Rani K. Hasan

Effect of Intravenous Fentanyl on Ticagrelor Absorption and Platelet Inhibition Among Patients Undergoing Percutaneous Coronary Intervention: The PACIFY Randomized Clinical Trial.

Fentanyl is a potent opiate commonly administered during cardiac catheterization procedures in North America.1 The question of whether fentanyl could have adverse consequences in patients undergoing percutaneous coronary intervention (PCI) is raised by recent research demonstrating that intravenous morphine significantly delays the absorption of oral P2Y12 platelet inhibitors.2 The presumed mechanism is slowed gastric emptying. The single-center PACIFY trial (Platelet Aggregation With Ticagrelor Inhibition and Fentanyl; ClinicalTrials.gov. Unique identifier: NCT02683707) randomized adults undergoing clinically indicated elective coronary angiography to receive the procedure with or without intravenous fentanyl.3 The study was approved by the Johns Hopkins Medicine Institutional Review Board, and all participants provided written informed consent. Eligible adults had not received P2Y12 inhibitors for 14 days before enrollment. Other exclusion criteria included preprocedural treatment with oral anticoagulants or opiates, platelet count <100 000/mm3, and impaired renal or hepatic function. All participants received subcutaneous lidocaine and intravenous midazolam at the start of the catheterization procedure and as needed thereafter. Doses of all drugs were at the discretion of treating providers. Patients and outcomes assessors were blinded; treating providers were not. Participants who required PCI received an oral dose of 180 mg ticagrelor at the conclusion of diagnostic angiography. Blood samples were collected at baseline and 0.5, 1, 2, 4, and 24 hours after the …

Should Statin Therapy Be Allocated on the Basis of Global Risk or on the Basis of Randomized Trial Evidence

Current clinical guidelines recommend the use of a global risk assessment tool, such as those pioneered by the Framingham Heart Study, to determine eligibility for statin therapy in patients with absolute risk levels greater than a certain threshold. In support of this approach, several randomized trials have reported that patients with high absolute risk clearly benefit from statin therapy. Therefore, the guideline recommendations would seem intuitive and effective, albeit on the core assumption that the mortality and morbidity benefits associated with statin therapy would be greatest in those with high predicted absolute risk. However, if this assumption is incorrect, using predicted absolute risk to guide statin therapy could easily result in underuse in some groups and overuse in others. Herein, the authors question the utility of global risk assessment strategies based on the Framingham risk score for guiding statin therapy in light of current data that have become available from more recent and robust prospective randomized clinical trials since the publication of the National Cholesterol Education Program Adult Treatment Panel III guidelines. Moreover, the Adult Treatment Panel III guidelines do not support treatment of some patients who may benefit from statin therapy. In conclusion, the authors propose an alternative approach for incorporating more recent randomized trial data into future statin allocation algorithms and treatment guidelines.

Statin Therapy in Primary Prevention: New Insights Regarding Women and the Elderly

events. 1 Therefore, the emphasis on primary and secondary prevention is imperative to provide high-quality and costeffective medical care that will improve survival and quality of life. Multiple studies have demonstrated a morbidity and mortality benefit in patients with established CVD treated with the lipid-lowering medications known as hydroxymethylglutaryl coenzyme A reductase inhibitors, or statins. 2‐6 A prospective meta-analysis conducted by the Cholesterol Treatment Trialists’ Collaboration included data from 90,056 patients in 14 randomized trials of statin treatment. They showed a 12% reduction in all-cause mortality per 39 mg/dl reduction in low-density lipoprotein cholesterol (p 0.0001), which reflected a 19% reduction in coronary mortality (p 0.0001). Statistically significant reductions were also observed in myocardial infarction, coronary heart disease (CHD) death, coronary revascularization, and fatal or nonfatal stroke. There was a 21% reduction for a composite of these end points. Reduction of low-density lipoprotein cholesterol by approximately 8 mg/dl in patients with preexisting CHD translated into 48 fewer participants sustaining major vascular events per 1,000 participants, compared to 25 fewer per 1,000 in participants with no CHD histories. Meta-analyses such as this have demonstrated the efficacy of statins and have influenced patient care by driving the inclusion of statins as part of the standard of care for patients with CHD, dyslipidemia, diabetes mellitus, and peripheral arterial disease. 7,8 The evident benefit of statin therapy for secondary prevention has in turn led to a greater emphasis on the use of statins in primary prevention. Most patients with atherosclerosis are asymptomatic, and half of all myocardial infarctions and strokes occur in patients with low-density lipoprotein cholesterol levels that are less than the currently recommended thresholds for treatment. In addition, the effect of statins and their role in primary prevention for women and the elderly have not been thoroughly evaluated. Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) allows clinicians to evaluate the effects of statin therapy for primary prevention of CVD in these 2 populations. 9 JUPITER enrolled 17,802 subjects (6,801 women) without histories of CHD, stroke, or diabetes who had lowdensity lipoprotein cholesterol levels 130 mg/dl and highsensitivity C-reactive protein (hsCRP) levels 2.0 mg/L. These subjects were randomized to rosuvastatin 20 mg/day versus placebo. Treatment with rosuvastatin in this low-risk population showed a 54% reduction in myocardial infarction, a 46% reduction in revascularization, and a 20% reduction in all-cause mortality compared to placebo. The trial was terminated early after a median of 1.9 years because of a significant treatment benefit in the overall study population. 9 Mora et al 10 recently conducted a gender-specific outcome analysis of JUPITER. At 12 months, the median changes in hsCRP and low-density lipoprotein cholesterol in treated women were 1.8 mg/L and 51 mg/dl, respectively. These decreases were similar to those observed for men in JUPITER. The relative risk reduction of the primary end point was similar and statistically significant in women (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.37 to 0.80, p 0.002) and men (HR 0.58, 95% CI 0.45 to 0.73, p 0.001). Gender-specific differences included greater reductions in unstable angina and revascularization in women (HR 0.24, 95% CI 0.11 to 0.51) compared to men (HR 0.63, 95% CI 0.46 to 0.85 p for heterogeneity 0.01). The hazard risk for all-cause death was nonsignificantly reduced for women and men but was significant when the 2 were combined. This study clearly demonstrated the benefit of statin therapy for primary prevention in women classified

