Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension (NCT00170950), a randomized phase 3 study. The primary outcome is Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel-group phase 3 trial. Its official title describes a prospective, multinational, multicenter comparison. The two assigned regimens were benazepril/amlodipine and benazepril/hydrochlorothiazide. The registry reports enrollment of 11506 and lists hypertension as the condition. It gives the study status as terminated; the reason for termination is not reported in the registry record.

The primary analysis population is identified as intent-to-treat: all randomized patients by assigned treatment group. The primary outcome timeframe runs from baseline to the first cardiovascular morbidity or mortality event, or to last exposure if no event occurred. Median duration of exposure was 33.4 months, with the 25th to 75th percentiles reported as 21 to 41 months. These exposure summaries describe follow-up in the trial; they do not establish that every participant had the same observation period.

The intervention descriptions specify dose escalation across three levels for each combination. The registry also gives instructions for morning dosing and for taking study medication after office-visit evaluations on visit days. It does not report the masking procedures in enough detail to identify which roles or personnel were masked. The original sample-size justification, planned statistical model, prespecified analysis details, interim-analysis plan, and reason for termination are not reported in the registry record.

The posted primary outcome is a percentage of patients with an event, while its title refers to time-to-event analysis. The record identifies the event window and exposure duration but does not include a detailed description of the statistical approach used to account for follow-up time. Consequently, the group percentages can be described as reported, but a particular survival model or censoring method should not be attributed to the trial from this record alone.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: All randomized patients by assigned treatment group

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity or Mortality Event, measured over For each patient, baseline to time of first CV morbidity or mortality event (or last exposure if no event occurred). (Median duration of exposure was 33.4 months. [25th to 75th percentiles: 21 to 41 months.]).

The primary endpoint was the percentage of patients with a first composite cardiovascular morbidity or mortality event. Cardiovascular morbidity comprised non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, resuscitated sudden death, or coronary revascularization. Cardiovascular mortality comprised death due to myocardial infarction, stroke, coronary intervention, congestive heart failure, sudden cardiac death, or other cardiovascular causes.

For each patient, the outcome window began at baseline and ended at the first qualifying event or last exposure if no event occurred. The registry reports median exposure duration of 33.4 months, with the 25th to 75th percentiles at 21 to 41 months. A composite endpoint brings several clinically relevant event types into one outcome, which can capture a broader range of cardiovascular outcomes than a single event type. Its interpretation depends on the definitions and relative importance of its components; the registry record does not report component-specific results for the primary composite.

The endpoint is expressed as a percentage, so the posted group values describe the proportion recorded as having an event during the stated observation window. The endpoint title's time-to-event wording does not by itself establish which time-to-event model or adjustment for differences in follow-up was used. That statistical detail is not reported in the registry record.

7. Results Posted in the Registry

• Benazepril/Hydrochlorothiazide: 11.8% (680/5762) versus 9.6% (551/5744) on control; risk difference 2.2 percentage points (95% CI 1.1 to 3.3), risk ratio 1.23 (1.11–1.37); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Benazepril/Hydrochlorothiazide: 10.3% (593/5762) versus 8.6% (494/5744) on control; risk difference 1.7 percentage points (95% CI 0.6 to 2.8), risk ratio 1.20 (1.07–1.34); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Benazepril/Hydrochlorothiazide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Benazepril/Hydrochlorothiazide: 6.3% (363/5762) versus 5.0% (287/5744) on control; risk difference 1.3 percentage points (95% CI 0.5 to 2.1), risk ratio 1.26 (1.08–1.47); unadjusted two-proportion z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Benazepril/Hydrochlorothiazide than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes concern a composite cardiovascular morbidity event and a composite of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke. Both are clinically related to the primary composite, which includes cardiovascular morbidity and mortality. Their overall direction is consistent with the primary comparison: the posted event percentages are higher for the benazepril/hydrochlorothiazide group than for benazepril/amlodipine. These outcomes provide context about related event definitions, but they are not independent confirmation of the primary finding.

