ACE Inhibitors

Post-ACS for patients with LVEF ≤ 40%, hypertension, diabetes, CKD, or an anterior STEMI: blocking angiotensin limits the adverse remodeling that turns an infarct into chronic heart failure.

Recommended in DCM (HFrEF benefit) and short-term in stable takotsubo. Avoided or used very cautiously in HCM (vasodilation worsens obstruction) and contraindicated in pregnancy (teratogenic) — a key PPCM safety point.

First-line for the proteinuric, hypertensive glomerulonephritis — they lower blood pressure and reduce proteinuria at the same time, which matters because proteinuria is itself the strongest modifiable predictor of progression. Stated directly: "first-line agents for managing proteinuria and lowering blood pressure in IgAN patients typically involve angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)," and in severe nephritic hypertension "ACE inhibitors, ARBs, and nifedipine" are used. Two guideline numbers steer the titration. The KDIGO 2025 IgA nephropathy guideline sets a blood-pressure target of ≤ 120/70 mm Hg — note it is now combined systolic and diastolic, not a systolic figure alone — "using a RASi as the first-choice drug," paired with sodium restriction under 2 g/day; textbook-level targets of 130/80, or under 125 systolic when proteinuria exceeds 1 g/day, sit alongside it as the older framing. The second number is the treatment target for proteinuria itself: maintain it below 0.5 g/day, and ideally below 0.3 g/day, accepting that extensive kidney scarring may make that unreachable — proteinuria being "the only validated early biomarker to help guide clinical decision-making." Do not confuse that target with the threshold for starting a glucocorticoid, which under KDIGO 2025 is proteinuria of 0.5 g/day or more despite supportive care — the point at which IgA-targeted therapy is added alongside, not instead of, the ACE inhibitor or ARB. The payoff for taking supportive care seriously is quantified — in the STOP-IgAN trial, about one-third of patients achieved satisfactory outcomes without any immunosuppression after a 6-month trial of optimized conservative measures including aggressive ACE inhibitor or ARB titration.

Pillar 1 (RAS inhibition): blocks the angiotensin II arm of the vicious cycle — less vasoconstriction, less remodeling, proven mortality benefit. Guidelines now prefer an ARNI (sacubitril/valsartan) first-line; an ACE inhibitor or ARB fills the pillar when an ARNI can’t be used.

First-line, and preferred when hypertension travels with heart failure, CKD with proteinuria, or diabetes with albuminuria — cardioprotective and renoprotective effects independent of the BP lowering itself. Never combined with an ARB: dual RAAS blockade adds hyperkalemia, hypotension and renal dysfunction without benefit.

Antiproteinuric, not merely antihypertensive — this is the concept worth carrying. ACE inhibitors and ARBs dilate the efferent arteriole, which reduces intraglomerular pressure and therefore reduces the protein driven across the filter, lowering systemic blood pressure as a second effect. They are used in diabetic nephropathy and other secondary causes, and for subnephrotic proteinuria in FSGS — and because blood pressure is often high in nephrotic syndrome, the same drug treats both problems. Like the diuretic, the dose needs continual reassessment as volume status changes.

Blood pressure in metabolic syndrome. NHLBI: "Medicines to lower your blood pressure: These include ACE inhibitors, angiotensin receptor blockers, diuretics, and beta blockers. Some diuretics and beta blockers can raise the risk of type 2 diabetes in people who have metabolic syndrome."

For PAD with hypertension — antihypertensive therapy reduces major cardiovascular events, to a target of SBP < 130 and DBP < 80 mm Hg, and the selective use of ACE inhibitors or ARBs is specifically recommended because they are the only antihypertensives with direct RCT evidence in PAD (ACC/AHA 2024, Class 1). The reassurance to teach: the old worry that lowering blood pressure would starve the leg and worsen claudication is not supported — treated hypertension improves walking and functional status, with no signal of harm to the limb. Hypertension is present in 35–55% of patients at PAD diagnosis.

First-line for hypertension in ADPKD. KDIGO: "For people with ADPKD and high BP, we recommend using renin-angiotensin system inhibitors (RASi) (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin II receptor blocker [ARB]) as first-line treatment to achieve the recommended target BP (1C)." Never combined: "We recommend avoiding any combination of ACEi, ARB, and direct renin inhibitor (DRI) therapy in patients with ADPKD, with or without diabetes (1B)."

[Scleroderma] Renal crisis — treatment only. "ACE inhibitors represent the sole effective treatment for scleroderma renal crisis." Keep giving it when creatinine rises: "continuation of the ACE inhibitor is crucial." Not prophylactic — "prophylactic use of ACE inhibitors is not recommended, as it does not prevent scleroderma renal crisis and is associated with increased morbidity and mortality." "Currently, no data support the efficacy of angiotensin receptor blockers or renin inhibitors in scleroderma renal crisis."

Hyperkalemia caution with tacrolimus — with potassium-sparing diuretics and ARBs (StatPearls).

Afterload and blood-pressure control where the ventricle, not the valve, is the problem: guideline-directed therapy for the LV dysfunction behind secondary (functional) MR, hypertension and HFrEF in chronic AR (vasodilators may slow progression but do not replace surgery), and heart failure in rheumatic heart disease. In aortic stenosis ACE inhibitors are for hypertension only — avoid excessive vasodilation, because the fixed valve cannot raise output to defend the pressure — and they do not slow AS progression; no drug does.

Slow heart rate & lower BP by blocking β-adrenergic receptors. Watch for bradycardia.

Lower LDL cholesterol via HMG-CoA reductase inhibition. Monitor for myopathy.

Injectable antibodies that protect the liver’s LDL receptors, cutting LDL cholesterol by about half and lowering cardiovascular events. Given subcutaneously every 2–4 weeks.

PPAR-α agonists that mainly lower triglycerides — used with diet for severe hypertriglyceridemia — with muscle, gallbladder, liver and kidney risks, highest for gemfibrozil combined with a statin.

Non-absorbed resins that trap bile acids in the gut, forcing the liver to use cholesterol and pull LDL from the blood. Constipation, drug binding and rising triglycerides are the issues to manage.

Six non-statin drugs with six targets: ezetimibe (intestinal cholesterol absorption), bempedoic acid (liver cholesterol synthesis), inclisiran (PCSK9 mRNA), niacin and icosapent ethyl (triglyceride-rich lipoproteins) and lomitapide (MTP, for homozygous FH only).