Wegmans Pharmacy

Ithaca, NY, United States

Wegmans Pharmacy

Ithaca, NY, United States

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Dinicolantonio J.J.,Wegmans Pharmacy | Dinicolantonio J.J.,Charles University
International Journal of Cardiology | Year: 2013

Objective Ascertain platelet inhibition and patient outcomes (PLATO) trial conduct. Methods We examined information from the FDA complete response review. Results FDA Medical Review indicated that (1) patients on ticagrelor monitored by the study sponsor had a lower odds ratio for the primary endpoint (p = 0.0004) versus ticagrelor patients monitored by a third party Clinical Research Organisation (CRO) independent of the study sponsor, (2) a significant interaction existed between ticagrelor and regions monitored by the study sponsor for all cause mortality through study end in favor of ticagrelor (p = 0.006), (3) ticagrelor faired worse than clopidogrel when regions were monitored independent of the study sponsor by a third party Contract Research Organisation (United States, Russia and Georgia), (OR = 1.21, 95% CI: 0.91 to 1.59, p = 0.2022), (4) 46% of all primary endpoint events favoring ticagrelor came from just two countries (Poland and Hungary), (5) PLATO was easy to unblind by breaking open a clopidogrel/dummy clopidogrel tablet with at least 452 patients being unblinded prior to the database lock, (6) significantly more cardiac events submitted for clopidogrel counted in the primary analysis as a myocardial infarction (MI) compared to those submitted for ticagrelor (p < 0.0001), (7) significantly more ticagrelor subjects hospitalized after an index event/hospitalization were not being reported as having a primary event compared to clopidogrel (p = 0.002 in favor of ticagrelor), (8) site-reported MI was not significantly reduced with ticagrelor versus clopidogrel, (9) an estimated 23 definite or possible cardiovascular events or deaths on ticagrelor were either not submitted for adjudication, inactivated, deleted or were downgraded to "softer" endpoints (this was not shown in the FDA review for clopidogrel), and (10) four FDA reviewers voted for non-approval of ticagrelor. Discussion The FDA report highlights what appear to be multiple serious deficiencies in the reporting of the PLATO results, which clinicians will not have gleaned from the primary publication alone. Individual clinicians may therefore wish to carefully reconsider their practice of ticagrelor prescription for this indication. Guideline bodies should also evaluate the information in its totality. © 2013 Elsevier Ireland Ltd.


Serebruany V.L.,Johns Hopkins University | Dinicolantonio J.J.,Wegmans Pharmacy
Thrombosis and Haemostasis | Year: 2013

Recent European Society of Cardiology (ESC) Guidelines declare superiority of prasugrel and ticagrelor over clopidogrel in non-ST segment elevation myocardial infarction (NSTEMI) and STEMI patients with acute coronary syndromes (ACS). The recommendations for NSTEMI and especially STEMI are based on a subgroup analyses yielded from a single trial with either prasugrel (TRITON), or ticagrelor (PLATO). In contrast, the United States (US) Guidelines present a more balanced, conservative, and evidence-based outlook suggesting no proven extra benefit of one P2Y12 antagonist over the other(s). It was the purpose of this study to scrutinise the evidence leading to the current ESC ACS Guidelines on oral antiplatelet agents and compare them with US recommendations. Matching the evidence from TRITON and PLATO primary publications with the data reported in the Food and Drug Administration (FDA) official reviews in light of their impact on current regional ACS Guidelines on antiplatelet P2Y12 inhibitors. The available body of evidence on the efficacy and safety of the new oral P2Y12 inhibitors challenge the ESC Guidelines, and supports the US recommendations. Some of the pivotal data with regard to the newer P2Y12 inhibitors (prasugrel and ticagrelor) on event definition, adjudication, questionable efficacy, and serious safety concerns were ignored by the European Task Force Members, while the other "beneficial" findings were exaggerated to a disproportional extent. We conclude that current ESC Guidelines, with regard to their recommendation of superiority of prasugrel or ticagrelor over clopidogrel, in contrast to the US, are overoptimistic, and not evidence based. Low clinical utilisation of prasugrel and especially ticagrelor worldwide in general, and Europe in particular suggests mismatch of prescription habits with issued ESC recommendations. © Schattauer 2013.


Dinicolantonio J.J.,Wegmans Pharmacy | Serebruany V.L.,Johns Hopkins University
International Journal of Cardiology | Year: 2013

