Bio

Bio


Clinical Focus: Cardiovascular Medicine

Research Focus:

My primary research interest is the design and conduct of multicenter clinical trials and analyses of important clinical cardiac issues using large patient databases. My research focuses on novel anticoagulation agents for the treatment of acute coronary syndromes and atrial fibrillation, the study of agents targeted to protect the myocardium during reperfusion therapy for acute myocardial infarction, and the evaluation of cardiovascular safety of diabetic therapies. I am also interested in the methodology of clinical trials. Current research activities include standardization of the definition of myocardial infarction used in clinical trials, the adjudication of suspected clinical endpoint events by Clinical Event Committees (CEC), and the efficient operational conduct of large multinational clinical trials.

Administrative Focus: Vice Chair of Clinical Research in the Department of Medicine and Member of the Stanford IRB

Professional Training:

1985 Stanford University, BS Chemistry
1989 University of Washington, MD
1993 University of Arizona, Internship/Residency/Chief Residency
1996 Duke University, Fellowship in Cardiology
1996 Duke University, Faculty in Cardiology
2013 Stanford University, Vice Chair of Clinical Research, Department of Medicine

Academic Appointments


Administrative Appointments


  • Vice Chair of Clinical Research, Department of Medicine (2013 - Present)

Research & Scholarship

Projects


  • Financial Disclosures, Stanford University

    Full financial disclosures prior to August 1, 2013 can be viewed at www.dcri.org.
    Full financial disclosures after August 1, 2013 can be viewed in the attached file - Mahaffey Disclosures Stanford Tracker 20131021

    Location

    Stanford

    For More Information:

Publications

Journal Articles


  • Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non-ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization A Substudy From the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) Trial CIRCULATION Wallentin, L., Lindholm, D., Siegbahn, A., Wernroth, L., Becker, R. C., Cannon, C. P., Cornel, J. H., Himmelmann, A., Giannitsis, E., Harrington, R. A., Held, C., Husted, S., Katus, H. A., Mahaffey, K. W., Steg, P. G., Storey, R. F., James, S. K. 2014; 129 (3): 293-303

    Abstract

    Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial.Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT ≥14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive groupHs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT.URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

    View details for DOI 10.1161/CIRCULATIONAHA.113.004420

    View details for Web of Science ID 000329880700006

    View details for PubMedID 24170388

  • Ischaemic cardiac outcomes in patients with atrial fibrillation treated with vitamin K antagonism or factor Xa inhibition: results from the ROCKET AF trial. European heart journal Mahaffey, K. W., Stevens, S. R., White, H. D., Nessel, C. C., Goodman, S. G., Piccini, J. P., Patel, M. R., Becker, R. C., Halperin, J. L., Hacke, W., Singer, D. E., Hankey, G. J., Califf, R. M., Fox, K. A., Breithardt, G. 2014; 35 (4): 233-241

    Abstract

    We investigated the prevalence of prior myocardial infarction (MI) and incidence of ischaemic cardiovascular (CV) events among atrial fibrillation (AF) patients.In ROCKET AF, 14 264 patients with nonvalvular AF were randomized to rivaroxaban or warfarin. The key efficacy outcome for these analyses was CV death, MI, and unstable angina (UA). This pre-specified analysis was performed on patients while on treatment. Rates are per 100 patient-years. Overall, 2468 (17%) patients had prior MI at enrollment. Compared with patients without prior MI, these patients were more likely to be male (75 vs. 57%), on aspirin at baseline (47 vs. 34%), have prior congestive heart failure (78 vs. 59%), diabetes (47 vs. 39%), hypertension (94 vs. 90%), higher mean CHADS2 score (3.64 vs. 3.43), and fewer prior strokes or transient ischaemic attacks (46 vs. 54%). CV death, MI, or UA rates tended to be lower in patients assigned rivaroxaban compared with warfarin [2.70 vs. 3.15; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.73-1.00; P = 0.0509]. CV death, MI, or UA rates were higher in those with prior MI compared with no prior MI (6.68 vs. 2.19; HR 3.04, 95% CI 2.59-3.56) with consistent results for CV death, MI, or UA for rivaroxaban compared with warfarin in prior MI compared with no prior MI (P interaction = 0.10).Prior MI was common and associated with substantial risk for subsequent cardiac events. Patients with prior MI assigned rivaroxaban compared with warfarin had a non-significant 14% reduction of ischaemic cardiac events.

