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Cardiovascular Benefits of Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade in Patients
Robert D Brook1, Niko Kaciroti2, George Bakris3
1Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Insights
Adding a calcium channel blocker (CCB) to an angiotensin-converting enzyme inhibitor (ACEI) is more effective for preventing cardiovascular events than using hydrochlorothiazide (HCTZ). This combination therapy benefits patients achieving lower blood pressure targets and those with resistant hypertension.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Management
Background:
- The 2017 hypertension guidelines introduced lower systolic blood pressure (BP) targets (<130 mm Hg) and redefined resistant hypertension.
- This study examines the cardiovascular benefits of combining a calcium channel blocker (CCB) versus hydrochlorothiazide (HCTZ) with an angiotensin-converting enzyme inhibitor (ACEI) under these new guidelines.
Purpose of the Study:
- To investigate if the 2017 hypertension guideline changes impact the cardiovascular benefits of CCB/ACEI versus HCTZ/ACEI combination therapy.
- To compare cardiovascular outcomes in patients achieving a systolic BP ≤130 mm Hg and those with apparent resistant hypertension.
Main Methods:
- Post hoc analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension trial (n=11,506).
- Comparison of the primary composite outcome (cardiovascular death, MI, stroke, angina hospitalization, sudden cardiac death resuscitation, coronary revascularization) between amlodipine/benazepril and HCTZ/benazepril treatment groups.
- Analysis stratified by patients achieving systolic BP ≤130 mm Hg and those with apparent resistant hypertension (≥4 antihypertensive medications).
Main Results:
- 5,221 patients (45.4%) achieved a systolic BP ≤130 mm Hg.
- Fewer primary endpoints occurred with amlodipine/benazepril (9.2%) vs. HCTZ/benazepril (10.9%) in patients achieving BP targets (adjusted HR 0.83).
- Fewer primary endpoints occurred with amlodipine/benazepril (12.8%) vs. HCTZ/benazepril (15.2%) in patients with apparent resistant hypertension (adjusted HR 0.81).
Conclusions:
- Combination therapy with CCB/ACEI is more effective than HCTZ/ACEI in preventing cardiovascular events.
- This benefit extends to hypertensive patients achieving aggressive BP targets and those with apparent resistant hypertension.
- Findings support the use of CCB/ACEI combination therapy for a broad range of hypertensive patients, including those managed under contemporary guidelines.
Background:
The 2017 hypertension guidelines lowered systolic blood pressure (BP) goals to <130 mm Hg and redefined resistant hypertension. We investigated if these changes alter the cardiovascular benefits demonstrated by combining a calcium channel blocker (CCB), rather than hydrochlorothiazide (HCTZ), with an angiotensin-converting enzyme inhibitor (ACEI).
Methods:
In this post hoc analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension trial (n = 11,506), we compared the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization) between the 2 combination-treatment limbs in patients achieving a systolic BP ≤130 mm Hg and those with "apparent resistant hypertension" (prescribed ≥4 antihypertensive medications).
Results:
Among study patients, 5,221 (45.4%) achieved a systolic BP ≤130 mm Hg. There were fewer primary endpoints in the amlodipine/benazepril (9.2%) vs. the HCTZ/benazepril (10.9%) limb (adjusted hazard ratio [HR] 0.83, 95% confidence interval [CI], 0.70-0.99). There were also fewer primary endpoints in the amlodipine/benazepril (12.8%) vs. the HCTZ/benazepril (15.2%) limb (n = 4,451, 38.7%) among patients with apparent resistant hypertension (HR 0.81, 95% CI, 0.70-0.95).
Conclusions:
Combination therapy adding a CCB, rather than HCTZ, to an ACEI was more effective in preventing composite cardiovascular events even in hypertensive patients achieving aggressive systolic BP targets as well as in those with apparent resistant hypertension. Our findings add support that most patients, including those following contemporary clinical guidelines, will benefit from this combination.
Clinical Trials Registration:
Trial Number NCT00170950.
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