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Antiatherosclerotic effects of antihypertensive drugs: recent evidence and ongoing trials
1Istituto di Clinica Medica e Terapia Medica, Università di Milano, Ospedale Maggiore, Italy.
Abstract:
The issue as to whether antihypertensive drugs may exert some antiatherosclerotic effect, at least partly independent of blood pressure lowering, has been explored in several experimental models of atherosclerosis, and a large body of evidence has been obtained in favor of a specific antiatherosclerotic action of calcium antagonists and ACE-inhibitors. On the clinical side, several studies are investigating the problem in hypertensive patients in whom progression of carotid intima-media thickness (IMT) and atherosclerotic plaques is explored by sensitive quantitative B-mode ultrasound techniques. The MIDAS has indicated a slower progression, at least in the first six months, of carotid plaques in isradipine treated patients than in diuretic-treated ones. However, MIDAS as a pioneer study has been particularly valuable in giving information on the rate of growth of IMT in hypertensive patients and on the best end-point to use in carotid ultrasound trials. Baseline data of the ongoing studies ELSA and VHAS have so far provided evidence of the very high prevalence of carotid atherosclerosis among hypertensive patients, an observation that makes the evaluation of the antiatherosclerotic action of some antihypertensive agents even more important. Finally, the PHYLLIS trial using a factorial design, beside exploring the antiatherosclerotic action of an ACE-inhibitor vs a diuretic, intends to evaluate the possible benefits of associating antihypertensive therapy with lipid lowering by a statin on the progression of carotid atherosclerosis.
Insights
Certain antihypertensive drugs, like calcium antagonists and ACE-inhibitors, may slow atherosclerosis progression independently of blood pressure reduction. Clinical trials are evaluating these effects on carotid intima-media thickness in hypertensive patients.
Area of Science:
- Cardiology
- Pharmacology
- Vascular Biology
Background:
- Antihypertensive medications are primarily used to manage high blood pressure.
- Emerging evidence suggests some antihypertensive drugs may possess antiatherosclerotic properties independent of their blood pressure-lowering effects.
- Calcium antagonists and angiotensin-converting enzyme (ACE) inhibitors have shown potential in experimental models.
Purpose of the Study:
- To investigate the potential antiatherosclerotic effects of antihypertensive drugs beyond blood pressure reduction.
- To evaluate the impact of specific antihypertensive agents on the progression of carotid atherosclerosis in hypertensive patients.
- To explore the combined effects of antihypertensive therapy and lipid-lowering statins on atherosclerotic progression.
Main Methods:
- Utilizing quantitative B-mode ultrasound to measure carotid intima-media thickness (IMT) and atherosclerotic plaque progression.
- Conducting clinical trials (MIDAS, ELSA, VHAS, PHYLLIS) in hypertensive populations.
- Employing factorial design in trials to assess individual drug effects and combination therapies.
Main Results:
- The MIDAS trial indicated slower carotid plaque progression with isradipine compared to diuretics in the initial six months.
- Baseline data from ELSA and VHAS highlight a high prevalence of carotid atherosclerosis in hypertensive patients.
- Ongoing trials are providing valuable insights into IMT growth rates and optimal endpoints for carotid ultrasound studies.
Conclusions:
- Certain antihypertensive drugs, particularly calcium antagonists and ACE inhibitors, demonstrate potential antiatherosclerotic effects.
- Hypertensive patients exhibit a high prevalence of carotid atherosclerosis, underscoring the importance of evaluating drug-specific vascular benefits.
- Further research, including combination therapy trials with statins, is crucial to fully elucidate the antiatherosclerotic potential of antihypertensive agents.