    View details for DOI 10.1093/eurheartj/eht428

    View details for PubMedID 24132190

  • Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data LANCET Steg, P. G., Bhatt, D. L., Hamm, C. W., Stone, G. W., Gibson, C. M., Mahaffey, K. W., Leonardi, S., Liu, T., Skerjanec, S., Day, J. R., Iwaoka, R. S., Stuckey, T. D., Gogia, H. S., Gruberg, L., French, W. J., White, H. D., Harrington, R. A. 2013; 382 (9909): 1981-1992

    Abstract

    Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor that was tested for percutaneous coronary intervention (PCI) in three large, double-blind, randomised trials. We did a pooled analysis of data from three trials that assessed the effectiveness of cangrelor against either clopidogrel or placebo in PCI.This prespecified, pooled analysis of patient-level data from three trials (CHAMPION-PCI, CHAMPION-PLATFORM, and CHAMPION-PHOENIX) compared cangrelor with control (clopidogrel or placebo) for prevention of thrombotic complications during and after PCI. Trial participants were patients undergoing PCI for ST-elevation myocardial infarction (11.6%), non-ST-elevation acute coronary syndromes (57.4%), and stable coronary artery disease (31.0%). Efficacy was assessed in the modified intention-to-treat population of 24,910 patients, with a prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h. The primary safety outcome was non-coronary artery bypass graft-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe or life-threatening bleeding at 48 h.Cangrelor reduced the odds of the primary outcome by 19% (3.8% for cangrelor vs 4.7% for control; odds ratio [OR] 0.81, 95% CI 0.71-0.91, p=0.0007), and stent thrombosis by 41% (0.5% vs 0.8%, OR 0.59, 95% CI 0.43-0.80, p=0.0008). Cangrelor reduced the odds of the secondary triple composite (all-cause death, myocardial infarction, or ischaemia-driven revascularisation at 48 h) by 19% (3.6% vs 4.4%, OR 0.81, 95% CI 0.71-0.92, p=0.0014). Efficacy outcomes were consistent across the trials and main patient subsets. These benefits were maintained at 30 days. There was no difference in the primary safety outcome (0.2% in both groups), in GUSTO moderate bleeding (0.6% vs 0.4%), or in transfusion (0.7% vs 0.6%), but cangrelor increased GUSTO mild bleeding (16.8% vs 13.0%, p<0.0001).Compared with control (clopidogrel or placebo), cangrelor reduced PCI periprocedural thrombotic complications, at the expense of increased bleeding.The Medicines Company.

    View details for DOI 10.1016/S0140-6736(13)61615-3

    View details for Web of Science ID 000328223700025

    View details for PubMedID 24011551

  • Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation JOURNAL OF THE AMERICAN HEART ASSOCIATION Steinberg, B. A., Holmes, D. N., Piccini, J. P., Ansell, J., Chang, P., Fonarow, G. C., Gersh, B., Mahaffey, K. W., Kowey, P. R., Ezekowitz, M. D., Singer, D. E., Thomas, L., Peterson, E. D., Hylek, E. M. 2013; 2 (6)

    Abstract

    Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown.We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more new-onset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during follow-up. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001).Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted.Clinicaltrials.gov. Unique identifier: NCT01165710.

    View details for DOI 10.1161/JAHA.113.000535

    View details for Web of Science ID 000330177900042

    View details for PubMedID 24275632

  • The Clinical Course of Treated Hyperparathyroidism Among Patients Receiving Hemodialysis and the Effect of Cinacalcet: The EVOLVE Trial JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Parfrey, P. S., Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Herzog, C. A., London, G. M., Mahaffey, K. W., Moe, S. M., Wheeler, D. C., Dehmel, B., Trotman, M., Modafferi, D. M., Goodman, W. G. 2013; 98 (12): 4834-4844

