Dr. Joe Saseen, PharmD, BCSP, BCACP, FAPhA, introduced the session speaking on the importance of angiotensin II. He noted that angiotensin II “does the magic” of regulating blood pressure, and it is a great opportunity to develop drugs that block angiotensin II. He says that there are a lot of diseases that can benefit from “blunting” the effects of angiotensin II.

While speaking on cardiovascular-renal systems, he noted that, “When the kidneys are diseased, the body suffers…there is a very strong relationship between declining kidney function and cardiovascular all-cause deaths.”

In addition to reiterating the correlation between kidney function and cardiovascular health, he described another “player” in our body—the metabolic system (e.g., pancreas, gut hormones, and liver). He added that disease to either the heart, kidney, or metabolic system will cause a disease on another since they are all interlinked. “The downstream effects of an alteration of one system affects the others, and the starting pathway is the renin-angiotensin-aldosterone pathway,” adding, “That’s why I’m grateful for drugs that target that pathway, but I’m more grateful that we have proof that some of our drugs that target the RAAS pathway really impact the long-term health in a positive way of people with these diseases.”

The primary agents used in hypertension, heart failure, and kidney disease are angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Quoting statistics from the Journal of the American College of Cardiology, Dr. Saseen indicated that long-term benefits of ACEis are:

• Mortality: 17% reduction (relative risk [RR] 0.83, 0.72-0.95)
• Stroke: 35% reduction (RR 0.65, 0.52-0.82)
• Cardiovascular events: 24% reduction (RR 0.76, 0.67-0.85).

He noted that ARB and ACEi therapies “are equal to each other in long-term benefit of hypertension.” He added that ARBs or ACEis are recommended as first-line options for diseases such as heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction, stable ischemic heart disease, diabetes mellitus, and chronic kidney disease (CKD).

Focusing on CKD progression and RAAS therapy, Dr. Saseen explained that studies run as far back as 1993 and the most recent study—called STOP-ACEi—withdrew ACEi therapy in patients with CKD stages IV or V. He explained, “Not to cast any doubt on the benefits [of RAAS therapy] but recognize when people are on dialysis or close to dialysis, it’s not harmful to continue or stop. It’s just that if they’re so far progressed that maybe the opportunity for long-term benefit has expelled, which is disappointing.” He went on to emphasize, “Catch them early. Treat people early before they go on dialysis.”

He added that serum creatinine levels with RAAS therapy may increase up to 30%. He said, “This sounds like a bad thing in these CKD patients, but let’s sort of expect that to happen but not overreact.” He noted that the large “jump” in serum creatinine can be due to bilateral renal artery stenosis, dehydration, or nonsteroidal anti-inflammatory drug use.

According to the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America Guideline for the Management of Heart Failure, the four medication classes utilized in the treatment for HFrEF are angiotensin receptor-neprilysin inhibitors (instead of an ACEi or ARB alone), beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. The guideline states that all four of these therapies can be started simultaneously at low doses. Dr. Saseen refers to these as the “four pillars of HFrEF treatment.”

Summarizing the session, Dr. Saseen noted that:

• The RAAS system regulates blood pressure, and many antihypertensive therapies target this pathway to minimize the effects of angiotensin II and/or aldosterone
• Evidence demonstrates that long-term RAAS inhibitor therapy provides significant benefits in patients with hypertension, heart failure, and kidney disease
• Monitoring of RAAS inhibitor therapy must include at least an assessment of kidney function and serum potassium.

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