Cardiovascular · Clinical trials
Coronary Artery Disease Clinical Trials
Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.
Indication overview
About coronary artery disease — and why its trials are hard
Coronary artery disease (CAD) is atherosclerotic narrowing of the coronary arteries, the leading cause of death worldwide, manifesting as stable angina, silent ischemia, acute coronary syndromes and sudden death. Management combines aggressive risk-factor modification, antithrombotic therapy and, when indicated, revascularization by PCI or CABG. The cornerstone of medical therapy is lipid lowering. Statins (e.g., atorvastatin, rosuvastatin) reduce LDL cholesterol and cardiovascular events across the risk spectrum, established by landmark trials such as 4S and the atorvastatin/rosuvastatin outcome programs. When statins are insufficient, ezetimibe (IMPROVE-IT) and PCSK9 inhibitors add further LDL reduction and event benefit; evolocumab (FOURIER) and alirocumab (ODYSSEY OUTCOMES) drove LDL to historically low levels with reduced ischemic events. Antiplatelet therapy with aspirin, and dual antiplatelet therapy adding a P2Y12 inhibitor, is central after events and stenting. Novel lipid targets that seemed promising, including CETP inhibitors and Lp-PLA2 inhibition, produced high-profile failures, reinforcing that LDL-lowering, not HDL-raising or inflammatory-enzyme inhibition alone, drives outcome benefit in CAD.
Approved therapies & pivotal evidence
What's been approved — and by how much it moved the endpoint
| Drug (brand) | Approved | Setting | Pivotal trial | Primary endpoint | Magnitude of benefit |
|---|---|---|---|---|---|
| Atorvastatin (Lipitor) | 1996 | LDL lowering / secondary and primary prevention | TNT / ASCOT-LLA | Major cardiovascular events | TNT: intensive 80 mg reduced major CV events vs 10 mg (HR ~0.78); ASCOT-LLA reduced nonfatal MI/fatal CHD ~36% |
| Rosuvastatin (Crestor) | 2003 | LDL lowering / primary prevention in elevated hsCRP | JUPITER | Composite of MI, stroke, revascularization, unstable angina, CV death | HR 0.56 vs placebo in patients with elevated hsCRP and normal LDL |
| Ezetimibe (Zetia) | 2002 | Add-on LDL lowering post-ACS | IMPROVE-IT | Composite CV death, MI, stroke, unstable angina, revascularization | Modest absolute benefit added to statin (HR 0.936); validated added LDL lowering translates to event reduction |
| Evolocumab (Repatha) | 2015 | PCSK9 inhibition in established atherosclerotic CVD | FOURIER | Composite CV death, MI, stroke, hospitalization for UA, revascularization | HR 0.85 vs placebo on top of statin; ~59% LDL reduction to median ~30 mg/dL |
| Alirocumab (Praluent) | 2015 | PCSK9 inhibition after recent ACS | ODYSSEY OUTCOMES | Composite CHD death, nonfatal MI, ischemic stroke, unstable angina | HR 0.85 vs placebo; absolute benefit greatest in those with baseline LDL >=100 mg/dL |
Where trials have failed
Drugs that missed their endpoint — and what contributed
The most instructive lessons in coronary artery disease development come from programmes that failed the endpoint that mattered.
| Drug / trial | Endpoint outcome | What contributed |
|---|---|---|
| Torcetrapib — ILLUMINATE | Terminated early for increased mortality and cardiovascular events despite raising HDL | Off-target effects raising blood pressure and aldosterone; CETP inhibition raised HDL but caused net harm |
| Dalcetrapib — dal-OUTCOMES | Stopped for futility; no reduction in recurrent CV events post-ACS | HDL-raising via CETP inhibition without meaningful LDL lowering produced no clinical benefit |
| Darapladib — STABILITY | Failed to reduce the primary composite of CV death, MI or stroke in stable CAD | Lp-PLA2 inhibition targeting vascular inflammation did not translate into outcome benefit |
Choosing the right endpoint
Primary endpoints that matter in coronary artery disease trials
- Major adverse cardiovascular events (MACE) — Composite of CV death, MI and stroke; the standard hard endpoint in CAD outcome trials
- LDL cholesterol reduction — Central surrogate; the magnitude of LDL lowering consistently predicts event reduction
- Coronary revascularization — Frequently included in expanded composites such as JUPITER and FOURIER
- Cardiovascular mortality — Key component; drove the early termination of torcetrapib's ILLUMINATE for harm
How iNGENū runs coronary artery disease trials
Physician-led design, built for FDA submission
Endpoint & biomarker strategy
Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.
FDA-ready data
Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.
Faster, lower-cost delivery
~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.
Request a fixed-milestone proposal and a tailored endpoint & feasibility summary for this indication.
Frequently asked questions
Coronary Artery Disease clinical trials — FAQs
Why did CETP inhibitors fail?
When are PCSK9 inhibitors added?
Is HDL-raising a useful target?
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