Use of low-dose acetylsalicylic acid for cardiovascular disease prevention: A practical, stepwise approach for pharmacists.

Low-dose acetylsalicylic acid (ASA) is recommended in patients with established cardiovascular disease. However, the role of ASA in those without cardiovascular disease (i.e., primary prevention) is less clear, which has led to discordance among Canadian guidelines. In 2018, 3 double-blind, randomized controlled trials were published that evaluated ASA 100 mg daily versus placebo in patients without established cardiovascular disease. In the ASPREE trial, ASA did not reduce the risk of all-cause death, dementia, or persistent physical disability in patients ≥70 years of age but increased the risk of major bleeding. In the ARRIVE trial, ASA failed to lower the risk of a composite of cardiovascular events but increased any gastrointestinal bleeding in patients at intermediate risk of cardiovascular disease. In the ASCEND trial, ASA significantly reduced the primary composite cardiovascular outcome in patients with diabetes for a number needed to treat of 91 over approximately 7.4 years. Yet major bleeding was increased with ASA for a number needed to harm of 112. Therefore, in most situations, ASA should not be recommended for primary cardiovascular prevention. However, there are additional indications for ASA beyond cardiovascular disease. Thus, a sequential algorithm was developed based on contemporary evidence to help pharmacists determine the suitability of ASA in their patients and play an active role in educating their patients about the potential benefits (or lack thereof) and risks of ASA. Can Pharm J (Ott) 2020;153:xx-xx.

Cardiovascular safety outcomes of new antidiabetic therapies.

PURPOSE: The cardiovascular safety outcomes of newer antidiabetic agents were reviewed. SUMMARY: Seven randomized, placebo-controlled trials involving patients with type 2 diabetes mellitus with or at risk for cardiovascular disease were reviewed. The trials examined the cardiovascular safety outcomes of the following agents: alogliptin, saxagliptin, and sitagliptin (dipeptidyl peptidase-4 [DPP-4] inhibitors); liraglutide, lixisenatide, and semaglutide (glucagon-like peptide-1 agonists); and empagliflozin (a sodium glucose cotransport-2 inhibitor). The DPP-4 inhibitor and lixisenatide trials showed a neutral effect on cardiovascular events (composite of cardiovascular death, myocardial infarction, or stroke, with or without unstable angina). Empagliflozin showed a significant reduction in cardiovascular events, cardiovascular death, all-cause death, and hospitalization due to heart failure (HF); liraglutide reduced cardiovascular events, cardiovascular death, and all-cause death, and semaglutide reduced cardiovascular events and nonfatal stroke. Most studies showed a neutral effect of the drug on hospitalization for HF; however, saxagliptin and alogliptin (in the subgroups of patients without a history of HF) showed a significant increase while empagliflozin showed a significant reduction in hospitalizations for HF. The data for empagliflozin, liraglutide, and semaglutide are compelling; however, further studies are necessary to confirm observed benefits and better characterize long-term safety and their use as a strategy to reduce cardiovascular events. CONCLUSION: A review of cardiovascular safety outcomes for new antidiabetic agents found that saxagliptin and alogliptin were associated with an increase in hospitalization for HF. The data for empagliflozin, liraglutide, and semaglutide showed a reduction in cardiovascular events and death or a neutral effect on cardiovascular endpoints.

Influenza Vaccination for Secondary Prevention of Cardiovascular Events: A Systematic Review.

