scta123
#243
I like in general the approach of combing several drugs in subclinical doses with different targets for the same condition. Much less side effects and better tolerability and outcomes. I don’t know why this is not practiced more in medicine.
adssx
#244
For hypertension, it’s now the recommended approach, see for instance the 2023 European guidelines:
11.10.3 Rationale for initial two-drug combination therapy
As discussed above and with the emphasis in the present guidelines on achieving a BP target of <130/80 mmHg in most patients, the majority of patients will require combination therapy. Although no RCT has ever compared major CV outcomes between initial combination therapy and monotherapy, multiple arguments support combination of two antihypertensive drugs as the initial treatment step. One, initial combination therapy is invariably more effective at BP-lowering than monotherapy, and indeed even low-dose combination therapy is usually more effective than maximal dose monotherapy. Furthermore, the combination of medications targeting multiple mechanisms (i) reduces the heterogeneity of the BP response to initial treatment and (ii) provides a steeper dose– response effect than that observed with escalating doses of monotherapy and (iii) is safe and well tolerated, with no or only a small increase in the risk of hypotensive episodes, even when given to patients with grade 1 hypertension. Two, initial two-drug combination is associated with a faster BP reduction compared with monotherapy, and observational evidence suggests that the time taken to achieve BP control is an important determinant of clinical outcomes, especially in high-risk patients, with a shorter time to control associated with lower risk risk. Three, evidence from the more general hypertensive population shows that compared with patients on initial monotherapy, those who start treatment with a two-drug combination reach more frequent BP control after 1 year, probably because initial combination treatment prevents therapeutic inertia, and initial two-drug combination is associated with a better long-term adherence and persistence to the prescribed treatment regimen. Studies from large treated cohorts of patients under antihypertensive treatment have also shown that initial combination treatment resulted in a lower risk of CV events compared with initial monotherapy followed by the traditional stepped-care approach.
11.10.5 Rationale for single-pill combination therapy
The 2013 and 2018 ESH/ESC guidelines favored the use of two antihypertensive drugs as an SPC, because reducing the number of pills to be taken daily improves adherence to treatment and increases the rate of BP control. This recommendation is endorsed by the present guidelines. […] It showed the potential to double BP control rates in treated patients from the present low level also with an improvement of outcomes. SPCs of a BB plus a diuretic or a CCB have been available since many years, while at the time of the 2018 ESC/ESH Hypertension Guidelines, additional SPCs were almost exclusively limited to a RAS blocker (ACEi or ARB) plus a CCB or a diuretic. In the 5 years from the 2018 Guidelines, a large number of new two-drug SPCs have been developed and tested for their ability to improve adherence to treatment and reduce CV outcomes. Available two-drug SPCs now extend to most ACEis or ARBs in combination with a long-acting CCB or a diuretic belonging to the Thiazide (usually hydrochlorothiazide) or Thiazide-like (indapamide or chlorthalidone) class. Moreover, two-drug SPCs are now available for a RAS blocker (ACEi or ARB) with a BB, including SPC containing nebivolol with additional vasodilatory action, and a CCB with a diuretic (e.g. amlodipine plus indapamide or nifedipine plus a Thiazide). The availability of three-drug SPCs has also grown and, although almost invariably based on a diuretic, a RAS blocker and a CCB, it now extends to different compounds within each of the three drug classes involved. This enables to tailor SPC treatment to different clinical requirements.
Unfortunately, not all combos are available everywhere. For instance, telmisartan/amlodipine, although on the WHO List of Essential Medicines, is not marketed in the UK.
1 Like
Tim
#245
@adssx
I just switched from lisinopril to Losartan. Lisinopril worked very well, but it was giving me a troublesome cough. I also dropped amlodipine, which had caused my feet to swell. So far, losartan isn’t doing the job. It may be because I take 9 g of sodium bicarbonate per day for acid reflux and acidosis. The bicarb has been a life saver, but I may need to lower the dose for a while. I also recently started taking a testosterone gel, which I get from my rapa supplier in India. Testosterone is known to boost BP, as is prednisone, even in the very low doses I was taking. So I’m probably asking too much of the losartan.
adssx
#246
Hi @Tim. Yes chronic cough is the most common side effect of ACEIs like lisinopril. Losartan is the least effective of ARBs. What’s your dose? Switch to telmisartan if you need stronger BP lowering.
