Does beta-blocker treatment after myocardial infarction reduce mortality?
Although recommended by guidelines and used as a so-called “quality indicator of hospital care,” the use of beta-blockers following myocardial infarction, when combined with optimum acute and chronic treatment, does not provide a further survival benefit. Beta-blocker use reduces subsequent re-infarction and angina symptoms, but these benefits begin to wane within 30 days. Heart failure and cardiogenic shock can occur with treatment, and patients often have trouble continuing treatment. (LOE = 1a)(www.essentialevidenceplus.com)
Bangalore S, Makani H, Radford M, et al. Clinical outcomes with B-blockers for myocardial infarction: a meta-analysis of randomized trials. Am J Med 2014;127(10):939-953.
Study design: Meta-analysis (randomized controlled trials)
Funding source: Self-funded or unfunded
Setting: Various (meta-analysis)
These authors assembled randomized trials by searching 3 databases, including Cochrane CENTRAL, and found a whopping 60 trials that enrolled more than 100,000 patients. They separately analyzed studies conducted in the "reperfusion era" (n = 12), since the large gains in mortality reduction associated with the availability of thrombolytics, stents, and grafts—as well as the routine use of aspirin and statins—may blunt any additional benefit of beta-blocker treatment. Two researchers independently selected studies for inclusion and evaluated them for bias. Although early studies showed a benefit with beta-blockers, modern era studies show no additional survival benefit when adding a beta-blocker to optimum treatment. Beta-blockers reduce re-infarction rates (number needed to treat [NNT] = 209) and angina symptoms (NNT = 26), but these benefits seemed to be limited to the first 30 days after the initial myocardial infarction. Rates of heart failure and cardiogenic shock are increased (numbers needed to treat to harm = 79 and 90, respectively).
Allen F. Shaughnessy, PharmD, MMedEd
Professor of Family Medicine
Do low-risk patients benefit from prolonged dual-antiplatelet therapy after treatment with drug-eluting stents?
Among patients treated with drug-eluting stents who don't experience a coronary event during the first year, continuing dual-antiplatelet therapy (DAPT) beyond 1 year provides no additional benefit. When the data from this study are pooled with those from other studies, the data not only show a lack of benefit but also demonstrate more frequent serious bleeding. (LOE = 1b)(www.essentialevidenceplus.com)
Collet JP, Silvain J, Barthélémy O, et al, for the ARCTIC investigators. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014;384(9954):1577-1585.
Study design: Randomized controlled trial (double-blinded)
Funding source: Industry + foundation
Setting: Outpatient (specialty)
These researchers report a planned extension of the ARCTIC-Interruption (a truly tortured 29-word acronym*) trial. In the original study, more than 2000 patients who recently received drug-eluting stents randomly received conventional antiplatelet therapy or DAPT on the basis of platelet function testing. After 1 year of follow up, the researchers found no difference between groups. In this planned extension, nearly 1300 of the original study participants were randomized to either continue or discontinue taking DAPT. Although the main reason for excluding patients from continuing was an interval coronary event, among the other reasons for ineligibility for re-randomization were bleeding, lack of adherence, and "no obvious reason." Please bear this in mind as you look at the data. In essence, those who continued in the study are "survivors" -- they tolerated DAPT, were adherent, and were likely to be a lower risk group than the original cohort. These factors, like run-in periods, tend to stack the deck in favor of the intervention. The patients were predominantly men who were 65 years of age. After an additional median follow-up of 17 months, approximately 4% of patients in each group experienced the combination endpoint of death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization. The rate of serious bleeding was also comparable in each group. The authors also pooled their data with those from other studies and similarly found no benefit beyond 1 year of treatment. However, the rate of serious bleeding was significantly higher in the DAPT group (0.8%) than in the control group (0.4%; number needed to treat to harm = 226; 95% CI 139 - 554). So, the methods would strengthen the conclusion that DAPT provides no additional benefit and is more harmful than single antiplatelet treatment. *For those interested, the full name of the study is Assessment by a double Randomisation of a Conventional antiplatelet strategy versus a monitoring-guided strategy for drug-eluting stent implantation, and of Treatment Interruption versus Continuation 1 year after stenting-Interruption trial.
Henry C. Barry, MD, MS
Michigan State University
East Lansing, MI
Does screening for asymptomatic coronary artery disease with computed tomography angiography improve outcomes for adults with type 1 or type 2 diabetes?
