Study reassures patients on safety of widely prescribed hypertension drug amlodipine

 I had to get off of Amlodipine since it gave me edema in my left side affected ankle. Took weeks after being off before it returned to normal. Now on nifedipine.

 

Study reassures patients on safety of widely prescribed hypertension drug amlodipine

A new paper in the journal Function, published by Oxford Univetrsity Press, finds that a widely prescribed drug for treating hypertension, amlodipine, is not dangerous for patients, despite recent concerns from researchers and clinicians that taking amlodipine may have risks.

Approximately 700,000 Americans die from hypertension each year and researchers believe some 116 million Americans (and one in five adults worldwide) have the disease, which is responsible for 7.6 million deaths per year. If untreated, hypertension significantly increases the risk of premature death through heart attack, stroke, or kidney disease.

One widely prescribed drug for treating hypertension is amlodipine, now taken regularly in pill form by over 70 million Americans. Amlodipine inhibits a type of calcium channel that is found on blood vessels. When the calcium channel opens, calcium enters the muscle and causes it to constrict, increasing blood pressure. Amlodipine prevents calcium from coming in, leading to vessel relaxation and a decrease in blood pressure.

Recently some researchers have questioned the benefit of amlodipine for treating hypertension. Studies suggested that amlodipine may activate a different type of calcium channel, resulting in changes to blood vessels and an increase in heart failure in patients. Removing amlodipine as a prescribed anti-hypertensive medication carries significant health implications, since hypertension is such a common health condition.

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A new study by research teams from National Institutes of Health and Glasgow University finds that taking amlodipine is unlikely to result in an increase in heart failure in patients. The researchers found that amlodipine appears to have unique chemical properties that caused the drug to mimic the calcium channel activation, without in fact opening the channels as clinicians worried. When the study's authors controlled for these chemical properties, they found that amlodipine did not activate calcium channels. A meta-analysis combining clinical trials and a prospective real-world analysis both showed that amlodipine was not associated with increased heart failure or other cardiovascular problems.

"Removal of amlodipine as a front-line therapy would most likely increase deaths from hypertension dramatically," said Anant Parekh, one of the study's authors. "The study recommends that amlodipine remain a first-line treatment for high blood pressure."

Source:

Oxford University Press USA

Journal reference:

Bird, G. S., et al. (2023) A reappraisal of the effects of L-type Ca2+ channel blockers on store-operated Ca2+ entry and heart failure. Function. doi.org/10.1093/function/zqad047.

Increase in Neurogenesis of Neural Stem Cells Cultured from Postnatal Mouse Subventricular Zone by Nifedipine

 Since I'm taking Nifedipine I was curious about this, but no luck, doesn't seem to be translated.

Increase in Neurogenesis of Neural Stem Cells Cultured from Postnatal Mouse Subventricular Zone by Nifedipine

L-type 칼슘 채널을 저해하는 저해제, nifedipine에 의한 쥐 뇌실하 영역 신경줄기세포의 신경세포로의 분화 촉진

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Ki-Youb Park (KAIST) ,  Man Su Kim (Inje University)

• 한국생명과학회
• 생명과학회지
• 생명과학회지 제32권 제2호

• 2022.02
• 108 - 118 (11 pages)

