3/24/2023 0 Comments Simultaneous vs sequential testing![]() 2 However, it should be noted that these medications are considered high value by recent cost-effectiveness analyses, despite their present increased price. Insurance coverage remains a barrier for these medications in the United States (US), where prior authorization forms and high copays hinder medication access at both the physician and the patient level. Other issues may include cost, particularly with the more novel SGLT2is and ARNIs. 13-16 Thus the current evidence suggests that a multi-drug treatment regimen is both safe and well-tolerated. 12 Furthermore, both ARNIs and SGLT2is, as well as the old mainstays of GDMT, have proved to be safe when used simultaneously, not only for outpatients, but also during hospitalization for HFrEF. 11 In DAPA-HF, 70-95% of patients were on an ACEI/ARB/ARNI, BB, or MRA, yet the adverse event rates were comparable between the experimental arm and the control arm. In the PARADIGM-HF trial comparing ARNI to standard of care, over 90% of patients in the experimental arm were on BBs and over 50% were on MRAs fewer patients in the experimental arm stopped their medication due to an adverse event, compared to the control arm of enalapril, though there was a run in phase to the trial. However, evidence suggests that the individual components of CDMMT are safe to use concomitantly. 8-10 If these medications are known to prolong life and improve quality of life, why are they not being prescribed? One possible concern for providers and patients alike is polypharmacy. Adherence with HFrEF treatment reduces death due to HF, as well as cardiovascular death or hospitalization due to HF in contrast, both nonadherence and underdosing have been associated with increased rates of HF decompensation and worse survival. Although SGLT2i are now formally recommended for HFrEF by both the American College of Cardiology (ACC) and the European Society of Cardiology (ESC), data surrounding current prescription patterns for HFrEF is not readily available. Worse still, target dosing is as low as 10-20% for ACEI/ARB, 10% for ARNI, 10-20% for BB, and 60-80% for MRA. 5-7 Current estimates suggest that ACE-I/ARB usage in HFrEF is about 60-80% ARNI usage is just above 10% BB usage is about 60-80% and MRA usage is about 30-60%. 2-4ĭespite these incredible advances in HFrEF treatment, utilization rates of both GDMT and CDMMT is dismal with large observational studies suggesting that pharmacotherapies are not being used at their optimal dosing, or worse, not being prescribed at all. 2,3 More recently, comprehensive disease modifying medical therapy (CDMMT) – namely angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter 2 inhibitors (SGLT2i), BBs, and MRAs – have been established as the mainstays of HFrEF care, with estimates suggesting that compared to limited conventional therapy with an ACEI/ARB + BB, use of CDMMT could further reduce cardiovascular mortality in HFrEF by 50%. 1 Subsequently, the use of guideline-directed medical therapy (GDMT) – comprised of an ACE-I or angiotensin receptor blocker (ARB), beta blocker (BB), and mineralocorticoid receptor antagonist (MRA) – became standard of care, with each medication providing additional survival benefit. The evidence for pharmacotherapy improving cardiovascular outcomes in heart failure (HF) with reduced ejection fraction (HFrEF) dates back over 30 years, since the first trials of angiotensin-converting enzyme inhibitors (ACE-I). From an individual perspective, treatment pathways like the rapid sequence initiation of CDMMT can help HFrEF patients quickly and safely start on medications shown to improve cardiovascular outcomes, and from a societal perspective, such pathways can help fill the treatment gap and standardize universal HFrEF care.Historically, the mainstays of HFrEF therapy were started individually and titrated slowly however, new evidence suggests that simultaneous initiation and rapid titration of comprehensive disease-modifying medical treatment namely ARNI, SGLT2i, BB, and MRA is safe, effective, and derives the maximum benefit for the patient.There is robust evidence behind the life-saving pharmacotherapies of chronic HFrEF, yet optimal utilization of such medications is lacking both in the United States and around the world.
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