BACKGROUND: Influenza is a common respiratory infection that may cause complications, including cardiovascular events. Influenza illness has been shown to double the risk of myocardial infarction, with the highest risk among patients with established cardiovascular disease. Vaccination against influenza has been associated with reductions in myocardial infarction, cerebrovascular disease, and death. OBJECTIVE: To evaluate the evidence for influenza vaccination as a strategy to reduce cardiovascular events specifically in patients with established cardiovascular disease. DATA SOURCES AND STUDY SELECTION: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched with the terms "influenza vaccine" and "cardiovascular disease". Included in this review were randomized controlled trials (RCTs), nonrandomized studies, and meta-analyses that compared influenza vaccination against control in patients with established cardiovascular disease and that reported clinically meaningful cardiovascular outcomes (defined as cardiovascular death, myocardial infarction, and stroke). DATA EXTRACTION AND SYNTHESIS: The search yielded 10 studies (3 nonrandomized studies, 5 RCTs, and 2 meta-analyses). The nonrandomized studies and the RCTs had inconsistent results with respect to cardiovascular death and adverse cardiovascular events. The 2 meta-analyses, which included the same 4 RCTs involving patients with established cardiovascular disease, showed that the influenza vaccine reduced cardiovascular death by about 50% relative to control. Vaccination also reduced major cardiovascular events by about 43%; the reduction was greater (54%) in the subgroup of patients with recent (≤ 1 year) acute coronary syndrome. However, these data are potentially confounded by small sample sizes, low event rates, and variable outcome reporting. There was also high clinical heterogeneity among the studies, which may not reflect contemporary practice. CONCLUSIONS: Given the limitations of these data, it is unclear whether the cardiovascular benefit with influenza vaccination in patients with cardiovascular disease is a true effect. Nevertheless, because of the potential benefit and the low risk of adverse events, the annual influenza vaccine should be recommended for all patients with established cardiovascular disease.

CONTEXTE: La grippe est une infection courante des voies respiratoires qui peut causer des complications, notamment des événements cardiovasculaires. On a montré que la grippe double les risques d'infarctus du myocarde. De plus, les patients atteints d'une maladie cardiovasculaire sont les plus menacés. La vaccination contre la grippe a été associée à une réduction des cas d'infarctus du myocarde, de maladie cérébrovasculaire et de décès. OBJECTIF: Évaluer les données probantes montrant que la vaccination contre la grippe permet de réduire le nombre d'événements cardiovasculaires chez les patients déjà atteints d'une maladie cardiovasculaire. SOURCES DES DONNÉES ET SÉLECTION DES ÉTUDES: Les bases de données MEDLINE et Embase et le Registre central Cochrane des essais aléatoires ont été interrogés en utilisant les termes « vaccin antigrippal ¼ et « maladie cardiovasculaire ¼. Les études retenues pour la présente revue de la littérature devaient être des essais cliniques à répartition aléatoire, des essais cliniques non aléatoires ou des méta-analyses. De plus, elles devaient comparer les résultats de patients vaccinés contre la grippe et atteints d'une maladie cardiaque à ceux d'un groupe témoin qui étaient aussi atteints d'une maladie cardiaque. Enfin, elles devaient signaler des résultats cardiovasculaires cliniquement significatifs (définis comme un décès d'origine cardiovasculaire, un infarctus du myocarde ou un accident vasculaire cérébral). EXTRACTION ET SYNTHÈSE DES DONNÉES: Dix études répondaient aux critères de recherche (trois essais cliniques non aléatoires, cinq essais cliniques à répartition aléatoire et deux méta-analyses). Les essais cliniques non aléatoires et les essais cliniques à répartition aléatoire présentaient des résultats variables en ce qui touche aux décès d'origine cardiovasculaire et aux événements cardiovasculaires indésirables. Les deux méta-analyses, qui avaient en commun quatre essais cliniques à répartition aléatoire concernant des patients atteints d'une maladie cardiovasculaire, montraient que le vaccin contre la grippe permettait de réduire le nombre de décès d'origine cardiovasculaire d'environ 50 % comparativement au groupe témoin. La vaccination a aussi réduit le nombre d'événements cardiovasculaires graves d'environ 43 %; le pourcentage était plus important (54 %) dans le sous-groupe de patients ayant récemment (à l'intérieur d'un an) souffert d'un syndrome coronarien aigu. Cependant, ces résultats sont potentiellement faussés par la petite taille des échantillons, les faibles taux d'événements et la variabilité avec laquelle on signale les résultats. Il y avait aussi une forte hétérogénéité clinique entre les études, ce qui pourrait ne pas être représentatif de la pratique actuelle. CONCLUSIONS: En raison des limites de ces données, on ignore si le vaccin antigrippal offre réellement des effets cardiovasculaires bénéfiques pour les patients atteints d'une maladie cardiovasculaire. Néanmoins, compte tenu des avantages potentiels et du faible risque d'événements indésirables, le vaccin annuel contre la grippe doit être recommandé pour tous les patients atteints d'une maladie cardiovasculaire.

