Faculty Bibliography

BACKGROUND: Dual antiplatelet therapy with aspirin and thienopyridines (clopidogrel or prasugrel) is required after placement of coronary stents to prevent thrombotic complications. Although current clinical practice guidelines recommend 12-month treatment after drug-eluting stent placement, even longer durations may prevent thrombotic events. STUDY DESIGN: The Dual Antiplatelet Therapy (DAPT) Study is comparing the benefits and risks of 12 versus 30 months of dual antiplatelet therapy in preventing stent thrombosis or major adverse cardiovascular and cerebrovascular events in subjects undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery obstructive lesions. The DAPT Study is a multicenter, international, randomized, double-blind, placebo-controlled trial that will enroll 15,245 subjects treated with drug-eluting stent (DES) and 5,400 subjects treated with bare-metal stents (BMS). All subjects will receive 12 months of open-label thienopyridine treatment in addition to aspirin. After 12 months, subjects who are free from death, myocardial infarction, or stroke (MACCE), repeat revascularization, and GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events will be randomized to receive either 18 additional months of thienopyridine (clopidogrel or prasugrel) (30 month DAPT arm) or placebo (12 month DAPT arm) plus aspirin. Coprimary end points are MACCE and stent thrombosis. The primary safety end point is GUSTO moderate or severe bleeding. CONCLUSIONS: This randomized trial is designed to define the relative safety and effectiveness of 12 versus 30 months of dual antiplatelet therapy across the broad spectrum of patients receiving coronary stents.

BACKGROUND: Aggressive blood pressure (BP) control has been advocated in patients with acute coronary syndrome, but few data exist in this population relative to cardiovascular outcomes. METHODS AND RESULTS: We evaluated 4162 patients enrolled in the PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction (PROVE IT-TIMI) 22 trial (acute coronary syndrome patients randomized to pravastatin 40 mg versus atorvastatin 80 mg). The average follow-up BP (systolic and diastolic) was categorized into 10-mm Hg increments. The primary outcome was a composite of death due to any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization after 30 days, and stroke. The secondary outcome was a composite of death due to coronary heart disease, nonfatal myocardial infarction, or revascularization. The relationship between BP (systolic or diastolic) followed a J- or U-shaped curve association with primary, secondary, and individual outcomes, with increased events rates at both low and high BP values, both unadjusted and after adjustment for baseline variables, baseline C-reactive protein, and on-treatment average levels of low-density lipoprotein cholesterol. A nonlinear Cox proportional hazards model showed a nadir of 136/85 mm Hg (range 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic) at which the incidence of primary outcome was lowest. The curve was relatively flat for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg. CONCLUSIONS: After acute coronary syndrome, a J- or U-shaped curve association existed between BP and the risk of future cardiovascular events, with lowest event rates in the BP range of approximately 130 to 140 mm Hg systolic and 80 to 90 mm Hg diastolic and a relatively flat curve for systolic pressures of 110 to 130 mm Hg and diastolic pressures of 70 to 90 mm Hg, which suggests that too low of a pressure (especially <110/70 mm Hg) may be dangerous. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00382460

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) for stable angina and acute coronary syndrome. This study analyzed the impact of bivalirudin-based anticoagulation strategy versus UFH-based anticoagulation strategy on long-term bleeding complications and major adverse cardiac events in patients undergoing PCI in routine clinical practice. From September 2005 to April 2009, 3,367 consecutive patients who underwent PCI for stable angina or non-ST-segment elevation acute coronary syndrome at Brigham and Women's Hospital were studied. Of these patients, 2,228 patients (66%) received UFH and 1,139 (34%) received bivalirudin. Bleeding complication and major adverse cardiac event rates were compared at discharge, 30 days, and 1 year. In a propensity-score matched analysis, bivalirudin-based anticoagulation strategy was associated with lower bleeding complications at 30 days (7.0% vs 13.7%, p = 0.001) and 1 year (12.7% vs 18.9%, p = 0.013). Major adverse cardiac event rates were not significantly different between groups at discharge, 30 days, and 1 year (6.4% vs 8.3%, p = 0.103; 9.4% vs 10.9%, p = 0.449; 12.1% vs 14.8%, p = 0.235, respectively). There was no difference in all-cause mortality rates between the 2 groups (0.9% vs 0.8%, p = 0.808, at discharge; 1.9% vs 3.6%, p = 0.112, at 30 days; 3.6% vs 5.5%, p = 0.195, at 1 year). In conclusion, in a real-world cohort of patients undergoing PCI, bivalirudin-based anticoagulation strategy is associated with a significant decrease in risk of bleeding complications after 30 days and 1 year compared to a UFH-based anticoagulation strategy with no increase in risk for major adverse cardiac events.

