Hypertension treatment -- Cochrane & other summaries
The teensy-weensy benefit of hypertension mediation and a new record for tiniest improvement in all-cause mortality.
[The following is a somewhat prettied up set of notes that I started late in 2022 when I began researching these pathetic products. For reasons I still can’t grasp, both my ancient Office 2000 Word and SubStack’s editor fail to catch many typos, so apologies for any that I still have missed.]
Hypertension studies from Cochrane + others:
Revised: 02-17-2023
(1)
Is there randomized controlled trial evidence to support the use of antihypertensive drugs over placebo for primary prevention in adults with mild hypertension?
Dane Gruenebaum
13 September 2018
https://doi.org/10.1002/cca.456
Clinical Answer:
In adults with mild hypertension without complications of cardiovascular or chronic kidney disease, randomized controlled trials including over 7,000 people suggest that there is no reduction in total mortality, overall cardiovascular events, stoke, or coronary heart disease when they are treated with antihypertensive drugs compared with placebo. Of note, the withdrawal rate due to adverse events in the treatment group was over 7%, roughly five times higher than the placebo group (72 vs. 15 per 1000 people), suggesting there are potentially more adverse effects associated with antihypertensive drugs than is often believed. While the trials were generally low quality, they seem to support the recommendation that lifestyle changes be the first line therapy for mild, uncomplicated hypertension.
My commentary: I have not yet tried any lifestyle changes, other than (slightly) reducing salt. My diet is far from optimal, but I would resist changing it much, to be honest.
(2)
Is there RCT evidence to support the use of antihypertensive drugs over placebo/no treatment for primary prevention in adults with mild to moderate hypertension?
Jane Burch, Juliana Ester Martin
30 November 2018
https://doi.org/10.1002/cca.1914
Clinical Answer:
Despite apparent benefits of antihypertensive therapy for primary prevention in adults with hypertension, all evidence is of very low to low quality, and reviewers did not assess some clinically relevant outcomes, making it difficult to draw firm conclusions.
Low-quality evidence suggests that adults aged 18 to 59 years with hypertension (baseline systolic 147 to 176 mmHg and diastolic 99 to 103 mmHg) treated for primary prevention (most often with first-line high-dose thiazides) are less likely to experience cardiovascular or cerebrovascular morbidity or death than those given placebo/no treatment during 2 to 10 years’ follow-up. However, event rates were low in both groups (on average, 32 vs 41 per 1000 people for cardiovascular morbidity/mortality and 6 vs 13 per 1000 people for cerebrovascular morbidity/mortality). Decreases in systolic and diastolic blood pressure at one year were greater with antihypertensive therapy, but these reductions were modest (on average, by ∼15 and 8 mmHg, respectively).
Researchers observed similar rates of all-cause mortality and morbidity/mortality due to coronary heart disease. Antihypertensive therapy seemed to be well tolerated, but more people withdrew from antihypertensive therapy as the result of adverse events, although the numbers were very low in both groups (32 vs 7 per 1000 people).
Despite apparent benefits of antihypertensive therapy and tolerability of treatment, all evidence was of very low to low quality, reviewers did not assess some clinically relevant outcomes, second-choice antihypertensive treatments varied across trials, and no trial assessed alternative first-line antihypertensive therapies such as long-acting calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin II receptor blockers.
My commentary: Drug tested was not what I'm on; therefore the results may not pertain to my case. As with Covid-19 "vaccines," the relative risk reduction looks impressive (~23%, 54%), but the absolute reduction is trivial: control group had 4.1% or 1.3% (average = 2.7%). They claimed similar numbers in both groups due to "coronary heart disease"; is this a subset of the other ailments?
Based upon this information, I should ask my MD(s) to clarify precisely why I need to be on a hypertension medication. Is it really of any benefit? While I've not yet suffered any adverse effects to my knowledge, I would prefer to be off the medication if it's not providing a clear benefit. As I've noted on my Statin worksheet, three of four grandparents lived well into 80s-90s. One did die (I think) from heart issues (in 1950s) but I lack details. Nor do I know medicines. Clearly, there were fewer available way back (last grandparent died ~1984). This was before statins were even available. There is little to no evidence of heart disease in both sides of my family.
