This meta-analysis of 147 (958,000 subjects) randomized controlled clinical trials related to antihypertensive drugs showed that five major antihypertensive drugs [thiazide diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor antagonists (ARBs)] were similar in preventing coronary heart disease and stroke. angiotensin-converting enzyme inhibitors (ACEI), and angiotensin receptor antagonists (ARB)] are similar in preventing coronary heart disease and stroke, with CCB being slightly more effective in preventing stroke and β-blockers having a preventive effect on coronary events in the early post-infarction period.
The investigators thus concluded that the current guidelines for the use of antihypertensive drugs could be simplified to mean that anyone reaching a certain age should take antihypertensive drugs, regardless of population blood pressure levels, without blood pressure measurement, to prevent coronary heart disease and stroke events. What to make of this conclusion? Let’s hear the experts break it down. The concept that everyone should take antihypertensive drugs is unacceptable. The purpose of the meta-analysis published in BMJ by Law et al. may have been to increase the use of antihypertensive drugs, but the findings may not be reliable.
1. Of the 147 trials, 74 were conducted in patients with coronary heart disease and 13 in stroke patients, and the subjects included were mainly high-risk patients, from which the conclusions obtained cannot be simply generalized to the prevention and treatment of hypertension in the general population.
2. These large sample meta-analyses are usually not of high quality and do not allow access to the original data of each patient. For example, in this meta-analysis, the change in blood pressure before and after treatment of patients refers to the difference between the average baseline blood pressure of the whole group of patients and the average blood pressure after treatment, i.e., the average data of thousands of people is taken as a measurement value, and its roughness is evident. Moreover, the trials analyzed were not homogeneous, and the criteria for defining endpoint events were inconsistent. Therefore, the results of this type of meta-analysis can at best only suggest hypotheses, and cannot confirm hypotheses, especially those with significant clinical significance.
The meta-analysis was conducted on people aged 60-69 years, but concluded that “anyone who reaches a certain age should take antihypertensive drugs”; the lower limit of baseline blood pressure in the efficacy analysis was 110/70 mmHg, but concluded that “blood pressure measurement is not necessary”. This seems to be an excessive inference, resulting in a less than rigorous conclusion.
4. The above conclusions are inconsistent with the results of some recent studies. For example, some pooled analyses have shown that although the benefit of antihypertensive treatment is mainly due to the reduction of blood pressure itself, there is still some extra-benefit of different drugs to lower blood pressure. National hypertension guidelines also recommend that various antihypertensive drugs have their own priority indications in different clinical situations. The International Verapamil/Gundopril Study (INVEST) and others suggest that, at least in patients with coronary artery disease, there is a “J-curve” relationship between blood pressure levels and the risk of major cardiovascular events, i.e., when blood pressure, especially diastolic blood pressure, is lowered below a certain lower limit, the risk of cardiovascular events increases, and these findings are gradually being recognized.
A large number of studies have shown that the higher the risk of cardiovascular events, the greater the benefit of using an effective preventive measure. Existing guidelines advocate the use of methods such as scoring to assess a patient’s overall cardiovascular risk and adopting a stratified prevention strategy based on the benefit-risk ratio. The statement in this meta-analysis that the clinical benefit of antihypertensive drugs is independent of the patient’s baseline risk level is contrary to evidence-based evidence and should not be taken lightly.
6. The claim that everyone uses antihypertensive drugs is not innovative. After the cardioprotective effects of aspirin, ACEI and statins were demonstrated, the idea that everyone should use these drugs was eventually either dismissed or not pursued. law et al. 6 years ago proposed the concept of preventing cardiovascular disease with a polypill, which consists of 6 drugs, including 3 antihypertensive drugs. They claim that taking this multi-pill can reduce the risk of coronary heart disease by 88% and the risk of stroke by 80% and should be taken by people over 55 years of age. The claim that everyone should take antihypertensive drugs is in a sense an extension of the multi-pill concept. However, the clinical benefits and safety of multi-pills have not yet been tested in high-quality clinical trials.
Therefore, conclusions derived from retrospective analysis, statistical processing and mathematical formulae alone are hardly convincing to the author. The meta-analysis published in the BMJ on May 19 included 147 randomized clinical trials of five different antihypertensive drugs, different blood pressure levels (110-180 mmHg systolic, 75-110 mmHg diastolic) and different amounts (single, two-drug, three-drug combination) and doses (half-dose, regular, double-dose) of the drugs. Double dose) were analyzed and an important antihypertensive idea was proposed: all 5 classes of antihypertensive drugs can prevent coronary heart disease (CHD) and stroke regardless of blood pressure levels, so antihypertensive drugs should be available to everyone. How to understand this idea?
1. It is an undisputed fact that patients benefit from blood pressure lowering, but there is a difference between blood pressure level and the degree of benefit. The higher the blood pressure level, the greater the benefit of lowering blood pressure. At lower blood pressure levels, the benefit of lowering blood pressure with the same type of drug or the same dose is visible, but smaller, due to its lower risk. Therefore, the intensity of blood pressure lowering can only be decided according to the level of blood pressure in order to be targeted.
2. Although investigators have suggested that the five classes of antihypertensive drugs have similar effects in reducing CHD and stroke, the study data still show individual differences in the drugs. For example, in hypertensive patients with a history of CHD, beta-blockers had a strong effect of reducing coronary events (30%), which was evident in the early post-myocardial infarction period (within a few years) and then gradually became similar to the effect of other antihypertensive drugs. This suggests that the 5 classes of drugs still have preferential selection properties in patients with different underlying diseases.
