Your institution's pharmacy committee wants clinical staff to review a new cardiovascular drug before Thursday's formulary vote. The evidence base is a single randomized controlled trial: CAREVA-1.
This experience works in two phases. First, you read the paper, formatted the way you'd encounter it in a journal. Then you work through five appraisal stations, making judgment calls about what the data actually says.
Veralozin 10 mg versus Placebo for Secondary Prevention of Major Adverse Cardiovascular Events in Post-Myocardial Infarction Patients: Results of the CAREVA-1 Randomized Controlled Trial
Department of Cardiology, University Medical Center Rotterdam; National Heart Institute, Lagos; Institut Cardiovasculaire de Paris; and 22 additional sites in Europe, North America, and Latin America.
Journal of Cardiovascular Medicine, Vol. 18 Issue 4 · DOI: 10.1016/j.jcvm.2026.02.041 · Open access
1.1 Study design and participants
CAREVA-1 was a phase III, multicenter, randomized, double-blind, placebo-controlled trial conducted at 148 sites in 22 countries across Europe, North America, and Latin America. Eligible patients were adults aged 40 to 80 years with a documented prior myocardial infarction, LDL-C ≥70 mg/dL, and stable statin therapy for at least 6 weeks before enrollment. Patients were excluded if they had an eGFR <30 mL/min/1.73m², severe hepatic impairment, active malignancy, pregnancy, or prior intolerance to agents with a similar mechanism.
1.2 Randomization and blinding
Patients were randomly assigned in a 1:1 ratio using a computer-generated sequence, stratified by geographic region and history of heart failure. Both patients and investigators were masked to treatment assignment. An independent clinical events committee, blinded to treatment allocation, adjudicated all primary and secondary endpoints.
1.3 Design specifications
| Element | Detail |
|---|---|
| Primary endpoint | Composite MACE: cardiovascular death, non-fatal MI, or non-fatal stroke at 5 years |
| Analysis | Intention-to-treat (ITT) as pre-specified primary; per-protocol as sensitivity |
| Statistical model | Cox proportional hazards; two-sided α = 0.05 |
| Power | 80% to detect ≥20% RRR assuming 12% placebo event rate over 5 years |
| Funding | Veral Therapeutics AG; independent academic steering committee; no publication restrictions |
1.4 Baseline characteristics
| Characteristic | Veralozin (n=2,100) | Placebo (n=2,100) |
|---|---|---|
| Age, years — mean (SD) | 63.2 (9.4) | 63.5 (9.1) |
| Female sex — no. (%) | 664 (31.6%) | 672 (32.0%) |
| White — no. (%) | 1,724 (82.1%) | 1,718 (81.8%) |
| LDL-C, mg/dL — mean (SD) | 88.4 (16.2) | 88.1 (15.9) |
| History of heart failure — no. (%) | 378 (18.0%) | 382 (18.2%) |
| Current smoker — no. (%) | 294 (14.0%) | 288 (13.7%) |
| eGFR <60 mL/min — no. (%) | 316 (15.0%) | 309 (14.7%) |
Table 1. Baseline characteristics. SD = standard deviation; LDL-C = low-density lipoprotein cholesterol; eGFR = estimated glomerular filtration rate.
2.1 Primary outcome
The primary composite outcome occurred in 163 of 2,100 patients (7.8%) in the Veralozin group and 210 of 2,100 patients (10.0%) in the placebo group over the 5-year follow-up period. This corresponded to a hazard ratio of 0.78 (95% confidence interval, 0.65 to 0.94; p = 0.008), a 22% relative risk reduction, and a 2.2 percentage-point absolute risk reduction. The number needed to treat to prevent one primary outcome event was 45 patients over 5 years.
2.2 Secondary outcomes and safety
Each component of the composite endpoint occurred numerically less frequently in the Veralozin group: cardiovascular death (3.2% vs. 4.0%), non-fatal MI (3.6% vs. 4.7%), and non-fatal stroke (1.8% vs. 2.2%). The subgroup analysis was consistent with the overall finding across age, sex, region, LDL-C tertile, and history of heart failure, with no statistically significant interaction detected. Serious adverse events occurred in 18.4% and 17.9% of the Veralozin and placebo groups, respectively. Liver enzyme elevations greater than 3 times ULN occurred in 1.4% of Veralozin patients versus 0.8% placebo. Adherence at 5 years was 74.2% in the Veralozin group and 78.1% in the placebo group.
In this large international randomized trial, Veralozin 10 mg daily added to standard care significantly reduced the risk of the primary composite cardiovascular endpoint compared with placebo in patients with prior MI on stable statin therapy. The hazard ratio of 0.78 (95% CI 0.65–0.94) was consistent across prespecified subgroups and persisted throughout the 5-year follow-up period, with curves separating early and maintaining a stable gap.
The 22% relative risk reduction corresponds to a 2.2 percentage-point absolute risk reduction and a number needed to treat of 45 over 5 years. The clinical relevance of this magnitude of benefit must be considered in the context of the patient population, which was high-risk by design (prior MI, elevated LDL-C on statin therapy). In patients with higher baseline event rates than the trial average, the absolute benefit would be expected to be greater.
The trial has important limitations. The enrolled population was predominantly male (68%) and White (82%), with a mean age of 63 years, limiting direct generalizability to older adults, women, and non-White populations who may carry different baseline risks. Patients with eGFR <30 mL/min were excluded, leaving the drug's benefit-risk profile in advanced renal impairment uncharacterized. Adherence declined to 74% in the treatment group by year 5. The per-protocol analysis (HR 0.74, 95% CI 0.62–0.89) suggested the ITT estimate may slightly underestimate efficacy in adherent patients. Cost-effectiveness analyses were not conducted as part of this trial.
Veralozin 10 mg daily significantly reduced major adverse cardiovascular events over 5 years in post-MI patients on statin therapy, with a statistically robust and consistent treatment effect. The safety profile was acceptable, with no unexpected signals. These data support consideration of Veralozin as adjunctive cardiovascular risk-reduction therapy in appropriately selected high-risk patients. Formulary bodies should weigh these findings against local cost, population fit, and the availability of existing alternatives.
Five appraisal stations. At each one, you make a judgment call about what the data actually says.
The abstract reports: "Veralozin significantly reduced the composite risk of major adverse cardiovascular events (HR 0.78; p = 0.008)." The relative and absolute numbers tell different stories about the same result.
The trial reached statistical significance with p = 0.008. That confirms the result is unlikely due to chance. It says nothing about whether the benefit is large enough to justify use in your patient population.
The point estimate is 0.78, but the confidence interval runs from 0.65 to 0.94. The entire interval lies below 1.0, yet it spans 29 percentage points of possible effect size.
The discussion flags it directly: 68% male, 82% White, mean age 63, eGFR ≥30. Think about how the patients in your institution compare to that profile.
You've read the paper and worked through the evidence. The committee asks for your position: should Veralozin go on the formulary?
What the trial shows: Veralozin 10 mg daily reduced composite MACE by 2.2 percentage points (ARR) over 5 years in a high-risk post-MI population on statin therapy, with a consistent signal across the full follow-up period.
What it doesn't resolve: Long-term safety beyond 5 years; effects in patients with renal impairment, women, or older adults; cost-effectiveness in health systems with constrained formularies.
The appraisal skill: Statistical significance is a starting point. The useful questions are about magnitude, population fit, and what a prevented event costs.