Appropriateness of Oral Drugs for Long-term Treatment of Lower Urinary Tract Symptoms in Older Persons

Results of a Systematic Literature Review and International Consensus Validation Process (LUTS-FORTA 2014)

Matthias Oelke; Klaus Becher; David Castro-Diaz; Emmanuel Chartier-Kastler; Mike Kirby; Adrianwagg; Martinwehling

Disclosures

Age Ageing. 2015;44(5):745-755. 

In This Article

Abstract and Introduction

Abstract

Aim: we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification.

Methods: to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process.

Results: for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin.

Conclusions: dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D).

Introduction

Drugs for the treatment of lower urinary tract symptoms (LUTS) rank among the most frequently prescribed medications for older men and women.[1] While there are several drug classes with proven efficacy available for their treatment (i.e. α-blockers, antimuscarinics, 5α-reductase inhibitors, phosphodiesterase type 5 (PDE5) inhibitors, and β3-agonists), there is no systematic comparative study on the published evidence base for their appropriateness or inappropriateness for this population.

Older people are more heterogeneous than younger individuals; they have more medical problems (multimorbidity) and take more medications as a consequence (polypharmacy). Pharmacotherapy for older persons requires clinicians to consider the alternations in pharmacodynamics and pharmacokinetics associated with ageing and the increased likelihood of drug–drug interactions and adverse events. The efficacy and safety of any proposed treatment may be different from that in younger people. For older persons with multimorbidity and/or geriatric syndromes (e.g. dementia), remaining life expectancy, and caregiver wishes and expectations also play a role in treatment decisions. Multimorbidity is extremely common in today's older people; those aged >80 years have an average of three diagnoses[2] leading to polypharmacy with 44% of men and 57% of women ≥65 years in the USA,[3] and one-third in Germany[4] taking five or more drugs.

When used appropriately, there are health benefits associated with multiple appropriate drugs but adverse reactions reported by the Food and Drug Administration tripled between 1995 and 2005. These reactions have been shown to be the fourth leading cause of death in the USA.[5] Choosing the right drug, for the right patient, at the right time, is also critically important in the management of LUTS in older people, because they are highly prevalent and bothersome in both men and women.[6]

The FORTA (Fit fOR The Aged) classification was introduced in 2008 with the aim of guiding physicians in their screening process for inappropriate or harmful medications and drug omissions in older patients in an everyday clinical setting.[7,8] FORTA represents the first classification system in which both negative and positive labelling is combined at the level of individual drug or drug groups. The system aims at the individual indications (implicit listing requiring patient characteristics/diagnoses) and is therefore different from negative lists such as the American Geriatrics Society Beers Criteria list,[9] the STOPP (Screening Tool of Older Person's Prescriptions) criteria[10] or the German PRISCUS list.[11] Involving a two-step Delphi process and rating by a total of 25 experts, the FORTA classification has led to a listing (FORTA list) of >200 different drugs/drug groups for over 20 main therapeutic areas with relevance to older people which is continuously expanded and refined.[12]

In brief (for details, see ref. 12), the FORTA classification labels, depending on the state of evidence for safety, efficacy and overall age-appropriateness, are assigned for individual drugs as follows:

  • Class A (absolutely): indispensable drug, clear-cut benefit in terms of efficacy/safety ratio proven for a given indication in older people.

  • Class B (beneficial): drugs with proven or obvious efficacy in older people, but limited extent of effect or safety concerns.

  • Class C (careful): drugs with questionable efficacy/safety profiles in older people, to be avoided or omitted in the presence of too many other drugs, lack of benefits or emerging side effects; review/find alternatives.

  • Class D (don't): avoid in older people, omit first, review/find alternatives.

For example, relevant antihypertensive drugs are classified as follows: ACE-inhibitors/angiotensin-receptor antagonists and long-acting dihydropyridine calcium antagonists: FORTA A; β-blockers/diuretics: FORTA B; spironolactone/moxonidine: FORTA C; clonidine/verapamil: FORTA D.[12] FORTA does not take the place of individual therapeutic considerations or decisions. Contraindications always take precedence over the FORTA classification and the system allows for exceptions. Application of the FORTA list has led to the first published endpoint effect of a listing approach: the rate of falls, a major geriatric problem, could be reduced by two-thirds and overall medication quality improved compared with standard care.[13]

In this article, we present the analysis and rating process of an independent multiprofessional international expert panel for the 16 most commonly prescribed oral drugs for long-term use in patients with LUTS, based on a systematic literature review and a subsequent two-step Delphi approach using the FORTA classification.

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