The meta-analysis provided important clinical information: when patients aged 60 to 69 years had blood pressure of 150/90 mmHg, a 30/10 mmHg increase in blood pressure was associated with a 10% increase in cardiovascular risk, and the risk increased by about 5% for each 10-year increase in age. standard doses of single drugs in the 5 drug classes reduced the risk of CHD by 25% and the risk of stroke by 35%, while half doses of all 3 drugs reduced the risk of CHD by 45% and the risk of stroke by 5%. The risk of CHD was reduced by 45% and the risk of stroke was reduced by 60% with all 3 drugs at half dose. This information suggests that ageing and increased blood pressure are important risk factors for cardiovascular events, and that effective blood pressure lowering and appropriate large blood pressure lowering may bring benefits in terms of reduced cardiovascular events.
However, the idea that everyone receives antihypertensive medication is not entirely appropriate, and a moderate reduction in blood pressure, with appropriate drug combinations selected according to patient risk, may be more conducive to a good prognosis. Therefore, when analyzing a clinical report, it is important to see the advantageous information in it, but also to carefully examine the possible problems in it to guide clinical practice.
Accurate blood pressure measurement to ensure benefit of antihypertensive treatment Wang Jiguang, Ruijin Hospital, Shanghai Jiaotong University School of Medicine Epidemiological studies have confirmed that elevated blood pressure is associated with a significantly increased risk of cardiovascular diseases such as stroke and coronary heart disease. Clinical trials have confirmed that in patients with hypertension, lowering blood pressure substantially reduces the risk of stroke and coronary heart disease. Basic research on blood pressure has greatly improved the understanding of cardiovascular neuroendocrine regulatory systems and has led to the development of diuretics, beta-blockers, CCBs, ACEIs, and ARBs for the treatment of cardiovascular disease.
All of these studies require accurate blood pressure measurement. Unfortunately, recently, there has been a proliferation of rhetoric that partially or wholly rejects the importance of blood pressure measurement in the prevention and treatment of cardiovascular disease. Most typically, a recent meta-analysis published in the BMJ presented two specious arguments.
(i) Everyone at cardiovascular risk should take antihypertensive drugs, especially multi-pill pills containing beta-blockers with diuretics, without the need for blood pressure measurement;
② Beta-blockers are more effective in preventing stroke and myocardial infarction than other types of antihypertensive drugs. Either of these ideas may have adverse effects on patients and physicians when put into practice. A multi-pill antihypertensive therapy should include a CCB with proven efficacy and fewer adverse effects and a renin system inhibitor for those with high blood pressure or whose blood pressure is not effectively controlled with monotherapy.
Multi-pill containing beta-blockers and diuretics, even in so-called small doses, cannot be widely used in chronic diseases such as hypertension. When the two drugs are combined, serious metabolic adverse effects lead to disorders of glucose metabolism, which can substantially increase the complexity and cost of disease management, if not the cardiovascular risk. Beta-blockers are undoubtedly one of the most important drugs in the field of cardiovascular disease treatment for coronary artery disease and heart failure not controlled by ACEI, but their limitations cannot be denied.
However, this meta-analysis conflates some placebo-controlled and antihypertensive clinical trials done in heart failure patients long before ACEI use in an attempt to create the illusion that “beta-blockers seem to be more effective in preventing stroke and myocardial infarction”. It is important to note that in the treatment of coronary artery disease and heart failure, the mechanism of action of β-blockers is never to lower blood pressure and therefore should not be confused with their antihypertensive benefit in the treatment of hypertension.
When hypertensive patients with blood pressure >140/90 mmHg are treated with antihypertensive drugs, only accurate blood pressure measurement is necessary to adequately lower blood pressure while avoiding adverse effects, especially the possible serious consequences of hypotension. Patients with coronary artery disease and heart failure who have normal blood pressure should monitor their blood pressure more closely when using antihypertensive drugs in order to avoid possible adverse effects from the drugs.
Antihypertensive treatment should follow guidelines Wang Wen, Fu Wai Cardiovascular Hospital, Beijing There are 200 million hypertensive patients in China, and the treatment rate was only 25% according to a survey in 2002, and it is estimated that it may increase to 30% in recent years, with 70% using antihypertensive drugs for various reasons. Some of the data from the meta-analysis published in the BMJ are informative, but the conclusion that antihypertensive drugs are used for every person regardless of blood pressure level lacks scientific evidence and is not advisable in clinical practice, especially in China.
China is a developing country with limited medical resources, and it is not possible or desirable to give antihypertensive drugs to everyone over a certain age. Of course, for those at high risk of cardiovascular disease (e.g., post-stroke, coronary heart disease, diabetes mellitus, chronic kidney disease patients), blood pressure levels >130/80 mmHg may benefit from antihypertensive therapy, and for this group of high-risk patients, they should receive antihypertensive medication even if their blood pressure levels do not meet the diagnostic criteria for hypertension.
For people with blood pressure levels <120/80 mmHg, no further significant benefit can be obtained from antihypertensive treatment. In conclusion, the main task of hypertension prevention and treatment in China is to increase the rate of hypertension treatment and thus improve the rate of blood pressure control.