AHA 2019 (American Heart Association)

November 16-18, 2019; Philadelphia, PA; Highlights Report #1 – Draft

Executive Highlights

  • Dr. John McMurray presented results from DAPA-HF in patients without type 2 diabetes, confirming the Farxiga’s consistent benefits in a wide patient population of people with heart failure with reduced ejection fraction. Importantly, on safety, no DKA or hypoglycemic events were recorded in the patient population without diabetes.

  • Dr. Elisabetta Patorno revealed additional results from the real-world EMPRISE study of Jardiance, demonstrating a decreased risk of hospitalization for heart failure (HHF) and similar risk of atherosclerotic cardiovascular events with Jardiance when compared to GLP-1s over a mean follow-up of 6.7 months.

  • Dr. Thomas Zelniker presented results from the first biomarker study from the DECLARE-TIMI 58 trial, showing that Farxiga treatment drove greater absolute risk reductions on CV death/hospitalization for heart failure risk in patients with higher baseline NT-proBNP and hsTnT levels. Dr. Zelniker concluded by positing that a combined biomarker approach that integrates these two measurements may yield important information regarding risk stratification and identification of which patients may benefit the most.

  • An early-morning media session promoting AHA and ADA’s joint Know Diabetes by Heart initiative, launched at AHA 2018, featured ADA President Elect Dr. Robert Eckel and Brigham cardiologist Dr. Jorge Plutzky in conversation with program Ambassadors Hyvelle Ferguson and Rob Taub. Above all else, panelists emphasized the need for better education on and understanding of the link between type 2 diabetes and heart disease.

Top Nine Highlights

1. DAPA-HF Analysis in Patients w/o Diabetes Confirms Consistent Heart Failure Benefits Irrespective of Diabetes Status and Across a Wide Spectrum of Baseline A1c Levels

After presenting initial results for the landmark DAPA-HF trial at ESC 2019, Dr. John McMurray gave an important follow-up presentation specifically examining the trial’s patient population without diabetes, confirming dapagliflozin’s consistent effects irrespective of type 2 diabetes status. As a reminder, 45% of study participants had known or undiagnosed diabetes (n=2,137), 37% had prediabetes (n=1,750) and 18% had normoglycemia (n=857) at baseline. On the primary composite endpoint, along with all other secondary endpoints, dapagliflozin’s effect was entirely consistent in the two separate subgroups of patients with and without diabetes at baseline (see table below). The robustness of dapagliflozin’s effects could further be seen across a continuous spectrum of baseline A1c levels as well (see slide below). From a regulatory perspective, these robust and consistent results seen in DAPA-HF should support the expansion of Farxiga’s label to treat HFrEF in a wide patient population of patients with and without diabetes – which should make it the first SGLT-2 inhibitor and diabetes drug to garner an indication outside of diabetes population, to our knowledge.

Endpoint

Diabetes

No Diabetes

P interaction

Composite Endpoint (CV death/hHF/urgent HF visit)

HR=0.75

HR=0.73

p=0.80

CV death

HR=0.79

HR=0.85

p=0.70

Worsening HF event

HR=0.77

HR=0.62

p=0.23

Clinically meaningful change in KCCQ-TS

Deterioration HR=0.78

Improvement HR=1.20

Deterioration HR=0.88

Improvement HR=1.12

p=0.74

Worsening renal function endpoint

HR=0.73

HR=0.67

p=0.86

All cause death

HR=0.78

HR=0.88

p=0.45

  • In terms of safety, rates of adverse events were understandably higher in people with diabetes; however, very importantly, no hypoglycemic or DKA events were observed in people without diabetes. This is a crucial point, as we’ve often heard that a barrier to cardiologists adopting SGLT-2 inhibitors is a reticence toward impacting glucose and concerns over diabetes-related adverse events such as hypoglycemia and DKA. The absence of these signals in the population without diabetes should assuage these concerns. Encouraging safety results here follow-up metabolic and glycemic data presented from DAPA-HF at EASD 2019, where minimal effects on glucose lowering were seen.

  • In setting the stage for this presentation of DAPA-HF results in patients without diabetes, Dr. Larry Allen provided historical context for how many drugs have been “repurposed” from their initial uses. For example, minoxidil was initially a hypertension therapy, but was then found to be efficacious in hair loss treatment. Sildenafil was initially an angina treatment, but is now used for erectile dysfunction. Rituximab was first used in oncology, but is now primarily used in rheumatoid arthritis. Aspirin was first used as an analgesic, but can now be used as a treatment in CAD and colorectal cancer. Dr. Allen wondered whether SGLT-2 inhibitors would be the latest therapy class to undergo such a transition, this time from being primarily a type 2 diabetes drug to now a heart failure (and potentially cardiorenal risk modifying) therapy.