    Abstract

    The clinical course of secondary hyperparathyroidism (sHPT) in patients on hemodialysis is not well described, and the effect of the calcimimetic cinacalcet on disease progression is uncertain.Our objective was to describe 1) the clinical course of sHPT in patients treated with phosphate binders and/or vitamin D sterols and 2) the impact of cinacalcet on the occurrence of severe unremitting HPT, defined by the persistence of markedly elevated PTH concentrations together with hypercalcemia or parathyroidectomy (PTX).This was a randomized, double-blind, placebo-controlled, global, multicenter clinical trial.Of 5755 patients screened with moderate to severe sHPT, 3883 patients on hemodialysis were included in the trial.Outcomes included PTX; severe, unremitting HPT; and use of commercial cinacalcet (a protocol violation). Intervention: Intervention was cinacalcet (30-180 mg daily) or placebo for up to 64 months.In the 1935 patients randomized to placebo, 278 patients (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate binder use, and baseline serum calcium, phosphorus, and PTH concentrations were associated with PTX. Commercial cinacalcet was started in 443 (23%) patients (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed in 470 patients (24%). In a multivariable Cox model, the relative hazard (comparing patients randomized to cinacalcet versus placebo) of severe unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative hazard differed little when adjusted by baseline clinical characteristics.Severe unremitting HPT develops frequently in patients on hemodialysis despite conventional therapy, and cinacalcet substantially reduces its occurrence.

    View details for DOI 10.1210/jc.2013-2975

    View details for Web of Science ID 000328477200057

    View details for PubMedID 24108314

  • Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes: An Analysis From the Prospective, Randomized PLATO Trial CIRCULATION Steg, P. G., Harrington, R. A., Emanuelsson, H., Katus, H. A., Mahaffey, K. W., Meier, B., Storey, R. F., Wojdyla, D. M., Lewis, B. S., Maurer, G., Wallentin, L., James, S. K. 2013; 128 (10): 1055-1065
  • A novel approach to systematically implement the universal definition of myocardial infarction: insights from the CHAMPION PLATFORM trial HEART Leonardi, S., Truffa, A. A., Neely, M. L., Tricoci, P., White, H. D., Gibson, C. M., Wilson, M., Stone, G. W., Harrington, R. A., Bhatt, D. L., Mahaffey, K. W. 2013; 99 (17): 1282-1287

    Abstract

    OBJECTIVE: To reassess the efficacy of cangrelor efficacy using the universal definition of myocardial infarction (MI). DESIGN: We adopted a novel approach to systematically implement the universal definition of MI. Two physicians blinded to treatment allocation reviewed plots of CK-MB and troponin values in relation to time of randomisation and percutaneous coronary intervention (PCI) to identify patients with stable or falling biomarkers pre-PCI (ie, primary cohort), and those with post-PCI CK-MB elevations. SETTING: The CHAMPION PLATFORM trial. PATIENTS: Non-ST-elevation acute coronary syndromes (95%) and stable angina patients (5%). INTERVENTIONS: Cangrelor versus placebo. MAIN OUTCOME MEASURES: The efficacy of cangrelor compared with placebo using the reclassified events (type 4a MI) and the original clinical events committee-adjudicated (CEC PCI-MI) results was investigated. RESULTS: Of 5295 patients, 3406 (64.4%) were in the primary cohort. Type 4a MI occurred in 4.3% (226 events/5295 patients) while original CEC PCI-MI occurred in 6.5% (344 events/5295 patients), a significant difference (p<0.0001). Using the reclassified MI events, the primary composite endpoint of death, MI, or ischaemia-driven revascularisation through 48 h occurred in 5.4% of patients (4.9% cangrelor, 6.0% placebo; OR 0.80; 95% CI 0.63 to 1.02) as opposed to 7.5% of the primary analyses (7.0% cangrelor, 8.0% placebo; OR 0.87; 95% CI 0.71 to 1.07). CONCLUSIONS: Systematic, strict implementation of the universal MI definition with emphasis on baseline assessment may enhance discrimination in detecting PCI-MI and may allow for more rigorous assessment of interventions in patients undergoing early PCI.

    View details for DOI 10.1136/heartjnl-2012-303103

    View details for Web of Science ID 000323162800012

    View details for PubMedID 23434768

  • Cardiac Troponin After Percutaneous Coronary Intervention and 1-Year Mortality in Non-ST-Segment Elevation Acute Coronary Syndrome Using Systematic Evaluation of Biomarker Trends JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tricoci, P., Leonardi, S., White, J., White, H. D., Armstrong, P. W., Montalescot, G., Giugliano, R. P., Gibson, C. M., Van de Werf, F., Califf, R. M., Harrington, R. A., Braunwald, E., Mahaffey, K. W., Newby, L. K. 2013; 62 (3): 242-251

