Identifying patterns of adverse event reporting for four members of the angiotensin II receptor blockers class of drugs: revisiting the Weber effect

McAdams, Mara; Governale, Laura; Swartz, Lynette; Hammad, Tarek A.; Pan, Gerald J. Dal

doi:10.1002/pds.1633

Cited by 50 publications

(40 citation statements)

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“…Other authors discovered that some NSAIDs had a Weber-like pattern, while others did not [36]. A recent report that correlated usage data with reported AEs also did not observe Weber-like patterns [37]. An analysis of new drugs approved in 2006 also showed no evidence to support the contention that the modern generalization of the Weber effect accurately describes current AE reporting trends [38].…”

Section: Introductionmentioning

confidence: 99%

The Weber Effect and the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS): Analysis of Sixty-Two Drugs Approved from 2006 to 2010

et al. 2014

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BackgroundThe United States Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) consists of adverse event (AE) reports linked to approved drugs. The database is widely used to support post-marketing safety surveillance programs. Sometimes cited as a limitation to the usefulness of FAERS, however, is the ‘Weber effect,’ which is often summarized by stating that AE reporting peaks at the end of the second year after a regulatory authority approves a drug. Weber described this effect in 1984 based upon a single class of medications prescribed in the United Kingdom. Since that time, the FDA has made a concerted effort to improve both reporting and the database itself. Both volume and quality of AE reporting has dramatically improved since Weber’s report, with an estimated 800,000 yearly reports now being logged into FAERS.ObjectiveThe aim of this study was to determine if current FAERS reporting follows the trend described by Weber.MethodsSixty-two drugs approved by the FDA between 2006 and 2010 were included in this analysis. Publicly available FAERS data were used to assess the ‘primary suspect’ AE reporting pattern for up to a 4-year period following each drug’s approval date.ResultsA total of 334,984 AE reports were logged into FAERS for the 62 drugs analyzed here. While a few of the drugs demonstrated what could be considered ‘Weber effect’ curves, a majority of the drugs showed little evidence for the effect. In fact, the general AE reporting pattern observed in this study appears to consist simply of increasing case counts over the first three quarters after approval followed by relatively constant counts thereafter.ConclusionsOur results suggest that most of the modern adverse event reporting into FAERS does not follow the pattern described by Weber. Factors that may have contributed to this finding include large increases in the volume of AE reports since the Weber effect was described, as well as a concerted effort by the FDA to increase awareness regarding the utility of post-marketing AE reporting.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-014-0150-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The Weber Effect and the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS): Analysis of Sixty-Two Drugs Approved from 2006 to 2010

et al. 2014

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“…Additionally, the first angiotensin receptor blockers (ARBs), some of which have uricosuric properties, were approved in 1995. As such, we were unable to assess the association of ARBs, such as losartan, with incident gout because we only considered diuretic exposure prior to the last ARIC study visit, which occurred prior to the introduction of these agents (28). Finally, we are unable to rule out the possibility that the inverse association of other antihypertensive medications is due to the fact that use of an antihypertension medication is also associated with other healthy behaviors beyond what we can adjust for in this analysis.…”

Section: Discussionmentioning

confidence: 99%

Diuretic use, increased serum urate levels, and risk of incident gout in a population‐based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study