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초록·키워드 목차

뇌실하 영역은 뇌에서 신경줄기세포가 분포하는 곳으로 평생에 걸쳐 새로운 신경세포를 생성하는 곳이다. 많은 세포 안팎의 인자들이 신경줄기세포의 세포 증식과 신경세포로의 분화에 영향을 미친다. 최근 들어, L-type 칼슘 채널이 신경계의 발달을 조절하고 뇌실하 영역에 있는 신경줄기세포, 신경세포로 분화 중인 세포, 그리고 성숙한 신경세포에 분포한다고 밝혀졌다. L-type 칼슘 채널의 저해제인 nifedipine은 고혈압의 치료제로 오랜 기간 사용되어 왔다. 신경줄기세포에 nifedipine을 사용하여 L-type 칼슘 채널을 저해하는 연구는 많이 없는 상황이다. 이번 연구에서, 우리는 5일령 쥐의 뇌실하 영역에서 배양한 신경줄기세포에 nifedipine을 처리하여 신경세포로의 분화에 미치는 영향을 관찰하였다. Nifedipine은 Tuj1을 발현하는 신경세포의 수를 증가시킨 반면, Olig2를 발현하는 희소 돌기 아교 세포(oligodendrocytes)의 수에는 큰 영향을 미치지 않았다. Nifedipine은 S기를 표지하는 5-ethynyl-2’-deoxyuridine (EdU)가 들어간 세포의 수를 증가시켰고, 세포 분열시 나타나는 인산화된 히스톤 H3(PH3)를 발현하는 세포의 수를 증가시켰다. Nifedipine은 신경세포로의 분화를 촉진하는 Dlx2 유전자의 전사를 증가시켰고, 초기 신경세포에서 보이는 Mash1의 양도 증가시켰다. Nifedipine 외 또다른 L-type 칼슘 채널의 저해제인 verapamil을 처리하자, 신경세포로의 분화가 소폭 증가하였으나, 통계적 유의미성은 매우 낮았다. T-type 칼슘 채널의 저해제 유전자인 Cav3.1, Cav3.2, Cav3.3가 발현함을 관찰하여, T-type 칼슘 채널의 저해제인 pimozide를 신경줄기세포에 처리하였으나, 신경세포로의 분화에는 변화가 없었다. 이러한 결과를 통해 nifedipine이 신경줄기세포의 초기 분화를 증진함을 알 수 있으며, L-type 칼슘 채널이 신경세포로의 분화에 관여함을 알 수 있다.

 

Mixing and Matching BP Meds? Consider the Implications for Dementia

 You'll have to ask your doctor if what you are taking is contributing to your already high dementia risk. With all this description I still don't know anything. But since they excluded people with stroke none of this may apply to us, your doctor better know the answer.

For your edification:

10 Drugs Commonly Prescribed for High Blood Pressure

I had to look up mine separately; nifediprine, is in a class of medications called calcium-channel blockers

Mixing and Matching BP Meds? Consider the Implications for Dementia

 

SPRINT analysis favors certain classes of antihypertensives

by Nicole Lou, Staff Writer, MedPage Today January 28, 2022

The theory that certain antihypertensives can be tied to less dementia was supported by a secondary analysis of the hypertension trial SPRINT.

Between study participants with high blood pressure (BP) who only used medications that stimulate type 2 and 4 angiotensin II receptors and those who only used receptor-inhibiting drugs, the former tended to have a lower risk of cognitive impairment nearly 5 years later:

• Amnestic mild cognitive impairment or probable dementia: 45 vs 59 cases per 1,000 person-years (HR 0.76, 95% CI 0.66-0.87)

• Amnestic MCI alone: 40 vs 54 cases per 1,000 person-years (HR 0.74, 95% CI 0.64-0.87)

• Probable dementia alone: 8 vs 10 cases per 1,000 person-years (HR 0.80, 95% CI 0.57-1.14)

"On a population level, shifting antihypertensive prescribing from inhibiting to stimulating regimens, while adhering to current hypertension guideline recommendations, could be a promising strategy to reduce the burden of dementia," according to study authors led by Zachary Marcum, PharmD, PhD, of the University of Washington in Seattle, writing in JAMA Network Open.

"This strategy would mean shifting the treatment paradigm from ACE [angiotensin-converting enzyme] inhibitors to angiotensin II receptor type 1 blockers and reducing the amount of inappropriate β-blocker use in the absence of coronary heart disease or heart failure with reduced ejection fraction," the researchers continued.

Dementia is a growing public health problem with no good preventive measures to date.

"For now, we cannot recommend in the clinical setting that antihypertensives be prescribed for mild cognitive impairment or dementia. Yet, this study lays a solid foundation for future research on specific types of antihypertensives for the prevention of cognitive decline in aging," according to memory specialist Zoe Arvanitakis, MD, MS, of Rush University Medical Center in Chicago.

"While the results are based on secondary analyses from data collected for another research question, the findings that a certain group of BP medications are associated with a lower risk of developing cognitive impairment are very exciting," she commented.

SPRINT included over 9,000 people ages 50 and older at higher risk of cardiovascular disease. Participants were randomized to an intensive treatment strategy (targeting systolic BP <120 mm Hg) or a standard treatment strategy (targeting systolic BP <140 mm Hg).

It was on the basis of this trial that American guidelines started recommending 130/80 mm Hg as the new BP target for most people in 2017.