    Abstract

    OBJECTIVES: We reviewed cardiac troponin (cTn) trends during non-ST-segment elevation acute coronary syndrome (NSTE ACS) in patients undergoing percutaneous coronary intervention (PCI) in EARLY ACS and SYNERGY and studied the relationship between post-PCI cTn and mortality. BACKGROUND: The prognostic value of cTn post-PCI is controversial. In patients with NSTE ACS, it is especially difficult to distinguish between cTn elevations due to PCI or index myocardial infarction (MI). METHODS: Time and cTn (indexed by upper limit of normal [ULN]) data pairs were plotted for 10,199 patients and independently reviewed by 2 physicians to identify patients in whom post-PCI cTn elevation could be distinguished from that of index MI. Post-PCI cTn peak was identified for each plot, and its relationship with 1-year mortality was evaluated using Cox modeling, correcting for 15 clinical variables from the EARLY ACS 1-year mortality model (including baseline cTn). We used an identical methodology to assess the association between creatine kinase-MB (CK-MB) and 1-year mortality. RESULTS: Patients with cTn (re)elevation post-PCI not evaluable were identified and excluded from further analysis (4198 [41%] with cTn rising prior to PCI; 229 [2%] with missing cTn). Among the remainder (N=5772 [57%]), in the multivariable model, peak cTn post-PCI was associated with a 7% increase in mortality (hazard ratio [HR] for 10x ULN increase, 1.07; 95% confidence interval [CI], 1.02-1.11; p=0.0038). Peak post-PCI CK-MB was significantly associated with 1-year mortality (HR for 1x ULN increase, 1.13; 95% CI, 1.05-1.21; p=0.0013). CONCLUSIONS: We used a methodology that differentiated post-PCI cTn (re)elevation from that of presenting MI in more than half of patients with NSTE ACS undergoing PCI. This identified a highly significant relationship between post-PCI cTn and 1-year mortality, with implication for both incorporating a cTn post-PCI MI definition and preventing PCI-related myonecrosis.

    View details for DOI 10.1016/j.jacc.2013.04.043

    View details for Web of Science ID 000321695500011

    View details for PubMedID 23684676

  • Use of Evidence-based Cardiac Prevention Therapy Among Outpatients with Atrial Fibrillation AMERICAN JOURNAL OF MEDICINE Hess, P. L., Kim, S., Piccini, J. P., Allen, L. A., Ansell, J. E., Chang, P., Freeman, J. V., Gersh, B. J., Kowey, P. R., Mahaffey, K. W., Thomas, L., Peterson, E. D., Fonarow, G. C. 2013; 126 (7): 625-?

    Abstract

    Patients with atrial fibrillation often have cardiovascular risk factors or known comorbid disease, yet the use of evidence-based primary and secondary prevention cardiac therapy among atrial fibrillation outpatients is unknown.Using baseline data collected between June 2010 and August 2011 from 174 sites participating in ORBIT-AF, a US national registry of patients with atrial fibrillation coordinated from Durham, NC, we examined professional guideline-recommended evidence-based therapy use for cardiovascular comorbid conditions and risk factors. Multivariable logistic regression was used to identify factors associated with receipt of all indicated evidence-based therapy.Among 10,096 enrolled patients, 93.5% were eligible for one or more evidence-based therapies. Among those eligible, 46.6% received all indicated therapies: 62.3% received an antiplatelet agent, 72.3% received a beta-blocker, 59.5% received an angiotensin-converting enzyme or angiotensin receptor blocker, 15.3% received an aldosterone antagonist, 65.7% received a statin, and 58.8% received an implantable cardioverter-defibrillator. A minority of patients with coronary artery disease, diabetes mellitus, heart failure, and peripheral vascular disease received all indicated therapies (25.1%, 43.2%, 42.5%, and 43.4%, respectively). A total of 52.4% of patients had controlled hypertension and 74.6% of patients with hyperlipidemia received a statin. Factors associated with nonreceipt of all indicated therapies included frailty, comorbid illness, geographic region, and antiarrhythmic drug therapy.The majority of eligible atrial fibrillation outpatients did not receive all guideline-recommended therapies for cardiovascular comorbid conditions and risk factors. This represents a potential opportunity to improve atrial fibrillation patients' quality of care and outcomes.

