The Impact of SGLT2 Inhibitors on Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: To evaluate the role of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with preserved ejection fraction (HFpEF). DATA SOURCES: A literature search of PubMed, the Cochrane Library, and Google Scholar databases (January 2015 to June 20, 2023) was performed with keywords: sodium-glucose co-transporter 2 inhibitors OR SGLT2 inhibitors OR bexagliflozin OR canagliflozin OR dapagliflozin OR empagliflozin OR ertugliflozin OR sotagliflozin AND heart failure OR heart failure with preserved ejection fraction, and terms related to CV outcomes including cardiovascular death, hospitalization, hospitalization for heart failure, mortality, death, and major adverse cardiovascular event (MACE). STUDY SELECTION AND DATA EXTRACTION: The reference list from retrieved articles as well as relevant review articles was considered. Pivotal randomized controlled trials and meta-analyses with a primary or secondary end point of CV death or heart failure hospitalization were included. Studies conducted solely in a diabetic patient population were excluded. DATA SYNTHESIS: Dapagliflozin and empagliflozin, in a broad population of heart failure patients including, HFrEF, HFmrEF, HFpEF, and without diabetes, have shown consistent improvement in the combined outcome of CV death and hospitalization for heart failure (HR 0.80, 95% CI 0.73-0.87) and in the reduction of heart failure hospitalizations (HR 0.74, 95% CI 0.67-0.83). In patients with HFpEF, cardiovascular mortality was not demonstrated (HR 0.88, 95% CI 0.77-1.00). Rates of adverse events were low. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Patients with HFpEF and NYHA class II-III with frequent symptoms or hospitalizations for heart failure derive the most benefit from SGLT2 inhibitors with an overall goal of a reduction in heart failure hospitalizations. CONCLUSIONS: The treatment of HFpEF has made progress, but there is still work to be done. Now, SGLT2 inhibitor therapy can be used to further help with symptom control and reduce overall hospitalizations for heart failure.

Direct Oral Anticoagulants for the Treatment of Venous Thromboembolism in Obesity.

Background: Direct oral anticoagulants (DOACs) are known to have similar efficacy with a decreased risk of bleeding when compared to warfarin for the treatment of venous thromboembolism (VTE). In patients with obesity, there are limited data regarding the safety and efficacy of DOACs. Despite concerns for both under- and over-dosing patients with extremes of body weight, there are no dose adjustment recommendations in the package inserts for any of the DOACs. Objective: To evaluate the safety and efficacy of DOACs versus warfarin for the treatment of VTE in patients with obesity. Methods: This single-center, retrospective cohort study included obese patients initiated on DOAC or warfarin therapy for VTE from January 2015 to January 2022. Patients with cancer, hypercoagulable disorders, end-stage kidney disease, or pregnancy were excluded. The primary endpoint was VTE recurrence. Secondary endpoints included major and minor bleeding. Results: A total of 120 patients met criteria for inclusion. Ninety-two received DOAC therapy and 28 received warfarin. The primary endpoint occurred in 4 patients in the DOAC group and 3 patients in the warfarin group (P = 0.35). Major bleeding occurred in 2 patients. Minor bleeding events occurred in 10 (8.33%) patients. Of those, 6 (6.5%) events occurred in patients receiving a DOAC and 4 (14.3%) events occurred in patients receiving warfarin (P = 0.28). Limitations of this study include the retrospective single-center study design. Conclusions: There was a comparable risk of bleeding and recurrent VTE between DOACs and warfarin in patients initiated on therapy for VTE.

Dual Antiplatelet Therapy After an Acute Nonminor Stroke.