  • Looking ahead, Farxiga is also being studied in HFpEF in the DELIVER trial. DELIVER (n=4,700) aims to examine the same primary endpoints of CV death and worsening of HF as DAPA-HF, but in patients with HFpEF, and is expected to complete in June 2021. Very notably, HFpEF is the form of heart failure thought to be more tightly linked to adiposity, obesity, and diabetes; moreover, current clinical evidence suggests that 30%-40% of people with HFpEF also have type 2 diabetes. There are no currently approved treatment options for HFpEF – Novartis’ Entresto (currently only indicated for HFrEF) just missed superiority in its HFpEF trial, PARAGON-HF. Lilly/BI’s Jardiance is also being studied in HFpEF in the EMPEROR-Preserved trial.

  • For more on DAPA-HF, see our original coverage of results from ESC 2019.

2. Real-World EMPRISE Study for Jardiance Expands to Include Comparison to GLP-1s, Demonstrating Superiority on Heart Failure but Not ASCV Outcomes

The Brigham’s Dr. Elisabetta Patorno presented a new analysis from EMPRISE, Lilly/BI’s ~35,000-patient real-world evidence program on SGLT-2 inhibitor Jardiance, demonstrating a decreased risk of hospitalization for heart failure (HHF) and similar risk of ASCV events with Jardiance when compared to GLP-1s over a mean follow-up of 6.7 months:


Dr. Patorno also presented an updated comparison of Jardiance to DPP-4 inhibitors, including more events than the analysis we saw at ADA 2019 and a slightly-longer mean follow-up of 5.8 months:


“HHF – specific” refers to a primary discharge diagnosis, while “HHF – broad” refers to any discharge diagnosis; ASCV events include MI, stroke, unstable angina (primary discharge diagnosis), or coronary revascularization. In our assessment and Dr. Patorno’s, these results are well-aligned with the understood clinical profile of SGLT-2s, GLP-1s, and DPP-4s based on an abundance of CVOT data, and they reinforce the emerging importance of SGLT-2s as a key treatment for people with type 2 diabetes and existing or risk for heart failure. Moreover, it’s always encouraging to see the positive effects from clinical trials borne out in the real world, as previous real-world evidence programs – AZ’s CVD-REAL, J&J’s EASEL – have also done. As more events make their way into this analysis, we’ll be interested to see whether Jardiance is associated with a lower risk for an ASCV events.

  • These results build on previous EMPRISE results shared at EASD 2019, where Dr. Patorno also presented, showing a 26-34% reduced risk of hospitalization for heart failure (hHF) with empagliflozin vs. GLP-1 agonists in patients with type 2 diabetes. As a reminder, Lilly/BI released the first results from EMPRISE in November 2018 and then presented in-depth heart failure outcomes in a poster at AHA 2018, which Dr. Patorno expanded upon in a presentation at ADA 2019. Review the outcomes from the original EMPA-REG OUTCOME trial here.

  • EMPRISE utilized three US claims databases (Optum, 65 million lives; MarketScan, 150M lives; and Medicare, 55M lives) from August 2014-September 2019 to assess the efficacy, safety, cost, and utilization of Jardiance in new users (within the past year; to avoid immortal time bias). Investigators propensity score matched patients 1:1 across >140 covariates, including baseline demographics, CV conditions and medications, and indicators of diabetes severity. Follow-up continued until treatment discontinuation or switching to comparator, occurrence of an outcome of interest, nursing home admission, death, plan disenrollment, or the end of study period. At each yearly data update, new Jardiance users are matched to new users of a comparator; the next update will come in September 2020, when data through September 2018 will become available. See patient characteristics here:

3. Type 2, Take 2: KOLs and Patients Talk Patient Education and Emphasize Early Intervention in Type 2 + CVD at Know Diabetes by Heart Event

