Margaret L. Ackman

Focused 2012 Update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy

The initial 2010 Canadian Cardiovascular Society (CCS) Guidelines for the Use of Antiplatelet Therapy in the Outpatient Setting were published in May 2011. As part of a planned re-evaluation within 2 years, we conducted an extensive literature search encompassing all topics included in the 2010 CCS Guidelines, and concluded that there were sufficient new data to merit revisiting the guidance on antiplatelet therapy for secondary prevention in the first year after acute coronary syndrome (ACS), percutaneous coronary intervention, or coronary artery bypass grafting, and the interaction between clopidogrel and proton pump inhibitors. In addition, new clinical trials information about the efficacy and safety of combining novel oral anticoagulants with antiplatelet therapy in ACS justified the addition of a new section of recommendations to the Guidelines. In this focused update, we provide recommendations for the use of clopidogrel, ticagrelor, and prasugrel in non-ST elevation ACS, avoidance of prasugrel in patients with previous stroke/transient ischemic attack, higher doses of clopidogrel (j) /day) for the first 6 days after ACS, and the preferential use of prasugrel or ticagrelor after percutaneous coronary intervention in ACS. For non-ACS stented patients, we recommend acetylsalicylic acid/clopidogrel for 1 year, with at least 1 month of therapy for bare-metal stent patients and 3 months for drug-eluting stent patients unable to tolerate year-long double therapy. We also consider therapy for patients with a history of stent thrombosis, the indications for longer-term treatment, discontinuation timing preoperatively, indications for changing agents, the management of antiplatelet therapy before and after bypass surgery, and use/selection of proton pump inhibitors along with antiplatelet agents.

Impact of Tobacco Smoking Cessation on Stable Clozapine or Olanzapine Treatment

Objective To examine the pharmacokinetic implications and potential clinical effects of tobacco smoking cessation in patients on stable clozapine or olanzapine treatment. Data sources A literature search of MEDLINE (1950–November 2009) and EMBASE (1980–November 2009) was conducted using the search terms smoking, tobacco, cigarette, cannabis, smoking cessation, cytochrome P450, antipsychotic, clozapine, and olanzapine. In addition, reference lists from publications identified were searched manually. Study selection and data extraction English-language articles and human studies were identified, yielding 111 returns. Articles that reported clinical outcomes following smoking cessation were selected. Pharmacokinetic data for these drugs were reviewed and articles that provided relevant background information were also included. Data synthesis Pharmacokinetic studies have demonstrated more rapid clearance of olanzapine and lower clozapine and norclozapine (desmethylclozapine) concentrations in smokers compared to nonsmokers. These studies also found that smokers require higher doses of these agents than nonsmokers. There are case reports of adverse clinical outcomes following smoking cessation in patients being treated with olanzapine and clozapine. Reports that included serum concentrations consistently found elevations following smoking cessation, and dosage reductions of 30–40% were required to achieve pre-cessation concentrations. Worsening psychiatric symptoms, somnolence, hypersalivation, extreme fatigue, extrapyramidal effects, and seizures have all been reported following smoking cessation in this patient group. Conclusions Pharmacists need to be aware of potential risks associated with smoking cessation in patients stabilized on clozapine or olanzapine. Toxicity as a result of recent smoking reduction or cessation may be a reason for hospital admission. For hospitalized patients, pharmacists should obtain information concerning smoking status, including cessation attempts. Nonspecific signs and symptoms of elevated clozapine or olanzapine concentrations should be considered in relation to clinical status while the patient is hospitalized. Measurement of baseline serum clozapine concentrations and/or empiric dosage adjustment in patients expected to have a prolonged hospital stay with forced smoking cessation may be appropriate.

Drug Interactions Between Antiplatelet or Novel Oral Anticoagulant Medications and Antiretroviral Medications

Objective: To review potential drug interactions between antiretroviral (ARV) medications and antiplatelets or novel oral anticoagulants (NOACs). Data Sources: A literature search of MEDLINE, PubMed, EMBASE, International Pharmaceutical Abstracts, and Google Scholar was performed using the search terms (1) clopidogrel or ticagrelor or prasugrel, (2) dabigatran or rivaroxaban or apixaban, and (3) antiretrovirals. Study Selection and Data Extraction: Any English language study or case report describing a drug interaction between an ARV and an antiplatelet or NOAC was included. Additional information was taken from pharmacokinetic studies of individual agents alone or information from similar drug interactions. Results: Two studies were identified through the literature search: one reporting an in vivo interaction between ritonavir and prasugrel and the other an in vitro interaction between efavirenz and clopidogrel. A case report describing a drug interaction between nevirapine and rivaroxaban was also located. Information from pharmacokinetic studies and from similar drug interactions allowed for a comprehensive review of potential drug interactions. Conclusions: There are potential drug interactions between ARVs, antiplatelet agents or NOACs. Management of these interactions may include selecting ARVs with a lower potential for drug interactions or choosing antiplatelet agents or NOACs least likely to interact with ARVs. With protease inhibitors or cobicistat, clopidogrel and dabigatran do not appear to have clinically significant interactions. Nonnucleoside reverse transcriptase inhibitors have a low potential for interactions with prasugrel and dabigatran. Clinically significant drug interactions are unlikely to occur between antiplatelet agents or NOACs and nucleoside reverse transcriptase inhibitors raltegravir, dolutegravir, or maraviroc.

