Thursday, November 27, 2014

The risk of GI bleeding associated with SSRIs with and without NSAIDs

Here are the findings of a recent systematic review and meta-analysis:

RESULTS: Fifteen case–control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case–control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42).
CONCLUSIONS: SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

Wednesday, November 26, 2014

More evidence that dabigatran increases the risk of MI

From a recent meta-analysis:

Background Signals of an increased risk of myocardial infarction (MI) have been identified with dabigatran etexilate in randomized controlled trials (RCTs).

Methods and Resules We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta‐analysis included all RCTs and the availability of outcome data for MI, other cardiovascular events, major bleeding, and all‐cause mortality. Among the 501 unique references identified, 14 RCTs fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the fixed‐effect model (FEM) for MI, other cardiovascular events, major bleeding, and all‐cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to 1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to 1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI 0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In RCTs using the 150‐mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to 1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The results of the 110‐mg BID dosage were mainly driven by the RE‐LY trial.

Conclusions This meta‐analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all‐cause mortality.

The data analysis is complex and it is helpful to read the body of the paper (free full test), particularly Table 2, for clarity.

Monday, November 24, 2014

Heart failure performance and outcomes

Here's a recent paper in JACC with some interesting findings:

Methods We assessed rates of compliance with care measures for patients hospitalized with acute or chronic heart failure in the ARIC (Atherosclerosis Risk In Communities) study surveillance catchment area from 2005 to 2009. Rates of compliance were compared between patients with a principal discharge diagnosis of heart failure and those with another principal discharge diagnosis.

I interject here to point out this important distinction. If the primary diagnosis is heart failure the hospital is under the “report card” and financial incentive of the heart failure performance measures. If the heart failure patient is discharged under a different primary diagnosis (with heart failure as a secondary) the hospital is not under the incentive. Keep that in mind in reading the results:

Results Of 4,345 hospitalizations of heart failure patients, 39.6% carried a principal diagnosis of heart failure. Patients with a principal heart failure diagnosis had higher rates of LV function assessment (89.1% vs. 82.5%; adjusted prevalence ratio [aPR]: 1.07; 95% confidence interval [CI]: 1.04 to 1.10) and discharge ACE inhibitor/angiotensin receptor blocker (ARB) in LV dysfunction (64.1% vs. 56.3%; aPR: 1.11; 95% CI: 1.03 to 1.20) as compared to patients hospitalized for another cause. LV assessment and ACE inhibitor/ARB use were associated with reductions in 1-year post-discharge mortality (adjusted odds ratio: 0.66, 95% CI: 0.51 to 0.85; adjusted odds ratio: 0.72, 95% CI: 0.54 to 0.96, respectively) that did not differ for patients with versus without a principal heart failure diagnosis.

So if heart failure is the principal diagnosis and the performance game is in play, participants adhere at a higher rate. That isn't surprising. What surprised me is that the differences were not greater. More interesting to me, though, was the improvement in outcomes associated with following the measures. On the one hand the finding is intuitive; after all, the administration of neurohumeral antagonists guided by assessment of ventricular function is evidence based and would be expected to help patients. On the other hand it is a new finding, in disagreement with prior research, which failed to show that such inherently beneficial and evidence based therapies made a difference in outcomes when associated with performance incentives.

As expressed many times here on the blog, I have a contrarian view of performance measures. This study doesn't change that view much. ACEIs and ARBs seemed to help patients whether their prescription was performance driven or not. The performance driven population (those with a primary diagnosis of heart failure) reflected slightly higher utilization than the comparison group and one could therefore infer that the incentive drove a modest reduction in mortality. Moreover, the idea is plausible. However, as cited in an accompanying editorial, the finding is in contrast to the prior body of research, not only for heart failure but across the whole range of performance measures.

Therein lies the conundrum: take an evidence based treatment (one proven in clinical trials to be beneficial), put it in a public incentive package and it no longer seems to work. The reason is that the way performance is structured, providers are incented to game the system mainly through coding and charting. That, they have discovered, is where the low hanging fruit is for reimbursement and favorable public reporting. Thus performance is not a valid surrogate for quality, either as a driver of patient care or a way to measure it.



Sunday, November 23, 2014

A process improvement tool for acute pancreatitis

From a recent article in the American Journal of Gastroenterology:

METHODS: Design/Setting: Observational study, entitled, The AP Early Response (TAPER) Project. Tertiary center emergency department (ED) and hospital. Participants: Two consecutive samplings of patients having ICD-9 code (577.0) for AP were generated from the emergency department (ED) or hospital admissions. Diagnosis of AP was based on conventional Atlanta criteria. The Pre-TAPER-CDS-Tool group (5/30/06–6/22/07) had 110 patients presenting to the ED with AP per 976 ICD-9 (577.0) codes and the Post-TAPER-CDS-Tool group (5/30/06–6/22/07) had 113 per 907 ICD-9 codes (7/14/10–5/5/11).

Intervention: The TAPER-CDS-Tool, developed 12/2008–7/14/2010, is a combined early, automated paging-alert system, which text pages ED clinicians about a patient with AP and an intuitive web-based point-of-care instrument, consisting of seven early management recommendations.

RESULTS: The pre- vs. post-TAPER-CDS-Tool groups had similar baseline characteristics. The post-TAPER-CDS-Tool group met two management goals more frequently than the pre-TAPER-CDS-Tool group: risk stratification (P less than 0.0001) and intravenous fluids greater than 6L/1st 0–24 h (P=0.0003). Mean (s.d.) hospital LOS was significantly shorter in the post-TAPER-CDS-Tool group (4.6 (3.1) vs. 6.7 (7.0) days, P=0.0126). Multivariate analysis identified four independent variables for hospital LOS: the TAPER-CDS-Tool associated with shorter LOS (P=0.0049) and three variables associated with longer LOS: Japanese severity score (P=0.0361), persistent organ failure (P=0.0088), and local pancreatic complications (less than 0.0001).

CONCLUSIONS: The TAPER-CDS-Tool is associated with changed clinician behavior and shortened hospital LOS, which has significant financial implications.

Saturday, November 22, 2014

Methamphetamine cardiomyopathy (MAC)

Here are some key points from a review:

MAC is a newly emerging entity and is somewhat poorly understood.

It appears to be mainly a dilated cardiomyopathy (systolic dysfunction).

It appears to be reversible upon cessation of the ingestion, acknowledging that there may be a point in time of irreversibility.

It is believed to be catecholamine mediated and as such has features in common with stress cardiomyopathy, including pathologic findings of contraction band necrosis.