Amlodipine: which dose did you use? The swelling is dose-dependent: really rare at 2.5 mg but quite common (10%) at 10 mg. Taking amlodipine with a sartan or ACEI reduces the risk VS amlodipine monotherapy.
If even only 2.5 mg causes swelling or if you want more BP lowering you can use a thiazide-like diuretic like indapamide 1.5 mg SR. In India they sell almost all the combinations as single pill (except for indapamide, they often use HCTZ or chlorthalidone instead) so it’s quite convenient.
(I think telmisartan and amlodipine are the best ARB and CCB respectively but I’m still unsure about HCTZ vs chlorthalidone vs indapamide…)
2 Likes
My mother is taking lisinopril right now. Should she switch to telmisartan?
What are the pros/cons of this switch?
adssx
#248
Switching is another thing than starting from scratch. I don’t know if it’s worth it (vs starting early in life when positive effects compounds over a long period of time). The con is that “if it ain’t broke don’t fix it”, she might use other drugs, with potential interactions, maybe the current dose is optimal, etc. Regarding the pros, the list is long: Why Telmisartan Is Best For Blood Pressure - Life Extension (for instance, telmisartan is one of the only hypertensive drugs that significantly increases insulin sensitivity)
1 Like
Yes, she’s also dangerously diabetic HBA1C of 8.4. I may ask her to talk to her doctor about switching to Telmisartan if it would help with her diabetes. She is only taking 2 g of Metformin for her diabetes.
adssx
#250
Doctors very rarely know that telmisartan increases insulin sensitivity unfortunately.
2 Likes
How big is the effect on insulin sensitivity? Minor or major?
adssx
#252
Significant: https://images.app.goo.gl/jBAYa5QMzTgvrQCH8
Telmisartan 80 mg reduces FPG and HbA1c by 10%. And HOMA-IR by 25%. So for someone with 8.4% HbA1c it would mean reaching 7.6%. These effects seem dose-dependent: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2710.2011.01295.x
I just read that telmisartan and Lisinopril can be used as a synergistic combination. As Telmisartan is an ARB and Lisinopril is an ACE. My mom’s BP is still too high as well.
1 Like
adssx
#254
I think that American and European guidelines recommend not to mix ARB with ACEI. I don’t know why, but I wouldn’t do it. The most common combination is (ACEI or ARB) + (CCB or thiazide diuretic).
1 Like
Maybe we’ll just go for empagliflozin first. However she is worried empagliflozin may cause side effects.
tj_long
#256
What do you think about this?
”This analysis shows that risk of cancer and specifically lung cancer increase with increasing cumulative exposure to ARBs.”
adssx
#257
A single unknown author (who is not even an oncologist) from a Turkish university. Unless there are other papers confirming this finding, that paper would go to the trash for me.
Here’s another paper coming out from German institutions in a specialized oncology journal: Risk of lung cancer and renin–angiotensin blockade: a concise review 2021
Results
International regulatory agencies (FDA, EMA) have concluded that the use of RAAS blockers is not associated with an increased risk of developing lung cancer. Co-administration of RAAS blockers to systemic therapy of advanced non-small cell lung cancer seems to have positive effects on the outcome.
Conclusion
Until more comprehensive analyses have been completed, there is no need to change clinical practise. Additional prospective randomized trials with long-term follow-up are needed to investigate the effects of these drugs on the development and progression of lung cancer.
2 Likes
adssx
#258
Lebanese and Swiss team of oncologists: The association between angiotensin receptor blockers and lung, bladder, and colon cancer development: A 10-year multicentric retrospective Lebanese study 2023
ARBs use was significantly protective (P value = 0.000) against overall cancer development (odds ratio [OR] = 0.127) and against each, lung (OR < 1), bladder (OR < 1), and colorectal cancers (OR < 1). A duration-response relationship was established. This protective effect and the time-dependent relationship remained unchanged after omitting the most relevant risk factors. In summary, a significant overall protective effect of ARBs against lung, bladder and colorectal cancers was found. This beneficial response was time-dependent.
The trash is indeed the correct destination for the Turkish paper.
4 Likes
Yes, we’ve got to really be more skeptical of one off papers by sketchy sources.
3 Likes
tj_long
#260
True, I agree. There are a lot of conflicting results.
Tim
#261
@Tomnook
What drove your BP to 220?
Tomnook
#262
@Tim
White coat syndrome. It was 200/110 at the first measurement in the doctor’s office and 220 at the second one. I’ve always been the same - an increase in bp with each successive measurement at the doctors…… never as high as this previously though.
1 Like