Because the endpoint definitions overlap, some events can contribute to more than one outcome. The results therefore cannot be treated as separate, unrelated replications. Nor does a similar direction establish that every component behaves alike. The registry does not report component-level breakdowns or analyses designed to compare the secondary outcomes with one another.

The registry lists no reported analyses for the secondary outcomes. Their posted comparison statistics are unadjusted recalculations, and the record does not report a multiplicity plan or adjustment. When several related outcomes are considered, unadjusted p-values do not account for the broader set of tests. This makes the secondary results less definitive than a single prespecified primary analysis would be, particularly when the analysis plan and hierarchy among outcomes are not recorded.

The secondary outcomes should therefore be read as supportive descriptive context, not as independent proof or as evidence that the treatment contrast applies to every cardiovascular endpoint. The record does not state whether these outcomes were prespecified in a formal testing hierarchy, whether any were designated confirmatory, or whether their analyses were adjusted for follow-up time. Those details are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time-to-event Analysis of Percentage of Patients With a Composite Cardiovascular (CV) Morbidity Event
• Time-to-event Analysis of Percentage of Patients With a Cardiovascular (CV) Mortality Event, Non-fatal Myocardial Infarction (MI), or Non-fatal Stroke

9. Statistical Interpretation

10. Statistical Methods Explained

The outcome is a binary event measure: each participant is classified according to whether a qualifying event was recorded during the outcome window. The group result is expressed as a percentage. For a comparison between groups, the risk difference describes the difference in those event proportions, with the comparison direction determined by which group is subtracted from which. In the posted primary contrast, the estimate compares benazepril/hydrochlorothiazide with benazepril/amlodipine.

What does a risk difference describe?

In general, a risk difference is an absolute contrast between two event proportions. It uses the same scale as the underlying proportion and is distinct from a relative measure such as a risk ratio. Its sign depends on the subtraction order. Here, the posted estimate is 0.022, and the comparison is oriented from the benazepril/amlodipine group to the benazepril/hydrochlorothiazide group. The interval accompanying that estimate describes uncertainty around the contrast under the calculation assumptions; it is not a range of individual participant outcomes.

How should the event percentages be understood?

The percentages count participants with an event over the stated observation period. They should not automatically be interpreted as rates per unit of time. The registry uses time-to-event wording and states that the endpoint window runs from baseline to first event or last exposure, but it does not report the specific analysis model. In general, time-to-event methods can use information about when an event occurred and can account for differing follow-up under specified assumptions. Whether and how those methods were used in this trial is not reported in the registry record.

The primary population is intent-to-treat, meaning participants are analyzed according to their randomized assignment rather than being regrouped according to treatment received. This approach generally preserves the randomized comparison and reflects assignment to a treatment strategy. The registry defines this population as all randomized patients by assigned group. It does not give a detailed account of participant-level exclusions, missing endpoint assessments, treatment discontinuations, or the handling of such cases, beyond stating that patients without an event were followed to last exposure for the endpoint window.

What does the p-value say?

In general, a p-value measures how incompatible the observed data are with a specified null model, if that model and its assumptions are true. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary unadjusted p-value is <0.001. Because the registry does not report the test or model behind a sponsor analysis and lists no reported analyses, the value is best treated as an unadjusted recalculation from posted summary statistics, not as a documented model-based trial analysis.

An unadjusted result does not account for testing multiple endpoints or comparisons. When several outcomes are examined, the chance of seeing an apparently unusual result among them can differ from the chance associated with a single prespecified test. In general, multiplicity procedures can control that issue, but the registry does not report a multiplicity plan or adjustment. This matters particularly when interpreting secondary outcomes, which are related to the primary endpoint and are reported without analyses in the registry.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than expected under a statistical model's assumptions. It can make standard errors too small if the model does not account for it, affecting intervals and tests. This concept is relevant to count or rate models when event data are more variable than the assumed distribution allows. The posted primary measure is a percentage of participants with an event, and the registry record does not report a count-model analysis or an assessment of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was detected or addressed in this trial.

