Impact case study database

Lang’s work has influenced guideline development and changed prescribing practice in both aortic stenosis and Type II diabetics with heart failure. His analysis of EHRs has been cited in professional body guidelines and scientific statements, leading to changes in prescribing practice. It also provided support for post-hoc analysis of clinical trials which identified potential benefits of RAS inhibitors in reducing hospital readmissions (thus benefitting patients and relieving pressure on health services) and mortality following transcatheter aortic valve implantation (TAVI) for aortic stenosis; this contributed to the design of the first study to prospectively explore the impact of RAS modulation in ventricular remodelling following TAVI.

Changing guidelines and practice and widening treatment options in Aortic Stenosis

By demonstrating that the use of RAS blockers in aortic stenosis is both safe and effective [R1], Lang influenced the development of American College of Cardiology (ACC) and American Heart Association (AHA) guidelines for the management of valvular heart disease; R1 is one of three studies cited in the 2014 Guidelines [E1] as underpinning evidence for the use of RAS blockers as anti-hypertensives in patients with aortic stenosis (Class 1, Level of Evidence: B). It also contributed to the development of advice on target blood pressure in aortic stenosis patients [E2]. The Guidelines Writing Committee Co-Chair writes [E3]:

… the evidence provided by Professor Lang’s research was used to support the recommendations for management of adults with aortic stenosis in both the 2014 and 2020 American College of Cardiology/American Heart Association Valvular Heart Disease Clinical Practice Guidelines.

R1 has also been cited in support of post-hoc analyses of large randomised controlled trials (e.g. PARTNER-2) [E4] and nationwide registry data [E5] investigating the benefit of RAS blockade in aortic stenosis patients undergoing TAVI. In both scenarios, treatment with RAS blockers was associated with reduced mortality 1-3 years post-procedure. In the case of treatment at discharge there was also a reduction in readmission to hospital due to heart failure [E5]. This secondary analysis contributed to the latest ACC/AHA guidelines on the use of RAS in TAVI, which state that “In patients who have undergone TAVI, RAS blockers may be considered to reduce the long-term risk of all-cause mortality” [E2]. R1 also helped to underpin the RASTAVI trial (NCT03201185) [E6], a randomised open label study examining the impact of RAS blockers on clinical outcomes and ventricular remodelling after TAVI. This work has directly influenced clinical practice guidelines on the treatment of hypertension in patients with aortic stenosis and indirectly contributed to the provision of additional medication options for aortic stenosis patients undergoing TAVI.

Changing guidelines and practice and widening treatment options in Type II diabetes with concomitant heart failure

In 2016, the FDA lifted its warning on the use of metformin in certain patients with reduced kidney function, acknowledging Lang’s evidence [R3] that metformin could safely be used in clinical practice outwith the then-current labelling indications [E7]. Prescribing practice has also changed in the UK: the BNF now advocates ‘caution’ when using metformin in patients with chronic stable heart failure rather than listing heart failure as a contraindication for metformin.

At around the same time the AHA issued a Scientific Consensus Statement [E8] which recognised Lang’s work demonstrating the safe use of metformin to achieve glycaemic control in patients suffering from Type II diabetes with concomitant heart failure. In 2019 the AHA and the Heart Failure Society of America (HFSA) issued a joint Scientific Statement [E9] identifying metformin as a treatment option in this group. This noted Lang’s evidence that metformin has a more acceptable safety profile than sulphonylureas and meant that patients with Type II diabetes and heart failure could be given metformin, which had previously been contraindicated in this group, thus changing clinical practice guidelines and widening treatment options.

Metformin can therefore be used to help achieve glycaemic control and HbA_1c targets as recommended by contemporary clinical practice guidelines. The underpinning evidence of Lang’s team [R5] and others has influenced the development of advice on glycaemic control in patients with Type II diabetes and heart failure [E9]; the Co-Chair of Authors of the 2019 AHA/HFSA Scientific Statement writes [E10]:

… the Dundee group’s research on metformin use has also been impactful… showing that metformin is safe and may be beneficial in patients with HF. In the 2019 Scientific Statement, we considered use of metformin in patients with DM at risk of or with established HF to be reasonable.

Based on the above, I recognize the influence of Professor Lang’s group in guiding doctors on how to treat patients with DM and HF and wholeheartedly support his research agenda.

The Co-Chairs of Authors of the AHA/HFSA Scientific Statement [E9] and the ACC/AHA Valve Disease Guidelines [E2] both confirm Lang’s work influence on approaches to treatment across the world; indeed, the latter states [E3]:

Professor Lang’s research on RAS blockers in aortic valvular heart disease is a major therapeutic advance that has significant clinical impact and provides the foundation for evidence-based guidelines.