Background: In select patients with minor ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is recommended if initiated early and continued for 21 to 90 days. Dual antiplatelet therapy use, in a broader population, has shown to increase the risk of bleeding without an increased antithrombotic benefit. An ongoing area of uncertainty is whether DAPT would benefit the nonminor stroke population when continued for 21 to 90 days.?s. Objective: To describe the effects of DAPT after a nonminor stroke. Methods: This single-center, retrospective cohort study included patients initiated on antiplatelet therapy started within 1 week of symptom onset for a nonminor ischemic stroke from January 2013 to January 2020. Patients with any bleeding disorder or National Institutes of Health Stroke Scale score <4 were excluded. The primary endpoint was major bleeding at 3 months. Secondary endpoints included recurrent stroke and minor bleeding. Results: A total of 158 patients met criteria for inclusion. Ninety (57%) received DAPT, and 68 (43%) received single antiplatelet therapy (SAPT). The primary endpoint occurred in 3 patients in the DAPT group and 1 patient in the SAPT group (P = 0.463). Minor bleeding occurred in 1 patient receiving DAPT and 2 patients receiving SAPT (P = 0.402). There were 10 patients in the DAPT group and 5 patients in the SAPT group who experienced recurrent stroke or transient ischemic attack (P = 0.429). Limitations of this study include the retrospective single-center study design. Conclusion: There was a comparable risk of bleeding and recurrent stroke between DAPT and SAPT in patients admitted with an acute nonminor stroke.

Safety of Nonvitamin K Antagonists Compared with Warfarin in Patients with Atrial Fibrillation and End-Stage Kidney Disease.

OBJECTIVES: This study evaluated the occurrence of major bleeding following the initiation of oral anticoagulation therapy in patients with end-stage kidney disease (ESKD) in a community teaching hospital. METHODS: This was a single-center retrospective study that enrolled patients admitted to the study hospital with ESKD and who received oral anticoagulation (warfarin or nonvitamin K oral antagonists [NOACs]). The primary endpoint was the occurrence of major bleeding at any time while taking oral anticoagulation. Key secondary endpoints included occurrence of minor bleeding, thrombotic events, and hospitalizations because of bleeding or thrombosis. RESULTS: There were 36 patients who received warfarin and 32 patients who received a NOAC. A major bleeding event occurred in 15 of 36 patients (42%) in the warfarin group and in 5 of 32 patients (16%) in the NOAC group (P = 0.032). Hospitalizations as a result of either a bleeding event or a thrombosis occurred in 19 of 36 patients (53%) in the warfarin group and in 8 of 32 patients (25%) in the NOAC group (P = 0.026). The majority of patients in the NOAC group (69%) received a reduced dose for the indication. CONCLUSIONS: Warfarin increased the risk of major bleeding in patients with ESKD compared with NOACs and did not reduce the risk of thrombotic events.

A Review of Direct Oral Anticoagulants in Patients With Stage 5 or End-Stage Kidney Disease.

OBJECTIVE: To evaluate the role of oral anticoagulation in patients with stage 5 chronic kidney disease (CKD-5) or end-stage kidney disease (ESKD). DATA SOURCES: A literature search of PubMed (January 2000 to July 1, 2021), the Cochrane Library, and Google Scholar databases (through April 1, 2021) was performed with keywords DOAC (direct-acting oral anticoagulant) OR NOAC or dabigatran OR rivaroxaban OR apixaban OR edoxaban AND end-stage kidney disease combined with atrial fibrillation (AF) or venous thromboembolism (VTE) OR pulmonary embolism OR deep-vein thrombosis. STUDY SELECTION AND DATA EXTRACTION: Case-control, cohort, and randomized controlled trials comparing DOACs to an active control for AF or VTE in patients with CKD-5 or ESKD and reporting outcomes of stroke, recurrent thromboembolism, or major bleeding were included. DATA SYNTHESIS: Nine studies were included. Efficacy data supporting routine use of warfarin or DOACs in CKD-5 or ESKD are limited. Rivaroxaban and apixaban may provide enhanced safety compared to warfarin in patients with AF. Data for VTE are limited to 1 retrospective study. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Because of the paucity of rigorous, prospective studies in CKD-5 or ESKD, OACs should not be broadly used in this population. It is clear that data regarding efficacy of DOACs cannot be reliably and safely extrapolated from the non-ESKD population. Therefore, use of OACs in this population should be individualized. CONCLUSIONS: If OACs for stroke prevention with AF are deemed necessary, apixaban or rivaroxaban can be considered. DOACs cannot currently be recommended over warfarin in patients with CKD-5 or ESKD and VTE.

