Cardinal Tweets.Volume 2 Issue 1

Summer 2014

Volume 2, Issue 1

William Linn, Pharm D, Department of Pharmacy Practice (210) 883-1077

TOPCAT 1 Bariatric Surgery in

T2DM 2 Azithromycin in Older

Patients with Pneumonia 3

2013 ACC/AHA Lipid Guidelines 4

Statin Patient-centered Care 5

Spironolactone for Heart Failure with Preserved Ejection

FractionPitt B, Pfeffer MA, Assmann SF for the TOPCAT Investigators. N Engl J Med 2014;370:1383-1392. Background Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. Methods In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. Results With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. Conclusions In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.) Bottom line: Mineralocorticoid-receptor antagonists have proven benefits in patients with heart failure and reduced ejection fractions. Their use in patients with a preserved ejection fraction is evolving.

Association of Bariatric Surgery With Long-term Remission of Type 2 Diabetes

and With Microvascular and Macrovascular Complications. Sjostrom L, Peltonen M, Jacobson P, Ahlin S, Anderson-Assarsson J, et al. JAMA. 2014;311(22):2297-2304. IMPORTANCE Short-term studies show that bariatric surgery causes remission of diabetes. The long-term outcomes for remission and diabetes-related complications are not known. OBJECTIVES To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS The Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden. Of patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline. For the current analysis, diabetes status was determined at SOS health examinations until May 22, 2013. Information on diabetes complications was obtained from national health registers until December 31, 2012. Participation rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41%in the control group and 90%, 76%, and 47% in the surgery group. For diabetes assessment, the median follow-up time was 10 years (interquartile range [IQR], 2-15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively. For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2-19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups, respectively. INTERVENTIONS Adjustable or nonadjustable banding (n = 61), vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures were performed in the surgery group, and usual obesity and diabetes care was provided to the control group. MAIN OUTCOMES AND MEASURES Diabetes remission, relapse, and diabetes complications. Remission was defined as blood glucose <110 mg/dL and no diabetes medication. RESULTS The diabetes remission rate 2 years after surgery was 16.4%(95%CI, 11.7%-22.2%; 34/207) for control patients and 72.3%(95%CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio [OR], 13.3; 95%CI, 8.5-20.7; P < .001).At 15 years, the diabetes remission rates decreased to 6.5%(4/62) for control patients and to 30.4%(35/115) for bariatric surgery patients (OR, 6.3; 95%CI, 2.1-18.9; P < .001). With long-term follow-up, the cumulative incidence of microvascular complications was 41.8 per 1000 person-years (95%CI, 35.3-49.5) for control patients and 20.6 per 1000 person-years (95%CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44; 95%CI, 0.34-0.56; P < .001). Macrovascular complications were observed in 44.2 per 1000 person-years (95%CI, 37.5-52.1) in control patients and 31.7 per 1000 person-years (95%CI, 27.0-37.2) for the surgical group (HR,0.68; 95%CI,0.54-0.85; P = .001). CONCLUSIONS AND RELEVANCE In this very long-term follow-up observational study of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care. These findings require confirmation in randomized trials. Bottom line: These long-term data from an observational study in Sweden support the benefits of bariatric surgery in obese patients with type 2 diabetes. Confirmation of these finding with randomized trials is important.

Association of Azithromycin With Mortality and Cardiovascular Events Among

Older Patients Hospitalized With Pneumonia. Mortensen EM, Halm EA, Pugh MJ, Copeland LA, Metersky M, et al. JAMA. 2014; 311 (21):2199-2208.

IMPORTANCE Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS Of 73 690 patients from 118 hospitals identified, propensity-matched groups were composed of 31 863 patients exposed to azithromycin and 31 863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95%CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1%vs 4.4%; OR, 1.17; 95%CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95%CI, 0.95-1.02), or heart failure (26.3%vs 26.2%; OR, 1.01; 95%CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use. Bottom line: In this national cohort of veteran patients hospitalized with pneumonia, treatment with azithromycin was associated with a significant reduction in mortality compared to patients not receiving azithromycin. For every 21 patients treated with azithromycin, 1 death was prevented within 90 days of hospitalization.

2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce

Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College

of Cardiology/American Heart Association Task Force on Practice Guidelines Stone NJ, Robinson J, Lichtenstein AH, Merz CNB, Blum CB, et al. Circ Published online November 12, 2013.

Treatment Categories Clinical ASCVD: Age < 75 years, High-intensity statin; age > 75 years, Moderate-intensity statin LDL-C ≥ 190 mg/dL: High-intensity statin Type 1 or 2 Diabetes (Age 40-75) with LDL-C < 190 mg/dL: Moderate-intensity statin; 10-y CHD risk ≥ 7.5%, High-intensity statin Age 40-75 & 10-y CHD risk ≥ 7.5%: Moderate-to-High intensity statin

Table 5. High- Moderate- and Low-Intensity Statin Therapy (Used in the RCTs reviewed by the Expert Panel)* High-Intensity Statin Therapy

Moderate-Intensity Statin Therapy

Low-Intensity Statin Therapy

Daily dose lowers LDL–C on average, by approximately ≥50%

Daily dose lowers LDL–C on average, by approximately 30% to <50%

Daily dose lowers LDL–C on average, by <30%

Atorvastatin (40†)–80 mg Rosuvastatin 20 (40) mg

Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin 20–40 mg‡ Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2–4 mg

Simvastatin 10 mg Pravastatin 10–20 mg Lovastatin 20 mg Fluvastatin 20–40 mg Pitavastatin 1 mg

Specific statins and doses are noted in bold that were evaluated in RCTs (17,18,46-48,64-67,69-78) included in CQ1, CQ2 and the CTT 2010 meta-analysis included in CQ3 (20). All of these RCTs demonstrated a reduction in major cardiovascular events. Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed in italics.

Bottom line: The data recommending high-intensity statin therapy is weak. Many lipidologists suggest that most patients receive moderate-intensity statin therapy. In very high risk patients the dose can be titrated up. In elderly patients or patients at high risk for side effects, low-intensity statin therapy is recommended.

Relative Risk Reduction With Statin Therapy

Scenario: Mr. Wilson comes into your pharmacy to pick up some 81 mg ASA. He is 65 years old. He is on simvastatin 20 mg daily because his 10-y CHD risk was 20%. His LDL-c is now 100 mg/dL. His doctor wants to double his dose of simvastatin to further decrease his chance of having a heart attack. Mr. Wilson would like your advice on whether he should increase the dose.