Faculty Bibliography

AIM: Patients with resistant hypertension are at high risk for adverse cardiovascular events. Efforts have been focused on lowering the surrogate endpoint of blood pressure (BP) with scant focus on reduction of hard cardiovascular endpoints. However, whether or not intensive lipid lowering is beneficial for reducing the risk of cardiovascular events in this high-risk cohort is not known. METHODS AND RESULTS: We evaluated 10 001 patients with coronary artery disease and a low-density lipoprotein cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enrolled in the Treating to New Targets trial. Treatment-resistant hypertension (TRH) was defined as BP >/=140 mmHg despite being on three antihypertensive agents or <140 mmHg on four or more agents. Subjects were followed up for a median duration of 4.9 years. The primary outcome was major cardiovascular events (composite of non-fatal myocardial infarction (MI), fatal coronary heart disease (CHD), resuscitated cardiac arrest, and stroke). Among the 10 001 patients in the trial, 1112 (11.1%) patients had TRH. Atorvastatin 80 mg, in patients with TRH, was associated with a significant reduction in the risk of the primary outcome (HR = 0.70; 95% CI 0.52-0.93; P = 0.01), driven largely by a significant reduction in CHD deaths (HR = 0.55; 95% CI 0.32-0.97; P = 0.04). In addition, atorvastatin 80 mg was associated with a reduction in major coronary events (HR = 0.67; 95% CI 0.49-0.93; P = 0.02), and any cardiovascular or coronary event and with a trend (P = 0.05) towards reduction in all-cause mortality (HR = 0.68; 95% CI 0.46-1.01) when compared with atorvastatin 10 mg. The results were similar when analysed for the two separate components of the TRH cohort. CONCLUSION: In subjects with TRH, intensive lipid lowering with atorvastatin 80 mg is associated with a significant reduction in cardiovascular events.

AIMS: Angiotensin receptor blockers (ARBs) are available in different dosages and it is common clinical practice to uptitrate if blood pressure goal is not achieved with the initial dose. Data on the incremental antihypertensive efficacy with uptitration are scarce. It is also unclear if antihypertensive efficacy of losartan is comparable with other ARBs. METHODS AND RESULTS: We systematically reviewed PubMed/EMBASE/Cochrane databases for all randomized clinical trials until December 2012 reporting 24 h ambulatory blood pressure (ABP) for most commonly available ARBs in patients with hypertension. Reduction in ABP with ARBs was evaluated at 25% of the maximum (max) dose, 50% of the max dose, and at the max dose. Comparison was made between 24 h BP-lowering effect of losartan 50 and 100 mg and other ARBs at 50% max dose and the max dose, respectively. Sixty-two studies enrolling 15 289 patients (mean age 56 years; 60% men) with a mean duration of 10 weeks were included in the analysis. Overall, the dose-response curve with ARBs was shallow with decrease of 10.3/6.7 (systolic/diastolic), 11.7/7.6, and 13.0/8.3 mmHg with 25% max dose, 50% max dose, and with the max dose of ARBs, respectively. Losartan in the dose of 50 mg lowered ABP less well than other ARBs at 50% max dose by 2.5 mmHg systolic (P < 0.0001) and 1.8 mmHg diastolic (P = 0.0003). Losartan 100 mg lowered ABP less well than other ARBs at max dose by 3.9 mm Hg systolic (P = 0.0002) and 2.2 mmHg diastolic (P = 0.002). CONCLUSION: In this comprehensive analysis of the antihypertensive efficacy of ARBs by 24 h ABP, we observed a shallow dose-response curve, and uptitration marginally enhanced the antihypertensive efficacy. Blood pressure reduction with losartan at starting dose and at max dose was consistently inferior to the other ARBs.

BACKGROUND: The 2013 American College of Cardiology Foundation/American Heart Association ST-segment elevation myocardial infarction (STEMI) guidelines have shifted focus from door-to-balloon (D2B) time to the time from first medical contact to device activation (contact-to-device time [C2D] ). HYPOTHESIS: This study investigates the impact of prehospital wireless electrocardiogram transmission (PHT) on reperfusion times to assess the impact of the new guidelines. METHODS: From January 2009 to December 2012, data were collected on STEMI patients who received percutaneous coronary interventions; 245 patients were included for analysis. The primary outcome was median C2D time in the PHT group and the secondary outcome was D2B time. RESULTS: Prehospital wireless electrocardiogram transmission was associated with reduced C2D times vs no PHT: 80 minutes (interquartile range [IQR], 64-94) vs 96 minutes (IQR, 79-118), respectively, P < 0.0001. The median D2B time was lower in the PHT group vs the no-PHT group: 45 minutes (IQR, 34-56) vs 63 minutes (IQR, 49-81), respectively, P < 0.0001. Multivariate analysis showed PHT to be the strongest predictor of a C2D time of <90 minutes (odds ratio: 3.73, 95% confidence interval: 1.65-8.39, P = 0.002). Female sex was negatively predictive of achieving a C2D time <90 minutes (odds ratio: 0.23, 95% confidence interval: 0.07-0.73, P = 0.01). CONCLUSIONS: In STEMI patients, PHT was associated with significantly reduced C2D and D2B times and was an independent predictor of achieving a target C2D time. As centers adapt to the new guidelines emphasizing C2D time, targeting a shorter D2B time (<50 minutes) is ideal to achieve a C2D time of <90 minutes.