I've found little favorable evidence to date; unless my MD or other source can provide a persuasive case, I'm inclined to drop these meds. Note: I'd be willing to continue on them IF there was strong evidence they don't have harmful side effects -- a high hurdle, I suspect.
(3) What are the effects of antihypertensive drugs for prevention of sudden cardiac death in hypertensive adults?
Jane Burch, Benilde Cosmi
19 April 2017
https://doi.org/10.1002/cca.1458 (full page downloaded)
Clinical Answer:
Moderate-quality evidence shows that adults with hypertension (140 mmHg systolic and/or 90 mmHg diastolic blood pressure) who received first-line antihypertensive treatment (diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, or calcium channel blockers) were no more likely to experience sudden cardiac death than those who did not. [How reassuring, but oddly stated!] Study results also show benefit in terms of myocardial infarction (moderate-quality evidence), with fewer non-fatal (on average, 17 versus 20 per 1000 people) and fatal (on average, 9 versus 12 per 1000 people) myocardial infarctions over four years of follow-up. However, event rates were very low, and more people taking antihypertensive agents withdrew from treatment as the result of adverse effects (on average, 48 versus 23 per 1000 people), showing that antihypertensive drugs as a primary preventive measure may not be acceptable for everyone with hypertension.
Pharmacotherapy for hypertension in adults aged 18 to 59 years (Review)
Musini et al, a 2017 Cochrane Review.
https://pubmed.ncbi.nlm.nih.gov/28813123/
This review looked at patients with starting readings around 140/90 or more … similar to my current diagnosis. “Authors' conclusions: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced.”
“This is the first systematic review of drug therapy in adults aged 18 to 59 years with elevated BP. The ARR in adults aged 18- to 59- years in this review for cardiovascular mortality and morbidity was small (0.9% [over five years]) with an NNTB of 112 over five years. It is important for clinicians and participants to know the approximate magnitude of benefit in this setting. For people aged 60- to 79-years the absolute reductions over five years were greater, total cardiovascular events, ARR 3.8% with an NNTB 26 over five years (Musini 2009).
For the 18-59 cohort, I calculate slightly different numbers (see "Summary of Findings"):
all-cause mortality as: (110-100)/1000 = 10/1000 = 1/100 / 3.8 years = 0.00263 = 0.263% ARR; RRR = 100/110 = 0.91 => 9% improvement.
An updated version of that 2009 study is available, which I'll look at next.
Musini et al, a 2019 Cochrane Review: similar, looking at ages 60 and up
https://pubmed.ncbi.nlm.nih.gov/31167038/
“Conclusions: Blood pressure-lowering drug treatment for healthy persons (60 years or older) with raised blood pressure reduces death, heart attacks, and strokes.” Ah, even Cochrane is getting vague…perhaps an influence from that Gates money and similar? Well, even so, I concede they’re probably telling the truth in that claim. Just the same, let’s try and find some hard figures, shall we? In “Summary of Findings” we find that overall mortality over (3.8 years mean) was 110 per 1000 and 100 per thousand between control and treatment respectively. I calculate a difference (improvement) of 110-100 = 10 per 1000 which is an ARR = 1% as they show. But wait, let’s annualize that. Then it’s 0.01/5 = 0.002 = 0.2% ARR.
The all cause deaths by itself is suspicious: recall that the study group is only persons aged sixty or more, and most of these had known health issues. Referring to the Social Security Life Table, averaging both sexes, at age 60 a person has just less than 1% annual death risk; age 71, 2%; by age 78%, 4%. And recall this is the entire population, not just sickos. Thus I find a claimed 1.1% all-cause annual mortality not credible. What’s going on? [The problem seems resolved, as I did some further digging, below…]
“Analysis 1.2” data shows (total mortality):
treatment had 1290/13368 = 0.0965 = 9.65% => 2.54% per annum.
control had 1376/12564 = 0.1095 = 10.95% => 2.88% per annum.