For the present analysis, Marcum's group analyzed the 8,685 people on BP-lowering medications at 6 months (mean age 67.7 years, 64.3% men). This cohort was split into three:

• 30.4% were users of only antihypertensives that stimulate type 2 and 4 angiotensin II receptors (e.g., angiotensin II receptor type 1 blockers, dihydropyridine calcium channel blockers, and thiazide diuretics)

• 17.7% were users of only inhibitors of type 2 and 4 angiotensin II receptors (e.g., ACE inhibitors, β-blockers, and nondihydropyridine calcium channel blockers)

• 51.9% were users of both types of BP-lowering medication

Dementia screening was conducted at 24 and 48 months after randomization, as well as at the closeout visit and an extended follow-up visit.

The investigators said the cognitive findings were consistent when incorporating the competing risk of death and were independent of systolic BP, cardiovascular risk factors, sociodemographic characteristics, and baseline cognitive function.

Yet negative control analyses suggested the presence of unmeasured confounding.

It was already known that before weighted propensity score matching, people only on stimulating antihypertensives were more likely to be women, Black participants, and randomized to intensive treatment; and less likely to have a history of cardiovascular disease, coronary revascularization, atrial fibrillation, and statin use, compared with users of inhibiting regimens.

"Both underadjustment caused by unmeasured confounding and overadjustment caused by inclusion of covariates measured after treatment initiation, which may be intermediate on the causal pathway between treatment and outcome, are possible," Marcum's group acknowledged.

For now, more research is merited, even in persons with no high BP. The next step may include randomized trials specifically testing whether antihypertensives prevent mild cognitive impairment or dementia, according to Arvanitakis.

"A clinical trial to test the hypothesis assessed in our study for primary prevention would take years to complete. Alternatively, observational studies in larger samples, using a new-user design, with validated cognitive outcomes could provide a useful replication," the researchers suggested.

They also cautioned that SPRINT had excluded people with diabetes, advanced kidney disease, symptomatic heart failure, or a history of stroke -- limiting the study's generalizability.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

The study was supported by grants from the National Institute on Aging.

Marcum reported no relevant conflicts of interest.

Primary Source

JAMA Network Open

Source Reference: Marcum ZA, et al "Association of antihypertensives that stimulate vs inhibit types 2 and 4 angiotensin II receptors with cognitive impairment" JAMA Netw Open 2022; DOI: 10.1001/jamanetworkopen.2021.45319.

 

ASCOT: Amlodipine outperforms atenolol in stroke prevention

 I had to get off of Amlodipine since it gave me edema in my left side affected ankle. Took weeks after being off before it returned to normal. Now on nifedipine.

ASCOT: Amlodipine outperforms atenolol in stroke prevention

Long-term results from the ASCOT trial demonstrated that an amlodipine-based BP-lowering regimen reduced stroke risk compared with an atenolol-based regimen, although no benefit in dementia risk was observed.

Since management of stroke risk factors may reduce later dementia, William N. Whiteley, PhD, Scottish senior clinical fellow in Centre for Clinical Brain Sciences at the University of Edinburgh, U.K., and colleagues evaluated whether dementia or stroke were linked to different BP-lowering regimens; atorvastatin or placebo; and mean BP, BP variability and mean cholesterol levels.

Source: Adobe Stock

In the ASCOT trial, patients with hypertension and at least three CVD risk factors were randomly assigned to an amlodipine- or atenolol-based BP-lowering regimen targeting a BP less than 140/90 mm Hg for 5.5 years. The researchers also randomly assigned patients with total cholesterol of 6.5 mmol/L or less to atorvastatin 10 mg or placebo for 3.3 years.

Of the 8,580 U.K. participants, researchers followed 7,300 for up to 21 years from randomization, with a median follow-up of 17 years. The mean age was 64 years, and most patients were men (81% in BP-lowering arm; 87% in lipid-lowering arm).

Results revealed that atorvastatin use for 3.3 years failed to affect stroke (adjusted HR = 0.92; 95% CI, 0.78-1.09; P = .341) or dementia (aHR = 0.98; 95% CI, 0.82-1.18; P = .837) compared with placebo. No associations between mean total cholesterol and later stroke or dementia were reported.