“Actually, It Is More of a Guideline Than a Rule”

In a classic scene from the iconic movie Ghostbusters (1984, directed by Ivan Reitman), Dr. Peter Venkman (played by Bill Murray) confesses to Dana Barrett (played by Sigourney Weaver), “I make it a rule never to get involved with possessed people.” However, after Dana starts to seduce him, Dr.

Alternative access for transcatheter aortic valve replacement in older adults: A collaborative study from France and United States

We examined the outcomes of older adults undergoing nontrans‐femoral (non‐TF) transcatheter aortic valve replacement (TAVR) procedures including trans‐apical (TA), trans‐aortic (TAo), trans‐subclavian (TSub), and trans‐carotid (TCa) techniques.

Nonprimary PCI at hospitals without cardiac surgery on-site: Consistent outcomes for all?

Background The CPORT‐E trial showed the noninferiority of nonprimary percutaneous coronary intervention (PCI) at hospitals without cardiac surgery on‐site (SoS) compared with hospitals with SoS for 6‐week mortality and 9‐month major adverse cardiac events (MACE). However, target vessel revascularization (TVR) was increased at non‐SoS hospitals. Therefore, we aimed to determine the consistency of the CPORT‐E trial findings across the spectrum of enrolled patients. Methods Post hoc subgroup analyses of 6‐week mortality and 9‐month MACE, defined as the composite of death, Q‐wave myocardial infarction, or TVR, were performed. Patients with and without 9‐month TVR and rates of related outcomes were compared. Results There was no interaction between SoS status and clinically relevant subgroups for 6‐week mortality or 9‐month MACE (P for any interaction = .421 and .062, respectively). In addition to increased 9‐month rates of TVR and diagnostic catheterization at hospitals without SoS, non‐TVR was also increased (2.7% vs 1.9%, P = .002); there was no difference in myocardial infarction–driven TVR, non‐TVR, or diagnostic catheterization. Predictors of 9‐month TVR included intra‐aortic balloon pump use, any index PCI complication, and 3‐vessel PCI, whereas predictors of freedom from TVR included SoS, discharge on a P2Y12 inhibitor, and stent implantation. Conclusions The noninferiority of nonprimary PCI at non‐SoS hospitals was consistent across clinically relevant subgroups. Elective PCI at an SoS hospital conferred a TVR benefit which may be related to a lower rate of referral for diagnostic catheterization for reasons other than myocardial infarction.

COMPUTED TOMOGRAPHY ANGIOGRAPHY-DERIVED CORONARY PLAQUE ARC CALCIFICATION IS ASSOCIATED WITH CULPRIT LESION STATUS IN ACUTE CORONARY SYNDROMES

Background: Recent studies have demonstrated that multidetector computed tomography angiography (CTA) can accurately detect the presence of obstructive CAD in symptomatic patients. CTA can also characterize atherosclerotic plaque morphology, which may help improve CAD risk prediction and management. Specifically, the extent of plaque arc calcification may predict coronary lesions that are likely to cause ACS.