Tips to prioritize appropriate risk reduction strategies in type 2 diabetes
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PHILADELPHIA — Multiple, evidence-based strategies can decrease CV events in high-risk people with diabetes, yet clinicians must individualize approaches based on patient preference, individual risk factors and cost, according to a speaker.
“Many amazing therapies dramatically improve outcomes,” Lawrence A. Leiter, MD, FRCPC, FACP, FACE, FAHA, FACC, director of the lipid clinic, associate director of the clinical nutrition and risk factor modification center, and associate scientist in the Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto, said during a presentation at the Heart in Diabetes CME Conference. “The challenge is, at the physician and patient level, how do you choose what is the most appropriate therapy?”
Approximately two-thirds of deaths in people with diabetes are attributable to CVD, Leiter said. Observational data from the Swedish National Diabetes Register has shown that optimal CV risk factor control of BP, LDL, albuminuria and tobacco use was associated with reduced risk for ischemic events; however, on average, type 2 diabetes with optimal CV risk factor control was associated with a 45% increase in risk for HF hospitalization. This suggests a multifaceted approach for CVD prevention in people with type 2 diabetes is needed, Leiter said.
Leiter pointed to the STENO 2 trial, which compared intensive therapies to achieve targets in glycemia, lipids, BP and microalbuminuria compared with a standard care arm for a composite outcome of CV death, MI, CABG, PCI, stroke, amputation and peripheral vascular disease surgery, with 21-years of follow-up. Compared with conventional therapy, intensive therapy showed dramatic reductions in all-cause and CV death; people receiving the intensive therapy survived a median 7.9 years longer vs. conventional therapy.
Conflicting evidence on glucose control
However, there is also conflicting evidence on glycemic control and reductions in CVD risk in type 2 diabetes. The ACCORD, ADVANCE, and the original UKPDS and VADT studies, which all involved glucose lowering, showed no evidence of benefit with respect to CVD risk, though MI was reduced by 15%, Leiter said. Yet, several analyses of large CV outcomes trials demonstrated that the trials that had the greatest glucose lowering showed the greatest CV risk reduction, Leiter said.
“I am not suggesting for a moment that the benefit [in the CV outcomes trials] was solely due to glucose lowering, but glucose control may have been partly responsible for the benefits seen in some of these trials,” Leiter said.
Leiter highlighted several other CV risk reduction strategies:
- Obesity is a major determinant for residual CV risk and there are now several proven interventions for weight management, like semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Eli Lilly), which show substantial body weight loss and approach results seen with bariatric surgery, Leiter said. “With different degrees of weight loss, you get different potential benefits,” he said. “We used to say modest weight reduction was beneficial ... We said that because we only had the ability to induce 5% weight loss. With these newer agents, we can do a whole lot better.”
- A BP target of 130/80 mm Hg or 140/80 mm Hg is recommended for people with diabetes, depending on the professional society guideline; data show intensive BP lowering provides greater benefits than less intensive lowering in type 2 diabetes, Leiter said. “A relatively recent meta-analysis looking at 16 trials with intensive BP lowering showed a significant reduction in all-cause and CV death,” Leiter said.
- Lipid lowering benefits people with diabetes; a meta-analysis of statin trials with a mean follow-up of 4.3 years showed people with and without diabetes saw a reduction in major vascular events and all-cause mortality. The REDUCE-IT trial similarly showed a reduction in the primary endpoint of CV death, MI, stroke, coronary revascularization and unstable angina for people assigned icosapent ethyl (Vascepa, Amarin) for triglyceride lowering vs. placebo.
- Aspirin has been shown to significantly reduce the risk for serious vascular events but also significantly increased major bleeding risk, Leiter said, adding that the absolute benefits from avoiding serious vascular events were largely counterbalanced by increased bleeding risk. In the ASCEND study, “There was no group in which the benefits [of aspirin] clearly outweighed the risks,” he said.
Consider patient preference, risks, costs
“Every class of residual CV risks represents an opportunity for directed risk reduction therapy,” Leiter said. “We have lipid risk, inflammatory risk, we have drugs that reduce metabolic risk and drugs that reduce thrombotic risk. So how do we compare benefits and choose which is the best drug for a patient?”
Leiter acknowledged there are challenges in prioritizing secondary prevention strategies. It is difficult to ascertain comparative benefits across trials given the different patient populations, varying trial designs, endpoints and durations of follow-up. Studies to date have not evaluated agents individually and have not investigated whether combinations of preventive drugs could provide synergistic effects, he said. Instead, clinical trials commonly add a new medication to the existing standard of care regimen.
“It is possible that the new drug could obviate the need for prior agents considered ‘standard,’” Leiter said.
“The simplistic answer is, we are going to do all of these things for all of our patients,” Leiter said. “Those of us who practice on a daily basis are fighting with our patients who do not want to take additional agents. Patients and many of our colleagues are pushing back against polypharmacy. So, we must make difficult decisions as to what is or what are the best drugs for a given patient.”
Choosing the best risk reduction strategy will depend on several factors, Leiter said: the degree of abnormality of the risk factor or factors, if measurable, physician comfort with the intervention, cost and access and patient preferences.
References:
- Bhatt DL, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1812792.
- Gaede P, et al. N Engl J Med. 2003;doi:10.1056/NEJMoa021778.
- Rawshani A, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1800256.
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Leiter LA. Session 3: State of the Art Cardio-Renal-Metabolic Diseases. Presented at: Heart in Diabetes; June 24-26, 2022; Philadelphia (hybrid meeting).
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