An early-morning media session promoting AHA and ADA’s joint Know Diabetes by Heart initiative, launched at AHA 2018, featured ADA President Elect Dr. Robert Eckel and Brigham cardiologist Dr. Jorge Plutzky in conversation with program Ambassadors Hyvelle Ferguson and Rob Taub. The program centered on the number “two”: While scientists have known for years that type 2 diabetes roughly doubles one’s risk of CVD and stroke, only about half of patients are aware of their increased risk. With this in mind, Know Diabetes by Heart has launched a new campaign to “Give your type 2 a take 2,” calling on patients to dig deeper into their health status. The conversation that followed offered a snapshot of the current zeitgeist surrounding patient engagement, education, and diabetes management at the intersection of type 2 diabetes and cardiovascular health. Perhaps above all else, panelists emphasized the need for better education on and understanding of the link between type 2 diabetes and heart disease. As Dr. Plutzky opened, “When people think diabetes, they think sugar. We want individuals wrestling with diabetes and doctors treating it to be thinking heart disease.” Ms. Ferguson offered her perspective as a “professional patient,” emphasizing that learning about diabetes is a choice every individual has to make and praising ADA and AHA for bringing quality information to an accessible source for patients. And importantly, Dr. Plutzky pointed out, patient understanding is the basis for better diabetes control: Patients have to push through many daily barriers to manage their diabetes well – for example, simply refilling a prescription can be frustrating for a number of reasons. If people living with diabetes better understand what they’re working for and against, he said, they’ll be more likely to stick with their disease management. 

  • The need for earlier intervention in the course of both diabetes and CVD emerged as a critical area for improvement. Dr. Eckel called for a greater emphasis on health across the lifetime and prevention of excess weight gain early in life, given the difficulty of losing and keeping off weight once the body’s set point has been altered. He offered a cautionary tale: it has taken 70 years to reduce tobacco use from ~50% to ~17% of the population, and obesity (an even more complicated issue) is going to be a very long-term fix. Ms. Ferguson pointed to the need for more openness and conversation around diabetes, detailing how her mother lived with type 2 diabetes for years. When Ms. Ferguson herself was diagnosed, she said, the severity and everyday struggle of diabetes did not dawn on her because of how quietly her mother lived with the disease. Only when Ms. Ferguson experienced both a stroke and heart attack did she realize how important managing her diabetes well really was, and she called on patients to talk about their disease and get their kids and families involved. Finding a silver lining among all of this, Dr. Plutzky noted that the long course of silent progression to diabetes and CVD means there’s expansive opportunity to intervene. He highlighted the importance of “knowing your numbers” (blood glucose/A1c, blood pressure, LDL cholesterol, and weight), tracking them over time, and intervening when appropriate.

  • Dr. Eckel addressed ESC’s new recommendation that an SGLT-2 or GLP-1 should be used as first-line therapy in patients with type 2 and either established CVD or at high CVD risk – eschewing metformin in a way other professional societies have been reluctant to. To this point, Dr. Eckel emphasized the importance of Dr. Greg Schwartz’s VA-IMPACT study of metformin in people with prediabetes and CVD (expected completion August 2024), reflecting just how unanswered the question of metformin and cardioprotection remains. Of course, no conversation about diabetes and CVD would be complete without mention of SGLT-2s and GLP-1s, and Dr. Plutzky highlighted an opportunity for patients to engage with their providers – whether in primary care, endocrinology, or cardiology – by asking whether these therapy classes might be right for them. When an attendee expressed concern over cost, Dr. Plutzky was adamant that the process of prior authorization and appealing to insurance is “burdensome but needs to be done,” and he was hopeful that new analyses on cost effectiveness will make coverage more attainable.

4. First DECLARE Biomarker Study Finds Greater Absolute Risk Reduction with Farxiga in Patients w/ Higher Baseline NT-proBNP and hsTnT Levels

Dr. Thomas Zelniker presented results from the first (of presumably many) biomarker studies from the DECLARE-TIMI 58 trial, showing that Farxiga treatment drove greater absolute risk reductions on CV death/hospitalization for heart failure risk in patients with higher baseline NT-proBNP and hsTnT levels. This was a prespecified biomarker analysis of the DECLARE trial. Analysis found that while dapagliflozin treatment consistently reduced relative risk of the CV death/hHF endpoint regardless of baseline biomarker values, a greater absolute risk reduction was seen in the patient population with higher baseline levels of these biomarkers (see slides below). Dr. Zelniker concluded by positing that a combined biomarker approach that integrates NT-proBNP and hsTnT levels may yield important information regarding risk stratification and identification of which patients may benefit the most (in terms of absolute risk reduction) from dapagliflozin treatment. We’ll be curious to see how informative this approach may be in comparison to other risk stratification tools which are not biomarker based – for example, a question that emerged during Q&A was how differentiating this type of assessment may be vs. simply stratifying patients based off of previous heart failure history. At ESC 2019, we saw the presentation of a clinical risk score tool for predicting heart failure risk that inputs five clinical variables: (i) prior heart failure (two points); (ii) atrial fibrillation (one point); (iii) coronary artery disease (one point); (iv) eGFR below 60 (one point); and two points for an UACR >300 or one point for UACR between 30-300. Adding the point values for each of these variables together for each patient gives the patient their individual Risk Score. We wonder how this biomarker data now presented from DECLARE may be integrated to create an even more robust risk stratification and patient identification tool.