BACKGROUND: Dry cough is a common, annoying adverse effect of all angiotensin-converting enzyme (ACE) inhibitors. The present study was designed to compare the rate of coughs reported in the literature with reported rates in the Physicians' Desk Reference (PDR)/drug label. METHODS: We searched MEDLINE/EMBASE/CENTRAL for articles published from 1990 to the present about randomized clinical trials (RCTs) of ACE inhibitors with a sample size of at least 100 patients in the ACE inhibitors arm with follow-up for at least 3 months and reporting the incidence or withdrawal rates due to cough. Baseline characteristics, cohort enrolled, metrics used to assess cough, incidence, and withdrawal rates due to cough were abstracted. RESULTS: One hundred twenty-five studies that satisfied our inclusion criteria enrolled 198,130 patients. The pooled weighted incidence of cough for enalapril was 11.48% (95% confidence interval [CI], 9.54% to 13.41%), which was ninefold greater compared to the reported rate in the PDR/drug label (1.3%). The pooled weighted withdrawal rate due to cough for enalapril was 2.57% (95% CI, 2.40-2.74), which was 31-fold greater compared to the reported rate in the PDR/drug label (0.1%). The incidence of cough has increased progressively over the last 2 decades with accumulating data, but it has been reported consistently several-fold less in the PDR compared to the RCTs. The results were similar for most other ACE inhibitors. CONCLUSION: The incidence of ACE inhibitor-associated cough and the withdrawal rate (the more objective metric) due to cough is significantly greater in the literature than reported in the PDR/drug label and is likely to be even greater in the real world when compared with the data from RCTs. There exists a gap between the data available from the literature and that which is presented to the consumers (prescribing physicians and patients).

BACKGROUND: In patients with carotid artery disease, carotid endarterectomy (CEA) and carotid stenting (CAS) are treatment options. Controversy exists as to the relative efficacy of the 2 techniques in preventing late events. METHODS AND RESULTS: The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited > 68,000 outpatients >/= 45 years of age with established atherothrombotic disease or >/= 3 risk factors for atherothrombosis. Patients with CAS or CEA were chosen and followed up prospectively for the occurrence of cardiovascular events. Propensity score matching was performed to assemble a cohort of patients in whom all baseline covariates would be well balanced. Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary outcome was stroke or transient ischemic attack. Tertiary outcome was a composite of death, myocardial infarction, or stroke and the individual outcomes. Of the 68 236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with 836 CEA patients. At the end of 2 years of follow-up, in the propensity score-matched cohort, CAS was associated with a risk similar to CEA for the primary (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01) composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48; 95% CI, 0.79 to 2.80). CONCLUSIONS: In a real-world cohort of patients with a history of carotid artery revascularization, CAS was comparable to CEA for late outcomes

