“. . . different classes of drugs can work for different people - what might be effective in one, might not be in another.”
Yes and this basic truth is not only underappreciated, it generally earns a yawn when pointed out. Not that is matters much but the interpretative problem flows from a peculiarity that has evolved most especially in medical science. I learned early – and had I not, it was also pounded intro my head – that the most useful information is often gleaned from the cases falling outside the area of significance. This area is defined by thousands of people in some medical investigations. And what do we know about them? Often nothing. Even in non-human studies where we could do much better, the focus is on targeted effects. The ITP studies appear to put little effort into understanding outliers, and their protocol criteria can exclude them definitionally.
Interesting re: telmisartan changing plasma empagliflozin concentration etc. Note: this in hypertensive diabetic RATS, if that is different in normotensive nondiabetic humans, I can’t say.
Pharmacokinetic interactions between three SGLT2 inhibitors and telmisartan: A focus on empagliflozin, ertugliflozin, and henagliflozin
“Our study manifested that telmisartan increased the plasma concentration-time curves (AUC0-t and AUC0–∞) and the maximum plasma concentrations (Cmax) of empagliflozin, whereas the apparent clearance (CLz/F) and apparent volume of distribution (Vz) significantly decreased(all p ＜ 0.05). Similarly, telmisartan increased the AUC0-t, AUC0-∞ and Cmax of henagliflozin and decreased the CLz/F(all p ＜ 0.05). When coadministered with ertugliflozin or henagliflozin, the AUC0-t and AUC0–∞of telmisartan decreased significantly and the CLz/F increased significantly(all p ＜ 0.05). Furthermore, PCR results demonstrated that telmisartan decreased the expression of BCRP expression in liver, intestines and kidney, P-gp expression in the intestines and kidney and OATP1B2 expression in liver tissue.”
Therefore, in Asian clinical practice, preferentially selecting an ARB with low P-gp inhibitory activity — such as olmesartan, valsartan, or losartan — over telmisartan may minimize avoidable bleeding risk, particularly in patients with elevated HAS-BLED scores.
If taken together with aspirin , does telmisartan increase the risk of GI bleeding and major bleeding? Would olmesartan potentially be a better choice?
Interesting. Because high dose telmisartan 80mg lowers afib risk - I posted a paper to that effect some time ago. Meanwhile, olmesartan seems to lower afib in pacemaker cases, but not otherwise per the ANTIPAF trial. Mabe that’s connected to P-gp inhibitory effect. In any case, at least telmisartan is not implicated in intracranial bleeding even in DOAC combo.
I find this interesting also because I take TM 80 mg and Empa 12.5 mg mostly to slow the age-related decline in kidney function. My unaided BP is ~120-125/70 (but with occasional higher peaks that TM has eliminated) and BG is on the right side of borderline but has been holding there for decades. When stipulated for the sake of analysis that rat study generalized and did the math, the implied nudges were small and since I’m taking the low dose of Empa, likely of no relevance. Another study I believe @CronosTempi posted earlier was of potentially greater concern suggesting that people like me who take both drugs might find that the TM is not slowing age related decline of kidney function.
Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD.
The AD protective benefits of telmisartan seem to be population-specific.
Blood-brain barrier-crossing blood pressure drugs linked to lower dementia risk
The contradiction is the earlier report (originally posted by Antoine):
Long-term risk of dementia with angiotensin receptor blockers versus angiotensin-converting enzyme inhibitors in hypertensive patients: A 15-year follow-up using the 45 and Up Study
So here we see olmesartan (which does not cross the BBB) was the standout wrt. both dementia and ACM, and by a country mile compared to telmisartan which barely lowered dementia HR, and was essentially a no show in ACM.
Meanwhile in the BBB crossing AHMs vs BBB non-crossing AHMs, we have the opposite effect, where telmi and cande result in robust lowering of dementia and ACM compared to olme and the rest of the BBB non-crossing cohorts.
Of course, we have to acknowledge statistical significance before drawing far going conclusions from apparent trend lines, and I wish they broke out the individual ARBs in the later report.