I used Frontline for years, and had no problems with it. A couple years ago, my vet had me try Nexgard. It's worked just as well, with no issues.
I've only had to deal with Lyme's once. A few years ago, I forgot to treat my Lab before we went on a vacation fishing trip to northern Wisconsin. Sure enough, one evening I found a tick on him. The only one he's ever had. A few weeks after getting home, I took him to the vet for his annual exam and shots, and he tested positive for Lyme's. But, we caught it really early. My vet said it was the faintest positive read he's ever seen. He put my boy on a round or antibiotics, and he never showed any ill effects. Dodged a bullet there.