A recent study has shown an association between high-potency statins and risk of acute kidney injury. However, these data are from observational studies, and it is not clear if similar signal is seen from randomized controlled trials. We evaluated the risk of renal-associated serious adverse events (SAEs) using statins versus placebo trials and the high-dose versus low-dose statin trials that were available to us. The outcome of interest was renal-related SAEs. The incidence of adverse events relating to kidney injury was determined through review of the adverse event database. The following outcomes were evaluated: (1) renal-related SAEs within 120 days of randomization (primary outcome), (2) renal-related SAEs after 120 days of randomization (secondary), and (3) drug discontinuation due to renal-related SAEs (secondary). There was no difference in the incidence of renal-related SAEs at 120 days (0.04% vs 0.10%, p = 0.162) between atorvastatin and placebo in the 24 placebo-controlled trials (10,345 patients on atorvastatin (10 to 80 mg/day) versus 8,945 patients on placebo) or in the high-dose versus low-dose statin trials including the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study (0.05% vs 0.02%, p = 0.625) or the Treating to New Targets (TNT) trial (0.0% vs 0.04%, p = 0.500) trial. Results were similar for renal-related SAEs after 120 days (placebo controlled trials [0.38% vs 0.36%, p = 0.905], IDEAL trial [0.56% vs 0.65%, p = 0.683], or the TNT trial [0.76% vs 1.04%, p = 0.168]) and for drug withdrawal due to renal-related SAE (placebo controlled trials [0.05% vs 0.04%, p = 1.00], IDEAL trial [0.02% vs 0.0%, p = 0.499], or the TNT trial [0.08% vs 0.12%, p = 0.754]). In conclusion, the results from clinical trials with data from 149,882 patient-years of follow-up fail to show any increase in renal-related SAEs with statins compared with controls.

BACKGROUND: The use of bivalirudin versus unfractionated heparin monotherapy in patients without ST-segment-elevation myocardial infarction is not well defined. METHODS AND RESULTS: The study population consisted of patients enrolled in the Evaluation of Drug-Eluting Stents and Ischemic Events (EVENT) registry with either non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease, who underwent percutaneous coronary intervention with either unfractionated heparin or bivalirudin monotherapy. Propensity score matching was used to adjust for baseline characteristics. The primary bleeding (in-hospital composite bleeding-access site bleeding, thrombolysis in myocardial infarction major/minor bleeding, or transfusion) and primary (in-hospital death/myocardial infarction) and secondary ischemic outcomes (death/myocardial infarction/unplanned repeat revascularization at 12 months) were evaluated. Propensity score matching yielded 1036 patients with non-ST-segment-elevation acute coronary syndromes and 2062 patients with stable ischemic heart disease. For the non-ST-segment-elevation acute coronary syndrome cohort, bivalirudin use was associated with lower bleeding (difference, -3.3% [-0.8% to -5.8%]; P=0.01; number need to treat=30) without increase in either primary (difference, 1.2% [4.1% to -1.8%]; P=0.45) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [1.3% to -1.3%]; P=1.00). Similarly, in the stable ischemic heart disease cohort, bivalirudin use was associated with lower bleeding (difference, -1.8% [-0.4% to -3.3%]; P=0.01; number need to treat=53) without increase in either primary (difference, 0.4% [2.3% to -1.5%]; P=0.70) or secondary ischemic outcomes, including stent thrombosis (difference, 0.0% [0.7% to -0.7%]; P=1.00) when compared with unfractionated heparin monotherapy. CONCLUSIONS: Among patients with non-ST-segment-elevation acute coronary syndromes or stable ischemic heart disease undergoing percutaneous coronary intervention, bivalirudin use during percutaneous coronary intervention when compared with unfractionated heparin monotherapy was associated with lower bleeding without significant increase in ischemic outcomes or stent thrombosis.

BACKGROUND: Great strides have been made in improving outcomes for patients with ST-elevation myocardial infarction (STEMI), predominately through initiatives focusing upon improving clinical processes "upstream" of percutaneous coronary intervention (PCI). The actual step-by-step mechanics of diagnostic angiography during STEMI and other aspects of the PCI procedure itself have received relatively little attention. OBJECTIVES AND METHODS: We hypothesized that there would be significant variation in how primary PCI for STEMI is performed in the United States. In order to better understand current US practice, an electronic survey consisting of seven focused questions was forwarded to 2,910 US interventional cardiologists who were members of the Society for Cardiovascular Angiography and Interventions (SCAI). RESULTS: Three hundred sixty-two responses were received (12.4%). Among respondents, the femoral artery was the preferred access site in 83% (vs. 17% radial). The use of a diagnostic catheter to visualize the non-culprit artery prior to using a guiding catheter for the culprit artery was the preferred approach for 58% of respondents, and an additional 23% preferred complete angiography with diagnostic catheters prior to guide insertion. However, a significant minority (19%) preferred starting directly with a guide catheter for the culprit artery and performing PCI prior to contralateral non-culprit artery visualization. Only 9% reported performing routine left ventriculography prior to PCI, with the majority (66%) choosing to perform ventriculography during/after PCI, and 25% reporting rare or no use of left ventriculography. Fewer than half of respondents (49%) reported routine aspiration thrombectomy use, despite a Class IIa ACC/AHA guidelines recommendation. CONCLUSIONS: There is significant variability in the self-reported mechanics of primary PCI by US interventional cardiologists. Some of this variability (e.g., sequence of catheters, and performance of left ventriculography prior to reperfusion) is not addressed by current guidelines/consensus documents, and may have clinical implications, reflecting the balance between the desire for timely reperfusion versus a more complete assessment of patient risk. (c) 2013 Wiley Periodicals, Inc.