McAdams‐DeMarco¹,

Maynard²,

Baer³

et al. 2011

Arthritis & Rheumatism

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Objective To quantify the role of diuretic use on gout development in an adult population with hypertension. Methods ARIC, a prospective population-based cohort from 4 US communities, consists of 4 visits over a 9-year period. Participants were included in this analysis if they answered the gout query, were free of gout at baseline, and had hypertension (medication to treat hypertension or a blood pressure ≥ 140/90 mmHg). Trained interviewers recorded antihypertensive use. Incident gout was defined as self-reported onset after baseline. Using a time-dependent Cox Proportional Hazards model, we estimated the hazard rate ratio (HR) of incident gout by time-varying diuretic use, adjusted for confounders, and tested for mediation by serum urate level. Results There were 5,789 hypertensive participants; 37% were treated with a diuretic. Use of any diuretic (HR=1.48, 95% CI: 1.11, 1.98), thiazide diuretic (HR=1.44, 95% CI: 1.00, 2.10), and loop diuretic (HR=2.31, 95% CI: 1.36, 3.91) was associated with incident gout compared with not using any diuretic, thiazide diuretic or loop diuretics, respectively. After adjusting for serum urate, the association between diuretic use and gout was null. Use of antihypertensive medication other than diuretic agents was associated with decreased gout risk (adjusted HR=0.64 95% CI: 0.49, 0.86) compared to untreated hypertension. The longitudinal change in serum urate was 0.72 mg/dL (95% CI: 0.57, 0.87) higher in those who initiated a diuretic compared with those who did not (p-value<0.001). Conclusions Thiazide and loop diuretics were associated with increased gout risk, an association mediated by a change in serum urate.

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“…Azilsartan medoxomil has also been shown to lower 24-hour BP significantly more than the maximum approved dose of valsartan, the most widely prescribed drug in the ARB class 25,27,44. Specifically, in head-to-head studies using ambulatory BP monitoring in hypertensive patients without serious comorbidities, treatment for 6 weeks with 80 mg azilsartan medoxomil lowered 24-hour systolic BP by 2–4 mmHg ( P < 0.01 to P < 0.001) more than 40 mg olmesartan medoxomil or 320 mg valsartan, respectively (Figure 2).…”

Section: Is There Anything Special About Azilsartan?mentioning

confidence: 99%

Differential pharmacology and benefit/risk of azilsartan compared to other sartans

Kurtz

Kajiya²

2012

VHRM

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Azilsartan, an angiotensin II type 1 (AT1) receptor blocker (ARB), was recently approved by regulatory authorities for treatment of hypertension and is the 8th ARB to join the clinical market. This article discusses the medical reasons for introducing a new AT1 receptor blocker and reviews the experimental and clinical studies that have compared the functional properties of azilsartan to those of other ARBs. The main question addressed is: Does azilsartan have distinguishing features that should motivate choosing it over any of the other sartans for use in clinical practice? Based on studies conducted to date in hypertensive patients without serious comorbidities, azilsartan appears to be characterized by a superior ability to control 24-hour systolic blood pressure (BP) relative to other widely used ARBs including valsartan, olmesartan, and candesartan, and presumably others as well (eg, losartan). Compared to these other ARBs, azilsartan may increase the BP target control and response rate by an absolute value of 8%–10%. Greater antihypertensive effects of azilsartan might be due in part to its unusually potent and persistent ability to inhibit binding of angiotensin II to AT1 receptors. Preclinical studies have indicated that azilsartan may also have potentially beneficial effects on cellular mechanisms of cardiometabolic disease and insulin sensitizing activity that could involve more than just blockade of AT1 receptors and/or reduction in BP. However, the clinical relevance of these additional actions is unknown. Given that the general ability of antihypertensive drugs to protect against target organ damage is largely mediated by their ability to decrease BP, the enhanced antihypertensive effects of azilsartan should serve to justify clinical interest in this ARB relative to other molecules in the class that have a lower capacity to reduce BP.

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Identifying patterns of adverse event reporting for four members of the angiotensin II receptor blockers class of drugs: revisiting the Weber effect

Abstract: A characteristic temporal pattern in the adjusted number of reports, in which the adjusted number was highest in the first year and declined thereafter, was identified. However, we did not observe a pattern consistent with the Weber effect for these four ARBs.

Cited by 50 publications

References 5 publications

The Weber Effect and the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS): Analysis of Sixty-Two Drugs Approved from 2006 to 2010

The Weber Effect and the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS): Analysis of Sixty-Two Drugs Approved from 2006 to 2010

Diuretic use, increased serum urate levels, and risk of incident gout in a population‐based study of adults with hypertension: The Atherosclerosis Risk in Communities cohort study

Differential pharmacology and benefit/risk of azilsartan compared to other sartans

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