Moreover, compared with an atenolol-based regimen, an amlodipine-based regimen for 5.5 years lowered the risk for stroke (aHR = 0.82; 95% CI, 0.72-0.93; P = .003) but not dementia (aHR = 0.94; 95% CI, 0.82-1.07; P = .334) during follow-up.

In other data, BP variability conferred a higher risk for dementia (HR per 5 mm Hg = 1.14; 95% CI, 1.06-1.24; P < .001) and stroke (per 5 mm Hg, HR = 1.21; 95% CI, 1.12-1.32; P < .001), adjusted for mean BP.

“Higher BP variability,” the researchers wrote, “is largely due to age-related stiffening of large arteries and loss of baroreflex function. Antihypertensive drugs have little beneficial effect in reducing variability, although dihydropyridine calcium channel blockers may have a modest effect.”

In conclusion, they wrote: “We demonstrate the importance of BP control with amlodipine rather than atenolol for stroke prevention and that starting amlodipine about 5 years earlier still has an important detectable effect on stroke incidence over 20 years. Despite this reduction in stroke in incidence, there was no reduction in dementia incidence, although dementia was almost as frequent as stroke over follow-up.”

 

Top News in Internal Medicine Certain blood pressure meds tied to suicide risk in study

So ask your doctor about this. Mine is Nifedipine is in a group of drugs called calcium channel blockers. So not listed here.

Certain blood pressure meds tied to suicide risk in study

MedicalXpress Breaking News-and-Events | October 18, 2019

A common type of blood pressure medication might be associated with an increased risk of suicide, a new study suggests.

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People taking angiotensin receptor blockers (ARBs) appear to be more likely to die by suicide, compared to those who take another type of blood pressure drug called ACE inhibitors, researchers found.
Patients using ARBs had a 63% increased risk of death by suicide over people on ACE inhibitors, the findings showed. But the study could not prove a cause-and-effect relationship.
"There is reason for some concern," said lead researcher Muhammad Mamdani, director of the Applied Health Research Center of the Li Ka Shing Knowledge Institute at St. Michael's Hospital, in Toronto. "Now would I be going en masse and change everybody's prescriptions? No, not just yet. We should have more work done in this area."
"But certainly if I had a choice as a patient, I would be choosing the ACE inhibitor over the ARB," Mamdani concluded.
ARBs and ACE inhibitors both work by interfering with the action of angiotensin II, a hormone in the body that causes blood vessels to constrict.
ARBs work by blocking the ability of angiotensin II to bind with receptors and command blood vessels to narrow, while ACE inhibitors actually lower the amount of the hormone produced within the body.
Both drugs are widely used to treat high blood pressure, chronic kidney disease, heart failure and diabetes, the study authors said in background notes.

• See Also: Determinants of suicide-related ideation in late life depression: Associations with perceived stress

Mamdani and his colleagues pursued their new research based on earlier studies suggesting ARBs might be linked to suicide risk.
Using Canadian health databases, the investigators identified 964 people who died by suicide within 100 days of being prescribed either an ARB or an ACE inhibitor. They then compared those people to a control group of just over 3,000 people also taking either type of blood pressure medication.
The results showed that people taking ARBs had a statistically significant higher risk of suicide than those on an ACE inhibitor.
"It is a fairly commonly used set of drugs, and lots of people would be affected by it. Certain people, especially if you're susceptible to mood disorders, may be even more at risk," Mamdani said.
He noted that ARBs might cause levels of angiotensin II to increase in the brain.
"That could be related to mood disorders, and that could trigger suicidal-type behavior," Mamdani suggested.
However, there's currently no evidence that angiotensin II has anything to do with moods or suicidal intent, said Dr. Robert Carey, dean emeritus of the University of Virginia School of Medicine.
"I think those speculations are exactly that," Carey said. "There is no realistic mechanism to which one could attribute that difference in suicide risk."
Carey noted that other factors that could influence suicide risk might have come into play with these patients. For example, some were taking antidepressants or benzodiazepines, "which might have had an influence on the suicide rate," he said.
The study also didn't assess underlying substance abuse, prior mental health hospitalizations, or previous emergency department visits, said Dr. Suzanne Steinbaum, a cardiologist with the Mount Sinai Hospital in New York City.
The study was published online Oct. 16 in JAMA Network Open.
"I don't think this could be construed as evidence to switch from ARBs to ACE inhibitors," Carey concluded. "The mechanism is absolutely up in the air and needs more basic study."
—Dennis Thompson

• See Also: Brain scans may provide clues to suicide risk?

