their limited adoption reflects concerns of higher costs for cardiac procedures and a lack of data confirming a significant reduction in vascular complications compared with manual compression. Recent data, however, suggest that VCD are improving, complication rates associated with their use may be decreasing, and their utilization may improve the process of care after femoral artery access. Challenges in the second decade of VCD experience will include performing definitive randomized trials, evaluating outcomes in higher-risk patients, and developing more ideal closure devices.

Significantly Improved Vascular Complications Among Women Undergoing Percutaneous Coronary Intervention: A Report From the Northern New England Percutaneous Coronary Intervention Registry

Background— Women are at a higher risk for bleeding/vascular complications (VC) related to cardiovascular procedures. Although the overall incidence of percutaneous coronary intervention (PCI)-related bleeding/VC has declined, the impact of this decline, specifically in women, is unknown. Methods and Results— We studied 13 653 female and 32 334 male consecutive cases, from 2002 to 2007, in the Northern New England PCI Registry. We sought to (1) compare absolute rates of bleeding/VC in women and men over time, (2) define predictors of bleeding/VC in women and men undergoing PCI, and (3) trend the impact of female gender in predicting bleeding/VC over time. Bleeding/VC was defined as any access-site vessel injury requiring surgical intervention or bleeding requiring transfusion. The overall risk of bleeding/VC was significantly higher in women versus men (4.5±1.3% versus 1.6±0.5%; P <0.004). Over time, there was a significant ( P <0.001) 50% decrease in absolute bleeding/VC rates in both women and men. After adjustment for baseline differences, female gender remained a significant predictor of increased risk in 2007 (odds ratio, 2.6; 95% CI, 1.74 to 3.91). Independent predictors of increased risk of bleeding/VC in women included older age, shock, renal failure, presentation with non-ST-elevation myocardial infraction and larger sheath sizes, whereas the use of fluoroscopy-guided access, closure devices, history of dyslipidemia or prior PCI, and use of bivalirudin were protective. Conclusion— Women undergoing PCI have had a significant decline in bleeding/VC rates during the last 6 years. Despite the improvement in procedural safety, female gender continues to be associated with a >2-fold risk of bleeding/VC compared with men. Received February 24, 2009; accepted July 27, 2009.Background—Women are at a higher risk for bleeding/vascular complications (VC) related to cardiovascular procedures. Although the overall incidence of percutaneous coronary intervention (PCI)-related bleeding/VC has declined, the impact of this decline, specifically in women, is unknown. Methods and Results—We studied 13 653 female and 32 334 male consecutive cases, from 2002 to 2007, in the Northern New England PCI Registry. We sought to (1) compare absolute rates of bleeding/VC in women and men over time, (2) define predictors of bleeding/VC in women and men undergoing PCI, and (3) trend the impact of female gender in predicting bleeding/VC over time. Bleeding/VC was defined as any access-site vessel injury requiring surgical intervention or bleeding requiring transfusion. The overall risk of bleeding/VC was significantly higher in women versus men (4.5±1.3% versus 1.6±0.5%; P<0.004). Over time, there was a significant (P<0.001) 50% decrease in absolute bleeding/VC rates in both women and men. After adjustment for baseline differences, female gender remained a significant predictor of increased risk in 2007 (odds ratio, 2.6; 95% CI, 1.74 to 3.91). Independent predictors of increased risk of bleeding/VC in women included older age, shock, renal failure, presentation with non–ST-elevation myocardial infraction and larger sheath sizes, whereas the use of fluoroscopy-guided access, closure devices, history of dyslipidemia or prior PCI, and use of bivalirudin were protective. Conclusion—Women undergoing PCI have had a significant decline in bleeding/VC rates during the last 6 years. Despite the improvement in procedural safety, female gender continues to be associated with a >2-fold risk of bleeding/VC compared with men.