The reported interval and p-value do not reveal all analytic choices. In general, confidence intervals depend on the statistical method, and p-values depend on the test and its assumptions. The registry does not identify a confidence level, an adjustment set, a method for handling competing events, or an analysis of proportional hazards. Those methods should not be inferred from the endpoint label alone.

The risk difference is presented alongside relative comparisons in the posted results, but interpretation should retain the measure's scale and orientation. Absolute and relative contrasts answer different questions: the former compares the difference in event proportions, while a relative measure compares one proportion to another. The registry's primary displayed comparison is an absolute risk difference. None of these summary measures, on its own, explains the mechanism of an observed difference or demonstrates causality beyond the design and assumptions of the randomized comparison.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.022, with a reported interval from 0.011 to 0.033. The interval is entirely on the positive side of zero, matching the direction of the posted group percentages. Its width expresses uncertainty in the comparison: the data are compatible with a range of positive contrasts under the assumptions used to calculate it, rather than identifying a single exact value.

A confidence interval is generally a range generated by a statistical procedure intended to reflect uncertainty in an estimate. It does not mean that there is a particular probability that the fixed underlying effect lies within this specific interval. The registry record does not report the confidence level or the interval method, so neither should be assumed. The posted interval accompanies a simple unadjusted recalculation from group summary statistics.

Precision is different from clinical importance. A relatively narrow interval may indicate that an estimate is statistically more precise, but it does not determine whether the contrast matters to patients or clinicians. Conversely, the point estimate alone can make uncertainty easy to overlook. The interval should be read together with the endpoint definition, event percentages, follow-up window, and the limitations of the recorded analysis details.

The record gives no adjusted interval from a sponsor-reported model and no analysis-level details for assessing the treatment of follow-up time. Thus, the interval is informative about the unadjusted contrast calculated from the posted summaries, but it cannot answer whether a model accounting for timing or other factors would produce the same precision. The original analysis method and confidence level are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial's original design calculation. For this binary percentage outcome, the entries are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The original trial's sample-size assumptions are not reported in the registry record.

The 80% power column gives the planned participants per arm under which a study would have an 80% chance of detecting the specified effect if that effect and the planning assumptions were correct. The 90% power column uses a higher chance of detection, so it requires more participants per arm for the same assumed effect. These are design-planning concepts, not a probability that the observed trial result is correct.

The entries for 100% of the observed effect use the full observed effect as the planning target. The rows for 75% and 50% of the observed effect ask what enrollment would be needed if the effect to detect were smaller. Smaller effects are harder to distinguish from random variation, so they require more participants per arm to attain the same target power. The figures should be interpreted as hypothetical planning requirements under the listed assumptions, not as a recommendation for a future study without further design information.

These calculations are not observed power. Observed power, when calculated from the result already seen, largely restates the effect estimate and its uncertainty; it does not add an independent measure of evidence. The planning values are more useful as illustrations of how enrollment requirements change when the target effect or desired power changes. They do not establish that the original trial was designed using these assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.096; treatment proportion p₁ = 0.118; average p̄ = 0.107.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4371 = 0.8567.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4368 = 0.3676.
4. n = (0.8567 + 0.3676)² / (0.0221)² = 3,072.4, rounded up to 3,073 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0959261838440111                          # control proportion
p1 <- 0.118014578271434                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(170950)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 3,073 (80% power), 4,113 (90% power)
 75% of observed effect: n per arm = 5,339 (80% power), 7,146 (90% power)
 50% of observed effect: n per arm = 11,731 (80% power), 15,704 (90% power)
power.prop.test: 3072.4 
Simulated power at n = 3,073 per arm: 0.799 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary endpoint and two secondary outcomes, but it does not report a testing hierarchy or a plan for controlling multiplicity. Multiplicity arises when several outcomes or comparisons are tested: without an adjustment or a prespecified strategy, the interpretation of each unadjusted p-value does not account for the full set of tests. This is a general statistical concern, not evidence that the trial used or failed to use a particular procedure.