OK, those are more reasonable, but we need to annualize. What’s the duration? I found 3.8 years “mean duration”; for reference, the participant’s mean age is 73.4 years. SS Table gives dirt nap probability at age 73 of about 2.4%.
OK, let’s stop over-using “OK,” OK?
Bloody well, let’s adjust the numbers (above). OK, now the control’s death rate passes the sanity test. 2.88 more than the 73-year-old figure that SSA gives, and is consistent with a group selected for high blood pressure.
Now I can make a better calculation as to the actual benefit of all-cause death improvement:
2.88 – 2.54 = 0.34% yearly (absolute); relative risk reduction ~= 12%.
Using my trusty life expectancy spreadsheet, that 12% relative risk reduction would snare me about 15 days by my life expectancy (age 82), and just over three months should I live to 100. As with all prior calculations, I say “big fucking deal.”
More Data: Kendrick’s comment in “A Statin Nation”
In Ch. 9, he takes a break from discussing cholesterol and mentions a 1985 hypertension study, the MRC trial of treatment of mild hypertension. (Link below, open access).
https://pubmed.ncbi.nlm.nih.gov/2861880/
[M]any years ago [ca. 1985], when the results of the Medical Research Council’s (MRC) trial on mild to moderate blood pressure lowering were presented at a cardiology conference in Scotland This was a landmark trial, the first ever large-scale placebo-controlled clinical study to ask the question. Does lowering mildly raised blood pressure work? Mildly raised, in those days, was anything over 160/110 which, today, would result in you being rushed into hospital with malignant hypertension. I exaggerate, but only slightly. In the MRC trial, 17,354 patients were recruited and there were 85,572 patient years of observation. After all this, there were 248 deaths in the treated group and 253 deaths in the placebo group. It turned out that treating nearly 9,000 people for five years resulted in five fewer deaths. That equates to very nearly 9,000 years of treatment to delay one death. There was absolutely no difference in CV mortality.
My first thought was, ‘Crikey, what a complete and utter waste of time.’ I raised my hand and gently suggested (I was young and naïve at the time) that this trial seemed to suggest that lowering blood pressure was not really very effective. Or perhaps I wasn’t so timid. The temperature in the lecture theatre suddenly plummeted about 30 degrees.
Now, whilst statins may be the most prescribed group of medicines in history, there are still more people taking various blood pressure lowering agents in total. So, you can see what impact the MRC trial had. Which reminds me of Winston Churchill’s ‘Men occasionally stumble over the truth, but most of them pick themselves up and hurry off as if nothing had happened.’
I checked his figures; at least the all-cause death numbers are what the study said. Using the supplied rates (incident per 1000 patient-years) I derive an absolute risk improvement of a whopping 0.01% annual. You read that correctly: one one-hundredth of a percent per annum. (I even went back to double-check it: Table VI on page 101: "All deaths" (rate per 1000 patient years): 5.9-5.8 = 0.1 per 1000 years = 0.0001 per year = 0.01% per year.)
This particular risk reduction boasts the dubious distinction of the tiniest reduction in all-cause mortality of any study I've seen, barely edging out the previous champion, (0.02%/year ARR) Aspirin in the primary and secondary prevention of vascular disease (Lancet, 2009 May 30; 373(9678): 1849–1860).
In fairness, the study did show good (relative) drop in stroke – as one would hope with blood pressure lowering – and a tiny improvement in non-fatal coronary events, but there were slightly more coronary deaths with treatment. Without exception, the absolute improvements were minuscule, avg. of stroke + coronary (all events) averaging to about 0.75 per 1000 patient-years = 0.00075 = 0.075%.
Overall Commentary: as with other cases, the improvements look good if couched in relative risk reduction, but rather trivial (my opinion, of course) in absolute. E.g. non-fatal, over 4 year period, drop from 2% to 1.7% (an improvement of 0.3% !!!) and for fatal, from 1.2% to 0.9%, an improvement of 0.3%. Divided by four (for annual rate, I assume) and it's even less impressive. Adverse or harmful effects must exist, and that argues against these even more. Again, ask my doctor "What am I taking these for???"