Systematic Review of Efficacy, Pharmacokinetics, and Administration of Intraventricular Aminoglycosides in Adults.

Due to increasing prevalence of intracranial device use and multidrug-resistant and nosocomial organisms, central nervous system (CNS) infections requiring treatment with intraventricular (IVT) aminoglycosides are becoming increasingly common. This article systematically reviews IVT aminoglycoside literature in adults and integrates available evidence to serve as a practical reference for clinicians. Medline (1946 to December 2015), Embase (1974 to December 2015), PubMed (1966 to December 2015), Google, and Google Scholar were searched using the term aminoglycoside combined individually with the terms IVT, meningitis, shunt infection, ventriculitis, and cerebral spinal fluid. Eighteen articles were included. IVT aminoglycosides were assessed in meningitis, ventriculitis, intracranial device infections and neurosurgery prophylaxis. No serious adverse effects following IVT aminoglycoside were reported. Dosages ranged from IVT gentamicin 4-10 mg daily, IVT tobramycin 5-10 mg daily, and IVT amikacin 5-50 mg daily. Duration of therapy should be individualized; however, continuing IVT antibiotics for 3 days and up to 21 days after cerebrospinal fluid (CSF) sterilization has been reported in literature. Most studies included concomitant intravenous antibiotic use. Therapeutic drug monitoring (TDM) was reported in five studies, with varying timing of CSF concentrations obtained. No clear relationship between CSF levels and efficacy or toxicity was evident. Based on current literature, IVT aminoglycosides for the treatment of sensitive gram-negative meningitis, ventriculitis, and CNS device-associated infections appear safe and effective. Optimal dosing regimens are unclear. It is reasonable to initiate IVT aminoglycoside at lowest dose in combination with IV therapy and continuing post CSF sterilization. Preservative-free formulations should be utilized to minimize adverse drug reactions. TDM should not be routinely utilized but reserved for more complicated patients. Further pharmacokinetic and clinical trials of IVT aminoglycosides are necessary to fill current therapeutic gaps. Due to the relatively limited cases of IVT aminoglycoside utilization, prospective, randomized, controlled trials are likely not feasible, and clinicians will have to rely on data from non-randomized and/or retrospective studies.

Collaborative Cardiovascular Risk Reduction in Primary Care II (CCARP II): Implementation of a systematic case-finding process for patients with uncontrolled risk factors.

BACKGROUND: Previous pharmacist interventions to reduce cardiovascular (CV) risk have been limited by low patient enrolment. The primary aim of this study was to implement a collaborative pharmacist intervention that used a systematic case-finding procedure to identify and manage patients with uncontrolled CV risk factors. METHODS: This was an uncontrolled, program implementation study. We implemented a collaborative pharmacist intervention in a primary care clinic. All adults presenting for an appointment with a participating physician were systematically screened and assessed for CV risk factor control by the pharmacist. Recommendations for risk factor management were communicated on a standardized form, and the level of pharmacist follow-up was determined on a case-by-case basis. We recorded the proportion of adults exhibiting a moderate to high Framingham risk score and at least 1 uncontrolled risk factor. In addition, we assessed before-after changes in CV risk factors. RESULTS: Of the 566 patients who were screened prior to visiting a participating physician, 186 (32.9%) exhibited moderate or high CV risk along with at least 1 uncontrolled risk factor. Physicians requested pharmacist follow-up for 60.8% (113/186) of these patients. Of the patients receiving the pharmacist intervention, 65.5% (74/113) were at least 50% closer to 1 or more of their risk factor targets by the end of the study period. Significant risk factor improvements from baseline were also observed. DISCUSSION: Through implementation of a systematic case-finding approach that was carried out by the pharmacist on behalf of the clinic team, a large number of patients with uncontrolled risk factors were identified, assessed and managed with a collaborative intervention. CONCLUSION: Systematic case finding appears to be an important part of a successful intervention to identify and manage individuals exhibiting uncontrolled CV risk factors in a primary care setting.