Impact of SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure with reduced ejection fraction.

Heart failure (HF) impacts more than 6 million Americans with an annual mortality rate approaching 22%. Along with optimizing guideline-directed management and therapy (GDMT), the development of treatment options to improve mortality and morbidity in patients with HF with reduced ejection fraction (HFrEF) is paramount. Cardiovascular outcome trials in patients with type 2 diabetes have shown that sodium-glucose cotransporter-2 (SGLT2) inhibitors improve both cardiovascular (CV) and renal outcomes and have consistently reduced hospitalizations for HF in patients with and without a previous history of HF. A precise mechanism by which SGLT2 inhibitors provide benefits for patients with HFrEF has not been identified, and it is probable that multiple pathways may best explain the outcomes seen in recent clinical trials. The mounting evidence that SGLT2 inhibitors reduce HF-related hospitalizations in patients with type 2 diabetes led to the publication of two pivotal trials, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial and the Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure (EMPEROR-Reduced) trial. Data from these publications demonstrate significant benefit of dapagliflozin and empagliflozin on a variety of CV and HF quality of life end points in patients with HFrEF independent of the presence of type 2 diabetes. Now, widespread application of the clinical findings from the DAPA-HF and EMPEROR-Reduced trials must follow with SGLT2 inhibitors incorporated into GDMT for HFrEF regardless of the presence or absence of diabetes. In this review, we examine key literature surrounding the CV outcome data for SGLT2 inhibitors with a specific focus on patients with HFrEF.

Efficacy and Safety of Nonvitamin K Oral Anticoagulants following Cardiac Valve Replacement.

OBJECTIVE: To compare the efficacy and safety of nonvitamin K oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) following bioprosthetic cardiac valve replacement. METHODS: This was a retrospective analysis conducted at a community teaching hospital in the southeastern United States between August 2015 and August 2018. Patients 18 years of age and older who underwent cardiac valve replacement and were prescribed oral anticoagulation were screened for inclusion. Patients were excluded if they had a mechanical valve replacement, experienced a venous thromboembolism, cerebrovascular accident, or acute coronary syndrome within 1 month before valve replacement, changed oral anticoagulation during the study period, were lost to follow-up, or declined to participate in the follow-up survey. The primary outcome was a composite of thromboembolic events within 90 days following bioprosthetic cardiac valve replacement. The safety outcome was major bleeding within 180 days of bioprosthetic cardiac valve replacement. RESULTS: The primary outcome of a composite of thromboembolic events within 90 days following bioprosthetic cardiac valve replacement occurred in 1 patient (4.3%) in the VKA group and 4 patients (7.4%) in the NOAC group. Major bleeding occurred in 2 patients (8.7%) in the VKA group and 0 patients in the NOAC group. CONCLUSION: Our study is the first to report the efficacy and safety of NOACs compared with VKA therapy following bioprosthetic cardiac valve replacement irrespective of an atrial fibrillation diagnosis. Notably, two of the thromboembolic events in the NOAC group occurred while therapy was held or inappropriately dosed; when these events are removed, the rate of thromboembolism is 3.8%. This rate is consistent with the VKA group. Our study adds to a small pool of literature regarding the use of NOACs following bioprosthetic cardiac valve replacement and suggests that NOACs may have similar efficacy and improved safety as compared with VKA therapy. Large randomized controlled trials are warranted to confirm our observations.

Timing of Anticoagulation in Atrial Fibrillation Status Post Cardioembolic Stroke.