The primary comparison is presented with an unadjusted p-value, and the secondary comparisons also have unadjusted results. The registry lists no reported analyses. It does not document whether the sponsor used a different analysis, whether the posted values were intended as confirmatory, or how outcome testing was prioritized. The reason for trial termination is also not reported in the registry record, so the termination status cannot be linked to any analysis or interim decision.

The primary population is stated to be intent-to-treat, with all randomized patients analyzed by assigned group. The record also describes event follow-up to the first qualifying event or last exposure when no event occurred. However, it does not describe how missing endpoint information, withdrawal, incomplete follow-up, or other deviations were handled in the analysis. The detailed missing-data procedures are not reported in the registry record.

In general, missing outcomes can affect a comparison if their occurrence is related to treatment assignment or the likelihood of an event. Analysts may use different assumptions or sensitivity analyses to examine this uncertainty. The registry does not report such methods or sensitivity analyses, so the effect of missing data cannot be evaluated from the available record.

The record's intent-to-treat label is useful, but it does not itself supply every detail needed to reproduce an analysis. The statistical model, handling of unequal observation time, covariate adjustment, multiplicity procedure, and interim-analysis plan are not reported in the registry record. Interpretation should distinguish those absences from a claim that the trial did or did not use a particular method.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: angina unstable (2.3%), myocardial infarction (2.2%), coronary artery disease (2.2%), atrial fibrillation (2.0%), angina pectoris (1.8%).

The registry reports serious adverse events affecting 1844 of 5740 participants at risk in the benazepril/amlodipine group and 2026 of 5757 at risk in the benazepril/HCTZ group. Other adverse events affected 3077 of 5740 at risk and 2663 of 5757 at risk, respectively. These are group-level counts and denominators; the record does not provide a statistical comparison or adjustment for exposure duration in these figures.

The serious-event terms listed include unstable angina at 2.3%, myocardial infarction at 2.2%, coronary artery disease at 2.2%, atrial fibrillation at 2.0%, angina pectoris at 1.8%, and pneumonia at 1.8%. The registry does not provide group-specific attribution for these listed terms in the posted summary, so they should not be read as a comparison between assigned treatments. Death counts are not reported in the registry record.

These safety figures should be interpreted as descriptive reporting, not as proof of a causal difference. The registry does not report event-level details, statistical tests, or a fuller explanation of how adverse events were collected and classified.

16. What the Result Does, and Does Not, Mean

The posted primary result describes a difference between randomized groups in the percentage experiencing the defined composite cardiovascular outcome during the recorded observation period. The benazepril/amlodipine group had a reported event percentage of 9.6, compared with 11.8 for benazepril/hydrochlorothiazide. The unadjusted risk-difference estimate and its interval indicate the direction and uncertainty of that group comparison. They do not establish the exact effect for every participant or guarantee that the same contrast would occur in another population.

The result applies to the trial's population and outcome definition as recorded: patients with high-risk hypertension, assigned to one of the two combination regimens, and followed from baseline to the first qualifying event or last exposure. Median duration of exposure was 33.4 months, with the 25th to 75th percentiles at 21 to 41 months. The posted percentages do not describe a universal individual prognosis or provide a complete account of when each event occurred.

A composite outcome combines several event types, so its overall result does not show which component contributed most. The primary event definition includes both morbidity and mortality categories, but the registry does not report their separate primary-endpoint results. It also does not report a detailed statistical model, confidence level, multiplicity procedure, or missing-data analysis. Those omissions limit how far the comparison can be interpreted beyond the posted summaries.

