https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61461-6.pdf

Towards a comprehensive public health response to population ageing

The Observational CER User's Guide serves as a resource for investigators and stakeholders when designing observational comparative effectiveness research (CER) studies, particularly those with findings that are intended to translate into decisions or actions. The User's Guide provides principles for designing research that will inform health care decisions of patients and other stakeholders. Furthermore, it serves as a reference for increasing the transparency of the methods used in a study and standardizing the review of protocols through checklists provided in every chapter.

Developing a Protocol for Observational Comparative Effectiveness Research: A User's Guide

The pattern of patients admitted to internal medicine wards has dramatically changed in the last 20-30 years. Elderly people are now the most rapidly growing proportion of the patient population in the majority of Western countries, and aging seldom comes alone, often being accompanied by chronic diseases, comorbidity, disability, frailty, and social isolation. Multiple diseases and multimorbidity inevitably lead to the use of multiple drugs, a condition known as polypharmacy. Over the last 20-30 years, problems related to aging, multimorbidity, and polypharmacy have become a prominent issue in global healthcare. This review discusses how internists might tackle these new challenges of the aging population. They are called to play a primary role in promoting a new, integrated, and comprehensive approach to the care of elderly people, which should incorporate age-related issues into routine clinical practice and decisions. The development of new approaches in the frame of undergraduate and postgraduate training and of clinical research is essential to improve and implement suitable strategies meant to evaluate and manage frail elderly patients with chronic diseases, comorbidity, and polypharmacy. Journal of Comorbidity 2011;1:28-44.

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Multiple diseases and polypharmacy in the elderly: challenges for the internist of the third millennium.

Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.

Background The age at which heart failure develops varies widely between countries and drug tolerance and outcomes also vary by age. We have examined the efficacy and safety of LCZ696 according to age in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin converting enzyme inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF).

Methods In PARADIGM-HF, 8399 patients aged 18–96 years and in New York Heart Association functional class II–IV with an LVEF ≤40% were randomized to either enalapril or LCZ696. We examined the pre-specified efficacy and safety outcomes according to age category (years): <55 ( n = 1624), 55–64 ( n = 2655), 65–74 ( n = 2557), and ≥75 ( n = 1563).

Findings The rate (per 100 patient-years) of the primary outcome of cardiovascular (CV) death or heart failure hospitalization (HFH) increased from 13.4 to 14.8 across the age categories. The LCZ696:enalapril hazard ratio (HR) was <1.0 in all categories ( P for interaction between age category and treatment = 0.94) with an overall HR of 0.80 (0.73, 0.87), P < 0.001. The findings for HFH were similar for CV and all-cause mortality and the age category by treatment interactions were not significant. The pre-specified safety outcomes of hypotension, renal impairment and hyperkalaemia increased in both treatment groups with age, although the differences between treatment (more hypotension but less renal impairment and hyperkalaemia with LCZ696) were consistent across age categories.

Interpretation LCZ696 was more beneficial than enalapril across the spectrum of age in PARADIGM-HF with a favourable benefit–risk profile in all age groups.

/pdf/efficacy-and-safety-of-lcz696-sacubitril-valsartan-according-58cx8kb4u8.pdf

Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF.

Methods: In the context of the Increasing the PaRticipation of the ElDerly in Clinical Trials (PREDICT) study, data from ongoing clinical trials regarding heart failure were extracted from the World Health Organization Clinical Trials Registry Platform on December 1, 2008. Main outcome measures were the proportion of trials excluding patients by an arbitrary upper age limit or by other exclusion criteria that might indirectly cause limited recruitment of older individuals. We classified exclusion criteria into 2 categories: justified or poorly justified. Results: Among 251 trials investigating treatments for heart failure, 64 (25.5%) excluded patients by an arbitrary upper age limit. Such exclusion was significantly more common in trials conducted in the European Union than in the United States (31/96 [32.3%] vs 17/105 [16.2%];P=.007) and in drug trials sponsored by public institutions vs those by private entities (21/59 [35.6%] vs 5/36 [13.9%];P=.02). Overall, 109 trials (43.4%) on heart failure had 1 or more poorly justified exclusion criteria that could limit the inclusion of older individuals. A similar proportion of clinical trials with poorly justified exclusion criteria was found in pharmacologic and nonpharmacologic trials. Conclusion: Despite the recommendations of national and international regulatory agencies, exclusion of older individuals from ongoing trials regarding heart failure continues to be widespread.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/226912/ioi05148_550_556.pdf

Roberta Ferretti

Papers

The persistent exclusion of older patients from ongoing clinical trials regarding heart failure.