AbstractContext Ticagrelor showed significant reductions in myocardial infarctions (MIs) compared to clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. However, there was no explanation as to whether there was an equal distribution of benefit throughout acute coronary syndrome (ACS) types. Objective To ascertain the safety and efficacy of ticagrelor compared to clopidogrel based on the type of ACS index event (ST-segment elevation myocardial infarction [STEMI], non-ST-segment elevation myocardial infarction [NSTEMI] and unstable angina [UA]). Results The FDA Complete Response Review (CRR) indicates that when MIs were broken down by index event type, ticagrelor fared better than clopidogrel only in patients with STEMI (136/3496 [4.2%] vs. 184/3530 [5.7%], hazard ratio (HR) 0.74 [0.59-0.93]), whereas patients with NSTEMI and UA showed no significant difference (288/4005 [7.9%] vs. 324/950 [8.9%], HR 0.87 [0.74-1.02] and 76/1549 [5.2%] vs. 75/1563 [5.1%], HR 1.02 [0.75-1.42]). Moreover, STEMI patients receiving early (< 24 h) percutaneous coronary intervention (PCI) showed an increase in 30 day MI or cardiovascular (CV) death on ticagrelor compared to clopidogrel, in both the United States (US) and outside-US (OUS) regions (5.0% vs. 1.8% and 3.2% vs. 2.9%, respectively). Conclusions Ticagrelor significantly reduced MIs compared to clopidogrel only in STEMI patients, with those receiving early PCI having worse outcomes with ticagrelor. Despite, NSTEMI patients showing no significant reduction in MI with ticagrelor vs. clopidogrel, CV mortality was significantly reduced. In summary, we cannot be sure what is driving the STEMI-MI benefit, the NSTEMI-CV mortality benefit, nor the overall mortality benefit for ticagrelor-treated patients compared to clopidogrel treated patients. © 2012 Elsevier Ireland Ltd.


DiNicolantonio J.J.,Wegmans Pharmacy | Hackam D.G.,University of Western Ontario
Expert Review of Cardiovascular Therapy | Year: 2012

β-blockers are a standard of care in many clinical settings such as acute myocardial infarction, heart failure and patients at risk for a coronary event. However, not all β-blockers are the same and they vary in properties such as lipophilicity, metabolic profile, receptor inhibition, hemodynamics, tolerability and antioxidant/anti-inflammatory effects. It has been unclear whether these differences affect outcomes or if one β-blocker should be preferred over another. This review will summarize the properties of metoprolol, atenolol and carvedilol, as well as comparative experimental and clinical trials between these agents. We will provide compelling evidence of why carvedilol should be a first-line β-blocker and why it offers many advantages over the β1-selective β-blockers.


Dinicolantonio J.J.,Wegmans Pharmacy
Postgraduate medicine | Year: 2013

Angiotensin-converting enzyme (ACE) inhibitors are a heterogeneous class, varying in pharmacologic properties, which have different therapeutic impacts on patient profiles, including lipophilicity, tissue-ACE binding, duration of action, half-life, and increased bradykinin availability. Among the ACE inhibitor class, the agent perindopril, in particular, has pleiotropic effects that are not equally shared by other ACE inhibitors, including bradykinin site selectivity and subsequent enhancement of nitric oxide and inhibition of endothelial cell apoptosis. Moreover, there is a large amount of evidence to suggest that perindopril therapy may reduce cardiovascular event rates in patients, yet perindopril is rarely prescribed in the United States. Ramipril is another ACE inhibitor with both a favorable clinical profile and impressive outcomes data. Our review compares the pharmacologic and trial data among perindopril, ramipril, and other ACE inhibitors. In patients with or at high risk for coronary heart disease who do not have heart failure, or in patients with heart failure with preserved ejection fraction, perindopril should be among the preferred treatment agents in the ACE inhibitor class. Ramipril has an impressive track record of improving cardiovascular outcomes, too, and should be considered a preferred agent among the ACE inhibitor class.


Dinicolantonio J.J.,Wegmans Pharmacy
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: In the Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) trial, dabigatran 150 mg was shown to be superior to warfarin for the prevention of stroke or systemic embolism. However, there are some concerns with the RE-LY trial, such as its open-label design, potential unblinding of "blinded" adjudicators, the use of concomitant warfarinaspirin (ASA), the disparity between baseline use of nonselective NSAIDs; the high unequal rate of drop-outs; unaccounted drop-ins; high rates of major bleeds in warfarin-treated patients, despite being a low risk population; and rates of major bleeds that do not match historic warfarin trials. Furthermore, although dabigatran offers potential advantages versus warfarin, there are disadvantages that must be taken into consideration before a patient is switched from the latter to the former. This review will summarize the flaws of the RE-LY trial as well as the clinically important advantages and disadvantages of dabigatran and warfarin. Areas covered: This review examines the differences between dabigatran and warfarin in terms of side effects, drugdrug interactions, drugfood interactions, and potential reasons for using one anticoagulant rather than the other. The main focus of this review is a discussion of the design, procedures and results of the RE-LY trial. Expert opinion: There seem to be major flaws with the RE-LY trial. A double-blinded trial should be performed testing dabigatran against warfarin to verify the results of the RE-LY trial. © 2012 Informa UK, Ltd.