BACKGROUND: Anticoagulation is the mainstay of secondary stroke prevention in patients with atrial fibrillation; however, few studies have assessed the optimal timing for initiation of anticoagulation post cardioembolic stroke. In the 2 weeks following an acute cardioembolic stroke, the risk of recurrent stroke is as high as 8%, but this risk must be balanced against the risk of hemorrhagic transformation with early initiation of anticoagulation. PURPOSE: This study described the time to initiation of anticoagulation and evaluated the in-hospital incidence of hemorrhagic and ischemic complications in 106 patients with atrial fibrillation post an acute cardioembolic stroke. METHODS: A single-center retrospective cohort study was conducted to describe the time to initiation of therapeutic anticoagulation in patients with atrial fibrillation admitted to the hospital for an acute cardioembolic stroke. The primary outcome was the time to initiation of anticoagulation from the time of stroke onset. Secondary outcomes included the incidence of in-hospital hemorrhagic and ischemic complications. RESULTS: The median time to initiation of anticoagulation was 59.5 hours after stroke onset for those who did not receive thrombolytic therapy and 82.6 hours for those who did received thrombolytic therapy. Out of 100 patients initiated on anticoagulation, no ischemic complications were observed. Four patients experienced a hemorrhagic conversion following initiation of anticoagulation. In 3 of these patients, anticoagulation was initiated within 48 hours of stroke onset. CONCLUSION: A small percentage of patients experienced an in-house hemorrhagic conversion when anticoagulation was initiated between 48 hours and 7 days.

Nebivolol for the treatment of heart failure.

PURPOSE. The pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of nebivolol are reviewed. SUMMARY. Nebivolol, a third-generation, highly ß(1)-specific ß-blocker, is labeled for the treatment of hypertension in the United States. In addition to its ß-blocking effects, nebivolol has been shown to increase endothelin-dependent nitric oxide, giving it a unique peripheral vasodilatory action. Nebivolol is extensively metabolized by cytochrome P-450 isoenzyme 2D6. In patients with heart failure, certain ß-blockers antagonize excessive adrenergic stimulation and can slow the progression of the disease. Clinical trials have compared nebivolol at target dosages of 5 and 10 mg once daily with placebo and, in small trials, with carvedilol in the treatment of adults with chronic heart failure. Nebivolol appears to have beneficial effects in patients with heart failure, including improvements in left ventricular ejection fraction, left ventricular volumes, and exercise capacity. In addition, the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure showed a reduction in morbidity and mortality after treatment with nebivolol when compared with placebo, though this effect appeared to be less than that of other ß-blockers currently recommended for the treatment of heart failure. Nebivolol was well tolerated in all clinical trials, with the most frequently reported adverse events including bradycardia, hypotension, and dizziness. To date, no large clinical trials have compared nebivolol with currently recommended ß-blockers in patients with heart failure. CONCLUSION. Nebivolol has beneficial effects in heart failure but cannot be considered equivalent to other currently accepted therapies.

Role of tissue plasminogen activator in acute ischemic stroke.

OBJECTIVE: To evaluate the literature regarding the use of intravenous tissue plasminogen activator (tPA) in the treatment of acute ischemic stroke, focusing on the appropriate usage criteria and administration time window. DATA SOURCES: A PubMed and MEDLINE search was performed (1990-November 2010) using the key words alteplase, tissue plasminogen activator, thrombolytic, ischemic stroke, and cerebrovascular accident. STUDY SELECTION AND DATA EXTRACTION: Clinical trials published in English were evaluated and relevant primary literature evaluating the use of tPA in acute ischemic stroke was included. DATA SYNTHESIS: The NINDS (National Institute of Neurological Disorders and Stroke) trial revealed clinical efficacy of tPA in the treatment of acute ischemic stroke when administered within 3 hours of stroke symptom onset and served as the foundation for the American Heart Association/American Stroke Association (AHA/ASA) acute ischemic stroke guideline recommendations. The ECASS (European Cooperative Acute Stroke Study) I, ECASS II, and ATLANTIS (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke), part A and B, trials each assessed the efficacy of tPA when administered beyond 3 hours of ischemic stroke onset, but the results of each trial did not support its use beyond 3 hours. The ECASS III trial showed clinical efficacy of tPA when administered up to 4.5 hours. The SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) and SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Register) registries evaluated the safety and efficacy of tPA at both 3 and 4.5 hours and showed promising results. In 2009, the AHA/ASA stroke guidelines were updated to support the use of tPA in select patients up to 4.5 hours after symptom onset. CONCLUSIONS: tPA is effective when administered up to 4.5 hours after ischemic stroke symptom onset in select patients. However, timely administration remains paramount to achievement of optimal therapeutic outcomes.

