Cardiovascular

Where Outcomes, Not Surrogates, Decide Approval.

Regulatory strategy for cardiovascular therapeutics — where the evidence bar is a multi-thousand-patient outcomes trial measured in MACE events.

Scale is the discipline

Cardiovascular Is Where a Trial Can Cost More Than the Molecule.

Most cardiovascular claims rest on hard clinical outcomes — death, myocardial infarction, stroke, heart-failure hospitalization — not on a lab value. Proving them takes event-driven trials with thousands of patients followed for years, adjudicated by a clinical events committee, and watched by a data safety board. The trial is the program's biggest risk and biggest cost.

Getting the endpoint, the population, the event assumptions, and the interim strategy right is what keeps that investment from being wasted. We design cardiovascular outcomes programs to answer the question once, at a size the division will accept and a cost the sponsor can bear.

Cardiology stress test with clinicians monitoring a patient
Event-driven

A cardiovascular outcomes trial ends when the events accrue, not when the calendar says — powering it honestly is everything.

Anatomy of the primary endpoint

MACE Is a Composite — and How You Build It Decides the Trial.

Major Adverse Cardiovascular Events bundles several hard outcomes into one primary endpoint so a trial can reach statistical power. Which components you include — and how you adjudicate them — shapes the size, the duration, and the claim.

Primary endpoint

MACE

A composite of hard cardiovascular outcomes, adjudicated by a blinded clinical events committee.

CV Death

Cardiovascular mortality — the component that carries the most regulatory weight and the hardest to argue with.

Myocardial Infarction

Non-fatal MI, defined by a universal definition the division expects to see applied consistently and adjudicated.

Stroke

Non-fatal stroke, often the component that expands or narrows the eligible population and the effect size.

Add heart-failure hospitalization and you have a four-point MACE that reaches power faster but dilutes the mortality signal. Drop it and the trial gets larger and longer but the claim gets cleaner. That single design choice ripples through cost, timeline, and the label — and it is exactly the decision we help sponsors make with the review division, not around it.
Six cardiovascular worlds

Not Every Cardiovascular Claim Needs the Same Trial.

Some indications turn on an accepted surrogate; others demand full outcomes. Knowing which is which — and where the precedent sits — sizes the entire program.

HFrEF · HFpEF

Heart Failure

Where CV death and HF hospitalization composites, quality-of-life measures, and the HFpEF challenge define a fiercely competitive outcomes space.

LDL · Lp(a)

Lipids & Dyslipidemia

Where LDL-lowering is an accepted surrogate but novel targets like Lp(a) still face the outcomes question — PCSK9, siRNA, and beyond.

BP · resistant HTN

Hypertension

Where blood pressure is a validated surrogate for most claims, but resistant hypertension and novel mechanisms invite outcomes expectations.

Efficacy vs bleeding

Thrombosis & Anticoagulation

Where the entire benefit–risk is a balance between preventing clots and causing bleeds, judged on hard events in large trials.

6MWT · rare

Pulmonary Hypertension

A rare-disease corner of cardiology, where six-minute walk distance and functional class enable smaller, surrogate-anchored trials.

Cross-cutting

Cardiometabolic Overlap

Where diabetes and obesity agents earn cardiovascular claims — the CVOT world that reshaped how the whole field is regulated.

Anatomical heart model representing cardiovascular benefit
Surrogate or outcome

LDL can stand in for benefit; a novel mechanism usually cannot. Knowing the difference sizes the trial.

The surrogate question

When a Lab Value Is Enough — and When Only Events Will Do.

Cardiology has some of the best-validated surrogates in medicine — LDL cholesterol and blood pressure among them — and some of the most cautionary history. The rosiglitazone era gave the field a lasting reflex: prove you do no cardiovascular harm, and don't assume a biomarker predicts benefit for a new mechanism.

We help sponsors make the case for a surrogate where the precedent supports it — and design the outcomes trial where it does not — including the cardiovascular safety strategy that even non-cardiac programs increasingly have to answer.

The economics of proof

A Cardiovascular Outcomes Trial Is a Bet the Whole Company Feels.

Because the endpoint is rare events, the trial is enormous — and the design choices that control its size and duration are among the highest-leverage decisions a cardiovascular sponsor makes.

Thousands

of patients, followed for years, are typical for a cardiovascular outcomes trial — event-driven enrollment and honest event-rate assumptions are non-negotiable.

Adjudicated

Every primary event is reviewed by a blinded clinical events committee — a charter and process the division scrutinizes as closely as the result.

Interim

Group-sequential and adaptive designs can stop early for benefit, harm, or futility — pre-specified with the DSMB so the trial is defensible.

Where cardiovascular programs stall

Six Failure Modes We Are Brought In to Prevent.

At this scale, a design error is not a delay — it is a nine-figure loss.

1

Event-rate assumptions that miss

Powering the trial on optimistic event rates, then running out of events — the classic way a cardiovascular outcomes trial becomes underpowered and inconclusive.

2

The wrong MACE composite

Choosing components that reach power fast but dilute the meaningful signal — or a clean composite the trial can't afford to power.

3

A surrogate the division won't accept

Assuming a biomarker predicts outcomes for a novel mechanism when the precedent only supports it for established ones.

4

Adjudication and DSMB gaps

A clinical-events-committee charter or data-safety-board plan that doesn't hold up to the scrutiny a large CV trial attracts.

5

Cardiovascular safety unaddressed

A non-cardiac program that ignored the CV-safety expectations the field's history built in, and met them too late.

6

No interim strategy

A rigid design with no pre-specified path to stop for overwhelming benefit or futility, leaving value and patients on the table.

People who have run the mega-trials

Cardiovascular Regulatory Leadership Built for Scale.

Our cardiovascular leads have designed outcomes trials, negotiated composite endpoints and surrogates, and managed the adjudication and safety-board machinery that large CV programs demand.

Cardiovascular regulatory scientist reviewing cardiac data

"A cardiovascular outcomes trial answers the question once, at enormous cost. Our job is to make sure it is the right question, sized right, so the answer is one the label can carry."

The discipline we bring across heart failure, lipids, hypertension, thrombosis, and pulmonary hypertension.

Outcomes-trial design (CVOT) MACE composites & adjudication Surrogate vs outcomes strategy Cardiovascular safety DSMB & interim analyses Cardiometabolic overlap

Planning a Cardiovascular Outcomes Trial? Size the Question Before You Fund the Answer.

Bring senior cardiovascular regulatory leadership in early — while the endpoint, population, and surrogate strategy are still open.

Senior-led. Embedded in your team. No junior hand-offs.