PCSK9 inhibitors & inclisiran

PCSK9 is a protein that destroys LDL receptors; block it and the liver clears far more LDL. The monoclonal antibodies evolocumab (Repatha) and alirocumab (Praluent), injected every 2–4 weeks, cut LDL a further ~50–60% on top of a statin — down to levels (~30 mg/dL) once thought impossible, with no 'too low' safety floor yet found. FOURIER and ODYSSEY OUTCOMES proved they reduce events; GLAGOV showed actual plaque regression. And uniquely among the mainstays, they lower Lp(a) ~20–30% (statins don't touch it). The safety record is exceptionally clean; the real downsides are the injection and the cost. Evidence ●●●●●

Inclisiran is a small-interfering-RNA (siRNA) that silences PCSK9 production in the liver. It delivers a similar ~50% LDL drop but is dosed just twice a year after a loading dose — a potential game-changer for adherence, since a nurse-given jab every six months is hard to forget. Its cardiovascular outcome trials (ORION-4, VICTORION-2 PREVENT) read out around 2026–27. Evidence ●●●●○ (LDL proven, hard outcomes pending)

For most people PCSK9 inhibitors are added to a statin rather than replacing one — statins are cheap, proven, and oral, while PCSK9s are expensive and injected. But for the truly statin-intolerant, for familial hypercholesterolaemia, and for anyone still far from goal on maximal oral therapy, they are transformative. The 'wins' the hype promises — raw power, clean safety, Lp(a) lowering, and plaque regression — are real; the catch is access and cost, not efficacy.