  • As background, NT-proBNP and hsTnT are established biomarkers that reflect hemodynamic stress and myocardial injury. Past studies have shown a strong correlation between higher levels of these markers and heart failure events and death.

5. Dr. Blumenthal Outlines Recommendations for Primary CV Prevention in Type 2s: Metformin Remains First-Line; Are GLP-1s & SGLT-2s Cost-Effective?

In their 2019 guidelines on primary prevention of cardiovascular disease, ACC/AHA recommend metformin as first-line pharmacotherapy and a GLP-1 or SGLT-2 as second-line for people with type 2 diabetes. Dr. Roger Blumenthal (Johns Hopkins) explained why metformin is a class IIa recommendation while GLP-1s and SGLT-2s are a lower, class IIb recommendation. He acknowledged robust data on the benefits of GLP-1s and SGLT-2s in secondary CV prevention (the LEADER trial for liraglutide, EMPA-REG OUTCOME for empagliflozin, etc.), but noted that evidence on primary CV prevention with these agents was lacking when the new guidelines were published in May. Full results from Lilly’s REWIND trial for GLP-1 agonist Trulicity (dulaglutide) were presented at ADA the following month: Compared to placebo, dulaglutide reduced risk for three-point MACE by 12% (HR=0.88, 95% CI: 0.79-0.99), and pertinent to Dr. Blumenthal’s discussion, this benefit held true for the 69% of participants (n=9,901 total) without pre-existing CVD. This result certainly suggests a cardioprotective benefit to GLP-1s in primary prevention, but Dr. Blumenthal emphasized that 12% relative risk reduction is “not a huge margin” and that this therapy class may not be cost-effective in a lower-risk population. We appreciate the importance of cost considerations in designing clinical guidelines, so that doctors can actually implement the recommendations for their real-world patients, many of whom are cost-constrained. Dr. Blumenthal captured this point well: “In Maryland at least, it’s very challenging to secure insurance coverage when we prescribe these newer diabetes medications.” That said, we think the science is there to support a meaningful primary prevention benefit to GLP-1 agonist treatment; lowering someone’s risk for a heart attack or stroke by 12% is nothing to scoff at, and we have to move the needle on CVD in diabetes however is possible. Mechanistically, there’s wide consensus among diabetes thought leaders that GLP-1s exert an anti-atherosclerotic effect, which would apply to patients whether or not they’ve had a prior CV event, though of course the magnitude of benefit is greater for sicker individuals (those with CVD and longer duration of diabetes). Longer-term data on use of these advanced agents could reveal cost-effectiveness in primary prevention. We sincerely hope that HCPs at least consider a GLP-1 agonist or SGLT-2 inhibitor for all patients with type 2 diabetes – there is so much room for these products to help more patients obtain better glycemic control and avoid devastating CV events. DECLARE was not mentioned during this talk, but we’d add that AZ’s SGLT-2 inhibitor Farxiga (dapagliflozin) showed significant reduction in hospitalization for heart failure/CV death in a primary prevention diabetes population (HR=0.83, 95% CI: 0.71-0.98).

  • Dr. Blumenthal underscored that lifestyle change and shared decision-making are perhaps the strongest recommendations in the ACC/AHA guidelines. Indeed, the class I recommendations for people with diabetes are (i) dietary counseling and (ii) ≥150 minutes of physical activity per week. Turning to blood pressure, Dr. Blumenthal quipped that “120 is the new 140,” but explained that lifestyle factors should be addressed first, followed by anti-hypertensive drugs at the 130/80 mmHg mark. Open patient-provider conversations ensure the best chance at success. Dr. Blumenthal encouraged HCPs to talk to their patients and “educate them on the strengths and limitations of each guideline.” What do the guidelines say about introducing a statin vs. what is right for this particular patient?