A retrospective characterization of worsening renal function in patients with acute decompensated heart failure receiving nesiritide.

UNLABELLED: Nesiritide is approved by Food and Drug Administration (FDA) for the treatment of patients with acute decompensated heart failure (ADHF) due its ability to rapidly reduce cardiac filling pressures and improve dyspnea. Numerous studies have shown that renal dysfunction is associated with unfavorable outcomes in patients with heart failure. In addition, there have been reports suggesting that nesiritide may adversely affect renal function and mortality. OBJECTIVE: The purpose of this retrospective analysis was to assess the effect of dose and duration of nesiritide use and the dose and duration of diuretic therapy on worsening renal function and increased in-hospital mortality in this patient population. METHODS: Seventy-five patients who were hospitalized for ADHF and who were treated with nesiritide for at least 12 hours were reviewed retrospectively. RESULTS: The mean increase in SCr was 0.5 mg/dL (range 0 - 4.4 mg/dL). Thirty-six percent of patients (27/75) met the primary endpoint with an increase in SCr>0.5 mg/dL. Treatment dose and duration of nesiritide did not differ between those patients who had an increase in SCr>0.5 mg/dL and those who did not (p=0.44 and 0.61). Concomitant intravenous diuretics were used in 85% of patients with an increase in SCr >0.5 mg/dL compared to 90% of patients without an increase in SCr>0.5 mg/dL (p=0.57). The in-hospital mortality rate was also higher at 35% in those patients with an increase in creatinine >0.5 mg/dL compared to 11% in those without (p=0.01). CONCLUSION: Nesiritide was associated with an increase in SCr > 0.5 mg/dL in approximately one-third of patients. The increase occurred independently of dose, duration of nesiritide therapy, blood pressure changes, and concomitant intravenous diuretic use. However, the increase in SCr was associated with an increase in hospital stay and in hospital mortality consistent with previous reports in the literature.

Leuconostoc species-associated endocarditis.

Leuconostoc species are gram-positive cocci belonging to the Streptococcaceae family. The species were generally regarded as nonpathogenic and of little importance in clinical microbiology until several occurrences of Leuconostoc infections were reported in the literature. Unlike many gram-positive bacteria, Leuconostoc species commonly demonstrate high-level resistance to vancomycin, with preserved sensitivity to most other antibacterial agents. We describe a 55-year-old man who developed endocarditis caused by Leuconostoc species sensitive to vancomycin. The patient received an aortic valve replacement and was treated with penicillin G and gentamicin; he experienced no further complications.

Thrombocytopenia associated with intravenous ciprofloxacin.

A variety of disease states, disorders, hereditary conditions, environmental toxins, and drugs may cause thrombocytopenia. Fluoroquinolones, however, are not thought to be common offenders. We report the case of a 72-year-old woman who was receiving intravenous ciprofloxacin for a urinary tract infection and developed thrombocytopenia during her hospital stay. Her platelet count dropped from 147 x 10(3)/mm3 on admission to as low as 21 x 10(3)/mm3 . On discontinuation of the drug, her platelet counts began to return to normal. After discharge, the patient continued to improve clinically. Four days after discharge, her platelet count was 197 x 10(3)/mm3 . In the primary literature, we found two case reports on thrombocytopenia associated with ciprofloxacin and one case report with alatrofloxacin. In addition, six additional case reports were found in non-English journals that describe fluoroquinolone-associated thrombocytopenia. Clinicians should be aware of the possible relationship between thrombocytopenia and fluoroquinolones, and platelet counts should monitored accordingly.