To read more, click here.

Use of Antihypertensives Associated With Decreased Risk of Dementia

I want to know if coffee is better for dementia prevention or my Nifedipine use (a calcium channel blocker). WHOM will know that answer? It is a fuckingly simple question. I don't care that the answer will be hard to figure out. Living with a stroke is hard.

Coffee May Lower Your Risk of Dementia Feb. 2013

 

Use of Antihypertensives Associated With Decreased Risk of Dementia

Antihypertensive drug use is negatively associated with dementia in elderly persons followed in general practices in Germany, according to a study published in the Journal of Alzheimer’s Disease.

“After another setback for the anti-amyloid strategy, dementia prevention is increasingly becoming an area of interest,” said Jens Bohlken, MD, Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany. “In view of this, our most important task is to find existing therapies that are associated with a reduction in dementia risk or at least an extension of the time to dementia onset.”

This study was based on data from the Disease Analyzer database (IQVIA), which compiles drug prescriptions, diagnoses, and basic medical and demographic data obtained directly and in anonymous format from computer systems used in the practices of general practitioners and specialists.

Researchers included 12,405 patients with documented blood pressure values and an initial diagnosis of all-cause dementia in 739 general practices in Germany between January 2013 and December 2017 (index date). Inclusion criteria were as follows: age 60 years at the index date, observation time of at least 12 months prior to the index date, and hypertension diagnosis prior to the index date.

After applying similar inclusion criteria, dementia cases were matched to 12,405 controls without dementia using propensity scores based on age, sex, index year, and co-diagnoses (ie, diabetes, hyperlipidaemia, stroke, heart disease, depression, intracranial injury, Parkinson’s disease, osteoporosis, and epilepsy). For the controls, the index date was that of a randomly selected visit between January 2013 and December 2017.

The primary outcome was the incidence of dementia as a function of the use of antihypertensive drugs.

The use of angiotensin II receptor blockers (odds ratios [ORs], 0.74-0.79), angiotensin-converting enzyme (ACE) inhibitors (ORs, 0.85-0.88), calcium channel blockers (ORs, 0.82-0.89), and beta blockers (OR = .88) were all associated with a decrease in dementia incidence.

In patients treated with calcium channel blockers, increasing the duration of treatment decreased the incidence of dementia.

“Antihypertensive therapy alone cannot guarantee that dementia will never occur,” noted Karel Kostev, PhD, IQVIA, Germany, Mannheim, Germany. “However, these findings highlight the importance of the prescription of antihypertensive drugs in the context of preventing hypertension-associated cognitive decline.”

The authors of the study also noted that further studies are needed to gain a better understanding of the medications associated with a decreased risk of dementia.

“We plan to investigate the role of lipid-lowering drugs, antidepressants, and further medications in the future,” they said.

The study is subject to some limitations, as the patients in the study were all aged 60 years or older, and this inclusion criterion was necessary for identifying dementia. However, previous research has shown that it is important for a life course-related prevention strategy to initiate hypertension treatment at a younger age. Moreover, data on patients’ lifestyle factors, including smoking and physical activity, education, and job, were also lacking. The strengths of this study are the number of patients available for analysis, which allowed the use of a case-control design, and the use of real-world data, with different diagnoses and medications available for analysis.

Reference: http://dx.doi.org/10.3233/JAD-190362

SOURCE: IOS Press

Study links type of blood pressure medication to increased variability and higher risk of death

You'll have to do like I did and Google your medication to see if it is one of the problem types, then talk to your doctor. Mine is nifedipine, a calcium channel blocker

Study links type of blood pressure medication to increased variability and higher risk of death

Two types of blood pressure medications—alpha blockers and alpha 2 agonist—show increased variability in blood pressure measurements between doctor visits, which is associated with an increased risk of death, according to new research from the Intermountain Medical Center Heart Institute in Salt Lake City.

As a result of the study findings, researchers are encouraging physicians encouraged to use other classes of blood pressure medications that show a decrease in mortality risk.

