Oh there are some targets that would be much worse to combine with a stimulant.
hERG channel blockade for one, is a huge source of preclinical drug failure, because lots of drugs block it, and its blockade is sufficient to induce a really nasty condition called
torsades des pointes, which progresses into an extremely dangerous ventricular tachycardia that often ends in death. It works via extending the qt interval in the heart, which on its own can cause heartbeats to intersect, causing the above mentioned torsades des pointes.
Drugs that poison the Na+/K+ ATPase (like digoxin) also are rather dangerous. The Na+/K+ ATPase provides the ionic gradient that powers the cell (initially driving calcium removing pumps. When it's action is weakened the heart will have stronger beats, but the therapeutic index of these compounds makes them extremely dangerous (typically used for end-phase heart failure).
Finally you have things that could give you a heart attack, but also could give you a seizure, like the sodium channel agonist aconitine from the plant wolfsbane (pro tip: if a plant has bane in its name, it's probably very nasty). Aconitine jams sodium channels open causing excitable cells to fire uncontrollably. It's kind of a coin toss whether your neurons overload first and you die of a seizure or if you have a heart attack first and die of that.