    View details for DOI 10.1016/j.amjmed.2013.01.037

    View details for Web of Science ID 000320649800028

    View details for PubMedID 23787195

  • Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA.CER) trial EUROPEAN HEART JOURNAL Leonardi, S., Tricoci, P., White, H. D., Armstrong, P. W., Huang, Z., Wallentin, L., Aylward, P. E., Moliterno, D. J., Van de Werf, F., Chen, E., Providencia, L., Nordrehaug, J. E., Held, C., Strony, J., Rorick, T. L., Harrington, R. A., Mahaffey, K. W. 2013; 34 (23): 1723-1731

    Abstract

    AimsThe TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI).Methods and resultsA blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79-0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77-0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73-0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73-1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46-0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81-1.02), there was a trend towards a higher effect (Pint = 0.077).ConclusionThe PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed.

    View details for DOI 10.1093/eurheartj/eht104

    View details for Web of Science ID 000320408500009

    View details for PubMedID 23530022

  • Effect of Platelet Inhibition with Cangrelor during PCI on Ischemic Events NEW ENGLAND JOURNAL OF MEDICINE Bhatt, D. L., Stone, G. W., Mahaffey, K. W., Gibson, C. M., Steg, P. G., Hamm, C. W., Price, M. J., Leonardi, S., Gallup, D., Bramucci, E., Radke, P. W., Widimsky, P., Tousek, F., Tauth, J., Spriggs, D., McLaurin, B. T., Angiolillo, D. J., Genereux, P., Liu, T., Prats, J., Todd, M., Skerjanec, S., White, H. D., Harrington, R. A. 2013; 368 (14): 1303-1313

    Abstract

    The intensity of antiplatelet therapy during percutaneous coronary intervention (PCI) is an important determinant of PCI-related ischemic complications. Cangrelor is a potent intravenous adenosine diphosphate (ADP)-receptor antagonist that acts rapidly and has quickly reversible effects.In a double-blind, placebo-controlled trial, we randomly assigned 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy to receive a bolus and infusion of cangrelor or to receive a loading dose of 600 mg or 300 mg of clopidogrel. The primary efficacy end point was a composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours after randomization; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was severe bleeding at 48 hours.The rate of the primary efficacy end point was 4.7% in the cangrelor group and 5.9% in the clopidogrel group (adjusted odds ratio with cangrelor, 0.78; 95% confidence interval [CI], 0.66 to 0.93; P=0.005). The rate of the primary safety end point was 0.16% in the cangrelor group and 0.11% in the clopidogrel group (odds ratio, 1.50; 95% CI, 0.53 to 4.22; P=0.44). Stent thrombosis developed in 0.8% of the patients in the cangrelor group and in 1.4% in the clopidogrel group (odds ratio, 0.62; 95% CI, 0.43 to 0.90; P=0.01). The rates of adverse events related to the study treatment were low in both groups, though transient dyspnea occurred significantly more frequently with cangrelor than with clopidogrel (1.2% vs. 0.3%). The benefit from cangrelor with respect to the primary end point was consistent across multiple prespecified subgroups.Cangrelor significantly reduced the rate of ischemic events, including stent thrombosis, during PCI, with no significant increase in severe bleeding. (Funded by the Medicines Company; CHAMPION PHOENIX ClinicalTrials.gov number, NCT01156571.).

    View details for DOI 10.1056/NEJMoa1300815

    View details for Web of Science ID 000316989900007

    View details for PubMedID 23473369

  • Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis NEW ENGLAND JOURNAL OF MEDICINE Chertow, G. M., Block, G. A., Correa-Rotter, R., Drueeke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T. C., Moe, S. M., Trotman, M., Wheeler, D. C., Parfrey, P. S. 2012; 367 (26): 2482-2494
  • Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial NEPHROLOGY DIALYSIS TRANSPLANTATION Chertow, G. M., Correa-Rotter, R., Block, G. A., Drueke, T. B., Floege, J., Goodman, W. G., Herzog, C. A., Kubo, Y., London, G. M., Mahaffey, K. W., Mix, T., Moe, S. M., Wheeler, D. C., Parfrey, P. S. 2012; 27 (7): 2872-2879