Using coronary computed tomography angiography (CCTA) to screen for coronary artery disease (CAD) in adults with type 1 or type 2 diabetes and no indication of existing CAD does not improve outcomes more than standard care. This should come as no surprise since screening for asymptomatic CAD with electron beam tomography (JAMA 2003;289:2215-23), carotid intima-media thickness (Stroke 2001;32:1532-8), and stress myocardial perfusion imaging (JAMA 2009;301:1547-55) also did not improve outcomes. Knowing with additional certainty that a patient is at risk for CAD rarely results in different medical therapy or improved compliance. Perhaps it's time to put the money spent on these types of studies toward more productive endeavors. (LOE = 1b-)(www.essentialevidenceplus.com)
Muhlestein JB, Lappe DL, Lima JA, et al. Effect of screening for coronary artery disease using CT angiography on mortality and cardiac events in high-risk patients with diabetes. The FACTOR-64 randomized clinical trial. JAMA 2014;312(21):2234-2243.
Study design: Randomized controlled trial (single-blinded)
Funding source: Industry + govt
Setting: Outpatient (any)
These investigators wished to determine whether routine screening for CAD with CCTA improves outcomes in adults with type 1 or 2 diabetes without any clinical evidence of CAD. Study eligibility criteria included a history of either type 1 or type 2 diabetes, 50 years or older for men and 55 years or older for women, and no evidence of existing CAD. Consenting patients (N = 900) randomly received (uncertain allocation concealment) screening for CAD with CCTA or no screening. Scan results were divided into 4 categories: (1) severe stenosis: greater than or equal to 70% stenosis in at least 1 major proximal or large coronary artery; (2) moderate stenosis: 50% to 69% stenosis; (3) mild stenosis: 10% to 49% stenosis; or (4) normal: less than 10% stenosis. Patients with severe stenosis were encouraged to undergo diagnostic coronary angiography; those with moderate stenosis underwent stress cardiac imaging and, if the result was abnormal, diagnostic coronary angiography. No further imaging was recommended for patients with mild stenosis or normal coronary arteries. All patients received cardiac risk factor management by their primary care physicians, and surgery or stenting as recommended on the basis of the coronary angiography results. Outcomes were assessed by a team masked to the treatment group assignment and the imaging results. Complete follow-up occurred for all patients for a median of 3.9 years. The study participants had a mean age of 62 years and a diagnosis of diabetes for an average of more than 12 years. Using both intention-to-treat and per-protocol (including only patients who underwent imaging as assigned and recommended) analyses, no significant differences occurred in the composite rate of all-cause mortality, nonfatal myocardial infarction, or unstable angina requiring hospitalization. Patients in the CCTA group did have a significantly increased use of statin therapy and high-intensity statin therapy at 1 year. However, the success rate for reaching prespecified aggressive risk factor reduction care targets at 1 year in CCTA patients was below 50%
David Slawson, MD
Director of Information Sciences
University of Virginia Health System
Does adding sitagliptin to existing therapy for type 2 diabetes mellitus improve outcomes?
The glass half full is that sitagliptin (Januvia) does not increase the risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM). The glass half empty is that it doesn't reduce them, either. And that's the important message: In patients with a mean glycated hemoglobin level of 7.2%, adding sitagliptin at a cost of approximately $350 per month does not affect cardiovascular outcomes at all. (LOE = 1b)(www.essentialevidenceplus.com)
Green JB, Bethel A, Armstrong PW, et al, for the TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;373(3):232-242.
Funding source: Industry
To date, the only drug shown to reduce the risk of cardiovascular events or death in patients with T2DM is metformin. Sitagliptin is one of a class of dipeptidyl peptidase 4 inhibitors that reduces glucose levels by decreasing glucagon levels and increasing insulin secretion. A previous meta-analysis found a 25% relative increase in the likelihood of hospitalization for heart failure with the use of these agents. In this study, the researchers recruited adults older than 50 years with T2DM; current treatment with metformin, pioglitazone, sulfonylurea, or insulin; and a glycated hemoglobin level between 6.5% and 8.0%. Patients with 2 or more recent episodes of severe hypoglycemia were excluded, as were patients with impaired renal function. The patients were randomized to receive sitagliptin 100 mg daily (50 mg if the glomerular filtration rate was 30 - 50 mL/min/1.73 m2) or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction or stroke, or hospitalization for unstable angina. This was designed as a noninferiority (or "no worse than") trial, with the stated goal of determining whether sitagliptin was no worse than placebo at causing cardiovascular events. However, the researchers also looked at whether sitagliptin was superior to placebo for preventing cardiovascular events. They recruited 14,735 patients and followed up for a median of 3 years. The groups were balanced at the beginning of the study, and the mean duration of T2DM was 12 years, with a mean glycated hemoglobin level of 7.2%. The drug did lower glycated hemoglobin levels a bit, by 0.4% after 4 months, but that decreased as time went on. There was no difference in the likelihood of the primary composite outcome, of a composite that did not include unstable angina, or of individual cardiovascular outcomes or mortality for both per protocol and intention-to-treat analyses. Death from any cause occurred in 7.5% in the sitagliptin group and 7.3% in the placebo group, and hospitalization for heart failure occurred in 3.1% in each group.
Mark H. Ebell, MD, MS
University of Georgia
POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).
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