BACKGROUND: Stress echocardiography is an established technique for diagnosis, risk stratification, and prognosis in patients with known or suspected coronary artery disease. The ability of stress echocardiography to predict clinical outcomes, such as coronary angiography and revascularization, has not been reported previously. The purpose of this study was to evaluate the clinical outcomes of coronary angiography, revascularization, and cardiac events in patients undergoing stress echocardiography. METHODS: A total of 3121 patients (mean age, 60 + or - 13 years; 48% men) undergoing stress echocardiography (41% treadmill, 59% dobutamine) were assessed. Follow-up (mean, 2.8 + or - 1.1 years) for subsequent coronary angiography, revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]), and confirmed hard events (nonfatal myocardial infarction or cardiac death) was obtained. RESULTS: Stress echocardiographic results were normal (peak wall motion score index [pWMSI], 1.0) in 66% and abnormal (pWMSI > 1.0) in 34% of patients. The pWMSI effectively risk-stratified patients into low-risk (pWMSI, 1.0; 0.8% per year), intermediate-risk (pWMSI, 1.1-1.7; 2.6% per year), and high-risk (pWMSI >1.7; 5.5% per year) groups for future cardiac events (P < .0001). Early coronary angiography (30 days following stress echocardiography) was performed in only 35 patients (1.7%) with normal stress echocardiographic results and 267 patients (25.5%) with abnormal stress echocardiographic results (P < .0001). Late coronary revascularization (2 years following stress echocardiography) occurred in 80 patients (PCI, 2.8%; CABG, 1.1%) with pWMSI values of 1.0, 123 patients (PCI, 13.5%; CABG, 7.3%) with pWMSI values of 1.1 to 1.7, and 102 patients (PCI, 12.7%; CABG, 9.6%) with pWMSI values > 1.7. Multivariate logistic regression analysis identified pWMSI as a predictor of coronary angiography (relative risk, 2.04; 95% confidence interval, 1.67-2.5), revascularization (relative risk, 1.91; 95% confidence interval, 1.68-2.17), and cardiac events (relative risk, 2.45; 95% confidence interval, 2.09-2.88) (all P values < .0001). Patients with markedly abnormal stress echocardiographic results (pWMSI > 1.7) had a significantly higher cardiac event rate in those who did not undergo coronary revascularization (9.6% per year vs 2.9% per year, P < .05). CONCLUSIONS: Stress echocardiography is an effective gatekeeper for coronary angiography and revascularization. Stress echocardiographic results influence clinical decision making in higher risk patients with significantly increased referral to coronary angiography and revascularization. Patients with markedly abnormal stress echocardiographic results (pWMSI > 1.7) were most likely to benefit from coronary revascularization

In patients presenting with acute coronary syndromes, 30-60% of patients have multiple significant coronary lesions. Patients presenting with acute coronary syndrome and multivessel disease have a significant increase in the incidence of major cardiovascular morbidity and mortality when compared with patients who have single-vessel disease. Although great progress has been made to reduce the extent of infarction through effective and rapid reperfusion due to faster time to reperfusion, potent antiplatelets, and antithrombotics, there is not much consensus as to how best to treat multivessel disease in patients presenting with acute coronary syndromes. We present a review of the current body of evidence for safety and efficacy of multivessel revascularization in patients presenting with acute coronary syndromes

The use of stress echocardiography has undergone considerable evolution in the past 3 decades. Although stress echocardiography was first introduced as a noninvasive diagnostic tool for determining the presence or absence of coronary artery disease (CAD), it later served a prognostic role as well. The importance of stress echocardiography in risk stratification and prognosis is substantially undervalued by clinicians. The identification of patients at risk for future cardiac events has become a primary objective in noninvasive evaluation of patients with suspected or known CAD. In particular, the ability of stress echocardiography to identify patients at low (< 1%), intermediate (1%-5%), or high (> 5%) risk for future cardiac events is essential to decision making in patient management. Moreover, previous studies have conclusively demonstrated the incremental prognostic value of stress echocardiography over clinical and treadmill exercise data in predicting future cardiac events. This article presents a primarily single-center experience of retrospective and observational studies that address the current role of stress echocardiography and summarize its use for risk stratification, prognosis, and determining clinical outcomes, as well as cost-effective integration of such information in patient management decision making