Box 1 delineates the search strategy and selection criteria for studies that informed this statement.ĭespite guideline-recommended treatment of ASCVD risk, including antihypertensive and high-intensity statin therapy, or antiaggregant agents, high-risk patients, especially those with established ASCVD, continue to experience cardiovascular events. Is it possible to selectively modify the pharmacological characteristics of a PPARα agonist to improve the profile of beneficial effects and address known safety issues associated with fibrate treatment? And, if this is feasible, would this represent a novel therapeutic class? This Joint Consensus Panel from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) evaluated these questions in the context of evidence for the first of the selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα). Hence, there is a clear need for new therapeutic options. However, these agents have limitations, most importantly due to pharmacokinetic interactions, such as increased risk of myopathy with statins for gemfibrozil, or side effects, which include reversible elevation in serum creatinine (with fenofibrate), as well as liver enzyme elevation. After statins, guidelines recommend peroxisome proliferator-activated receptor alpha (PPARα) agonists-fibrates-for management of hypertriglyceridemia. Elevated plasma triglycerides (TG), with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common pattern of dyslipidemia, especially in those with insulin resistant conditions such as T2DM. Ītherogenic dyslipidemia, however, remains a major unmet clinical need in such populations.
Furthermore, escalation in the prevalence of NAFLD in these regions, particularly the Middle East and Latin America, has contributed to this increasing ASCVD burden independent of traditional risk factors. While this burden affects all regions, it presents a particular threat in low- and middle-income countries, which have the largest populations affected by obesity and diabetes. Over the last 20 years, chronic lifestyle-related diseases such as visceral obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) have exacerbated the burden of death and disability due to ASCVD.
STONE JORDAN BLUEPRINT PRO ACTIVATION TRIAL
The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.Ītherosclerotic cardiovascular disease (ASCVD) presents a growing global health challenge. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potentialĪ consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) FoundationĬardiovascular Diabetology volume 18, Article number: 71 ( 2019)
0 kommentar(er)