"This study helped us identify blood pressure medications that produce more consistent blood pressure and better mortality outcome data," said Brian Clements, DO, an internal medicine physician with the Intermountain Medical Center Heart Institute and lead author of the study. "Those medications include ace inhibitors, angiotensin receptor blockers, calcium channel blockers, and thiazide diuretics. People who are on other types of blood pressure medications have an increased risk of death."

Results of the study will be presented at the 2018 American College of Cardiology Scientific Session in Orlando on March 12.

The systolic blood pressure reading (the upper number) indicates how much pressure blood is exerting against the artery walls when the heart beats. According to the American Heart Association, normal blood pressure is less than 120/80. Elevated blood pressure is between 120-129/80, and anything over 130/80 is categorized as stage one and two high blood pressure.

Prior research has shown that patients with large variances in blood pressure between doctor visits are at an increased risk of death.

The Intermountain Medical Center Heart Institute researchers looked for connections between the type of blood pressure medication a patient was using and the variations in blood pressure readings to see if certain classes of medications reduced the visit-to-visit blood pressure variability.

More than 10,500 patients with at least seven recorded blood pressure medications between January 2007 and December 2011 were followed for five years—through June 2016. Researchers tracked the range of variances in blood pressure measurements and the class of blood pressure medication each patient was using.

"Patients should know what their blood pressure is, and if it's up and down all the time, the patient should work with their physician to explore options for the best blood pressure medications that will reduce variances," added Dr. Clements. "Where possible, the two types of medications that show an increase in variances should be avoided."

Researchers say the next steps are to look at other medications that are proven to reduce the variability in blood pressure measurements and better evaluate methods for taking evidence-based blood pressure measurements.

In most people, systolic blood pressure rises steadily with age due to increased stiffness of large arteries, long-term build-up of plaque, and increased incidence of cardiac and vascular disease, according to the American Heart Association.

"Hypertension affects many people—roughly one in three adults in America, according to the American Heart Association," said Dr. Clements. "But because of the variables that affect blood pressure measurements, finding ways to more accurately measure blood pressure can better identify effective treatments for patients who have hypertension."

Dr. Clements also recommends that people control their environment when measuring their blood pressure to help reduce additional variables from influencing the measurement.

• Sit or lay down for 15 minutes prior to taking your blood pressure.
• Don't do things that will cause you stress, since that may raise your blood pressure.
• Use a blood pressure cuff that fits. Make sure it's not too tight or too large.

Explore further: Extreme swings in blood pressure are just as deadly as having consistently high blood pressure

Provided by: Intermountain Medical Center

Mitigation of calcium channel blocker-related oedema in hypertension by antagonists of the renin–angiotensin system

Three weeks after stopping my amlodipene for high blood pressure the swollen left ankle is still there. Right ankle(good leg) never swelled up. I wasn't warned about edema when I started taking the drug. Now on nifedipine.

I'll have to see what my doctor can do about this.

Mitigation of calcium channel blocker-related oedema in hypertension by antagonists of the renin–angiotensin system

A de la Sierra¹

¹University of Barcelona, Barcelona, Spain

Correspondence: Dr A de la Sierra, Hypertension Unit, Department of Internal Medicine, Hospital Clinic 170-Villarroel, Barcelona 08036, Spain. E-mail: ASIERRA@clinic.ub.es

Received 23 July 2008; Revised 8 November 2008; Accepted 24 November 2008; Published online 15 January 2009.

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Abstract

This review is aimed at examining calcium channel blocker (CCB)-related oedema and how this can be attenuated through the use of agents that inhibit the renin–angiotensin system. CCBs are effective antihypertensive agents, but their propensity for causing oedema may reduce compliance. A review of the literature has indicated that the absolute incidence of this side effect is difficult to determine because reported rates vary widely, a factor that may stem from differences in the surveillance technique (active vs passive). In a recent trial incorporating active surveillance, 25% of patients who received amlodipine 10 mg per day experienced oedema. CCB-induced oedema is caused by increased capillary hydrostatic pressure that results from preferential dilation of pre-capillary vessels. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) cause post-capillary dilation and normalize hydrostatic pressure, and are thus ideally suited for prevention/reversal of CCB-induced oedema. The efficacy of this strategy was proven using both subjective and objective techniques. ARB/CCB and ACEI/CCB combination therapy is also more effective than CCB monotherapy in controlling blood pressure. These combinations represent an important advance in the management of hypertension.