  • On weight loss, Dr. Blumenthal advised measuring BMI (class I) as well as waist-to-hip circumference (class IIa). There’s some evidence that the latter metric has more prognostic ability than high BMI. As we see it, supporting patients in weight loss and obesity management is probably the weakest realm of primary CV prevention currently – HCPs are much more comfortable talking about and treating lipid levels, blood pressure, and even glucose. Showing patients the link between a specific weight-related measurement and long-term health outcomes in a de-stigmatized way is mission-critical.

6. Dr. Verma Identifies Type 2s with PAD as Very High Risk Group; Post-Hocs of LEADER & SUSTAIN 6 Show Enhanced CV Benefit in Participants with Baseline PAD

Expert cardiologist Dr. Subodh Verma showed that type 2s with peripheral arterial disease (PAD) derive extra CV benefit from GLP-1 agonists liraglutide and semaglutide, given higher baseline risk. He presented post-hoc analyses of LEADER (Novo Nordisk’s CVOT for Victoza) and SUSTAIN 6 (Novo Nordisk’s CVOT for Ozempic). LEADER enrolled 1,184 participants with PAD (12.7%), while SUSTAIN 6 enrolled 460 (14%). First, Dr. Verma confirmed his hypothesis that PAD is associated with significantly greater risk for MACE events regardless of therapy. Patients with comorbid type 2 diabetes + PAD experienced 36% more primary outcome events (non-fatal MI, non-fatal stroke, or CV death) compared to patients without PAD in LEADER (HR=1.36, 95% CI: 1.17, 1.58, p<0.0001). In SUSTAIN 6, risk for the same composite primary outcome was 33% higher in the PAD subgroup vs. the non-PAD subgroup (HR=1.33, 95% CI: 0.94, 1.83, p=0.09); note that this finding did not reach statistical significance, but that’s likely due to the smaller total sample size in the semaglutide CVOT.

Next, Dr. Verma described the greater absolute risk reduction for MACE with both liraglutide and semaglutide in type 2s with PAD. In LEADER, Victoza reduced risk for the primary endpoint by 23% vs. placebo in the PAD subgroup (HR=0.77, 95% CI: 0.58, 1.01, p=0.06) and by only 11% vs. placebo in the non-PAD subgroup (HR=0.89, 95% CI: 0.79, 1.00, p=0.05). Notably, the number needed to treat (NNT) to prevent one MACE outcome was only 24 (!) among participants with baseline PAD vs. 70 among those without baseline PAD. The same trend held true for Ozempic in SUSTAIN 6: Relative risk reduction was 39% in the PAD subgroup (NNT 22) and 23% in the non-PAD subgroup (NNT 53).

  • In our view, the most important takeaway from Dr. Verma’s presentation was that presence of PAD should signal to a healthcare provider that a patient is at very high risk for CV morbidity/mortality. The HCP should swiftly prescribe a cardioprotective GLP-1 agent, whether that’s liraglutide, semaglutide, or dulaglutide (Lilly’s Trulicity). In an ideal world, payers would also recognize that PAD confers especially high CV risk and would more generously reimburse GLP-1 agonists to avoid expensive hospitalizations. During Q&A, Dr. Verma alluded to a potential difference in CV effects between human GLP-1-based molecules (e.g. liraglutide, semaglutide, dulaglutide) and exendin 4-based molecules (e.g. exenatide). Ultimately, however, he underscored that within-class differences are trivial. Getting a patient with type 2 diabetes and PAD on any GLP-1 agonist (whatever is most affordable given the individual’s health plan) is key.

 

7. Dr. Yancy Characterizes SGLT-2 Inhibitors as Heart Failure Medicine; Reviews DAPA-HF Results and Looks Ahead to EMPEROR-Reduced