The finding is not a recommendation to start, stop, or change treatment. Treatment decisions require clinical context beyond a registry result. The record also lists the trial as terminated, but does not report why; no explanation of the termination or its relation to the findings should be inferred. The result is best understood as a randomized group comparison accompanied by uncertainty and incomplete analysis documentation, not as proof of a universal effect or a complete safety assessment.

17. Why This Trial Matters Statistically

This trial is statistically notable for comparing two active combination regimens in a randomized, double-masked, parallel-group design and reporting a cardiovascular composite over follow-up. Randomization supports a treatment-group comparison by assignment, while the intent-to-treat population preserves that assignment in the primary analysis as described in the registry. These design features help frame the result, but they do not replace the need for a transparent analysis plan.

The primary outcome is a composite rather than a single event. Composites can make a broad outcome practical to study, but the overall contrast may be influenced by which components occur and how they are defined. Without component-specific primary results, readers cannot determine whether the composite pattern was distributed across event types or concentrated in a subset. That distinction matters when assessing the meaning of a group-level endpoint.

The registry reports percentages and an unadjusted risk difference with an interval, enabling readers to consider both the observed contrast and its precision. At the same time, the record does not report the model, confidence level, multiplicity strategy, or detailed handling of follow-up and missing outcomes. These omissions illustrate why numerical results need to be read alongside the methods that generated them.

Finally, the available planning illustrations show how assumed effect size and desired power affect enrollment needs, while not documenting the original design calculation. Separating hypothetical planning from the trial's actual design is important: planning calculations based on an observed effect cannot establish what assumptions guided the study or provide observed power. The record therefore offers useful outcome summaries but leaves key design and analysis details unavailable.

18. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the reason the trial was terminated. The status alone does not establish whether termination was related to efficacy, safety, recruitment, funding, or another cause. The record also does not describe any interim analyses or stopping rules, so the timing and rationale for termination cannot be evaluated statistically.

Although the official title describes a prospective, multinational, multicenter trial, the record does not provide site-level information or details needed to assess variation across centers. It describes the study as double-masked but does not identify which participants, clinicians, outcome assessors, or other roles were masked, or how masking was maintained.

The outcome is titled as a time-to-event analysis but reported as a percentage of patients with an event. The registry does not identify the underlying model or explain how differing exposure duration was handled. The primary timeframe is tied to last exposure for patients without an event, and median exposure was 33.4 months, with the 25th to 75th percentiles at 21 to 41 months. The posted summary does not allow a reader to reconstruct individual event timing or assess censoring assumptions.

The record does not report a detailed statistical analysis plan, multiplicity control, adjusted analyses, missing-data procedures, sensitivity analyses, or component-specific primary outcomes. It also does not provide group-specific context for the listed serious-event terms. These limitations restrict independent evaluation of the analysis and safety summaries; they do not establish that unreported procedures were or were not conducted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Avoiding Cardiovascular Events Through Combination Therapy in Patients Living With Systolic Hypertension — NCT00170950.
• Registry record last updated 2023-10-24; status last verified 2023-10.
• Results first posted 2011-05-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

22. Record Summary

NCT00170950 is a randomized, double-masked, parallel-group phase 3 trial comparing benazepril/amlodipine with benazepril/hydrochlorothiazide in patients with high-risk hypertension. The registry reports enrollment of 11506 and lists the status as terminated.

The primary endpoint was the percentage of patients with a first composite cardiovascular morbidity or mortality event. The reported percentages were 9.6 for benazepril/amlodipine and 11.8 for benazepril/hydrochlorothiazide. The unadjusted risk-difference estimate was 0.022, with an interval from 0.011 to 0.033 and p < 0.001.

The registry also reports two related secondary outcomes and descriptive adverse-event figures. It does not report the original sample-size justification, detailed analysis methods, multiplicity plan, missing-data procedures, or reason for termination. The posted comparison estimates are unadjusted recalculations from the group summaries, and should be interpreted with those reporting limitations in mind.