    Abstract

    Secondary hyperparathyroidism (sHPT) and other abnormalities associated with chronic kidney disease-mineral bone disorder can contribute to dystrophic (including vascular) calcification. Dietary modification and variety of medications can be used to attenuate the severity of sHPT. However, it is unknown whether any of these approaches can reduce the high risks of death and cardiovascular disease in patients with end-stage renal disease.The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial was designed to test the hypothesis that treatment with the calcimimetic agent cinacalcet compared with placebo (on a background of conventional therapy including phosphate binders +/- vitamin D sterols) reduces time to death or non-fatal cardiovascular events (specifically myocardial infarction, unstable angina, heart failure and peripheral arterial disease events) among patients on hemodialysis with sHPT. This report describes baseline characteristics of enrolled subjects with a focus on regional variation.There were 3883 subjects randomized from 22 countries, including the USA, Canada, Australia, three Latin American nations, Russia and 15 European nations. The burden of overt cardiovascular disease at baseline was high (e.g. myocardial infarction 12.4%, heart failure 23.3%). The median plasma parathyroid hormone concentration at baseline was 692 pg/mL (10%, 90% range, 363-1694 pg/mL). At baseline, 87.2% of subjects were prescribed phosphate binders and 57.5% were prescribed activated vitamin D derivatives. Demographic data, comorbid conditions and baseline laboratory data varied significantly across regions.EVOLVE enrolled 3883 subjects on hemodialysis with moderate to severe sHPT. Inclusion of subjects from multiple global regions with varying degrees of disease severity will enhance the external validity of the trial results.

    View details for DOI 10.1093/ndt/gfr777

    View details for Web of Science ID 000306669100039

    View details for PubMedID 22529163

  • Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease - A randomized trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stone, G. W., Midei, M., Newman, W., Sanz, M., Hermiller, J. B., Williams, J., Farhat, N., Mahaffey, K. W., Cutlip, D. E., Fitzgerald, P. J., Sood, P., Su, X., Lansky, A. J. 2008; 299 (16): 1903-1913

    Abstract

    A thin, cobalt-chromium stent eluting the antiproliferative agent everolimus from a nonadhesive, durable fluoropolymer has shown promise in preliminary studies in improving clinical and angiographic outcomes in patients with coronary artery disease.To evaluate the safety and efficacy of an everolimus-eluting stent compared with a widely used paclitaxel-eluting stent. Design, Setting, andThe SPIRIT III trial, a prospective, randomized, single-blind, controlled trial enrolling patients at 65 academic and community-based US institutions between June 22, 2005, and March 15, 2006. Patients were 1002 men and women undergoing percutaneous coronary intervention in lesions 28 mm or less in length and with reference vessel diameter between 2.5 and 3.75 mm. Angiographic follow-up was prespecified at 8 months in 564 patients and completed in 436 patients. Clinical follow-up was performed at 1, 6, 9, and 12 months.Patients were randomized 2:1 to receive the everolimus-eluting stent (n = 669) or the paclitaxel-eluting stent (n = 333).The primary end point was noninferiority or superiority of angiographic in-segment late loss. The major secondary end point was noninferiority assessment of target vessel failure events (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months. An additional secondary end point was evaluation of major adverse cardiac events (cardiac death, myocardial infarction, or target lesion revascularization) at 9 and 12 months.Angiographic in-segment late loss was significantly less in the everolimus-eluting stent group compared with the paclitaxel group (mean, 0.14 [SD, 0.41] mm vs 0.28 [SD, 0.48] mm; difference, -0.14 [95% CI, -0.23 to -0.05]; P < or = .004). The everolimus stent was noninferior to the paclitaxel stent for target vessel failure at 9 months (7.2% vs 9.0%, respectively; difference, -1.9% [95% CI, -5.6% to 1.8%]; relative risk, 0.79 [95% CI, 0.51 to 1.23]; P < .001). The everolimus stent compared with the paclitaxel stent resulted in significant reductions in composite major adverse cardiac events both at 9 months (4.6% vs 8.1%; relative risk, 0.56 [95% CI, 0.34 to 0.94]; P = .03) and at 1 year (6.0% vs 10.3%; relative risk, 0.58 [95% CI, 0.37 to 0.90]; P = .02), due to fewer myocardial infarctions and target lesion revascularization procedures.In this large-scale, prospective randomized trial, an everolimus-eluting stent compared with a paclitaxel-eluting stent resulted in reduced angiographic late loss, noninferior rates of target vessel failure, and fewer major adverse cardiac events during 1 year of follow-up.clinicaltrials.gov Identifier: NCT00180479.

    View details for Web of Science ID 000255163800024

    View details for PubMedID 18430909

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