Importance of cardiovascular outcome trials

Here’s the punchline: HPS2‑THRIVE (niacin/laropiprant) and ILLUMINATE (torcetrapib, a CETP inhibitor) showed that changing surrogate markers (raising HDL, lowering LDL or CRP) is not enough—only randomized outcomes trials that measure heart attacks, strokes, and deaths can tell us if a therapy truly helps. Why it matters: Torcetrapib impressively raised HDL and lowered LDL, yet ILLUMINATE was stopped early because deaths and cardiovascular events increased—off‑target harm (e.g., blood‑pressure rise) outweighed lipid changes. In HPS2‑THRIVE, adding niacin to statins improved HDL/TG but did not reduce major vascular events and increased serious adverse effects (infection, bleeding, new‑onset diabetes, liver/skin issues). So, we need large, well‑designed outcome trials before adopting therapies; prioritize therapies with proven event reduction (e.g., statins, ezetimibe add‑on, PCSK9 inhibitors) rather than chasing surrogate improvements.