Northwestern’s Dr. Clyde Yancy argued that new data on SGLT-2 inhibitors should alter best practices for treating heart failure. He focused on DAPA-HF, AZ’s trial investigating Farxiga (dapagliflozin) in patients with chronic heart failure, with or without diabetes. Farxiga lowered risk for the primary endpoint of CV death/hospitalization for heart failure/urgent heart failure visit by 26% vs. placebo (HR=0.74, 95% CI: 0.65-0.85, p=0.00001). Dr. Yancy was especially impressed by the low number needed to treat (NNT) – only 21. He additionally emphasized that Farxiga is a once-daily pill requiring no titration; in other words, it’s easy for patients to take and for HCPs to prescribe, making it a no-brainer that this SGLT-2 inhibitor should be incorporated into the recommended approach to heart failure. Dr. Yancy also mentioned that Lilly/BI’s EMPEROR-Reduced trial of Jardiance (empagliflozin) is forthcoming, expected to complete in June 2020. This readout will provide more evidence on how SGLT-2s could play a role in heart failure treatment outside the context of type 2 diabetes. All signs point to heart failure benefit as a class effect of SGLT-2 inhibitors, and we look very forward to EMPEROR results. (Of note, Lilly/BI’s EMPEROR-Preserved trial is expected to complete around the same time, and will provide the first RCT data on an SGLT-2 in heart failure with preserved ejection fraction.)

  • Dr. Yancy advocated for a new heart failure classification scheme as well, adding heart failure with mid-range ejection fraction (HFmEF) in between HFpEF and HFrEF. It was fitting that he followed Dr. Scott Solomon’s presentation on Novartis’ Entresto, which continues to provide significant benefits to patients with ejection fraction >40%, though the effects drop-off at the highest percentages of ejection fraction (>62.5%). Dr. Solomon shared interesting evidence that ejection fraction in heart failure may be more of a spectrum rather than a dichotomy, and Dr. Yancy picked up on this point with the concept of HFmEF.

8. Cost Simulation Analysis Finds Amarin’s Vascepa Cost-Effective at $4.16/day in High CV Risk Patients

Dr. William Weintraub presented results from a cost-effectiveness analysis of Amarin’s Vascepa (icosapent ethyl) which found the therapy to be cost-effective at its price point of $4.16/day. The model used incorporated results from the REDUCE-IT trial to determine lifetime health benefits, health care costs, and cost-effectiveness of Vascepa vs. placebo. With these inputs, the model predicts QALYs over patients’ lifetimes of 11.61 and 11.35 for Vascepa and placebo, respectively. Notably, over 85% of the model’s simulations showed that Vascepa would be cost-effective (defined as <$50,000/QALY gained) at $4.16/day.

  • We’re glad to see Amarin’s commitment to making Vascepa broadly available at an affordable price point for most patients. In the company’s press release accompanying these results, CEO Mr. John Thero is quoted as saying: “This analysis helps to validate something we’ve long believed, and that is central to our mission. It is possible to deliver significant innovation that meaningfully addresses our nation’s most prevalent and costly health epidemic, reduces impacts on patients and families, and drives down costs longer term in the health system. We are working to make this therapy broadly available for improved patient care in high risk patients subject to appropriate regulatory review.” We note that this has been a sustained messaging point for Amarin, as management has consistently stressed that they see the therapy as more of a “volume than pricing” opportunity. As a reminder, Vascepa is currently under review at FDA for an expanded label and CV indication; following a 16-0 Ad Comm vote in favor of its approval, we see a CV indication as a strong likelihood for Vascepa moving forward (with the only question being how broad the indicated patient population will be).

  • ICER also recently released its cost-effectiveness analysis of Vascepa, finding the therapy to provide a net benefit and be cost-effective for its intended patient population.

9. DAPA-HF Age Analysis: Dapagliflozin Consistent Across Baseline Age, w/ Absolute Risk Reduction Greatest in Older Patients

Dr. Felipe Martinez presented an analysis of DAPA-HF by age showing that treatment effects in terms of relative risk reductions were consistent irrespective of age, with greater absolute risk reductions in older patients because of higher baseline risk in this population. When binned by age groups (<55 years, 55-64 years, 65-74 years, and >75 years), dapagliflozin treatment showed consistent relative risk reductions on the primary outcome of CV death/hHF/urgent HF visit. Similar consistent effects were seen when age was treated as a continuous variable as well (see slides below). Regarding safety, renal serious adverse events were higher in older patients in the placebo group, but with a lower numerical number of events in these same patients treated with dapagliflozin, hinting at a potential benefit. Other safety events were also consistent across age, even in elderly patients – a highly reassuring sign, given the burden of polypharmacy in this patient population. Importantly, these results should support Farxiga’s use in a wider patient population with HFrEF regardless of age. These results were also simultaneously published in Circulation

 

--by Ann Carracher, Payal Marathe, Martin Kurian, and Kelly Close