The Prevalence of Natural Health Product Use in Patients with Acute Cardiovascular Disease

Background Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown. Objective To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease. Methods Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canadas definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview. Results 88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80% male; 41% admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78% of patients) and 75% of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chinese medicines (9%), homeopathic preparations (1%) and other products including amino acids, essential fatty acids and probiotics (35%). In a multivariable model, only older age was associated with increased NHP use (OR 1.5 per age decile [95%CI 1.03 to 2.2]). When compared to the interview, the highest rate of NHP documentation was the pharmacist history (41%). NHP were documented in 22% of patients by the physician and 19% by the nurse. Conclusions NHP use is common in patients admitted with acute cardiovascular disease. However, health professionals do not commonly identify NHP as part of the medication profile despite its potential importance. Structured interview appears to be the best method to accurately identify patient use of NHP.

Triple antithrombotic therapy in patients with atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation.

PURPOSE The efficacy and safety of triple antithrombotic therapy in patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) with stent implantation are reviewed. SUMMARY A systematic literature search of PubMed, EMBASE, and International Pharmaceutical Abstracts identified a total of 10 cohort studies and one meta-analysis investigating triple antithrombotic therapy in this patient population. With respect to efficacy, evidence from nonrandomized studies supports the superiority of triple antithrombotic therapy over dual antiplatelet therapy at preventing major adverse cardiac events and all-cause mortality. With respect to safety, the heterogeneous methodology and definitions for bleeding in the studies do not allow for easy interpretation and quantification of bleeding risk. There appears to be qualitative consistency that the rate of bleeding is higher with triple antithrombotic therapy compared with dual antiplatelet therapy. The meta-analysis, as well as a recent large registry data cohort study, demonstrated a twofold increase in the risk of major bleeding with triple antithrombotic therapy. CONCLUSION The heterogeneous methodology of the available studies does not allow for conclusive interpretation and quantification of the efficacy and safety of triple antithrombotic therapy in patients with AF undergoing PCI with stent implantation compared with dual antiplatelet therapy. Evidence from small cohort studies support the benefit of triple antithrombotic therapy at reducing major adverse cardiac events and all-cause mortality with higher rates of bleeding.

The Role of Direct Oral Anticoagulants in Patients With Coronary Artery Disease

Despite contemporary management, patients with coronary artery disease (CAD) remain at high risk for thrombotic events. Several randomized controlled trials have evaluated the use of direct oral anticoagulants (DOACs) in patients with CAD, including in the setting of acute coronary syndrome (ACS) and stable CAD, and in patients with concomitant atrial fibrillation. Trials of apixaban and dabigatran in patients with ACS demonstrate no benefit with an increased risk of bleeding. Conversely, rivaroxaban at a reduced dose of 2.5 mg twice daily reduced thrombotic events and all-cause mortality when added to dual antiplatelet therapy in patients with ACS. Similarly, the addition of low-dose rivaroxaban to acetylsalicylic acid reduced the risk of thrombotic events in patients with stable CAD. However, the addition of a DOAC to antiplatelet therapy increased the risk of major bleeding. In patients with atrial fibrillation undergoing percutaneous coronary intervention, dual-pathway or low-dose triple therapy regimens including dabigatran or rivaroxaban reduced bleeding risk compared to traditional warfarin-based triple therapy, although it remains unclear whether these regimens preserve antithrombotic efficacy. DOAC–based antithrombotic regimens prove useful in patients with CAD in various settings; however, careful selection of patients and regimens per trial protocols are critical to achieving net benefit.

A pharmacist’s guide to the 2012 update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy

The initial Canadian Cardiovascular Society (CCS) Guidelines on the Use of Antiplatelet Therapy1 covered chronic antiplatelet therapy for a number of diseases and patient subgroups. The 2012 Focused Update2 specifically addressed the issues of antiplatelet therapy for secondary prevention in the first year after acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and the interaction between clopidogrel and proton pump inhibitors (PPIs). The updating of these topics and the prominence of the newer antiplatelet agents in the guidelines make them of particular relevance to pharmacists. The intent of this publication is to highlight components of the guidelines that are most likely to affect the practice of pharmacists and provide practical information to assist pharmacists in managing patients on antiplatelet therapy.

Review of the top 5 cardiology studies of 2013-14:

Within the field of cardiology, many trials are published each year; however, only a portion of these address clinical questions relevant to pharmacists in general practice, and an even smaller number have the potential to change patient care. This article presents 5 recent cardiovascular studies deemed to be the most pertinent to pharmacy practice.

Patient Tool in Combination Antiplatelet Rx Resource Kit Supports Seamless Care in ACS

Cardiovascular patients receiving dual antiplatelet therapy may benefit from a resource kit that explains the role of medication in acute coronary syndrome. This initiative from The Canadian Cardiovascular Pharmacists Network/Réseau Canadian des Pharmaciens Impliqués en Soins Cardiovasculaires (CCPN/RCPC) is a tool for hospital and community pharmacists striving to support patients who are being discharged after having an acute coronary syndrome. The kit includes: Information sheets for patients and their community pharmacists and family physicians Suggested strategies on reimbursement issues.