DiNicolantonio J.J.,Wegmans Pharmacy | Serebruany V.L.,Wegmans Pharmacy
Diabetes | Year: 2013

Ticagrelor, a novel reversible antiplatelet agent, has a Food and Drug Administration (FDA) black box warning to avoid maintenance doses of aspirin (ASA) .100 mg/daily. This restriction is based on the hypothesis that ASA doses .100 mg somehow decreased ticagrelor's benefit in the Platelet Inhibition and Patient Outcomes (PLATO) U.S. cohort. However, these data are highly postrandomized, come from a very small subgroup in PLATO (57% of patients in the U.S. site), and make no biological sense. Moreover, the ticagrelor-ASA interaction was not significant by any multivariate Cox regression analyses. The Complete Response Review for ticagrelor indicates that for U.S. PLATO patients, an ASA dose .300 mg was not a significant interaction for vascular outcomes. In the ticagrelor-ASA .300 mg cohort, allcause and vascular mortality were not significantly increased (hazard ratio [HR] 1.27 [95% CI 0.84-1.93], P = 0.262 and 1.39 [0.87-2.2], P = 0.170), respectively. Furthermore, for major adverse cardiovascular events (MACEs), 30-day all-cause mortality, and 30-day vascular mortality, the strongest interaction is the diabetes-ASA interaction. That is, patients who had diabetes had significantly fewer MACEs through study end (0.49 [0.34- 0.63], P < 0.0001), significantly less 30-day all-cause mortality (0.33 [0.20-0.56], P < 0.0001), and significantly less 30-day vascular mortality (0.35 [0.22-0.55], P < 0.0001), respectively, when given high-dose (300-325 mg) ASA, regardless of treatment (clopidogrel or ticagrelor) assignment. The black box warning for the use of maintenance ASA doses .100 mg with ticagrelor is inappropriate for patients with diabetes and not evidence based. Copyright © 2013 by the American Diabetes Association.


Dinicolantonio J.J.,Wegmans Pharmacy
Future Cardiology | Year: 2012

Furosemide is the most widely prescribed loop diuretic in the setting of systolic heart failure (HF), yet torsemide has been shown to have less inter- and intra-individual variation in bioavailability and a longer duration of action compared with furosemide. Thus, a systematic review and meta-analysis of randomized controlled trials comparing torsemide versus furosemide in patients with systolic HF using OVID MEDLINE, Excerpta Medica (Embase), Web of Science, PubMed and Google Scholar was performed. Extracted data included study design, sample characteristics, intervention, outcomes and control for potential confounding factors. A DerSimonian and Laird random-effects model was used to compute summary risk ratios for HF and cardiovascular (CV) readmission outcomes. Two randomized trials comparing furosemide with torsemide in 471 patients with systolic HF were identified. Compared to furosemide, torsemide significantly reduced total HF readmissions (relative risk [RR]: 0.41, 95% CI: 0.28-0.61, p < 0.0001) and HF readmissions (RR: 0.53, 95% CI: 0.33-0.84, p = 0.008) as well as CV readmissions (RR: 0.77, 95% CI: 0.60-0.98, p = 0.03) in patients with "at least 1 readmission." Moreover, compared with furosemide, torsemide caused a 14% reduction in all-cause mortality (RR: 0.86 [0.53-1.39], p = 0.54). Compared with furosemide, torsemide significantly reduces HF and CV-related hospital readmissions in systolic HF. Furthermore, torsemide is associated with a trend in reducing all-cause mortality. © 2012 Future Medicine Ltd.


DiNicolantonio J.J.,Wegmans Pharmacy
Expert review of cardiovascular therapy | Year: 2012

Statins are a standard of care in many clinical settings such as acute myocardial infarction and for patients having or at risk of cardiovascular (CV) disease. This is based on a plethora of data showing reductions in CV events and mortality. The CV benefit of statins can be partly explained by their ability to inhibit of HMG-CoA reductase, which subsequently lowers cholesterol and decreases the formation of mevalonate. However, the inhibition of the mevalonate pathway decreases the formation of coenzyme Q10 (CoQ10) within the body. It has been a long-standing theory that statin-associated muscle pain (myalgia) is caused, or at least partly contributed by, a reduction in CoQ10 levels in muscle mitochondria. One of the main side effects of statins is myalgia, which causes the patient to either stop their statin or significantly reduce the dose of their statin. The question of whether CoQ10 can help treat statin myopathy is a common one encountered by clinicians in current day practice.


DiNicolantonio J.J.,Wegmans Pharmacy
Expert Opinion on Pharmacotherapy | Year: 2012

Introduction: Hydrochlorothiazide (HCTZ) has not been shown to reduce mortality or cardiovascular events when given as a single agent. In fact, HCTZ increased cardiovascular death and coronary artery disease (CAD) compared to placebo and usual care in 2 randomized trials, yet it is the most prescribed diuretic in the United States (U.S.). The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure does not recommend one thiazide diuretic over another. However, there are more clinical data for chlorthalidone and indapamide than HCTZ. Areas covered: This review summarizes the differences between HCTZ, chlorthalidone and indapamide for pharmacological profile, surrogate marker data and clinical trial data. Expert opinion: The use of the term 'thiazide diuretic' should be replaced with 'non-thiazide sulfonamide diuretic' for chlorthalidone and indapamide. Furthermore, chlorthalidone and indapamide, rather than HCTZ, should be recommended due to the lack of evidence and potential harm of the latter. © 2012 Informa UK, Ltd.

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