Telmisartan usage tied to increased lung cancer risk?

[superbigd]

I've come across multiple articles / studies stating that telmisartan is tied to increased risk of developing lung cancer specifically. What are your thoughts on this? stewie, gotgame, and notably lil slice?

A lot of information spread on prom about the "longevity" benefits if telmisartan, as illustrated in the life extension articles. The proposed increase in longevity is due to improved insulin sensitivity, mitochondrial function, and increased fat utilization from energy expenditure.

https://www.researchgate.net/public...se_of_Telmisartan_and_the_Incidence_of_Cancer

https://www.medscape.com/viewarticle/723447

https://www.cnbc.com/id/100780900
"The FDA must act now," Marciniak wrote senior FDA officials, noting he had found raw data from patients in drug studies showing a 24 percent increase in the risk of lung cancer compared to patients taking placebos or other drugs, the Journal reported.

 

[MyNameIsJeff]

As a user of Telmisartan, I hastily went to check the literature

The upshot is: Based on the currently available evidence, there is no increase in cancer risk from ARBs in general and Telmisartan in particular. Let's go through some studies.

First a study that supports the claim that ARBs increase cancer risk: Sipahi et al. (2010) conduct a meta-analysis of 5 RCTs with an ARB used. They find that ARBs increase the risk of developing cancer by 8 percent. So a person taking an ARBs would be 8% more likely to develop cancer than a person not taking it.
In addition, they find that ARBs increase the risk of lung cancer by 25 percent.

Findings
Telmisartan was the study drug in 30 014 (85·7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7·2% vs 6·0%, risk ratio [RR] 1·08, 95% CI 1·01–1·15; p=0·016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1·11 (95% CI 1·04–1·18, p=0·001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0·9% vs 0·7%, RR 1·25, 1·05–1·49; p=0·01). No statistically significant difference in cancer deaths was observed (1·8% vs 1·6%, RR 1·07, 0·97–1·18; p=0·183).

Interpretation
This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

https://www.sciencedirect.com/science/article/pii/S1470204510701066

Now this is only one study among many. Another meta-analysis (Teo et al., 2011) based on 15 RCTs finds no effect of ARBs on cancer overall and lung cancer in particular.

Results Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95–1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94–1.10), combination versus ARB alone 1.02 (95% CI 0.91–1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97–1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91–1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment.

Conclusion There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls.

https://journals.lww.com/jhypertens...of_telmisartan,_irbesartan,_valsartan,.1.aspx

So what could explain the different finding of the two studies? Let's see what Teo et a. (2011) argue:

However, a meta-analysis by Sipahi et al. [23] of selected ARB trials suggested a small but statistically significant increase in the risk of cancer. The majority of the data regarding some ARBs in this meta-analysis were obtained from preliminary data from US Food and Drug Administration databases, but the analyses were not based on an intention-to-treat approach, and furthermore, did not include several other large ARB trials. A more recent meta-analysis of antihypertensive treatment trials did not report excess cancer risk with ARBs but suggested that the risk might be increased with the combination of ARB and ACEi [24]

Now we can also see where that FDA employee referenced in OP's post got the idea about increased lung cancer. He and the Sipahi et al. (2010) study used a flawed methodology and only data from a limited number of studies. The Teo et a. (2011) study on the other hand uses all available RCTs with ARBs in their meta-analysis and employ a better methodology. So if you had to pick between the studies, clearly the Teo et a. (2011) paper finding no effect is superior.

One could be concerned that since Telmisartan has some important differences from other ARBs, the the cancer could also differ. First, Teo et a. (2011) found no evidence for this and their study design would have been able to detect such a differential effect.
Tascilar et al. (2016) perform a meta analysis of observational studies (which is not ideal of course), but they also find that Telmisartan does not increase cancer risk.

RESULTS:
The cohort consisted of 62,109 new ARB users, which included 3,438 telmisartan and 58,671 other ARB users. Compared with other ARBs, telmisartan use was not associated with an increased risk of cancer overall (16.3 vs. 15.0 per 1,000 person-years, respectively; adjusted HR: 0.93, 95% CI: 0.81-1.06) or by cancer site (lung, HR: 0.91, 95% CI: 0.55-1.51; breast, HR: 1.28, 95% CI: 0.90-1.82; prostate, HR: 0.79, 95% CI: 0.53-1.18; colorectal, HR: 1.41, 95% CI 0.95-2.10).

CONCLUSIONS:
Compared with other ARBs, telmisartan is not associated with an increased risk of cancer. This study provides reassurance as to the short-term safety of telmisartan.

https://www.ncbi.nlm.nih.gov/pubmed/27557862