Yet Another Kendrick Quote
[The American Heart Association] have now decreed that any systolic blood pressure of 130mmHg shall be considered hypertension. This is utterly ridiculous. To quote Richard Lehman in the BMJ: ‘it reclassifies about half the population as “hypertensive”. Here lies a glimmer of hope. When this level of absurdity is reached, people might start to question the notion of “hypertension” altogether.’ Quite.
A Statin Nation, ch. 16
Kendrick cites the above quote as “The BMJ, 25 November 2017, ‘Education’, p. 325”; I think the citation is bad, but the following may be the article (paywall):
https://www.bmj.com/content/359/bmj.j5357
[Feb. 21, 2024]
Follow-Up: Yet Another Covert Ad for the Medical-Industrial Complex
Obviously my site is rather moribund, but I like to add the occasional postscript to satisfy both of my readers. I haven’t been researching this topic in the past year, but this article was served to me by Firefox’s Pocket service. It was just too much for me, and thus as a sort of therapy, the present verbiage. Here’s the problem article:
Now, the usual disclaimers, or credit where due: Yes, I suppose hypertension can be an issue at times. But I’m interested in discerning between a patient’s need and the medical system’s greed. Nothing new here, but I’ll harp on a couple of the standout problems here:
“[N]early half of Americans ages 20 years and up – or more than 122 million people – have high blood pressure, according to a 2023 report from the American Heart Association. And even if your numbers are normal right now, they are likely to increase as you age; more than three-quarters of Americans age 65 and older have high blood pressure.”
Hmm…let me check…nope, no word at all about those ever-lowering thresholds for what constitutes “high blood pressure.” I’ve dealt with that topic elsewhere. But it’s worth mentioning again: Just how much credibility are we to attach to a claim that nearly half of the adult population has a problem that must be treated? Why is it a problem now, or very recently, and was not in decades past? It’s not as if the risks of high blood pressure are a very recent discovery.
I can’t easily vet the claim of by what degree raised blood pressure increases the risk of death by heart attack or stroke. Right off the bat, my skepticism asks: Isn’t it more important to consider the risk of death from all causes? I notice this aspect is almost never mentioned in such a context. Drugs almost always have side effects, and people who are treated for hypertension will likely be on at least two! There’s also the question of absolute vs. relative risk: Doubling one’s risk sounds scary, but the absolute risk per year may actually be quite small.
Meager credit where due: To improve, change one’s diet and exercise more. Even most of the diet advice is correct. Well, nearly so: they are still wrong, not just slightly, but dead wrong, about saturated fat.
I see there’s the admonition to limit salt: Well, I’ve covered that in another essay too. But worth a quick repeat: Yes, excess salt (sodium) will increase blood pressure, but the amount is so trivial (for most people) that it’s not worth the bother. You are far more likely to incur health issues with too low sodium.
Nor did I see a single word about limiting carbohydrates. It’s excess sugar and junk carbs that drive many chronic health issues, and hypertension is only one side effect of those.
“Most patients need two to three medications to lower blood pressure to normal or healthy levels.” (!!!)
Well, I already took a cheap shot at that. Jeez, I was only on a single med for my mild hypertension. Oh, did I ever mention that I lowered mine ten points or so, likely by going low carb? I haven’t been on any Rx meds for over a year and the good readings continue.
Summary:
This is just another public service announcement for the healer’s guild. Yes, there is a bit of truth in there as usual: Here’s a health risk, here are several things you can do about it, but you really should be under our continuing care and taking at least a couple profitable medications we’ll sell you. But there are also several glaring errors which I hope I’ve pointed out. Yet one more example of the problem of profit motive trumping what might be in the best interests of the patient’s health.
Uh Oh -- Temptation
“A recent meta-analysis demonstrated that lowering systolic blood pressure by 5 mm Hg through medication reduces the risk of major cardiovascular events by about 10%, irrespective of baseline blood pressure or previous diagnosis of cardiovascular disease.”
Yet another study I might take a look at. Well, not today. Maybe later.
Wow, very interesting