Matthew J. Sorrentino

Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.

We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a trans-dermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60–90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia. (Anesth Analg 1994;79:1133–40)

Plasma lipoprotein (a) protein concentration and coronary artery disease in black patients compared with white patients

PURPOSE This study examines the relation between lipoprotein (a) protein levels and other lipid parameters and coronary artery disease in white and black patients. PATIENTS AND METHODS Plasma lipoprotein (a) protein levels were measured prior to coronary angiography in a population of 127 white and 111 black patients. Each angiogram was given a total coronary artery disease score based on the number and severity of atherosclerotic coronary lesions. RESULTS White and black patients exhibited no differences in total plasma cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. Black patients had higher lipoprotein (a) protein levels than white patients (8.6 versus 4.0 mg/dL; p < 0.0001). The extent and severity of coronary artery disease was the same in white and black patients. White and black patients with coronary artery disease had higher lipoprotein (a) levels than patients without coronary lesions (4.37 versus 1.99 mg/dL, p = 0.027 for white; 9.23 versus 6.87 mg/dL, p = 0.072 for black). In both groups of patients, there was a weak but significant positive correlation between lipoprotein (a) protein levels and coronary artery disease score. CONCLUSION Lipoprotein (a) is higher in patients with coronary artery disease. Black patients have higher plasma lipoprotein (a) protein levels than white patients and a comparable degree of coronary artery disease. It follows that the cardiovascular pathogenicity of lipoprotein (a) is not significantly greater in black patients despite higher lipoprotein (a) levels.

Adoption of a clinical pharmacogenomics implementation program during outpatient care–initial results of the University of Chicago “1,200 Patients Project”

Pharmacogenomic testing is viewed as an integral part of precision medicine. To achieve this, we originated The 1,200 Patients Project which offers broad, preemptive pharmacogenomic testing to patients at our institution. We analyzed enrollment, genotype, and encounter‐level data from the first year of implementation to assess utility of providing pharmacogenomic results. Results were delivered via a genomic prescribing system (GPS) in the form of traffic lights: green (favorable), yellow (caution), and red (high risk). Additional supporting information was provided as a virtual pharmacogenomic consult, including citation to relevant publications. Currently, 812 patients have participated, representing 90% of those approached; 608 have been successfully genotyped across a custom array. A total of 268 clinic encounters have occurred at which results were accessible via the GPS. At 86% of visits, physicians accessed the GPS, receiving 367 result signals for medications patients were taking: 57% green lights, 41% yellow lights, and 1.4% red lights. Physician click frequencies to obtain clinical details about alerts varied according to color severity (100% of red were clicked, 72% yellow, 20% green). For 85% of visits, clinical pharmacogenomic information was available for at least one drug the patient was taking, suggesting relevance of the delivered information. We successfully implemented an individualized health care model of preemptive pharmacogenomic testing, delivering results along with pharmacogenomic decision support. Patient interest was robust, physician adoption of information was high, and results were routinely utilized. Ongoing examination of a larger number of clinic encounters and inclusion of more physicians and patients is warranted.

Redefining Hypertension — Assessing the New Blood-Pressure Guidelines

Redefining Hypertension Shifting the threshold for hypertension to 130/80 mm Hg, as the new guidelines do, will overburden our primary care physician workforce, and many people will receive pharmacologic therapy that will carry more risk than benefit.

Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs

OBJECTIVE To comprehensively assess the pharmacogenomic evidence of routinely used drugs for clinical utility. METHODS Between January 2, 2011, and May 31, 2013, we assessed 71 drugs by identifying all drug/genetic variant combinations with published clinical pharmacogenomic evidence. Literature supporting each drug/variant pair was assessed for study design and methods, outcomes, statistical significance, and clinical relevance. Proposed clinical summaries were formally scored using a modified AGREE (Appraisal of Guidelines for Research and Evaluation) II instrument, including recommendation for or against guideline implementation. RESULTS Positive pharmacogenomic findings were identified for 51 of 71 cardiovascular drugs (71.8%), representing 884 unique drug/variant pairs from 597 publications. After analysis for quality and clinical relevance, 92 drug/variant pairs were proposed for translation into clinical summaries, encompassing 23 drugs (32.4% of drugs reviewed). All were recommended for clinical implementation using AGREE II, with mean ± SD overall quality scores of 5.18±0.91 (of 7.0; range, 3.67-7.0). Drug guidelines had highest mean ± SD scores in AGREE II domain 1 (Scope) (91.9±6.1 of 100) and moderate but still robust mean ± SD scores in domain 3 (Rigor) (73.1±11.1), domain 4 (Clarity) (67.8±12.5), and domain 5 (Applicability) (65.8±10.0). Clopidogrel (CYP2C19), metoprolol (CYP2D6), simvastatin (rs4149056), dabigatran (rs2244613), hydralazine (rs1799983, rs1799998), and warfarin (CYP2C9/VKORC1) were distinguished by the highest scores. Seven of the 9 most commonly prescribed drugs warranted translation guidelines summarizing clinical pharmacogenomic information. CONCLUSION Considerable clinically actionable pharmacogenomic information for cardiovascular drugs exists, supporting the idea that consideration of such information when prescribing is warranted.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0–75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7–3.5), P < 0.0001). No pharmacogenomically high‐risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision‐making is achievable through clinical integration of genomic medicine.

Bleeding Risk Prediction Models in Atrial Fibrillation

Novel, nonvitamin K antagonist oral anticoagulants (OACs) have demonstrated similar or superior efficacy to warfarin for ischemic stroke prevention in patients with atrial fibrillation (AF). As the prevalence of AF rises in a growing elderly population, these agents are becoming central to the routine practice of clinicians caring for these patients. Though the benefits are clear, the decision to treat the elderly patient with AF with long-term oral OACs is often a dilemma for the clinician mindful of the risk of major bleeding. Several bleeding risk prediction models have been created to help the clinician identify patients for whom the risk of bleeding is high, and would potentially outweigh the benefits of OAC therapy. In this review, we discuss the features of 8 bleeding risk prediction models, including the recently described HEMORR2HAGES, HAS-BLED, and ATRIA models, and approaches to assessing bleeding risk in clinical practice.

Predictors of Hypertension Control in a Diverse General Cardiology Practice

J Clin Hypertens(Greenwich). 2010;12:570–577.

Beta blockers for CHF. Adrenergic blockade dramatically reduces morbidity and mortality.

PREVIEW Congestive heart failure (CHF) afflicts more than 4 million people in the United States, and about 500,000 new cases are diagnosed each year. Heart failure is one of the most common reasons for hospitalization in this country, and morbidity and mortality rates are high. However, as this article points out, the prognosis in patients with CHF can be significantly improved by appropriate drug therapy. Drs Garg and Sorrentino review evidence supporting the use of beta blockers in CHF and provide practical information about when and how to use these drugs.

Mitral valve prolapse. Avoiding complications of a progressive disease.

Mitral valve prolapse is a common disorder, but it carries low morbidity and mortality. Patients require close follow-up, however, to prevent development of serious complications. In addition, patients with thickened mitral valve leaflets or mitral regurgitation require antibiotic prophylaxis against infective endocarditis. Family members of patients with primary mitral valve prolapse should be screened for the disease, because it often is asymptomatic.